General Best Practice Guidelines for Immunization: Introduction

Suggested citation: Kroger A, Bahta L, Long S, Sanchez P. General Best Practice Guidelines for Immunization. 

[www.cdc.gov/vaccines/hcp/acip-recs/general- recs/downloads/general-recs.pdf]. Accessed on [DATE].

1

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General Best Practice Guidelines for 

Immunization

BEST PRACTICES GUIDANCE 

Kroger A, Bahta L, Long S, Sanchez P
General Best Practice Guidelines for Immunization: Introduction

Suggested citation: Kroger A, Bahta L, Long S, Sanchez P. General Best Practice Guidelines for Immunization. 

[www.cdc.gov/vaccines/hcp/acip-recs/general- recs/downloads/general-recs.pdf]. Accessed on [DATE].

2

General Best Practice Guidelines for 

Immunization

Kroger A, Bahta L, Long S, Sanchez P

1. Introduction

The Centers for Disease Control and Prevention (CDC) recommends routine vaccination 

to prevent 17 vaccine-preventable diseases that occur in infants, children, adolescents, or 

adults. This report provides information for clinicians and other health care providers 

about concerns that commonly arise when vaccinating persons of various ages. Providers 

and patients must navigate numerous issues, such as the timing of each dose, screening 

for contraindications and precautions, the number of vaccines to be administered, the 

educational needs of patients and parents, and interpreting and responding to adverse 

events. Vaccination providers help patients understand the substantial body of 

(occasionally conflicting) information about vaccination. 

This vaccination best practice guidance is intended for clinicians and other health care 

providers who vaccinate patients in varied settings, including hospitals, provider offices, 

pharmacies, schools, community health centers, and public health clinics. The updated 

guidelines include 1) new information on simultaneous vaccination and febrile seizures; 

2) enhancement of the definition of a “precaution” to include any condition that might 

confuse diagnostic accuracy; 3) confirmation that if a patient is not acutely moderately or 

severely ill, vaccination during hospitalization is a best practice; 4) more descriptive 

characterization of anaphylactic allergy; 5) incorporation of protocols for management of 

anaphylactic allergy; 6) allowances for alternate route (subcutaneous instead of 

intramuscular) for hepatitis A vaccination; 7) an age cutoff of 12 years through 17 years of 

age for validating a dose of intradermal influenza vaccine; 8) deletion of much of the 
General Best Practice Guidelines for Immunization: Introduction

Suggested citation: Kroger A, Bahta L, Long S, Sanchez P. General Best Practice Guidelines for Immunization. 

[www.cdc.gov/vaccines/hcp/acip-recs/general- recs/downloads/general-recs.pdf]. Accessed on [DATE].

3

content from storage and handling, including storage units, temperature monitoring, and 

expiration dates (because this content is now codified and continually updated in the 

CDC’s Vaccine Storage and Handling Toolkit, available at 

https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html.); 9) incorporation 

of Infectious Diseases Society of America guidance on vaccination of persons with altered 

immunocompetence; 10) timing of intramuscular administration in patients with 

bleeding disorders; 11) updated data on vaccination record policy; 12) additional impacts 

of the Affordable Care Act (1,2) on adult vaccination; and 13) updated programmatic 

contact information on source material for vaccine information. 

The guidance is organized in the following 10 documents: 1) Timing and Spacing of 

Immunobiologics; 2) Contraindications and Precautions; 3) Preventing and Managing 

Adverse Reactions; 4) Vaccine Administration; 5) Storage and Handling of 

Immunobiologics; 6) Altered Immunocompetence; 7) Special Situations; 8) Vaccination 

Records; 9) Vaccination Programs; and 10) Vaccine Information Sources. A glossary 

follows (see Appendix 1: Glossary). 

This report will help vaccination providers to assess vaccine benefits and risks, use 

recommended administration practices, understand the most effective strategies for 

ensuring that vaccination coverage in the population remains high, and communicate the 

importance of vaccination to reduce the effects of vaccine-preventable disease. These best

practice guidelines are intended for use in the United States; vaccine availability, use, and 

epidemiologic circumstances might differ in other countries and might warrant different 

guidance.
General Best Practice Guidelines for Immunization: Introduction

Suggested citation: Kroger A, Bahta L, Long S, Sanchez P. General Best Practice Guidelines for Immunization. 

[www.cdc.gov/vaccines/hcp/acip-recs/general- recs/downloads/general-recs.pdf]. Accessed on [DATE].

4

REFERENCES

1. The Patient Protection and Affordable Care Act, Pub. L. No. 111-148 (2010).

2. U.S. Department of Health and Human Services. Read the law: the Affordable 

Care Act, section by section. 2015; https://www.hhs.gov/healthcare/about- thelaw/read-the-law/index.html. Accessed 9 March, 2017.
General Best Practice Guidelines for Immunization: History 5

2. History

The best practice guidelines in this report update the previous ACIP General 

Recommendations on Immunization (1) and are based both on review and analysis of 

available scientific evidence and on expert opinion of the diverse group of health-care 

providers and public health officials who are members of GRWG. This group includes 

professionals from academic medicine (pediatrics, family practice, and pharmacy); 

international (Canada), federal, and state public health professionals; and a member 

from the nongovernmental Immunization Action Coalition (see Appendix 2: 

Membership). This revision involved consensus-building based on new evidence from 

the published literature and opinion from subgroups of subject matter experts consulted 

on specific topics.

The process by which the guidelines were drafted varied for each document; each 

document is therefore discussed individually below. ACIP voted to accept the proposed 

guidance in October 2014; for additional information, see 

www.cdc.gov/vaccines/acip/meetings/meetings-info.html. 
General Best Practice Guidelines for Immunization: History 6

Timing and Spacing of Immunobiologics

GRWG met monthly beginning in January 2011, and formed a subgroup to focus on 

review of guidelines around administration of simultaneous vaccination and febrile 

seizures. Meetings were held in April, May, and June 2011 to discuss the evidence. Other 

issues related to timing and spacing of vaccinations were discussed between February 

2012 and September 2014 over 7 meetings (in February 2012, June 2012, August 2012,

November 2012, January 2013, January 2014, May 2014, and September 2014). The 

evidence supporting this document is based on expert opinion and arrived at by 

consensus. Presentations of the evidence were made to ACIP in June 2011, October 

2011, and February 2013. Major changes include 1) guidance for simultaneous 

vaccination in the context of a risk for febrile seizures and 2) clarification of the use of 

the grace period between doses of the measles, mumps, rubella, and varicella vaccine 

(MMRV).

Contraindications and Precautions

GRWG met monthly and focused on revisions to the Contraindications and Precautions 

section beginning in January 2012, over 6 meetings (January 2012, February 2012, June

2012, August 2012, November, 2012, December 2012, and January 2013; see 

www.cdc.gov/vaccines/acip/meetings/meetings-info.html). The evidence supporting 

this document is based on a review of the published literature. Publications about 

vaccination during surgery, hospitalization, and anesthesia were obtained from the 

databases PubMed and MDConsult, searched from 1973 to 2014 using the MeSH 

(medical subject headings) terms “anesthesia” and “immunization”. The search and 

selection of studies was limited to English-language and human studies. The search and 

selection process yielded 20 publications, including review articles, observational 

studies, and letters to the editor. Presentations of proposed best practices were made to 

ACIP in February 2013 and a vote from ACIP affirming the language below was made in 

October 2014. Major changes include 1) enhancement of the definition of a “precaution” 

to include any condition that might confuse diagnostic accuracy and 2) guidance to 

vaccinate during a hospitalization if a patient is not acutely moderately or severely ill.
General Best Practice Guidelines for Immunization: History 7

Preventing and Managing Adverse Reactions

GRWG met monthly and focused on revisions to the Preventing and Managing Adverse 

Reactions section beginning in April 2013, following revision to the document by the 

Allergy Subgroup. Selected members from this subgroup participated in the April 2013 

main work group call. GRWG then met again in May 2013. The evidence supporting this 

document is based on expert opinion and arrived at by consensus. Presentations of 

proposed guidance were made to ACIP in June 2013, and a vote from ACIP affirming the 

language below was made in October 2014. Major changes included 1) more descriptive 

characterization of anaphylactic allergy and 2) incorporation of protocols for managing 

adverse reactions. ACIP voted to accept the proposed statement in October 2014.

Vaccine Administration

An addition to the 2017 Vaccine Administration best practices was presented to ACIP on 

October 16, 2018, about health care provider exposure to vaccine components.

Storage and Handling of Immunobiologics

GRWG met in December 2013 to discuss Storage and Handling of Immunobiologics and 

met one additional time in January 2014. The evidence supporting this document is 

based on expert opinion and arrived at by consensus. A presentation of proposed 

language was made to ACIP in February 2014, and a vote from ACIP approving the 

language below was made in October 2014. Most of the 2011 language was removed 

because this content is now codified and continually updated in the CDC’s Vaccine 

Storage and Handling Toolkit, available at 

www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html. This content included 

Storage Units, Monitoring Storage Temperature, Vaccine Inventory, and Vaccine 

Transport.
General Best Practice Guidelines for Immunization: History 8

Altered Immunocompetence

GRWG met twice in March and April 2014 to discuss best practices guidance for Altered 

Immunocompetence. This section incorporates general content from the Infectious 

Diseases Society of America (IDSA) policy statement 2013 IDSA Clinical Practice

Guideline for Vaccination of the Immunocompromised Host (2), to which CDC 

provided input in November 2011. The evidence supporting this document is based on 

expert opinion and arrived at by consensus. ACIP voted to accept this proposed 

statement in June 2015.

Special Situations

GRWG met in April 2012 and then in 4 follow-up meetings in May, August, and 

November 2012, and January 2013. A focal point of discussion involved best practices 

guidance for intramuscular administration of persons with increased bleeding risk.

Subject matter experts from the National Center for Birth Defects and Developmental 

Disabilities (NCBDDD) were invited to a work group meeting, and revisions to the 

guidance involving the timing of intramuscular administration were made in 

collaboration with these subject matter experts, primarily to ensure that ACIP’s best 

practices guidance does not conflict with NCBDDD recommendations regarding the 

timing of clotting factor deficiency replacement. The evidence supporting this 

document is based on expert opinion and arrived at by consensus.

GRWG presented the Special Situations section to ACIP in February 2013. ACIP voted to 

accept the proposed statement in June 2015.
General Best Practice Guidelines for Immunization: History 9

Vaccination Records

GRWG met in August and September 2013, and presented the vaccination records 

language to ACIP in October 2013. The evidence supporting this document is based on 

expert opinion and arrived at by consensus. ACIP voted to accept this proposed best 

practices guidance in June 2015.

Vaccination Programs

GRWG met in April 2014. The major revision to this section is the addition of language 

related to Affordable Care Act (3,4) coverage of adult vaccination. The evidence 

supporting this document is based on expert opinion and arrived at by consensus.

GRWG presented this section to ACIP in June 2014. ACIP voted to accept this proposed 

statement in June 2015.

Vaccination Information Sources

GRWG met in September 2014 and presented this section to ACIP. The evidence 

supporting this document is based on expert opinion and arrived at by consensus. ACIP 

voted to accept this proposed statement in June 2015.
General Best Practice Guidelines for Immunization: History 10

REFERENCES

1. Kroger AT, Sumaya CV, Pickering LK, Atkinson WL. General recommendations 

on immunization: recommendations of the Advisory Committee on Immunization 

Practices (ACIP). MMWR Recomm Rep. 2011:1- 60.

2. Rubin L, Levin M, Ljungman P, et al. 2013 IDSA clinical practice guidelinefor 

vaccination of the immunocompromised host. Clin Infect Dis.

2014;58(3):e44-100. DOI: 10.1093/cid/cit684

3. The Patient Protection and Affordable Care Act, Pub. L. No. 111-148 (2010).

4. U.S. Department of Health and Human Services. Read the law: the Affordable 

Care Act, section by section. 2015; https://www.hhs.gov/healthcare/about- thelaw/read-the-law/index.html. Accessed 9 March, 2017.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 11

3. Timing and Spacing of Immunobiologics

Updates

Major changes to the best practice guidance for timing and spacing of immunobiologics 

include 1) guidance for simultaneous vaccination in the context of a risk for febrile seizures 

and 2) clarification of the use of the grace period between doses of MMRV.

General Principles for Vaccine Scheduling

Optimal response to a vaccine depends on multiple factors, including the type of vaccine, age 

of the recipient, and immune status of the recipient. Recommendations for the age at which 

vaccines are administered are influenced by age-specific risks for disease, age-specific risks 

for complications, age-specific responses to vaccination, and potential interference with the 

immune response by passively transferred maternal antibodies. Vaccines are generally 

recommended for members of the youngest age group at risk for experiencing the disease for 

which vaccine efficacy and safety have been demonstrated.

Vaccines can be divided into two general categories: live or non-live. Most live vaccines used 

in the United States are “live attenuated”, meaning that the microbe in the vaccine is alive but 

has been weakened (attenuated) through serial passage in cultures, or produced through 

genetic technology. One live vaccine licensed for use in the United States (oral adenovirus 

vaccine) is not attenuated. Live vaccines must replicate in order to induce an immune 

response. Several factors can interfere with replication, and these are a driving factor in the 

principles of timing and spacing of live vaccine. These principles will be discussed later in 

this chapter. Non-live vaccines can include whole or fractional vaccines produced by 

inactivating (killing) the microbe; or fractional vaccines such as recombinant vaccines, 

produced through genetic technologies. Also included under the category of non-live vaccines 

are toxoids, which generate an antibody response to toxins produced by a microbe rather 

than to the microbe itself. Several recently developed non-live vaccines do not contain 

antigen but employ RNA or DNA to instruct the recipient’s own cellular mechanism to 

generate antigenic material. Some vaccines described as “live attenuated” (e.g., Jynneos 

Smallpox/Monkeypox vaccine) do not replicate and for the purposes of timing and spacing 

recommendations behave like non-live vaccines. 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 12

Certain vaccines available outside the U.S. might be categorized differently as to vaccine type 

(e.g., live attenuated JE vaccine and live oral polio vaccine) (Table 3-1).

Tetanus and diphtheria toxoids require booster doses to maintain protective antibody 

concentrations (1). Unconjugated polysaccharide vaccines do not induce T-cell memory, and 

additional doses (although they elicit the same or a lower antibody concentration) might 

increase the duration of protection. Conjugation with a protein carrier improves the 

effectiveness of polysaccharide vaccines by inducing T-lymphocyte–dependent immunologic 

function (2). Many vaccines that stimulate both cell-mediated immunity and neutralizing 

antibodies (e.g., live, attenuated virus vaccines) can usually induce prolonged immunity, even 

if antibody titers decline over time (3). Subsequent exposure to such viruses usually results in 

a rapid anamnestic antibody response without viremia.

Approximately 90%-95% of recipients of a single dose of certain live vaccines administered 

by injection at the recommended age (i.e., measles, rubella, and yellow fever vaccines) 

develop protective antibodies, generally within 14 days of the dose. For varicella and mumps 

vaccines, 80%-85% of vaccines are protected after a single dose. However, because a limited 

proportion (5%-20%) of measles, mumps, and rubella (MMR) or varicella vaccinees fail to 

respond to 1 dose, a second dose is recommended to provide another opportunity to develop 

immunity (4). 

Of those who do not respond to the first dose of the measles component of MMR or varicella 

vaccine, 97%-99% respond to a second dose (5,6).

The Recommended Immunization Schedules for Persons Aged 0 Through 18 Years and 

the Recommended Adult Immunization Schedule are revised annually. Physicians and other 

health-care providers should ensure that they are following the most up-to-date schedules, which 

are available from CDC at www.cdc.gov/vaccines/schedules/hcp/index.html. 

Spacing of Multiple Doses of the Same Antigen

Vaccination providers should adhere to recommended vaccination schedules (Table 3-2).

Administration at recommended ages and in accordance with recommended intervals 

between doses of multidose antigens provides optimal protection.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 13

Administration of doses of a multidose vaccine using intervals that are shorter than 

recommended might be necessary in certain circumstances, such as impending international 

travel or when a person is behind schedule on vaccinations but needs rapid protection. In 

these situations, an accelerated schedule can be implemented using intervals between doses 

that are shorter than intervals recommended for routine vaccination (7). The accelerated or 

minimum intervals and ages for scheduling catch-up vaccinations are available at 

www.cdc.gov/vaccines/schedules/hcp/index.html. Vaccine doses should not be administered 

at intervals less than these minimum intervals or at an age that is younger than the minimum 

age.*(a)

Before administering a vaccine dose, providers might need to verify that all previous doses 

were administered after the minimum age and in accordance with minimum intervals (Table 

3-2). In clinical practice, vaccine doses occasionally are administered at intervals less than 

the minimum interval or at ages younger than the minimum age. Doses administered too 

close together or at too young an age can lead to a suboptimal immune response. However, 

administering a dose a few days earlier than the minimum interval or age is unlikely to have a 

substantially negative effect on the immune response to that dose. Known as the “grace 

period”, vaccine doses administered ≤4 days before the minimum interval or age are 

considered valid; however, local or state mandates might supersede this 4-day guideline 

(7).(b) (Day 1 is the day before the day that marks the minimum age or minimum interval for

a vaccine.) The scenario most applicable to the grace period is a visit to a provider several 

days prior to the date indicated by the minimum interval, such as for a mild illness. Followup is unlikely soon after or even for a longer period of time following this mild illness visit; 

this therefore raises the question of whether vaccines be administered during the mild illness 

visit to avoid missed opportunities to vaccinate. Because of the unique schedule for rabies 

vaccine and the accelerated Twinrix schedule the 4-day guideline does not apply to this 

vaccine (8, personal communication, Hepatitis A subject matter experts). Doses of any 

vaccine administered ≥5 days earlier than the minimum interval or age should not be 

counted as valid doses and should be repeated as age appropriate. The repeat dose should be 

spaced after the invalid dose by the recommended minimum interval (Table 3-2). For 

example, if the first and second doses of Haemophilus influenzae type b (Hib) were 

administered only 14 days apart, the second dose would be invalid and need to be repeated 

because the minimum interval from dose 1 to dose 2 is 4 weeks. 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 14

The repeat dose should be administered ≥4 weeks after the invalid dose (in this case, the 

second) (7). The repeat dose is counted as the valid second dose. If the first and second doses 

of hepatitis A vaccine were administered less than 6 months apart, the second dose is invalid 

and should be repeated 6 months after the invalid second dose (7). However, if this repeat 

dose (the third dose) is administered anytime 6 months or more after the first dose, the 

series can be considered complete. If the minimum interval between the second and third 

dose of hepatitis B vaccine is violated, or if the minimum age of the third dose is violated, the 

third dose of hepatitis B vaccine is invalid. The repeat dose can be administered as early as 8 

weeks after the 2nd valid dose as long as the dose is also after 24 weeks of age and 16 weeks 

after the 1st dose. (9)

If the first dose in a series is given ≥5 days before the recommended minimum age, the dose 

should be repeated on or after the date when the child reaches at least the minimum age (7). 

If the vaccine is a live vaccine, ensuring that a minimum interval of 28 days has elapsed from 

the invalid dose is recommended (7). For example, if the first dose of varicella vaccine were 

inadvertently administered at age 10 months, the repeat dose would be administered no 

earlier than the child’s first birthday (the minimum age for the first dose). If the first dose of 

varicella vaccine were administered at age 11 months and 2 weeks, the repeat dose should be 

administered no earlier than 4 weeks thereafter, which would occur after the first birthday.

Certain vaccines (e.g., adult tetanus and diphtheria toxoids [Td], pediatric diphtheria and 

tetanus toxoids [DT], tetanus toxoid) produce increased rates of local or systemic reactions in 

certain recipients when administered more frequently than recommended (10, 11).

Careful record keeping, maintenance of patient histories, use of immunization information 

systems (IISs), and adherence to recommended schedules can decrease the incidence of such

reactions without adversely affecting immunity.

Simultaneous Administration

Simultaneous administration of vaccines is defined as administering more than one vaccine 

on the same clinic day, at different anatomic sites, and not combined in the same syringe. 

Experimental evidence and extensive clinical experience provide the scientific basis for 

administering vaccines simultaneously (12). 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 15

Simultaneously administering all vaccines for which a person is eligible at the time of a visit 

increases the probability that a child, adolescent, or adult will be vaccinated fully by the 

appropriate age (13). A study conducted during a measles outbreak demonstrated that 

approximately one-third of measles cases among unvaccinated but vaccine-eligible preschool 

children might have been prevented if MMR had been administered at the same visit when 

another vaccine was administered (14). Simultaneous administration also is critical when 

preparing for foreign travel in the near future and when a health-care provider is uncertain 

that a patient will return for additional doses of vaccine.

With some exceptions, simultaneously administering the most widely used live and non-live 

vaccines has produced seroconversion rates and rates for adverse reactions similar to those 

observed when the vaccines are administered separately (12, 15-17). Routine administration 

of all age-appropriate doses of vaccines simultaneously is recommended for children for 

whom no specific contraindications exist at the time of the visit (7). MMR and varicella 

vaccine can be administered simultaneously (7). Live, attenuated influenza vaccine (LAIV) 

does not interfere with the immune response to MMR or varicella vaccines administered at 

the same visit (18). No data exist about the immunogenicity of oral Ty21a typhoid vaccine 

when administered concurrently or within 30 days of live-virus vaccines. In the absence of 

such data, if typhoid vaccination is warranted, administration should not be delayed because 

of recent administration of live, attenuated virus vaccines (19). 

Simultaneous administration of pneumococcal polysaccharide vaccine (PPSV) and 

inactivated influenza vaccine elicits a satisfactory antibody response without increasing the 

incidence or severity of adverse reactions (20). Simultaneous administration of PPSV23 and 

inactivated influenza vaccine is recommended for all persons for whom both vaccines are 

indicated. Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) 

and inactivated influenza vaccine (IIV) can be administered simultaneously (21). Hepatitis B 

vaccine administered with yellow fever vaccine is as safe and immunogenic as when these 

vaccines are administered separately (22). Measles and yellow fever vaccines have been 

administered safely at the same visit and without reduction of immunogenicity of either 

component (23,24).
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 16

During the 2010-2011 influenza season, surveillance systems detected safety signals for 

febrile seizures in young children following IIV and PCV13 vaccines (25). CDC studied the 

health-care visit records of more than 200,000 vaccinated children ages 6 months through 

59 months through the Vaccine Safety Datalink Project during the 2010-2011 influenza 

season. The analyses found that febrile seizures following IIV and PCV13 vaccines given to 

this age group were rare, but did occur at higher than expected rates. The risk for febrile 

seizures peaked in children age 16 months and were more common when the 2 vaccines were 

given during the same health-care visit. In this group, about one additional febrile seizure 

occurred among every 2,200 children vaccinated. After assessing benefits and risks, ACIP 

continues to recommend IIV and PCV13 be given concomitantly if both are recommended 

(25,26).

There are 2 exceptions to the recommendation that vaccines should be administered 

simultaneously. In persons with anatomic or functional asplenia and/or HIV infection, 

quadrivalent meningococcal conjugate vaccine (MCV4)-D (MenACWY-D, Menactra) and 

pneumococcal conjugate vaccine (PCV)13 (PCV13, Prevnar 13) should not be administered 

simultaneously (27). This is based on immunogenicity studies that showed reduced antibody 

concentrations for 3 serotypes of pneumococcus (subtypes 4, 6B, and 18C) when PCV7 was 

administered simultaneously with MenACWY-D. For persons with anatomic or functional 

asplenia and/or HIV, PCV13 should be administered first and MenACWY-D 4 weeks later.

In patients recommended to receive both PCV13 and PPSV23, the 2 vaccines should not be 

administered simultaneously (28). PCV13 should be administered first. If PPSV23 has been 

administered first, PCV13 should be administered no earlier than 8 weeks later in children 6-

18 years, and one year later in adults 19 years and older. Immunogenicity studies evaluating 

responses to PCV13 and PPSV23 administered in series showed a better immune response 

when PCV13 was administered first. An evaluation of immune response after a second 

pneumococcal vaccination administered 1 year after the initial study doses showed that 

subjects who received PPSV23 as the initial study dose had lower antibody responses after 

subsequent administration of PCV13 than those who had received PCV13 as the initial dose 

followed by a dose of PPSV23, regardless of the level of the initial response to PPSV23 

(29,30).
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 17

Depending on which vaccines are administered during the first year of life, a child might 

receive up to 9 injections at the 12- through 15-month visit (MMR, varicella, Hib, PCV13, 

pediatric diphtheria and tetanus toxoids and acellular pertussis [DTaP], inactivated 

poliovirus [IPV], hepatitis A, hepatitis B [HepB], and influenza vaccines). Although there is 

no exact limit on the number of injections, with a little flexibility, a provider can ensure that 

the primary series doses are given without administering too many injections at each visit. To 

reduce the number of injections at the 12- through 15-month visit, the hepatitis B series and 3 

doses of IPV (31) can be administered before the child’s first birthday.

There are many other examples of ways the vaccination schedule provides flexibility. The 

majority of children aged 1 year who have received 2 Hib vaccine doses (polyribosylribitol 

phosphate-meningococcal outer membrane protein [PRP-OMP]) or 3 Hib vaccine doses 

(PRP-tetanus [PRP-T]) and 3 previous doses of DTaP and PCV13 have protection against 

Hib, diphtheria, pertussis, tetanus, and pneumococcus, which lasts throughout infancy 

(2, 32). The third (PRP-OMP) or fourth (PRP-T) dose of the Hib series and the fourth doses 

of DTaP and PCV13 are critical in boosting antibody titer and ensuring continued protection 

(2, 33-35). The fourth dose of DTaP is recommended at age 15-18 months but may be 

administered as early as age 12 months if 6 months have elapsed since the third dose and if 

there is concern that the child might not return by age 18 months (33). For infants at low risk 

for infection with hepatitis B virus (i.e., mother tested negative for hepatitis B surface antigen 

[HBsAg] at the time of delivery and is not in a high risk group), the hepatitis B series can be 

completed at any time for children aged 6-18 months (36). The minimum age for 

administration of combination vaccines is the oldest minimum age for any of the individual 

components; the minimum interval between doses is equal to the greatest minimum interval 

of any of the individual components. Recommended spacing of doses should be 

maintained (Table 3-2).

Combination Vaccines

Combination vaccines merge equivalent component vaccines into single products to prevent 

more than one disease or to protect against multiple strains of infectious agents causing the 

same disease. Licensed combination vaccines can be used whenever any components of the 

combination are indicated and its other components are not contraindicated and if licensed 

by the Food and Drug Administration (FDA) for that dose in the series. 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 18

Use of combination vaccines can reduce the number of injections patients receive and 

alleviate concern associated with the number of injections (29,37,38). Studies have 

demonstrated that parents and providers might be uncomfortable with multiple injections 

during single visits (39-41). Potential advantages of combination vaccines include 1) 

improved vaccine coverage rates (42), 2) timely vaccination coverage for children who are 

behind in the schedule (43, 44), 3) reduced shipping and stocking costs, 4) reduced costs for 

extra health care visits necessitated by deferral of vaccination, and 5) facilitation of 

additional new vaccines into vaccination programs.

Potential disadvantages of combination vaccines include the following: 1) adverse events that 

might occur more frequently after administration of a combination vaccine compared with 

administration of separate antigens at the same visit, such as fever that occurs with the 

combination MMRV vaccine and combination DTaP-HepB-IPV vaccine (45,46); 2) confusion 

and uncertainty about selection of vaccine combinations and schedules for subsequent doses, 

especially when vaccinations are given by multiple providers who might be using different 

products; 3) reduced pathogen coverage if the combination product covers fewer types of one 

particular vaccine-preventable disease-causing agent (47); 4) extra doses of certain antigens 

in the combination product (e.g., a provider who administers 4 doses of DTaP-HepB-IPV 

vaccine will give an extra dose of hepatitis B component); and 5) a shorter shelf-life than the 

individual component vaccines. The economic impact of the use of combination vaccines is 

unclear because combination products have the potential for either increased or decreased 

costs compared with single-antigen component vaccines. The price of a combination vaccine 

might exceed the total price of separate vaccines containing the same antigens. However, 

combination vaccines might represent a better overall economic value if the direct and 

indirect costs of extra injections, delayed or missed vaccinations, and additional handling 

and storage are taken into consideration (48).

Licensed Combination Vaccines

In this report, a combination vaccine is defined as a product containing components that can 

be divided equally into independently available routine vaccines. A dash ( – ) between 

vaccine products indicates that products are supplied in their final form by the manufacturer 

and do not require mixing or reconstitution by the user. A slash ( / ) indicates that the 

products must be mixed or reconstituted by the user. 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 19

Seven combination vaccines for which separate antigens or antigen combinations exist have 

been licensed by FDA since 1996 in the United States (Table 3-3) (49-55). In the future, 

combination vaccines might include increasing numbers of components in different arrays to 

protect against these and other diseases. The use of a combination vaccine generally is 

preferred over separate injections of the equivalent component vaccines (56). Considerations 

should include provider assessment,(c) patient preference, and the potential for adverse 

events. An exception is the first dose of MMRV. Unless the parent or caregiver expresses a 

preference for MMRV vaccine, MMR and varicella vaccine should be administered for the 

first dose for children aged 12-47 months (see Contraindications and Precautions) (45).

Situations might arise in which one component of a combination vaccine is specifically 

preferred to another component in that same vaccine. Future research considerations for 

newly licensed combination vaccines should focus on safety of doses that are not needed 

because a patient is already vaccinated against the agents, whether the combination vaccine 

will improve the timeliness of vaccination, and potential reduced costs from disease 

prevention resulting from timely vaccination.

Combination Vaccines and FDA Licensure

Only combination vaccines licensed by FDA should be used (56). Vaccination providers 

should not combine separate vaccines into the same syringe to administer together unless 

mixing is indicated for the patient’s age and is explicitly specified on the FDA-approved 

product label inserts. Only 2 combination vaccines, (DTaP-IPV/Hib vaccine, marketed as 

Pentacel, and Hib-MenCY, marketed as MenHibrix) contain separate antigen components for 

which FDA approves mixing by the user. The safety, immunogenicity, and effectiveness of 

unlicensed combinations are unknown.

Interchangeability of Formulations

FDA generally licenses a combination vaccine based on studies demonstrating that the 

product’s immunogenicity (or efficacy) and safety are comparable or equivalent to 

monovalent or combination products licensed previously (38). 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 20

FDA licensure also generally indicates that a combination vaccine may be used 

interchangeably with monovalent formulations and other combination products with similar 

component antigens produced by the same manufacturer to continue the vaccination series. 

For example, DTaP, DtaP-IPV/Hib, DtaP-HepB-IPV, and future DtaP vaccines that contain 

similar acellular pertussis antigens from the same manufacturer may be used 

interchangeably if licensed and indicated for the patient’s age (35).

Interchangeability of Combination Vaccines from Different 

Manufacturers

Licensure of a vaccine by FDA does not necessarily indicate that the vaccine is 

interchangeable with products from other manufacturers. Such data are ascertained and 

interpreted more readily for diseases with known correlates of protective immunity (e.g., 

specific serologic markers). For diseases without such surrogate laboratory markers, 

prelicensure field vaccine efficacy (phase III) trials or postlicensure surveillance generally are 

required to determine protection (57). ACIP prefers that doses of vaccine in a series come 

from the same manufacturer; however, if this is not possible or if the manufacturer of doses 

given previously is unknown, providers should administer the vaccine that they have 

available.

Vaccine Supply

Although vaccination providers should stock sufficient quantities of combination and 

monovalent vaccines needed to vaccinate children, adolescents, and adults against all 

diseases for which vaccines are recommended (29, 38), all available types or brand-name 

products need not be stocked. Potential advantages of stocking a limited number of vaccines 

include 1) reducing confusion and potential errors when staff members must handle 

redundant products and formulations, 2) minimizing waste when less commonly used 

products expire, 3) decreasing cold storage capacity requirements, and 4) minimizing 

administrative costs related to accounting, purchasing, and handling. The National Pediatric 

Vaccine Stockpile exists to offset supply challenges (58).
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 21

Extra Doses of Vaccine Antigens

Administering extra antigens contained in a combination vaccine should be avoided in most 

situations (56). Using combination vaccines containing certain antigens not indicated at the 

time of administration to a patient might be justified when 1) the extra antigen is not 

contraindicated, 2) products that contain only the needed antigens are not readily available, 

and 3) potential benefits to the patient outweigh the potential risk for adverse events 

associated with the extra antigens. An extra dose of many live-virus vaccines and Hib or 

hepatitis B vaccine has not been found to be harmful (59,60). However, the risk for an 

adverse event might increase when extra doses are administered at an earlier time than the 

recommended interval for certain vaccines (e.g., tetanus toxoid vaccines and PPSV) 

(20, 33, 61).

A vaccination provider might not have vaccines available that contain only the antigens 

needed as indicated by a child’s vaccination history. Alternatively, although the indicated 

vaccines might be available, the provider might prefer to use a combination vaccine to reduce 

the required number of injections. In such cases, the benefits and risks of administering the 

combination vaccine with an unneeded antigen should be carefully considered and discussed 

with the patient or parent.

When non-live vaccines (which are often adsorbed to aluminum-salt adjuvants) are 

administered, the reactogenicity of the vaccine must be considered in balancing the benefits 

and risks of extra doses (56). Because clinical experience suggests low reactogenicity, an 

extra dose of Hib or hepatitis B vaccine may be administered as part of a combination 

vaccine to complete a vaccination series for another component of the combination. 

Administration of extra doses of tetanus toxoid vaccines earlier than the recommended 

intervals can increase the risk for severe local reactions (21, 34). Examples of such vaccines 

include DtaP, DT (for children), and Td (for adolescents and adults). Extra doses of tetanustoxoid–containing vaccines might be appropriate for certain patients, including for children 

who previously received DT or Td vaccine and need protection from pertussis (in DtaP or 

Tdap) or for immigrants with uncertain vaccination histories.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 22

Conjugate Vaccine Carrier Proteins

Protein conjugates used in Hib conjugate vaccines produced in the United States include 

tetanus toxoid (in PRP-T) which is also used as a component of DtaP and Tdap vaccines (21).

Simultaneous or sequential vaccination with Hib and these tetanus-toxoid containing 

vaccines is recommended when both are indicated (56). MCV4 and PCV13 both contain 

diphtheria-toxoid conjugates. There has been concern about simultaneous administration of 

vaccines containing like conjugates. One brand of MCV4, MenACWY-D (Menactra), 

demonstrates reduced immunogenicity of the antibody response to Streptococcal pneumonia 

strains when administered simultaneously with PCV13 compared with separate 

administration. It is recommended to space these vaccines by 28 days in a person with 

anatomic asplenia (47). Simultaneous or sequential vaccination of MCV4-CRM (Menveo), 

PCV13, and Tdap (34, 62), all of which contain diphtheria toxoid, is not associated with 

reduced immunogenicity or increase in local adverse events.

Nonsimultaneous Administration

There is no evidence that non-live vaccines interfere with the immune response to other nonlive vaccines or to live vaccines. Any non-live vaccine can be administered either 

simultaneously or at any time before or after a different non-live vaccine or live vaccine 

(Table 3-4). The 2 exceptions, as mentioned above, are a 4-week interval between PCV13 and 

MenACWY-D in a person with anatomic asplenia and the separation of doses between PCV13 

and PPSV23 (6-12 months recommended for non-high risk, 8 week minimum) if PCV13 is 

given first, 8 weeks in children 6-18 years, and 1 year minimum in adults 19 years and older if 

PPSV23 is given first (27). 

Limited data are available regarding interference between live vaccines used in the United 

States. The immune response to one live-virus vaccine might be impaired if administered 

within 28 days (i.e., 4 weeks) of another live-virus vaccine (63,64). In a study conducted in 2 

U.S. health maintenance organizations, the risk for varicella vaccine failure (i.e., varicella 

disease in a vaccinated person) among persons who received varicella vaccine within 28 days 

of MMR vaccination was threefold higher than among persons who received varicella vaccine 

>28 days after MMR vaccination (65). Another study determined that the response to yellow 

fever vaccine is not affected by monovalent measles vaccine administered 1-27 days earlier 

(23). 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 23

The effect of nonsimultaneous administration of rubella, mumps, varicella, and yellow fever 

vaccines is unknown.

Two or more injectable or nasally administered live vaccines not administered on the same 

day should be separated by at least 4 weeks (Table 3-4), to minimize the potential risk for 

interference. If 2 such vaccines are separated by <4 weeks, the second vaccine administered 

should not be counted and the dose should be repeated at least 4 weeks later. On the day a 

live injectable or intranasal vaccine will be administered, providers should ensure that no live 

injectable or intranasal vaccine was given in the previous 28 days.

The 4-day grace period discussed earlier, which may be used to shorten the minimum 

interval between doses of the same vaccine, should not be applied to this 4-week interval 

between 2 different live vaccines (56). Confusion about this prohibition may arise when 2 live 

vaccines whose intervals are identical are administered simultaneously. For example, if MMR 

and varicella vaccines are administered on the same day, the second dose of each vaccine 

could come due 4 weeks later (depending on the patient’s age). If either vaccine had been 

given alone at both time points, the 4-day grace period could be applied to the second dose. 

But in this situation the live vaccine rule prevents the grace period from being applied to the 

second dose of either vaccine, because Varicella-2, if administered earlier than 4 weeks, could 

potentially be affected by MMR1, and likewise MMR2 could be affected by Varicella-1. Note 

that this prohibition also applies if the combination MMRV is used rather than individual 

MMR and varicella vaccines.

The oral vaccines Ty21a typhoid vaccine and rotavirus can be administered simultaneously 

with or at any interval before or after other live vaccines (injectable or intranasal) if indicated 

(66).

Spacing of Vaccines and Antibody-Containing Products

Live Vaccines

Ty21a typhoid, yellow fever, LAIV, and rotavirus vaccines may be administered at any time 

before, concurrent with, or after administration of any antibody-containing preparation such 

as immune globulin, hyperimmune globulin, or intravenous immune globulin (IGIV) (67). 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 24

Blood (e.g., whole blood, packed red blood cells, and plasma) and other antibody-containing 

blood products (e.g., immune globulin, hyperimmune globulin, and IGIV) can inhibit the 

immune response to measles and rubella vaccines for ≥3 months. The effect of blood and 

immune globulin preparations on the response to mumps and varicella vaccines is unknown; 

however, commercial immune globulin preparations contain antibodies to these viruses. 

Blood products available in the United States are unlikely to contain a substantial amount of 

antibody to yellow fever virus. The length of time that interference with injectable live-virus 

vaccine (other than yellow fever) can persist after the antibody-containing product is a 

function of the amount of antigen-specific antibody contained in the product (68,70). 

Therefore, after an antibody-containing product is received, live vaccines (other than Ty21a 

typhoid, yellow fever, LAIV, and rotavirus vaccines) should be delayed until the passive 

antibody has degraded (Table 3-5). In circumstances where there is high-risk of vaccinepreventable disease it is acceptable to administer a dose of vaccine prior to completion of this 

interval. If a dose of injectable live-virus vaccine (other than yellow fever) is administered 

after an antibody-containing product but at an interval shorter than recommended in this 

report, the vaccine dose should be repeated. The repeat dose should be administered at the 

interval indicated for the antibody-containing product, after the invalid dose of vaccine 

(Table 3-6). Immunogenicity and safety of dengue vaccine after administration of 

intravenous immunoglobulin (IGIV) and other immunoglobulin containing products has not 

been studied. Clinicians considering dengue vaccine for persons who recently received blood 

products (including IGIV) or other immunoglobulin containing products should delay prevaccination testing and administration of vaccine doses by 12 months. 

Although passively acquired antibodies can interfere with the response to rubella vaccine, the 

low dose of anti-Rho(D) globulin or any other blood product administered to postpartum 

women have not been demonstrated to reduce the response to the RA27/3 strain rubella 

vaccine (71). Congenital rubella syndrome and congenital varicella are conditions with 

considerable morbidity and represent a true risk in future pregnancies. Because of the 

importance of rubella and varicella immunity among women of child-bearing age (4, 72), the 

postpartum vaccination of women without evidence of immunity to rubella or varicella with 

MMR, varicella, or MMRV vaccines should not be delayed because of receipt of anti-Rho(D) 

globulin or any other blood product during the last trimester of pregnancy or at delivery. 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 25

Any reduction in immunity caused by anti-Rho(D) globulin or other blood products is 

outweighed by the opportunity to generate immunity. These women should be vaccinated 

immediately after giving birth and, if possible, tested ≥3 months later to ensure immunity to 

rubella and, if appropriate, to measles (2). Measles and rubella serologies have a low falsepositive rate and are therefore acceptable for use in this limited postpartum context.

Interference might occur if administration of an antibody-containing product becomes 

necessary after administration of MMR or varicella vaccines. Usually, vaccine virus 

replication and stimulation of immunity occurs 1-2 weeks after vaccination. If the interval 

between administration of any of these vaccines and subsequent administration of an 

antibody-containing product is <14 days, vaccination should be repeated after the 

recommended interval (Tables 3-5 and 3-6) unless serologic testing indicates a protective 

antibody response (7).

A humanized mouse monoclonal antibody product (palivizumab) is available as prophylaxis 

for serious lower respiratory tract disease from respiratory syncytial virus among infants and 

young children. This product contains only antibody to respiratory syncytial virus and does 

not interfere with the immune response to licensed live or non-live vaccines.

Non-live Vaccines

Antibody-containing products interact less with non-live vaccines compared with live 

vaccines (73). Therefore, administering non-live vaccines either simultaneously with or at 

any interval before or after receipt of an antibody-containing product should not 

substantially impair development of a protective antibody response (Table 3-5). The vaccine 

or toxoid and antibody preparation should be administered at different sites using the 

standard recommended dose.

Interchangeability of Single-Component Vaccines from 

Different Manufacturers

Certain vaccines that provide protection from the same diseases are available from different 

manufacturers, and these vaccines usually are not identical in antigen content or in amount 

or method of formulation. 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 26

Manufacturers use different production processes, and their products might contain different 

concentrations of antigen per dose or a different stabilizer or preservative.

Available data indicate that infants who receive sequential doses of different Hib conjugate, 

hepatitis B, and hepatitis A vaccines produce a satisfactory antibody response after a 

complete primary series (74-77). 

All brands of Hib conjugate, hepatitis B,(d)hepatitis A, rotavirus,(e) and quadrivalent 

meningococcal conjugate vaccines are interchangeable within their respective series. 

If different brands of a particular vaccine require a different number of doses for series 

completion (e.g., Hib and rotavirus vaccines) and a provider mixes brands in the primary 

series, the higher number of doses is recommended for series completion (e.g., doses of 

either rotavirus or Hib vaccine). For Hib vaccines, any monovalent or combination conjugate 

vaccine is acceptable for the booster dose of the series, if only one product was used for the 

primary series (56).

Limited data are available about the safety, immunogenicity, and efficacy of using acellular 

pertussis (i.e., DTaP) vaccines from different manufacturers for successive doses of the 

pertussis series. Data from one study indicate that for the first 3 doses of the DTaP series, 1-2 

doses of Tripedia (Sanofi Pasteur) followed by Infanrix (GlaxoSmithKline) for the remaining 

dose (or doses) is comparable to 3 doses of Tripedia with regard to immunogenicity, as 

measured by antibodies to diphtheria, tetanus, and pertussis toxoids, and filamentous 

hemagglutinin (78). However, in the absence of a clear serologic correlate of protection for 

pertussis, the relevance of these immunogenicity data for protection against pertussis is 

unknown. When feasible, the same brand of DTaP vaccine should be used for all doses of the 

vaccination series (56). If vaccination providers do not know or have available the type of 

DTaP vaccine previously administered to a child, any DTaP vaccine may be used to continue

or complete the series (56). For a child who needs 2 doses of influenza vaccine (IIV or LAIV), 

it is preferable to use the same type of vaccine for both doses. However, if the child is eligible 

for either IIV or LAIV, and the type of vaccine used for the first dose is not available, either 

vaccine can be used for the second dose (56). In a postlicensure study, meningococcal 

conjugate vaccines from different manufacturers were evaluated for successive doses of 

meningococcal conjugate vaccine. Persistence of antibodies were studied in recipients of 

MCV4-CRM after previous receipt of either MCV4-CRM or MenACWY-D. 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 27

The percentage of persons with protective titers were the same for all serogroups. 

No data exist on the use of MenACWY-D after MCV4-CRM. Health-care providers should use 

every opportunity to provide a dose when indicated, regardless of the vaccine brand used for 

the previous dose or doses. For vaccines in general, vaccination should not be deferred 

because the brand used for previous doses is not available or is unknown (29, 79).

Lapsed Vaccination Schedule

Vaccination providers should administer vaccines as close to the recommended intervals as 

possible. However, intervals between doses that are longer than recommended typically do 

not reduce final antibody concentrations, although protection might not be attained until the 

recommended number of doses has been administered. With some exceptions (e.g. oral 

typhoid vaccine) an interruption in the vaccination schedule does not require restarting the 

entire series of a vaccine or toxoid or addition of extra doses (7).

Unknown or Uncertain Vaccination Status

Vaccination providers frequently encounter persons who do not have adequate 

documentation of vaccinations. With the exception of influenza vaccine and PPSV23, 

providers should only accept written, dated records as evidence of vaccination; self-reported 

doses of influenza vaccine and PPSV23 are acceptable (61,80). The rationale for acceptance 

for influenza vaccine is that the time period of recall is one year or less, making it very likely 

that correct recall will occur. The rationale for acceptance for PPSV23 is high frequency of 

vaccination leads to an increased rate of local reactions due to the reactogenicity of this 

vaccine. Although vaccinations should not be postponed if records cannot be found, an 

attempt to locate missing records should be made by contacting previous health care 

providers, reviewing state or local IISs, and searching for a personally held record. If records 

cannot be located within a reasonable time, these persons should be considered susceptible 

and started on the age-appropriate vaccination schedule. While serology should generally 

NOT be performed to ascertain evidence of immunity, serologic testing for immunity is an 

alternative to vaccination for certain antigens (e.g., measles, rubella, hepatitis A, and 

tetanus). 
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 28

However, commercial serologic testing might not always be sufficiently sensitive or 

standardized for detection of vaccine-induced immunity (with the exception of hepatitis B 

vaccination at 1-2 months after the final dose), and research laboratory testing might not be 

readily available. An exception to the prohibition on serologic testing is dengue. Laboratory 

testing to ascertain immunity to dengue (of which serology is one option) must be performed 

prior to vaccination, and only those individuals who are positive should be vaccinated.

(a) During measles outbreaks, if cases are occurring among infants aged <12 months, measles vaccination of infants as young as 6 months 

can be used as an outbreak control measure. However, doses administered at ages <12 months should not be counted as part of the 

series (81).

(b) In certain situations, local or state requirements might mandate that doses of selected vaccines be administered on or after specific 

ages. For example, a school entry requirement might not accept a dose of MMR or varicella vaccine administered before the child’s first 

birthday. ACIP recommends that physicians and other health-care providers comply with local or state vaccination requirements when

scheduling and administering vaccines.

(c) Provider assessment should include number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient 

return, and storage and cost considerations.

(d) The exception is the 2-dose hepatitis B vaccination series for adolescents aged 11-15 years. Only Recombivax HB (Merck Vaccine 

Division) should be used in the schedule. Engerix-B (GlaxoSmithKline) is not approved by FDA for this schedule.

(e)Based on expert opinion.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 29

TABLE 3-1 Types of Vaccines

Vaccine Category Examples

Live Oral adenovirus vaccine*

Live attenuated ACAM2000 smallpox vaccine

Bacille Calmette Guerin (BCG) vaccine

Dengue vaccine

Ebola vector vaccine

Live attenuated influenza vaccine (LAIV)

Live oral typhoid vaccine (Ty21a)

Measles-mumps-rubella – containing (MMR, 

MMRV)

Oral cholera vaccine

Rotavirus vaccines (RV1, RV5)

Varicella (Var) vaccine

Yellow Fever vaccine

Non-live Anthrax vaccine

COVID-19 vaccines (Pfizer, Moderna, 

Novavax)

Haemophilus influenzae type b (Hib) 

vaccines

Hepatitis A (HepA) vaccines

Hepatitis B (HepB) vaccines

Human papillomavirus (HPV) vaccines

Inactivated poliovirus vaccine (IPV)

Inactivated typhoid vaccine (Typhim Vi)

Influenza vaccines (IIV4, RIV4)

Japanese Encephalitis Vaccine (JEV)

Meningococcal conjugate (MenACWY) 

vaccine

Pneumococcal conjugate vaccines (PCV13, 

PCV20, PCV15)

Pneumococcal polysaccharide vaccine 

(PPSV23)

Rabies vaccine

Recombinant zoster vaccine (RZV)

Respiratory syncytial virus vaccine (RSV)

Serogroup B meningococcal (MenB) vaccines 

(MenB-FHbp, MenB-4C)

Tetanus-toxoid, diphtheria-toxoid, or 

pertussis-containing vaccines (DTaP, Tdap, 

DT, Td, DTaP-HepB-IPV, DTaP-IPV/Hib, 

DTaP-IPV, DTaP-IPV-Hib-HepB)†

Non-replicating§ COVID-19 vaccine (Janssen)

Jynneos smallpox/monkeypox vaccine * Oral adenovirus vaccine is used primarily in the military for prevention of adenovirus 

infection. It should not be confused with Janssen COVID-19 vaccine which is used for the 

prevention of SARS-CoV-2 infection

† The tetanus-toxoid components of these vaccines are toxoids, not vaccines.

§ These vaccines do not replicate and therefore behave like non-live vaccines.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 30

TABLE 3-2. Recommended and minimum ages and intervals between 

vaccine doses(a),(b),(c),(d)

Known as the “grace period”, vaccine doses administered ≤4 days before the minimum 

interval or age are considered valid; however, local or state mandates might supersede 

this 4-day guideline

“3 calendar months” (or fewer) can be converted into weeks per the formula “1 month = 4 

weeks”

Vaccine and 

dose 

number

Recommended 

age for this dose

Minimum 

age for this 

dose

Recommended 

interval to next 

dose

Minimum 

interval to 

next dose

DEN4CYD-1 9—16 years 9 years 6 months 5 months after 

age at 1st dose

DEN4CYD-2 9—16 years 9 years + 5 

months

6 months 5 months after 

age at second 

dose

DEN4CYD-3 9—16 years 9 years +10 

months

— —

DTaP-1(e) 2 months 6 weeks 8 weeks 4 weeks

DTaP-2 4 months 10 weeks 8 weeks 4 weeks

DTaP-3 6 months 14 weeks 6-12 months(f) 6 months(f)

DTaP-4 15-18 months 15 months(f) 3 years 6 months

DTaP-5(g) 4-6 years 4 years — —

HepA-1(e) 12-23 months 12 months 6-18 months 6 months

HepA-2 ≥18 months 18 months — —

HepB-1(h) Birth Birth 4 weeks-4 months 4 weeks

HepB-2 1-2 months 4 weeks 8 weeks-17 months 8 weeks

HepB-3(i) 6-18 months 24 weeks — —

Hib-1(j) 2 months 6 weeks 8 weeks 4 weeks

Hib-2 4 months 10 weeks 8 weeks 4 weeks

Hib-3(k) 6 months 14 weeks 6-9 months 8 weeks

Hib-4 12-15 months 12 months — —

HPV Two Dose Series(l)
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 31

HPV-1 11-12 years 9 years 6 months 5 months

HPV-2 11-12 years (+6 

months)

9 years + 5 

months(m)

— —

HPV Three Dose Series

HPV-1(n) 11-12 years 9 years 1-2 months 4 weeks

HPV-2 11-12 years (+1-2 

months)

9 years (+4 

weeks)

4 months 12 weeks(n)

HPV-3(n) 11-12 years (+6 

months)

9 years (+5 

months)

— —

Influenza, 

inactivated(o)

≥6 months 6 months(p) 4 weeks 4 weeks

IPV-1(e) 2 months 6 weeks 8 weeks 4 weeks

IPV-2 4 months 10 weeks 8 weeks-14 months 4 weeks

IPV-3 6-18 months 14 weeks 3-5 years 6 months

IPV-4(q) 4-6 years 4 years — —

LAIV(o) 2-49 years(r) 2 years 4 weeks 4 weeks

MenACWY-1(s) 11-12 years 2 months(t) 4-5 years 8 weeks

MenACWY-2 16 years 11 years (+8 

weeks)(u)

— —

MenB-1 Healthy adolescents: 

16-23 years

16 years Bexsero: 4 weeks

Trumenba: 6 

months(c)

Bexsero: 4 

weeks

Trumenba: 6 

months(c)

Persons at increased 

risk: ≥10 years

10 years Bexsero: 4 weeks

Trumenba: 1-2 

months(c)

Bexsero: 4 

weeks

Trumenba: 1 

month

MenB-2 Healthy adolescents: 

16-23 years (+1 

month)

16 years (+1 

month)

— —

Persons at increased 

risk: ≥10 years (+1 

month)

10 years (+1 

month)

Bexsero: —

Trumenba: 4-5 

months(c)

Bexsero: —

Trumenba: 4 

months(c)
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 32

MenB-3(v) Persons at increased 

risk: ≥ 10 years (+ 6 

months(c))

10 years (+ 6 

months(c))

— —

MMR-1(w) 12-15 months 12 months 3-5 years 4 weeks

MMR-2(w) 4-6 years 13 months — —

PCV13-1(j, x) 2 months 6 weeks 8 weeks 4 weeks

PCV13-2 4 months 10 weeks 8 weeks 4 weeks

PCV13-3 6 months 14 weeks 6 months 8 weeks

PCV13-4 12-15 months 12 months — —

PCV15 See footnote x below

PCV20 See footnote x below

PPSV-1 — 2 years 5 years 5 years

PPSV-2(y) — 7 years — —

Rotavirus-1(z) 2 months 6 weeks 8 weeks 4 weeks

Rotavirus-2 4 months 10 weeks 8 weeks 4 weeks

Rotavirus-3(z) 6 months 14 weeks — —

Td 11-12 years 7 years 10 years 5 years

Tdap(aa) ≥11 years 7 years — —

Varicella-1(w) 12-15 months 12 months 3-5 years 12 weeks(bb)

Varicella-2(w) 4-6 years 15 months(cc) — —

RZV - 1 ≥50 years 50 years(dd) 2-6 months 4 weeks

RZV - 2 ≥50 years (+ 2-6 

months)

50 years — —
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 33

Abbreviations: DEN4CYD = dengue vaccine; DTaP = diphtheria and tetanus toxoids and acellular pertussis; HepA = 

hepatitis A; HepB = hepatitis B; Hib = Haemophilus influenzae type b; HPV = human papillomavirus; IPV = 

inactivated poliovirus; LAIV = live, attenuated influenza vaccine; MenACWY = quadrivalent meningococcal conjugate 

vaccine; MenB = serogroup B meningococcal vaccine; MenB-4C = Bexsero; MenB-FHbp = Trumenba; MMR = 

measles, mumps, and rubella; MMRV

= measles, mumps, rubella, and varicella; MPSV4 = quadrivalent meningococcal polysaccharide vaccine; PCV13 = 

pneumococcal conjugate vaccine; PPSV23= pneumococcal polysaccharide vaccine; PRP-OMP = polyribosylribitol 

phosphate-meningococcal outer membrane protein conjugate; RZV = recombinant zoster vaccine; Td = tetanus and 

diphtheria toxoids; Tdap = tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis.

(a) Combination vaccines are available. Use of licensed combination vaccines is generally preferred to separate 

injections of their equivalent component vaccines. When administering combination vaccines, the minimum age for 

administration is the oldest age for any of the individual components. The minimum interval between doses is equal to 

the greatest interval of any of the individual components.

(b) Information on travel vaccines, including typhoid, Japanese encephalitis, and yellow fever, is available at 

https://www.cdc.gov/travel. Information on other vaccines that are licensed in the United States but not distributed, 

including anthrax and smallpox, is available at http://emergency.cdc.gov/bioterrorism/ .

(c) “Months” refers to calendar months.

(d) Within a number range, a hyphen (-) should be read as “through.”

(e) Combination vaccines containing the hepatitis B component are available (see Table 3-3). These vaccines should not 

be administered to infants aged <6 weeks because of the other vaccine components (i.e., Hib, DTaP, HepA, and IPV).

(f) The minimum recommended age for DTaP-4 is 15 months, with a recommended 6 months from DTaP-3 (the 

recommended interval between DTaP-3 and DTaP-4 is 6 months). However, DTaP4 need not be repeated if given on 

or after 12 months of age and at least 4 months after DTaP-3. The 4-day grace period can be applied when validating 

past doses and can be applied to the minimum age of 12 months and the minimum interval of 4 months between 

DTaP-3 and DTaP-4. The 4-day grace period can be used when planning doses ahead of time, but should be applied to 

the minimum age of 15 months and the minimum interval between DTaP-3 and DTaP-4 of 6 months. 

(g) If a fourth dose of DTaP is given on or after the fourth birthday, a fifth dose is not needed if the interval between the 

third dose and fourth dose is at least 6 months. 

(h) Adjuvanted Hepatitis B vaccine (HepB-CgG) can be administered to adults 18 years old and older on a two dose 

schedule, the first and second dose separated by 4 weeks.

(i) HepB-3 should be administered at least 8 weeks after HepB-2 and at least 16 weeks after HepB-1 and should not be 

administered before age 24 weeks.

(j) For Hib and PCV13, children receiving the first dose of vaccine at age ≥7 months require fewer doses to complete the 

series.

(k) If PRP-OMP (Pedvax-Hib, Merck Vaccine Division) was administered at ages 2 and 4 months, a dose at age 6 

months is not necessary. The final dose has a minimum age of 12 months.

(l) A two-dose schedule of HPV vaccine is recommended for most persons beginning the series between 9 through 14 

years of age. See HPV vaccine-specific recommendations for details. 

www.cdc.gov/mmwr/volumes/65/wr/pdfs/mm6549a5.pdf

(m) If a patient is eligible for a 2-dose HPV series, and the second dose is given less than four weeks after the first dose, 

it is an invalid dose. Administer another dose 6-12 months after the first dose. If the second dose is given less than five 

months after the first dose, but more than four weeks after the first dose, the next dose should be administered at least 

12 weeks after the second dose, and at least 6-12 months after the first dose. The 4-day grace period may be used. If 

the third dose was administered before December 16, 2016, and was administered 12 weeks after the 2nd dose, and 16 

weeks after the first dose, it is a valid dose. The 4-day grace period may be used. If the third dose was administered on 

or after December 16, 2016, and was administered 12 weeks after the 2nd dose and 5 months after the first dose, it is a 

valid dose. The 4-day grace period may beused.

(n) The minimum age for HPV-3 is based on the baseline minimum age for the first dose (i.e., 9 years) and the 

minimum interval of 5 months between the first and third dose. If the third dose was administered before December 

16, 2016, and was administered 12 weeks after the 2nd dose, and 16 weeks after the first dose, it is a valid dose. The 4- 

day grace period may be used. If the third dose was administered on or after December 16, 2016, and was

administered.

(o) One dose of influenza vaccine per season is recommended for most persons. To determine which children younger 

than 9 years should receive 2 doses in a single season, please see influenza vaccine-specific recommendations (82). If a 

dose of LAIV is administered to a child 6 months to 2 years of age in error, the dose does not need to be repeated.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 34

(p) The minimum age for inactivated influenza vaccine varies by vaccine manufacturer. See package insert for vaccinespecific minimum ages.

(q) A fourth dose is not needed if the third dose was administered at ≥4 years and at least 6 months after the previous 

dose.

(r) If a dose of LAIV is administered to someone 6 months to 2 years of age, the dose does NOT need to be repeated. If 

someone is still indicated for dose 2 of the prime-boost, and younger than 2 years of age, the second dose should be 

IIV.

(s) Revaccination with meningococcal vaccine is recommended for previously vaccinated persons who remain at high 

risk for meningococcal disease (47).

(t) MenACWY-D (Menactra) can be given as young as 9 months for high-risk persons. MenACWY-CRM (Menveo) can 

be given as young as 2 months for high-risk persons. Hib-MenCY can be given as young as 6 weeks for high-risk 

persons. Hib-MenCY is given as a 4-dose series at 2 months, 4 months, 6 months and 12-18 months. MenACWY-TT 

(MenQuadfi) can be given as young as 2 years for high-risk persons.

(u) For routine non-high risk adolescent vaccination, the minimum age for the booster dose is 16 years.

(v) This dose is not necessary if Bexsero is correctly administered, or if Trumenba is correctly administered to healthy 

adolescents.

(w) Combination MMRV vaccine can be used for children aged 12 months-12 years. See text for details.

(x) Infants and children can optionally receive PCV15 instead of PCV13. High-risk adults 19 years through 64 years 

who are known to have not received any pneumococcal vaccine or whose PCV13 history is unknown should receive 

either PCV20 or PCV15. Adults 65 years old and older who are known to have not received any pneumococcal 

vaccine or whose PCV13 history is unknown should receive either PCV20 or PCV15. If PCV15 is administered and if 

PPSV23 naïve, a dose of PPSV23 should be administered a year later. On the basis of shared clinical decisionmaking, adults 65 years old and older who have received a complete series of pneumococcal vaccine can receive a 

dose of PCV20 at least five years after the most recent dose. For adults who have started the recommended 

pneumococcal vaccine series with PCV13 but have not received all recommended doses, look at ACIP Vaccine 

Recommendations and Schedules for details.

(y) A second dose of PPSV23 5 years after the first dose is recommended for persons aged ≤65 years at highest risk for 

serious pneumococcal infection and those who are likely to have a rapid decline in pneumococcal antibody 

concentration (61).

(z) The first dose of rotavirus must be administered at age 6 weeks through 14 weeks and 6 days. The vaccine series 

should not be started for infants aged ≥15 weeks, 0 days. Rotavirus should not be administered to children older than 8 

months, 0 days of age regardless of the number of doses received between 6 weeks and 8 months, 0 days of age. If 2 

doses of Rotarix (GlaxoSmithKline) are administered as age appropriate, a third dose is not necessary.

(aa) Only 1 dose of Tdap is recommended. Subsequent doses should be given as Td or Tdap. For management of a 

tetanus-prone wound in persons who have received a primary series of tetanus-toxoid–containing vaccine, the 

minimum interval after a previous dose of any tetanus-containing vaccine is 5 years.

(bb) A special grace period of 2 months, based on expert opinion, can be applied to the minimum interval of 3 months, 

when evaluating records retrospectively, which results in an acceptable minimum interval of 4 weeks. An additional 4 

days should not be added on to this grace period.

(cc) A special grace period of 2 months, based on expert opinion, can be applied to the minimum age of 15 months when 

evaluating records retrospectively, which results in an acceptable minimum age of 13 months. An additional 4 days 

should not be added on to this grace period.

(dd) If a 1st dose of recombinant zoster vaccine is administered to someone 18 – 49 years of age, the dose does not need 

to be repeated. A 4 day grace period can be added to the absolute minimum age of 18 years when evaluating records 

retrospectively.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 35

TABLE 3-3. FDA-licensed combination vaccines(a)

Vaccine(b) Trade name 

(year licensed)

Age range Routinely recommended 

ages

HepA-HepB Twinrix (2001) ≥18 years Three doses on a schedule of 

0, 1, and 6 months

DTaP-HepB-IPV Pediarix (2002) 6 weeks-6 years Three-dose series at 2, 4, 

and 6 months of age

MMRV ProQuad (2005) 12 months-12 

years

Two doses, the first at 12-15 

months, the second at 4-6 

years

DTaP-IPV Kinrix (2008) 4-6 years Fifth dose of DTaP and 

fourth dose of IPV

DTaP-IPV/Hib Pentacel (2008) 6 weeks-4 years Four-dose schedule at 2, 4,

6, and 15-18 months of age

Hib-MenCY MenHibrix (2012) 6 weeks-18 

months

Four-dose schedule at 2, 4,

6, and 12-15 months of age(c)

DTaP-IPV Quadracel (2015) 4-6 years Fifth dose of DTaP and 

fourth or fifth dose of IPV

DTaP-IPV-HibHepBVaxelis (2018) 6 weeks – 4 

years

Three-dose series at 2, 4, 

and 6 months of age

Abbreviations: DT = diphtheria and tetanus toxoids; DTaP = diphtheria and tetanus toxoids and acellular pertussis; 

FDA = Food and Drug Administration; HepA = hepatitis A; HepB = hepatitis B; Hib = Haemophilus influenzae type b; 

IPV = inactivated poliovirus; MMR = measles, mumps, and rubella; MMRV = measles, mumps, rubella, and varicella; 

Td = tetanus and diphtheria toxoids; Tdap = tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis.

Source: (82).

(a) Although MMR, DTaP, DT, Td, and Tdap are combination vaccines, they are not included on this list because they 

are not available in the United States as single-antigen products.

(b) In descriptions of combination vaccines, dash (-) indicates products in which the active components are supplied in 

their final (combined) form by the manufacturer; slash ( / ) indicates products in which active components must be 

mixed by the user.

(c) Hib-MenCY can be used for routine dosing of Hib vaccine but is recommended only for meningococcal vaccination 

in persons at high-risk of meningococcal disease.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 36

TABLE 3-4. Guidelines for spacing of live and non-live antigens

Antigen combination Recommended minimum interval between doses

Two or more non-live (a),(b),(c) May be administered simultaneously or at any interval 

between doses

Non-live and live (d) May be administered simultaneously or at any interval 

between doses

Two or more live injectable (d) 28 days minimum interval, if not administered 

simultaneously

Source: (83).

(a) Certain experts suggest a 28-day interval between tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis 

(Tdap) vaccine and tetravalent meningococcal conjugate vaccine if they are not administered simultaneously.

(b) In persons with functional or anatomic asplenia, MCV-D and PCV13 should not be administered simultaneously and 

should be spaced by 4 weeks. Likewise for persons with immunosuppressive high-risk conditions indicated for PCV13 

and PPSV23, PCV13 should be administered first, and PPSV23 should be administered no earlier than 8 weeks later. 

For persons 65 years old or older indicated for PCV13 and PPSV23, PCV13 should be administered first and PPSV23 

should be administered 6-12 months later. For persons with high-risk conditions indicated for PCV15 and PPSV23, the 

interval between PCV15 and PPSV23 should be one year, for those with immunosuppressive high-risk conditions the 

interval may be shortened to 8 weeks.

(c) For providers who wish to use Menactra in patients indicated for DTaP, the two vaccines should be administered 

simultaneously. If they cannot be administered simultaneously, administer Menactra first, and then administer 

DTaP 6 months later.

(d) The live oral vaccines Ty21a typhoid vaccine and rotavirus vaccine may be administered simultaneously with or 

at any interval before or after non-live or live injectable vaccines.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 37

TABLE 3-5. Guidelines for administering antibody-containing products(a) 

and vaccines

Type of 

administration

Products administered Recommended minimum 

interval between doses

Simultaneous 

(during the same 

clinic day)

Antibody-containing products and 

non-live antigen

Can be administered 

simultaneously at different 

anatomic sites or at any time 

interval between doses

Antibody-containing products and 

live antigen

Should not be administered 

simultaneously.(b) If 

simultaneous administration of 

measles-containing vaccine or 

varicella vaccine is unavoidable, 

administer at different sites and 

revaccinate or test for 

seroconversion after the 

recommended interval (see 

Table 3-6)

Nonsimultaneous Administered 

first

Administered 

second

Antibodycontaining 

products

Non-live 

antigen

No interval necessary

Non-live 

antigen

Antibodycontaining 

products

No interval necessary

Antibodycontaining 

products

measles, 

mumps, rubella 

vaccine, 

varicella 

vaccine, and 

combined 

measles, 

mumps, rubella, 

varicella vaccine 

antigens

Dose related(b),(c)
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 38

MMR vaccine, 

varicella vaccine, 

and combined 

measles, mumps, 

rubella, varicella 

vaccine antigens

Antibodycontaining 

products

2 weeks(b)

(a) Blood products containing substantial amounts of immune globulin include intramuscular, subcutaneous, and 

intravenous immune globulin, specific hyperimmune globulin (e.g., hepatitis B immune globulin, tetanus immune 

globulin, varicella zoster immune globulin, and rabies immune globulin), whole blood, packed red blood cells, plasma, 

and platelet products.

(b) Yellow fever vaccine; rotavirus vaccine; oral Ty21a typhoid vaccine; and live, attenuated influenza vaccine are 

exceptions to these recommendations. These live, attenuated vaccines can be administered at any time before or after 

or simultaneously with an antibody-containing product.

(c) The duration of interference of antibody-containing products with the immune response to the measles component 

of measles-containing vaccine, and possibly varicella vaccine, is dose related (see Table 3-6).
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 39

TABLE 3-6. Recommended intervals between administration of antibodycontaining products and measles- or varicella-containing vaccine, by 

product and indication for vaccination

Product/Indication Dose (mg IgG/kg) 

and route(a)

Recommended interval 

before measles- or live 

varicella-containing 

vaccine(b) administration 

(months)(c)

Blood transfusion

RBCs, washed 10 mL/kg, negligible 

IgG/kg IV

None

RBCs, adenine-saline added 10 mL/kg (10 mg 

IgG/kg) IV

3

Packed RBCs (hematocrit 65%)(d) 10 mL/kg (60 mg 

IgG/kg) IV

6

Whole blood (hematocrit 35%-

50%)(d)

10 mL/kg (80-100

mg IgG/kg) IV

6

Plasma/platelet products 10 mL/kg (160 mg 

IgG/kg) IV

7

Botulinum Immune Globulin 

Intravenous (Human)

1.0 mL/kg (50 mg 

IgG/kg) IV

6

Cytomegalovirus IGIV 150 mg/kg maximum 6

Hepatitis A IG

Contact prophylaxis 0.1 mL/kg (16.5

mg IgG/kg) IM

6(e)

International travel, <1 month stay 0.1 mL/kg (16.5

mg IgG/kg) IM

6(e)

International travel, ≥1 month stay 0.2 mL/kg (33 mg 

IgG/kg) IM

6(e)

Hepatitis B IG 0.06 mL/kg (10 mg 

IgG/kg) IM

3

IGIV

Replacement therapy for immune 

deficiencies(f)

300-400 mg/kg IV(e) 8
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 40

Immune thrombocytopenic 

purpura treatment

400 mg/kg IV 8

Postexposure varicella prophylaxis 400 mg/kg IV 8

Postexposure measles prophylaxis 

for immunocompromised contacts

400 mg/kg IV 8

Immune thrombocytopenic 

purpura treatment

1000 mg/kg IV 10

Kawasaki disease 2 g/kg IV 11

Measles prophylaxis IG

Standard (i.e., 

nonimmunocompromised) contact

0.50 mL/kg (80 mg 

IgG/kg) IM

6

Monoclonal antibody to 

respiratory syncytial virus F 

protein (e.g., Synagis 

[MedImmune])(g)

15 mg/kg IM None

Rabies IG 20 IU/kg (22 mg 

IgG/kg) IM

4

Tetanus IG 250 units (10 mg 

IgG/kg) IM

3

Varicella IG 125 units/10 kg (60-

200 mg IgG/kg) IM, 

maximum 625 units

5
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 41

Abbreviations: HIV = human immunodeficiency virus; IG = immune globulin; IgG = immune globulin G; IGIV = 

intravenous immune globulin; mg IgG/kg = milligrams of immune globulin G per kilogram of body weight; IM = 

intramuscular; IV = intravenous; RBCs = red blood cells.

(a) This table is not intended for determining the correct indications and dosages for using antibody-containing products. 

Unvaccinated persons might not be protected fully against measles during the entire recommended interval, and 

additional doses of IG or measles vaccine might be indicated after measles exposure. Concentrations of measles 

antibody in an IG preparation can vary by manufacturer’s lot. Rates of antibody clearance after receipt of an IG 

preparation also might vary. Recommended intervals are extrapolated from an estimated half-life of 30 days for 

passively acquired antibody and an observed interference with the immune response to measles vaccine for 5 months 

after a dose of 80 mg IgG/kg. Sources: Mason W, Takahashi M, Schneider T. Persisting passively acquired measles 

antibody following gamma globulin therapy for Kawasaki disease and response to live virus vaccination [Abstract 311]. 

Presented at the 32 meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy, Los Angeles, 

California, October, 1992, AND Siber GR, Werner BG, Halsey NA, et al. Interference of immune globulin with measles 

and rubella immunization. J Pediatr. 1993;122(2):204-211. DOI: 10.1016/S0022-3476(06)80114-9, AND Mason WH, 

Schneider TL, Takahashi M. Duration of passively acquired measles antibody and response to live virus vaccination 

allowing gamma globulintherapy for Kawasaki syndrome. Prog Pediatr Cardiol. 1992;1(1):82. DOI: 10.1016/S1058-

9813(06)80067-6. The extrapolation is performed by counting months from 80 mg down to (1-3 mg) (e.g. 80 >>> 40 

>> >20 >> >10 >>> 5>>>2.5....equal to FIVE intervals) and adding a grace month, so 80 mg values take a “6 month” 

interval)

(b) Does not include recombinant zoster vaccine, since this vaccine is non-live.

(c) The interval between blood/passive antibody products and testing for history of dengue infection (which is mandatory 

prior to administration of dengue vaccine) should be 12 months

(d) Assumes a serum IgG concentration of 16 mg/mL.

(e) The reason the interval is 6 months (and not 4 months) is that the quantity of 16.5 IgG/kg does not reflect the upper 

ceiling of the quantity of measles IgG in the product.

(f) Measles vaccination is recommended for children with mild or moderate immunosuppression from HIV infection, 

and varicella vaccination may be considered for children with mild or moderate immunosuppression from HIV 

infection, but both are contraindicated for persons with severe immunosuppression from HIV or any other 

immunosuppressive disorder.

(g) Contains antibody only to respiratory syncytial virus.
General Best Practice Guidelines for Immunization: Timing and Spacing of Immunobiologics 42

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General Best Practice Guidelines for Immunization: Contraindications and Precautions 51

4. Contraindications and Precautions

Updates

Major changes to the best practice guidance in this section include 1) enhancement of the 

definition of a “precaution” to include any condition that might confuse diagnostic 

accuracy and 2) recommendation to vaccinate during a hospitalization if a patient is not 

acutely moderately or severely ill.

General Principles

National standards for pediatric vaccination practices have been established and include 

descriptions of valid contraindications and precautions to vaccination (2). Persons who 

administer vaccines should screen patients for contraindications and precautions to the 

vaccine before each dose of vaccine is administered (Table 4-1). Screening is facilitated by 

consistent use of screening questionnaires, which are available from certain state 

vaccination programs and other sources (e.g., the Immunization Action Coalition, 

http://www.immunize.org).

Contraindications

Contraindications (conditions in a recipient that increases the risk for a serious adverse 

reaction) to vaccination are conditions under which vaccines should not be administered. 

Because the majority of contraindications are temporary, vaccinations often can be 

administered later when the condition leading to a contraindication no longer exists. A 

vaccine should not be administered when a contraindication is present; for example, 

MMR vaccine should not be administered to severely immunocompromised persons (1). 

However, certain conditions are commonly misperceived as contraindications (i.e., are 

not valid reasons to defer vaccination).

Severely immunocompromised persons generally should not receive live vaccines (3). 

Because of the theoretical risk to the fetus, women known to be pregnant generally should 

not receive live, attenuated virus vaccines (4). Persons who experienced encephalopathy 

within 7 days after administration of a previous dose of pertussis- containing vaccine not 

attributable to another identifiable cause should not receive additional doses of a vaccine 

that contains pertussis (4,5). 
General Best Practice Guidelines for Immunization: Contraindications and Precautions 52

Severe Combined Immunodeficiency (SCID) disease and a history of intussusception are 

both contraindications to the receipt of rotavirus vaccines (6).

Precautions

A precaution is a condition in a recipient that might increase the risk for a serious adverse 

reaction, might cause diagnostic confusion, or might compromise the ability of the 

vaccine to produce immunity (e.g., administering measles vaccine to a person with 

passive immunity to measles from a blood transfusion administered up to 7 months 

prior) (7). A person might experience a more severe reaction to the vaccine than would 

have otherwise been expected; however, the risk for this happening is less than the risk 

expected with a contraindication. In general, vaccinations should be deferred when a 

precaution is present. However, a vaccination might be indicated in the presence of a 

precaution if the benefit of protection from the vaccine outweighs the risk for an adverse 

reaction.

The presence of a moderate or severe acute illness with or without a fever is a 

precaution to administration of all vaccines (Table 4-1). The decision to administer or 

delay vaccination because of a current or recent acute illness depends on the severity of 

symptoms and etiology of the condition. The safety and efficacy of vaccinating persons 

who have mild illnesses have been documented (8-11). Vaccination should be deferred 

for persons with a moderate or severe acute illness. This precaution avoids causing 

diagnostic confusion between manifestations of the underlying illness and possible 

adverse effects of vaccination or superimposing adverse effects of the vaccine on the 

underlying illness. After they are screened for contraindications, persons with 

moderate or severe acute illness should be vaccinated as soon as the acute illness has 

improved. Studies indicate that failure to vaccinate children with minor illnesses can 

impede vaccination efforts (12–14). Among persons whose compliance with medical 

care cannot be ensured, use of every opportunity to administer appropriate vaccines is 

critical.

Hospitalization should be used as an opportunity to provide recommended vaccinations. 

Health-care facilities are held to standards of offering influenza vaccine for hospitalized 

patients, so providers are incentivized to vaccinate these patients at some point during 

hospitalization (15). Likewise, patients admitted for elective procedures will not be 

acutely ill during all times during their hospitalization. Most studies that have explored 
General Best Practice Guidelines for Immunization: Contraindications and Precautions 53

the effect of surgery or anesthesia on the immune system were observational, included 

only infants and children, and were small and indirect, in that they did not look at the

immune effect on the response to vaccination specifically (16-35). They do not provide 

convincing evidence that recent anesthesia or surgery significantly affect response to 

vaccines. Current, recent, or upcoming anesthesia/surgery/hospitalization is not a 

contraindication to vaccination, but certain factors might lead a provider to consider 

current, recent, or upcoming anesthesia/surgery/hospitalization as a precaution (16-35). 

Efforts should be made to ensure vaccine administration during the hospitalization or at 

discharge. For patients who are deemed moderately or severely ill throughout the 

hospitalization, vaccination should occur at the earliest opportunity (i.e., during 

immediate post-hospitalization follow-up care, including home or office visits) when 

patients’ clinical symptoms have improved.

A personal or family history of seizures is a precaution for MMRV vaccination; this is 

because a recent study found an increased risk for febrile seizures in children 12-23 

months who receive MMRV compared with MMR and varicella vaccine (36).

Neither Contraindications Nor Precautions

Clinicians or other health-care providers might misperceive certain conditions or 

circumstances as valid contraindications or precautions to vaccination when they 

actually do not preclude vaccination (2) (Table 4-2). These misperceptions result in 

missed opportunities to administer recommended vaccines (37).

Routine physical examinations and procedures (e.g., measuring temperatures) are not 

prerequisites for vaccinating persons who appear to be healthy. The provider should ask 

the parent or guardian if the child is ill. If the child has a moderate or severe illness, the 

vaccination should be postponed.
General Best Practice Guidelines for Immunization: Contraindications and Precautions 54

TABLE 4-1. Contraindications and precautions(a) to commonly used vaccines

Vaccine Citation Contraindications Precautions

Dengue–

ONLY use in 

persons who 

have 

laboratory 

confirmation 

of previous 

dengue 

infection 

AND reside 

in endemic 

dengue areas

(b)

(38) Lack of laboratory 

evidence of previous 

dengue infection

Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Severe

immunodeficiency (e.g.,

hematologic and solid 

tumors, receipt of 

chemotherapy, 

congenital 

immunodeficiency, 

long-term 

immunosuppressive 

therapy(c) or patients 

with HIV infection who 

are severely 

immunocompromised)

 

 

Pregnancy

HIV infection without evidence of 

severe immunosuppression

Moderate or severe acute illness 

with or without fever

DT, Td (4) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

GBS <6 weeks after previous dose of 

tetanus-toxoid–containing vaccine

History of Arthus-type 

hypersensitivity reactions after a 

previous dose of diphtheria-toxoid—

containing or tetanus-toxoid–

containing vaccine; defer vaccination 

until at least 10 years have elapsed 

since the last tetanus-toxoidcontaining vaccine

Moderate or severe acute illness with 

or without fever
General Best Practice Guidelines for Immunization: Contraindications and Precautions 55

DTaP (39) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Encephalopathy (e.g., 

coma, decreased level of 

consciousness, 

prolonged seizures), not 

attributable to another 

identifiable cause, 

within 7 days of 

administration of 

previous dose of DTP or 

DTaP

Progressive neurologic disorder, 

including infantile spasms, 

uncontrolled epilepsy, progressive 

encephalopathy; defer DTaP until 

neurologic status clarified and 

stabilized

GBS <6 weeks after previous dose of 

tetanus-toxoid–containing vaccine

History of Arthus-type 

hypersensitivity reactions after a 

previous dose of diphtheria-toxoid–

containing or tetanus-toxoid–

containing vaccine; defer vaccination 

until at least 10 years have elapsed 

since the last tetanus-toxoid–

containing vaccine

Moderate or severe acute illness with 

or without fever

Hepatitis A (40) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Moderate or severe acute illness with 

or without fever

Hepatitis B (41) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Hypersensitivity to yeast

Moderate or severe acute illness with 

or without fever

Hib (42) Severe allergic reaction 

(e.g., anaphylaxis) after

Moderate or severe acute illness with 

or without fever
General Best Practice Guidelines for Immunization: Contraindications and Precautions 56

a previous dose or to a 

vaccine component

Age <6 weeks

HPV(d) (43) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component, 

including yeast

Moderate or severe acute illness with 

or without fever

IIV(e) (44) Severe allergic reaction 

(e.g., anaphylaxis) after 

previous dose of 

influenza vaccine or to 

vaccine component

GBS <6 weeks after a previous dose of 

influenza vaccine

Moderate or severe acute illness with 

or without fever

IPV (45) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Pregnancy

Moderate or severe acute illness with 

or without fever
General Best Practice Guidelines for Immunization: Contraindications and Precautions 57

LAIV(f) (44) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Concomitant use of 

aspirin or salicylatecontaining medication 

in children and 

adolescents

LAIV4 should not be 

administered to persons 

who have taken 

oseltamivir or zanamivir 

within the previous 48 

hours, peramivir within 

the previous 5 days, or 

baloxavir within the 

previous 17 days.(h)

Pregnancy

Children aged 2 through 

4 years who have 

received a diagnosis of 

asthma or whose 

parents or caregivers 

report that a health care 

provider has told them 

during the preceding 12 

months that their child 

had wheezing or asthma 

or whose medical record 

indicates a wheezing 

episode has occurred 

during the preceding 12 

months.

Persons with active 

cerebrospinal 

fluid/oropharyngeal 

communications/leaks.

GBS <6 weeks after a previous dose of 

influenza vaccine

Asthma in persons aged 5 years old or 

older

Medical conditions which might 

predispose to higher risk of 

complications attributable to 

influenza(g)

Moderate or severe acute illness with 

or without fever
General Best Practice Guidelines for Immunization: Contraindications and Precautions 58

Close contacts and 

caregivers of severely 

immunosuppressed 

persons who require a 

protected environment.

Persons with cochlear 

implants (due to the 

potential for CSF leak, 

which might exist for 

some period of time 

after implantation. 

Providers might 

consider consultation 

with a specialist 

concerning risk of 

persistent CSF leak if an 

age-appropriate 

inactivated or 

recombinant vaccine 

cannot be used).

Altered 

Immunocompetence

Anatomic or functional 

asplenia (e.g. sickle cell 

disease

MenACWY (46) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component, 

including yeast

Moderate or severe acute illness with 

or without fever

Preterm birth (MenACWY-CRM)(i)

MenB (46,48) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Moderate or severe acute illness with 

or without fever

Pregnancy

Latex sensitivity (MenB-4c)
General Best Practice Guidelines for Immunization: Contraindications and Precautions 59

MMR(j),(k) (1) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Pregnancy 

Known severe

immunodeficiency (e.g.,

from hematologic and 

solid tumors, receipt of 

chemotherapy, 

congenital 

immunodeficiency, 

long-term 

immunosuppressive 

therapy(c) or patients 

with HIV infection who 

are severely 

immunocompromised)

Family history of altered 

immunocompetence(m)

Recent (≤11 months) receipt of 

antibody-containing blood product 

(specific interval depends on product)

History of thrombocytopenia or 

thrombocytopenic purpura

Need for tuberculin skin testing or 

interferon-gamma release assay 

(IGRA) testing(l)

Moderate or severe acute illness with 

or without fever

MPSV4 (49) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Moderate or severe acute illness with 

or without fever

PCV13, 

PCV15, 

PCV20

(50) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose of PCV 

or any diphtheriatoxoid– containing 

vaccine or to a 

component of a vaccine 

(PCV or any diphtheriatoxoid– containing 

vaccine)

Moderate or severe acute illness with 

or without fever

PPSV23 (51) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Moderate or severe acute illness with 

or without fever

RIV (44) Severe allergic reaction 

(e.g., anaphylaxis) to 

any component of the 

vaccine

GBS <6 weeks after a previous dose of 

influenza vaccine

Moderate or severe acute illness with 

or without fever
General Best Practice Guidelines for Immunization: Contraindications and Precautions 60

Rotavirus (6) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

SCID

History of 

intussusception

Altered immunocompetence other 

than SCID

Chronic gastrointestinal disease

Spina bifida or bladder exstrophy(n)

Moderate or severe acute illness with 

or without fever

Tdap (52) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Encephalopathy (e.g., 

coma, decreased level of 

consciousness, 

prolonged seizures), not 

attributable to another 

identifiable cause, within 

7 days of administration 

of previous dose of DTP, 

DTaP, or Tdap

GBS <6 weeks after a previous dose of 

tetanus-toxoid–containing vaccine

Progressive or unstable neurological 

disorder, uncontrolled seizures, or 

progressive encephalopathy until a 

treatment regimen has been 

established and the condition has 

stabilized

History of Arthus-type 

hypersensitivity reactions after a 

previous dose of diphtheria-toxoid—

containing or tetanus-toxoid–

containing vaccine; defer vaccination 

until at least 10 years have elapsed 

since the last tetanus-toxoid–

containing vaccine

Moderate or severe acute illness with 

or without fever

Varicella(j),(k

)

(53) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Known severe 

immunodeficiency (e.g., 

from hematologic and 

solid tumors, receipt of 

chemotherapy, 

congenital 

immunodeficiency, 

long-term 

immunosuppressive 

therapy(c) or patients 

with HIV infection who 

are severely

immunocompromised)(j)

Pregnancy

Family history of altered 

immunocompetence(m)

Recent (≤11 months) receipt of 

antibody-containing blood product 

(specific interval depends on product)

Moderate or severe acute illness with 

or without fever

Receipt of specific antiviral drugs 

(acyclovir, famciclovir, or 

valacyclovir) 24 hours before 

vaccination (avoid use of these 

antiviral drugs for 14 days after 

vaccination)

Use of aspirin or aspirin-containing 

products(o)
General Best Practice Guidelines for Immunization: Contraindications and Precautions 61

Zoster (54) Severe allergic reaction 

(e.g., anaphylaxis) after 

a previous dose or to a 

vaccine component

Moderate or severe acute illness with 

or without fever

Abbreviations: DT = diphtheria and tetanus toxoids; DTaP = diphtheria and tetanus toxoids and acellular pertussis; 

DTP = diphtheria toxoid, tetanus toxoid, and pertussis; GBS = Guillain-Barré syndrome; Hib = Haemophilus influenzae 

type b; HIV = human immunodeficiency virus; HPV = human papillomavirus; IIV = inactivated influenza vaccine; IPV = 

inactivated poliovirus; LAIV = live, attenuated influenza vaccine; MenACWY = quadrivalent meningococcal conjugate 

vaccine; MMR = measles, mumps, and rubella; MPSV4 = quadrivalent meningococcal polysaccharide vaccine; PCV13 = 

pneumococcal conjugate vaccine; PPSV23= pneumococcal polysaccharide vaccine; SCID = severe combined 

immunodeficiency; RIV=recombinant influenza vaccine; Td = tetanus and diphtheria toxoids; Tdap = tetanus toxoid, 

reduced diphtheria toxoid, and acellular pertussis.

(a) Events or conditions listed as precautions should be reviewed carefully. Benefits of and risks for administering a 

specific vaccine to a person under these circumstances should be considered. If the risk from the vaccine is believed to 

outweigh the benefit, the vaccine should not be administered. If the benefit of vaccination is believed to outweigh the 

risk, the vaccine should be administered. Whether and when to administer DTaP to children with proven or suspected 

underlying neurologic disorders should be decided on a case-by-case basis.

(b) Only persons with laboratory confirmation of immunity according to strict guidance at

https://www.cdc.gov/dengue/vaccine/hcp/testing.html should receive dengue vaccination.

(c) Substantially immunosuppressive steroid dose is considered to be ≥2 weeks of daily receipt of 20 mg or 2 mg/kg body 

weight of prednisone or equivalent.

(d) HPV vaccine is not recommended during pregnancy

(e) When applying this contraindication to ccIIV, the history of severe allergic reaction (e.g., anaphylaxis) must be specific 

to the event occurring following a dose of ccIIV. Likewise, when applying this contraindication to RIV, the history of 

severe allergic reaction (e.g., anaphylaxis) must be specific to the event occurring following a dose of RIV. A history of 

severe allergic reaction (e.g., anaphylaxis) to a non-ccIIV vaccine or to a component specific to components not 

contained in ccIIV, is a precaution to ccIIV. A history of severe allergic reaction (e.g., anaphylaxis) to a non-RIV vaccine 

or to a component specific to components not contained in RIV is a precaution to RIV.

(f) In addition, ACIP recommends LAIV not be used for pregnant women, immunosuppressed persons, and children aged 

2-4 years who have asthma or who have had a wheezing episode noted in the medical record within the past 12 months, 

or for whom parents report that a health care provider stated that they had wheezing or asthma within the last 12 months. 

LAIV should not be administered to persons who have taken influenza antiviral medications within the previous 48 

hours. Persons who care for severely immunosuppressed persons who require a protective environment should not 

receive LAIV, or should avoid contact with such persons for 7 days after receipt.

(g) See reference: Grohskopf LA, Alyanak E, Ferdinands JM, et al. Prevention and Control of Seasonal Influenza with 

Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-2022 Influenza 

Season. MMWR Recomm Rep 2021;70(No. RR-5):1-30.
General Best Practice Guidelines for Immunization: Contraindications and Precautions 62

(h) These values are based on the clearance of the particular antiviral. LAIV4 should not be administered to persons who 

have taken oseltamivir or zanamivir within the previous 48 hours, peramivir within the previous 5 days, or baloxavir 

within the previous 17 days. This “contraindication” is due to concern with reduced effectiveness of the vaccine. To obtain 

specific information, please refer to Grohskopf LA, Alyanak, E, Broder KR, et. al. Prevention and Control of Seasonal 

Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 

2020–21 Influenza Season. MMWR Recomm Rep 2020;69 (No. RR-8:1-26. Also at 

https://www.cdc.gov/mmwr/volumes/69/rr/pdfs/rr6908a1-H.pdf 

(i) This precaution applies to infants younger than 9 months old

(j) HIV-infected children may receive varicella vaccine if CD4+ T-lymphocyte count is ≥15% and should receive MMR 

vaccine if they are aged ≥12 months and do not have evidence of current severe immunosuppression (i.e., individuals 

aged ≤5 years must have CD4+T lymphocyte [CD4] percentages ≥15% for ≥6 months; and individuals aged >5 years must 

have CD4+percentages ≥15% and CD4+≥200 lymphocytes/mm3 for ≥6 months) or other current evidence of measles, 

rubella, and mumps immunity. In cases when only CD4+cell counts or only CD4+percentages are available for those 

older than age 5 years, the assessment of severe immunosuppression can be based on the CD4+values (count or 

percentage) that are available. In cases when CD4+percentages are not available for those aged ≤5 years, the assessment 

of severe immunosuppression can be based on age-specific CD4+counts at the time CD4+counts were measured; i.e., 

absence of severe immunosuppression is defined as ≥6 months above age-specific CD4+count criteria: CD4+count >750 

lymphocytes/mm3 while aged ≤12 months and CD4+count ≥500 lymphocytes/mm3 while aged 1 through 5 years.

Sources: (1,50).

(k) MMR and varicella-containing vaccines can be administered on the same day. If not administered on the same 

day, these vaccines should be separated by at least 28 days.

(l) If active tuberculosis is suspected, MMR should be delayed. Measles vaccination might suppress tuberculin reactivity 

temporarily. Measles-containing vaccine can be administered on the same day as tuberculin skin or IGRA testing. If 

testing cannot be performed until after the day of MMR vaccination, the test should be postponed for ≥4 weeks after the 

vaccination. If an urgent need exists to skin test or IGRA, do so with the understanding that reactivity might be reduced 

by the vaccine.

(m) family history of congenital or hereditary immunodeficiency in first-degree relatives (e.g., parents and siblings), 

unless the immune competence of the potential vaccine recipient has been substantiated clinically or verified by a 

laboratory

(n) For RV1 only, based on latex in product/packaging. Note that anaphylactic allergy to latex is covered in the 

contraindication, and would also be isolated to RV 1 in the case of latex. For more details, see (55).

(o) No adverse events associated with the use of aspirin or aspirin-containing products after varicella vaccination have 

been reported; however, the vaccine manufacturer recommends that vaccine recipients avoid using aspirin or aspirincontaining products for 6 weeks after receiving varicella vaccines because of the association between aspirin use and 

Reye syndrome after varicella. Vaccination with subsequent close monitoring should be considered for children who have 

rheumatoid arthritis or other conditions requiring therapeutic aspirin. The risk for serious complications associated with 

aspirin is likely to be greater in children in whom natural varicella develops than it is in children who receive the vaccine

containing attenuated VZV. No association has been documented between Reye syndrome and analgesics or antipyretics 

that do not contain aspirin.”
General Best Practice Guidelines for Immunization: Contraindications and Precautions 63

TABLE 4-2. Conditions incorrectly perceived as contraindications or 

precautions to vaccination (i.e., vaccines may be given under these 

conditions)

Vaccine Conditions commonly misperceived as 

contraindications or precautions

General for all 

vaccines, including 

DTaP, pediatric 

DT, adult Td, 

adolescent-adult 

Tdap, IPV, MMR,

Hib, hepatitis A, 

hepatitis B, 

varicella, rotavirus, 

PCV13, IIV, LAIV, 

PPSV23, 

MenACWY, MPSV4,

HPV, and herpes 

zoster

Mild acute illness with or without fever

Lack of previous physical examination in well-appearing 

person

Current antimicrobial therapy(a) 

Convalescent phase of illness

Preterm birth (hepatitis B vaccine is an exception in certain 

circumstances)(b)

Recent exposure to an infectious disease

History of penicillin allergy, other nonvaccine allergies, 

relatives with allergies, or receiving allergen extract 

immunotherapy

History of GBS(c)

DTaP Fever within 48 hours after vaccination with a previous dose of 

DTP or DTaP

Collapse or shock-like state (i.e., hypotonic hyporesponsive 

episode) within 48 hours after receiving a previous dose of 

DTP/DTaP

Seizure ≤3 days after receiving a previous dose of DTP/DTaP

Persistent, inconsolable crying lasting ≥3 hours within 48 

hours after receiving a previous dose of DTP/DTaP 

Family history of seizures

Family history of sudden infant death syndrome 

Family history of an adverse event after DTP or DTaP 

administration

Stable neurologic conditions (e.g., cerebral palsy, wellcontrolled seizures, or developmental delay)

Hepatitis B Pregnancy

Autoimmune disease (e.g., systemic lupus erythematosus or 

rheumatoid arthritis)

HPV Immunosuppression

Previous equivocal or abnormal Papanicolaou test 

Known HPV infection

Breastfeeding

History of genital warts

IIV Nonsevere (e.g., contact) allergy to latex, thimerosal, or egg 

Concurrent administration of Coumadin (generic: warfarin) or 

aminophylline

IPV Previous receipt of ≥1 dose of oral polio vaccine
General Best Practice Guidelines for Immunization: Contraindications and Precautions 64

LAIV Health-care providers that see patients with chronic diseases 

or altered immunocompetence (an exception is providers for 

severely immunocompromised patients requiring care in a 

protected environment)

Breastfeeding

Contacts of persons with chronic disease or altered 

immunocompetence (an exception is contacts of severely 

immunocompromised patients requiring care in a protected 

environment)

MMR(d),(e) Positive tuberculin skin test

Simultaneous tuberculin skin or interferon-gamma release 

assay (IGRA) testing(f)

Breastfeeding

Pregnancy of recipient’s mother or other close or household 

contact

Recipient is female of child-bearing age 

Immunodeficient family member or household contact 

Asymptomatic or mildly symptomatic HIV infection 

Allergy to eggs

PPSV23 History of invasive pneumococcal disease or pneumonia

Rotavirus Prematurity

Immunosuppressed household contacts 

Pregnant household contacts

Tdap History of fever of ≥40.5°C (≥105°F) for <48 hours after 

vaccination with a previous dose of DTP or DTaP 

History of collapse or shock-like state (i.e., hypotonic

hyporesponsive episode) within 48 hours after receiving a 

previous dose of DTP/DTaP

History of seizure <3 days after receiving a previous dose of 

DTP/DTaP

History of persistent, inconsolable crying lasting >3 hours 

within 48 hours after receiving a previous dose of DTP/DTaP 

History of extensive limb swelling after DTP/DTaP/Td that is 

not an Arthus-type reaction

History of stable neurologic disorder 

History of brachial neuritis

Latex allergy that is not anaphylactic 

Breastfeeding

Immunosuppression

Varicella Pregnancy of recipient’s mother or other close or household 

contact

Immunodeficient family member or household contact(g) 

Asymptomatic or mildly symptomatic HIV infection 

Humoral immunodeficiency (e.g., agammaglobulinemia)
General Best Practice Guidelines for Immunization: Contraindications and Precautions 65

Zoster Therapy with low-dose methotrexate (≤0.4 mg/kg/week), 

azathioprine (≤3.0 mg/kg/day), or 6-mercaptopurine (≤1.5 

mg/kg/day) for treatment of rheumatoid arthritis, psoriasis, 

polymyositis, sarcoidosis, inflammatory bowel disease, or other 

conditions

Health-care providers of patients with chronic diseases or 

altered immunocompetence

Contacts of patients with chronic diseases or altered 

immunocompetence

Unknown or uncertain history of varicella in a U.S.-born 

person

Abbreviations: DT = diphtheria and tetanus toxoids; DTP = diphtheria toxoid, tetanus toxoid, and pertussis; 

DTaP = diphtheria and tetanus toxoids and acellular pertussis; GBS = Guillain-Barré syndrome; HBsAg = hepatitis 

B surface antigen; Hib = Haemophilus influenzae type b; HIV = human immunodeficiency virus; HPV = human 

papillomavirus; IIV = inactivated influenza vaccine; IPV = inactivated poliovirus; LAIV = live, attenuated influenza 

vaccine; MenACWY = quadrivalent meningococcal conjugate vaccine; MMR = measles, mumps, and rubella; 

MPSV4 = quadrivalent meningococcal polysaccharide vaccine; PCV = pneumococcal conjugate vaccine; PPSV23= 

pneumococcal polysaccharide vaccine; Td = tetanus and diphtheria toxoids; Tdap = tetanus toxoid, reduced 

diphtheria toxoid, and acellular pertussis.

(a) Antibacterial drugs might interfere with Ty21a oral typhoid vaccine, and certain antiviral drugs might interfere 

with varicella-containing vaccines and LAIV4.

(b) Hepatitis B vaccination should be deferred for infants weighing <2,000 g if the mother is documented to be 

HBsAg negative. Vaccination should commence at chronological age 1 month or at hospital discharge. For infants 

born to HBsAg-positive women, hepatitis B immune globulin and hepatitis B vaccine should be administered 

within 12 hours after birth, regardless of weight.

(c) An exception is Guillain-Barré syndrome within 6 weeks of a dose of influenza vaccine or tetanus-toxoid–

containing vaccine, which are precautions for influenza vaccines and tetanus-toxoid containing vaccines, 

respectively.

(d) MMR and varicella vaccines can be administered on the same day. If not administered on the same day, these 

vaccines should be separated by at least 28 days.

(e) HIV-infected children should receive immune globulin after exposure to measles. HIV-infected children can 

receive varicella and measles vaccine if CD4+ T-lymphocyte count is >15%. (55).

(f) Measles vaccination might suppress tuberculin reactivity temporarily. Measles-containing vaccine can be 

administered on the same day as tuberculin skin or IGRA testing. If testing cannot be performed until after the day 

of MMR vaccination, the test should be postponed for at least 4 weeks after the vaccination. If an urgent need 

exists to skin test or IGRA, do so with the understanding that reactivity might be reduced by the vaccine.

(g) If a vaccinee experiences a presumed vaccine-related rash 7-25 days after vaccination, the person should avoid 

direct contact with immunocompromised persons for the duration of the rash.
General Best Practice Guidelines for Immunization: Contraindications and Precautions 66

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General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 72

5. Preventing and Managing Adverse Reactions

Updates

Major changes to the best practice guidance include 1) more descriptive characterization 

of anaphylactic allergy and 2) incorporation of protocols for managing adverse reactions.

 

Benefit and Risk Communication

Parents, guardians, legal representatives, and adolescent and adult patients should be 

informed about the benefits of and risks from vaccines in language that is culturally 

sensitive and at an appropriate educational level. Opportunity for questions should be 

provided before each vaccination. Discussion of the benefits of and risks from vaccination 

is sound medical practice and is required by law.

The National Childhood Vaccine Injury Act of 1986 (1) requires that vaccine information 

materials be developed for each vaccine covered by the Act (uscode.house.gov). These 

materials, known as vaccine information statements (VISs), must be provided by all public 

and private vaccination providers each time a vaccine is administered. Copies of VISs are 

available from state health authorities responsible for vaccination and from CDC 

(www.cdc.gov/vaccines/hcp/vis/index.html). Translations of VISs into languages other 

than English are available from certain state vaccination programs and from the 

Immunization Action Coalition website (http://www.immunize.org). The act does not 

require that a signature be obtained; however, documentation of consent might be 

recommended or required by certain state or local health authorities or school authorities.

Some parents or patients question the need for or safety of vaccinations and want to 

discuss the risks from and benefits of certain vaccines. Some refuse certain vaccines or 

reject all vaccinations for personal or religious reasons. Having a basic understanding of 

how patients and parents of patients view vaccine risk and developing effective 

approaches to address vaccine safety concerns are imperative for vaccination providers.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 73

Each person understands and reacts to vaccine information on the basis of different 

factors, including previous experience, education, personal values, method of data 

presentation, perceptions of the risk for disease and perceived ability to control these 

risks, and risk tolerance. In some circumstances, decisions about vaccination are based on 

inaccurate information about risk provided by the media and certain websites. Websites 

and other sources of vaccine information may be inaccurate or incomplete. Health care 

providers can be a pivotal source of science-based credible information by discussing with 

parents and patients the risks from and benefits of vaccines, which helps patients make 

informed decisions.

When a parent or patient initiates a discussion about a perceived vaccine adverse reaction, 

the health care provider should discuss the specific concerns and provide factual 

information, using appropriate language. Effective, empathetic vaccine risk 

communication is essential in responding to misinformation and concerns, with health 

care providers recognizing that risk assessment and decision-making can be difficult and 

confusing. Certain vaccines might be acceptable to a parent who is resistant to other 

vaccines. This partial acceptance can be used to facilitate additional communication. Their 

concerns can be addressed using the VIS and offering other resource materials (e.g., 

vaccination information from CDC: www.cdc.gov/vaccines/hcp/vis/index.html).

The American Academy of Pediatrics (AAP) does not recommend that providers exclude 

from their practice patients whose parents or guardians question or refuse vaccination. 

However, an effective public health strategy is to identify common ground and discuss 

measures that need to be followed if the decision is to defer vaccination (2). Health care 

providers should reinforce key points about each vaccine, including safety, and emphasize 

risks for disease among unvaccinated children. Parents should be advised of state laws 

regarding entry to schools or child-care facilities, which might require that unvaccinated 

children be excluded from the facility during outbreaks (www.cdc.gov/vaccines/imzmanagers/coverage/schoolvaxview/requirements/index.html). These discussions should 

be documented in the patient’s medical record, including the refusal to receive certain 

vaccines (i.e., informed refusal). When a vaccine is refused when first offered the provider 

should take the opportunity to offer the vaccine again at the next visit.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 74

Preventing Adverse Reactions

Vaccines are intended to produce active immunity to specific antigens. An adverse 

reaction is an undesirable side effect that occurs after a vaccination. Vaccine adverse 

reactions are classified as 1) local, 2) systemic, or 3) allergic (additional information is 

available at 

https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm09383

3.htm. Local reactions (e.g., redness) are usually the least severe and most frequent. 

Systemic reactions (e.g., fever) occur less frequently than local reactions, and severe 

allergic reactions (e.g., anaphylaxis) are the least frequent reactions. Severe adverse 

reactions are rare (3).

Some of the systemic reactions may be complicated by the onset of syncope. Syncope 

(vasovagal or vasodepressor reaction) can occur after vaccination and is most common 

among adolescents and young adults. In 2005, the Vaccine Adverse Event Reporting 

System (VAERS) began detecting a trend of increasing syncope reports that coincided with 

the licensure of 3 vaccines for adolescents: human papillomavirus (HPV), MenACWY, and 

Tdap (4). Of particular concern among adolescents has been the risk for serious secondary 

injuries, including skull fracture and cerebral hemorrhage. Of 463 VAERS reports of 

syncope during January 1, 2005, to July 31, 2007, a total of 41 listed syncope with 

secondary injury with information on the timing after vaccination, and the majority of 

these syncope reports (76%) occurred among adolescents. Among all age groups, 80% of 

reported syncope episodes occur within 15 minutes of vaccine administration (additional 

information is available at www.cdc.gov/vaccinesafety/concerns/fainting.html). Providers 

should take appropriate measures to prevent injuries if a patient becomes weak or dizzy or 

loses consciousness. Adolescents and adults should be seated or lying down during 

vaccination.Vaccine providers, particularly when vaccinating adolescents, should consider 

observing patients (with patients seated or lying down) for 15 minutes after vaccination to 

decrease the risk for injury should they faint (4). If syncope develops, patients should be 

observed until the symptoms resolve.

Although allergic reactions are a common concern for vaccine providers, these reactions 

are uncommon and anaphylaxis following vaccines is rare, occurring at a rate of 

approximately one per million doses for many vaccines (5). 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 75

Epinephrine and equipment for managing an airway should be available for immediate 

use (6). The best practice to prevent allergic reactions is to identify individuals at 

increased risk by obtaining a history of allergy to previous vaccinations and vaccine 

components that might indicate an underlying hypersensitivity. Acute allergic reactions 

following vaccinations might be caused by the vaccine antigen, residual animal protein, 

antimicrobial agents, preservatives, stabilizers, or other vaccine components (7). 

Components of each vaccine are listed in the respective package insert. An extensive list of 

vaccine components and their use, as well as the vaccines that contain each component, 

has been published (8) and also is available from CDC 

(www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/b/excipient-table- 2.pdf). 

Additional information and tables of potential allergens in different vaccines are available 

at (http://www.vaccinesafety.edu/components-Allergens.htm). The allergens identified in 

the history can be cross-checked against the allergens identified in package inserts.

 

Managing Acute Vaccine Reactions

Vaccine providers should be familiar with identifying immediate-type allergic reactions, 

including anaphylaxis, and be competent in treating these events at the time of vaccine 

administration. Providers should also have a plan in place to contact emergency medical 

services immediately in the event of a severe acute vaccine reaction.

Allergic reactions can include: local or generalized urticaria (hives) or angioedema; 

respiratory compromise due to wheezing or swelling of the throat; hypotension; and 

shock. Immediate-immunoglobulin E (IgE)–mediated (type 1) immune reactions, such as 

anaphylaxis, usually occur within minutes of parenteral administration and involve 

specific IgE interactions with discrete antigens (9,10). Rapid recognition and initiation of 

treatment are required to prevent possible progression to respiratory failure or 

cardiovascular collapse. It is important to note that urticaria may not be present in all 

cases of anaphylaxis. For respiratory or cardiovascular symptoms, or other signs or 

symptoms of anaphylaxis, immediate intramuscular epinephrine is the treatment of 

choice (11,12). Additional doses of epinephrine as well as other drugs also might be 

indicated (Tables 5-1 and 5-2) (12). Considering the availability of emergency services, 

providers should plan for the availability of at least 3 doses of epinephrine (in dosing 

formulations appropriate to each and every age/group served by the provider) for a 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 76

hypothetical emergency situation. If hypotension is present, the patient should be placed 

in a recumbent position with the legs elevated. Maintenance of the airway, oxygen 

administration, and intravenous normal saline might be necessary. 

After the patient is stabilized, arrangements should be made for immediate transfer to an 

emergency facility for additional evaluation and treatment. Because anaphylaxis may 

recur after patients begin to recover, monitoring in a medical facility for several hours is 

advised, even after complete resolution of symptoms and signs. Additional information on 

management of patients with anaphylaxis has been published (9).

Persons Who Have Had an Allergic Reaction Following a 

Previous Immunization

For an individual patient who has experienced an immediate reaction to immunization, it 

is important to identify the type of reaction that occurred, obtain a history of prior allergic 

reactions, and try to identify the particular agent responsible. An algorithm approach to 

these patients has been published (13) and additional advice is available for allergists on 

the evaluation of these adverse events (10). In general, a history of a severe allergic 

reaction to a vaccine should be considered a contraindication to additional doses of the 

same vaccine (13). Referral of the individual to an allergist for evaluation is usually 

indicated to possibly determine the component responsible, before making decisions 

regarding administration of the additional doses of the same vaccine or other vaccines that 

have the same components. Patients who have not had a severe allergic reaction following 

a vaccine, but who have a history of possible allergy to a vaccine component can often be 

vaccinated safely after careful evaluation (6).

Influenza Vaccination of Persons with a History of Egg 

Allergy

Severe allergic and anaphylactic reactions can occur in response to a number of influenza 

vaccine components, but such reactions are rare (6). All but the recombinant inactivated 

influenza vaccine may have come into contact with egg protein. The use of influenza 

vaccines for persons with a history of egg allergy has been reviewed recently by ACIP (14). 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 77

VAERS data mining did not identify a higher than expected proportion of serious allergic 

events after influenza vaccination during the 2011-2012 season, relative to all other 

reported vaccines and adverse events in the database. Persons with a history of egg allergy 

should receive recombinant inactivated vaccine (if 18 years or older), or IIV.

Other measures, such as dividing and administering the vaccine by a 2-step approach and 

skin testing with vaccine, are not recommended (10).

All vaccines should be administered in settings in which personnel and equipment for 

rapid recognition and treatment of anaphylaxis are available. ACIP recommends that all 

vaccination providers be certified in cardiopulmonary resuscitation (CPR), have an office 

emergency plan, and ensure that all staff are familiar with the plan (6). Some persons who 

report allergy to egg might not be egg-allergic. Those who are able to eat lightly cooked egg 

(e.g., scrambled egg) without reaction are unlikely to be allergic.

Egg-allergic persons might tolerate egg in baked products (e.g., bread or cake). Tolerance 

to egg-containing foods does not exclude the possibility of egg allergy (15). Egg allergy can 

be confirmed by a consistent medical history of adverse reactions to eggs and eggcontaining foods, plus skin and/or blood testing for IgE antibodies to egg proteins.

A previous severe allergic reaction to influenza vaccine, regardless of the component 

suspected to be responsible for the reaction, is a contraindication to future receipt of the 

vaccine (14).

Yellow Fever Vaccination of Persons with a History of Egg 

Allergy

Yellow fever vaccine contains egg protein. There have been insufficient studies to 

determine which patients with egg allergy may be able to receive yellow fever vaccine, but 

there are reports of patients with true egg allergy safely receiving yellow fever vaccine after 

evaluation by specialists with expertise in the management of allergic reactions (16,17). 

According to the manufacturer, persons who are able to eat eggs or egg products may 

receive the vaccine (18). However, potential hypersensitivity reactions might occur in 

persons with a history of minor reactions to eggs. 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 78

For egg-sensitive persons, a scratch test or intradermal test can be performed before 

administering the vaccine to check for reactivity. 

If a person has a severe egg-sensitivity or has a positive skin test to the vaccine, but the 

vaccination is recommended because of their travel destination-specific risk, 

desensitization can be performed under direct supervision of a physician experienced in 

the management of anaphylaxis. 

The desensitization procedure is detailed in the product insert (see yellow fever 

recommendations at 

https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm09407

4.htm). 

Vaccines with MMR or Varicella Components and Persons 

with a History of Egg Allergy

Varicella vaccine is grown in human diploid cell cultures and can safely be administered to 

persons with a severe allergy to eggs or egg proteins (19). Measles and mumps vaccine 

viruses are grown in chick embryo fibroblast tissue culture. However, persons with a 

severe egg allergy can receive measles- or mumps-containing vaccines in the usual manner 

because the content of these proteins is extremely low (20). The rare severe allergic 

reactions after measles- or mumps-containing vaccines or varicella are thought to be 

caused by other components of the vaccine (e.g., gelatin) (21-24). MMR, MMRV, varicella 

and other vaccines contain hydrolyzed gelatin as a stabilizer.

Vaccines and Persons with a History of Allergy to 

Substances Other than Eggs

Persons who have had an anaphylactic reaction to gelatin or gelatin-containing products 

should be evaluated by an allergist prior to receiving gelatin-containing vaccines (6).

Certain vaccines contain trace amounts of antimicrobial agents or other preservatives 

(e.g., neomycin or thimerosal), although allergies to these are rare. No licensed vaccine 

contains penicillin or penicillin derivatives.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 79

Most often, neomycin hypersensitivity manifests as contact dermatitis, a delayed-type 

(cell-mediated) immune response rather than immediate-hypersensitivity (IgE-mediated 

allergy)–type response (25,26). A history of delayed-type reactions to neomycin is not a 

contraindication for administration of neomycin-containing vaccines. There has only been 

1 reported case of immediate hypersensitivity reaction following a neomycin-containing 

vaccine (27). Persons who have had anaphylactic reactions to neomycin should be 

evaluated by an allergist prior to receiving vaccines containing neomycin (6).

Thimerosal, an organic mercurial compound in use since the 1930s, is added to certain 

immunobiologics as a preservative. Since mid-2001, vaccines routinely recommended for 

infants younger than 6 months of age have been manufactured without thimerosal as a 

preservative (14). Live, attenuated vaccines have never contained thimerosal. Thimerosalfree formulations of inactivated influenza vaccine are available. Inactivated influenza 

vaccine also is available in formulations with only trace amounts of thimerosal, which 

remains as a manufacturing residual but is not added at the higher concentration that 

would be necessary for it to function as a preservative. Thimerosal at a preservative 

concentration is present in certain other vaccines that can be administered to children 

(e.g., Td and DT). Information about the thimerosal content of vaccines is available from 

FDA at 

https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096

22 8. 

Reactions to thimerosal have been described as local delayed-type hypersensitivity 

reactions with only rare reports of immediate reactions (28-31). Thimerosal elicits positive 

delayed-type hypersensitivity patch tests in 1%-18% of persons tested; however, these tests 

have no relevance to acute allergic reactions that might occur within minutes or hours 

after immunization (32,33). The majority of persons do not experience reactions to 

thimerosal administered as a component of vaccines even when patch or intradermal tests 

for thimerosal indicate hypersensitivity (31). A local or delayed-type hypersensitivity 

reaction to thimerosal is not a contraindication to receipt of a vaccine that contains 

thimerosal (34). 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 80

Latex is sap from the rubber tree. Latex contains naturally occurring plant proteins that 

can be responsible for immediate-type allergic reactions. Latex is processed to form either 

natural rubber latex products such as gloves or dry, natural rubber products such as 

syringe plunger tips and vial stoppers. Synthetic rubber is also used in gloves, syringe 

plungers, and vial stoppers but does not contain the latex proteins linked to immediatetype allergic reactions. Natural rubber latex or dry, natural rubber used in vaccine 

packaging generally is noted in the manufacturers’ package inserts.

Immediate-type allergic reactions due to latex allergy have been described after 

vaccination, but such reactions are rare (35).

If a person reports a severe anaphylactic allergy to latex, vaccines supplied in vials or 

syringes that contain natural rubber latex should be avoided if possible (6). If not, if the 

decision is made to vaccinate, providers should be prepared to treat immediate allergic 

reactions due to latex, including anaphylaxis. The most common type of latex 

hypersensitivity is a delayed-type (type 4, cell-mediated) allergic contact dermatitis (36). 

For patients with a history of contact allergy to latex, vaccines supplied in vials or syringes 

that contain dry natural rubber or natural rubber latex may be administered.

Reporting Adverse Events After Vaccination

Modern vaccines are safe and effective; however, adverse events have been reported after 

administration of all vaccines (3). More complete information about adverse reactions to a 

specific vaccine is available in the package insert for each vaccine and from CDC at 

www.cdc.gov/vaccines/vac-gen/side-effects.htm. An adverse event is an untoward event 

that occurs after a vaccination that might be caused by the vaccine product or vaccination 

process. These events range from common, minor, local reactions to rare, severe, allergic 

reactions (e.g., anaphylaxis). Reporting to VAERS helps establish trends, identify clusters 

of adverse events, or generate hypotheses. However, establishing evidence for cause and 

effect on the basis of case reports and case series alone is usually not possible, because 

health problems that have a temporal association with vaccination do not necessarily 

indicate causality.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 81

Many adverse events require more detailed epidemiologic studies to compare the 

incidence of the event among vaccinees with the incidence among unvaccinated persons. 

Potential causal associations between reported adverse events after vaccination can be 

assessed through epidemiologic or clinical studies.

The National Childhood Vaccine Injury Act of 1986 (1) requires health care personnel and 

vaccine manufacturers to report to VAERS specific adverse events that occur after 

vaccination. The reporting requirements are different for manufacturers and health care 

personnel. Manufacturers are required to report all adverse events that occur after 

vaccination to VAERS, whereas health-care providers are required to report events that 

appear in the reportable events table on the VAERS website at 

https://vaers.hhs.gov/docs/VAERS_Table_of_Reportable_Events_Following_Vaccinat

ion.pdf. 

In addition to the mandated reporting of events listed on the reportable events table, 

health care personnel should report to VAERS all events listed in product inserts as 

contraindications, as well as all clinically significant adverse events, even if they are 

uncertain that the adverse event is related causally to vaccination (6). Persons other than 

health care personnel also can report adverse events to VAERS.

General information on VAERS is available at https://vaers.hhs.gov/index.html. Specific 

information for healthcare providers is available 

at https://vaers.hhs.gov/resources/infoproviders.html. Reporting to VAERS is fully 

electronic and can be done using an online reporting tool or a writable PDF; instructions 

are available at https://vaers.hhs.gov/reportevent.html. Further assistance on VAERS 

reporting is available through email at info@VAERS.org and the VAERS toll free number 

1-800-822-7967.

National Vaccine Injury Compensation Program

The National Vaccine Injury Compensation Program, established by the National 

Childhood Vaccine Injury Act of 1986 (1), is a no-fault system in which persons thought to 

have experienced an injury or to have died as a result of administration of a covered 

vaccine can seek compensation. 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 82

The program became operational on October 1, 1988, and is intended as an alternative to 

civil litigation under the traditional tort system in that negligence need not be proven. 

Claims arising from covered vaccines must first be adjudicated through the program 

before civil litigation can be pursued.

The program relies on the Vaccine Injury Table, which lists the vaccines covered by the 

program and the injuries (including death), disabilities, illnesses, and conditions for which 

compensation might be awarded. The table defines the time during which the first 

symptom or substantial aggravation of an injury must appear after vaccination to be 

eligible. Successful claimants receive a legal presumption of causation if a condition listed 

in the table is proven, thus avoiding the need to prove actual causation in an individual 

case. Claimants also can prevail for conditions not listed in the reportable events table if 

they prove causation for covered vaccines. 

Additional information is available from the Health Resources and Services 

Administration (HRSA at https://www.hrsa.gov/vaccine-compensation/index.html or by 

telephone at 800-338- 2382). Persons who would like to file a claim for vaccine injury 

should contact the U.S. Court of Federal Claims (717 Madison Place, N.W., Washington, 

DC 20005; telephone: 202-357-6400).
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 83

TABLE 5-1: Rapid overview: Emergent management of anaphylaxis in 

infants and children(a)

Diagnosis is 

made 

clinically:

The most common signs and symptoms are cutaneous (e.g., sudden onset of generalized 

urticaria, angioedema, flushing, pruritus). However, 10 to 20% of patients have no skin 

findings.

Danger signs: Rapid progression of symptoms, evidence of respiratory distress (e.g., stridor, 

wheezing, dyspnea, increased work of breathing, retractions, persistent cough, cyanosis), signs 

of poor perfusion, abdominal pain, vomiting, dysrhythmia, hypotension, collapse.

Acute 

management:

The first and most important therapy in anaphylaxis is epinephrine. There are NO absolute 

contraindications to epinephrine in the setting of anaphylaxis.

Airway: Immediate intubation if evidence of impending airway obstruction from angioedema. 

Delay may lead to complete obstruction. Intubation can be difficult and should be performed 

by the most experienced clinician available. Cricothyrotomy may be necessary.

IM epinephrine (1 mg/mL preparation): Epinephrine 0.01 mg/kg should be injected 

intramuscularly in the mid-outer thigh. For large children (>50 kg), the maximum is 0.5 mg 

per dose. If there is no response or the response is inadequate, the injection can be repeated in 

5 to 15 minutes (or more frequently). If epinephrine is injected promptly IM, patients respond 

to one, two, or at most, three injections. If signs of poor perfusion are present or symptoms are 

not responding to epinephrine injections, prepare IV epinephrine for infusion (see below).

Place patient in recumbent position, if tolerated, and elevate lower extremities.

Oxygen: Give 8 to 10 L/minute via facemask or up to 100% oxygen, as needed.

Normal saline rapid bolus: Treat poor perfusion with rapid infusion of 20 mL/kg. Reevaluate 

and repeat fluid boluses (20 mL/kg), as needed. Massive fluid shifts with severe loss of 

intravascular volume can occur. Monitor urine output.

Albuterol: For bronchospasm resistant to IM epinephrine, give albuterol 0.15 mg/kg 

(minimum dose: 2.5 mg) in 3 mL saline inhaled via nebulizer. Repeat, as needed.

H1 antihistamine: Consider giving diphenhydramine 1 mg/kg (max 50 mg) IV given over 5 

minutes, or cetirizine (children age 6 months to 5 years can receive 2.5 mg IV, those 6 to 11 years 

of age can receive 5 or 10 mg IV, over 2 minutes).

H2 antihistamine: Consider giving famotidine 0.25 mg/kg (max 20 mg) IV, over at least 2 

minutes.

Glucocorticoid: Consider giving methylprednisolone 1 mg/kg (max 125 mg) IV.

Monitoring: Continuous noninvasive hemodynamic monitoring and pulse oximetry monitoring 

should be performed. Urine output should be monitored in patients receiving IV fluid 

resuscitation for severe hypotension or shock.

Treatment of 

refractory 

symptoms:

Epinephrine infusion:(b) In patients with inadequate response to IM epinephrine and IV saline, 

give epinephrine continuous infusion at 0.1 to 1 mcg/kg/minute, titrated to effect.

Vasopressors:(b) Patients may require large amounts of IV crystalloid to maintain blood 

pressure. Some patients may require a second vasopressor (in addition to epinephrine). All 

vasopressors should be given by infusion pump, with the doses titrated continuously according

to blood pressure and cardiac rate/function monitored continuously and oxygenation 

monitored by pulse oximetry

IM: intramuscular; IV: intravenous.

(a) A child is defined as a prepubertal patient weighing less than 40 kg.

(b) All patients receiving an infusion of epinephrine and/or another vasopressor require continuous noninvasive 

monitoring of blood pressure, heart rate and function, and oxygen saturation. We suggest that pediatric centers 

provide instructions for preparation of standard concentrations and also provide charts for established infusion 

rate for epinephrine and other vasopressors in infants and children.

Source: Campbell RL, Kelso JM. Anaphylaxis: Emergency treatment. In: UpToDate, 

Post TW (Ed), UpToDate, Waltham, MA. (Accessed on December 9, 2021) 

Source: (37).
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 84

Table 5-2: Rapid overview: Emergency management of anaphylaxis in 

adults

Diagnosis is made clinically: The most common signs and symptoms are cutaneous 

(e.g., sudden onset of generalized urticaria, 

angioedema, flushing, pruritus). However, 10 to 20% of 

patients have no skin findings.

Danger signs: Rapid progression of symptoms, 

respiratory distress (e.g., stridor, wheezing, dyspnea, 

increased work of breathing, persistent cough, 

cyanosis), vomiting, abdominal pain, hypotension, 

dysrhythmia, chest pain, collapse.

Acute management: The first and most important treatment in anaphylaxis 

is epinephrine. There are NO absolute contraindications 

to epinephrine in the setting of anaphylaxis.

Airway: Immediate intubation if evidence of impending 

airway obstruction from angioedema. Delay may lead to 

complete obstruction. Intubation can be difficult and 

should be performed by the most experienced clinician 

available. Cricothyrotomy may be necessary.

Promptly and simultaneously, give: IM epinephrine (1 mg/mL preparation): Give 

epinephrine 0.3 to 0.5 mg intramuscularly, preferably 

in the mid-outer thigh. Can repeat every 5 to 15 

minutes (or more frequently), as needed. If 

epinephrine is injected promptly IM, most patients 

respond to one, two, or at most, three doses. If 

symptoms are not responding to epinephrine 

injections, prepare IV epinephrine for infusion.

Place patient in recumbent position, if tolerated, and 

elevate lower extremities.

Oxygen: Give 8 to 10 L/minute via facemask or up to 

100% oxygen, as needed.

Normal saline rapid bolus: Treat hypotension with 

rapid infusion of 1 to 2 liters IV. Repeat, as needed. 

Massive fluid shifts with severe loss of intravascular 

volume can occur.

Albuterol (salbutamol): For bronchospasm resistant to 

IM epinephrine, give 2.5 to 5 mg in 3 mL saline via 

nebulizer. Repeat, as needed.

Adjunctive therapies: H1 antihistamine:(a) Consider giving cetirizine 10 mg 

IV (given over 2 minutes) diphenhydramine 25 to 50 

mg IV (given over 5 minutes) (for relief of urticaria 

and itching only)

H2 antihistamine:(a) Consider giving famotidine 20 

mg IV (given over 2 minutes).

Glucocorticoid:(a) Consider giving methylprednisolone 

125 mg IV.

Monitoring: Continuous noninvasive hemodynamic 

monitoring and pulse oximetry monitoring should be 

performed. Urine output should be monitored in 

patients receiving IV fluid resuscitation for severe 

hypotension or shock.

Treatment of refractory symptoms: Epinephrine infusion(b),: For patients with inadequate 

response to IM epinephrine and IV saline, give

epinephrine continuous infusion, beginning at 0.1 

mcg/kg/minute by infusion pump(c) . Titrate the dose 

continuously according to blood pressure, cardiac rate 

and function, and oxygenation.

Vasopressors(b: Some patients may require a second 

vasopressor (in addition to epinephrine). All 

vasopressors should be given by infusion pump, with 

the doses titrated continuously according to blood 

pressure and cardiac rate/function and oxygenation 

monitored by pulse oximetry.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 85

Glucagon: Patients on beta blockers may not respondto 

epinephrine and can be given glucagon 1 to 5 mg IV 

over 5 minutes, followed by infusion of 5 to 15 

mcg/minute. Rapid administration of glucagon can 

cause vomiting.

Instructions on how to prepare and administer epinephrine for IV continuous infusions are available as 

separate tables in UpToDate.

IM: intramuscular; IV: intravenous.

(a) These medications should not be used as initial or sole treatment.

(b) All patients receiving an infusion of epinephrine and another vasopressor require continuous noninvasive 

monitoring of blood pressure, heart rate and function, and oxygen saturation.

(c) For example, the initial infusion rate for a 70 kg patient would be 7 mcg/minute. This is consistent with the 

recommended range for non–weight-based dosing for adults, which is 2 to 10 mcg/minute. Non–weight-based 

dosing can be used if the patient's weight is not known and cannot be estimated.

Source: Campbell RL, Kelso JM. Anaphylaxis: Emergency treatment. In: UpToDate, Post 

TW (Ed), UpToDate, Waltham, MA. (Accessed on December 9, 2021)

Source: (37).
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 86

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systemic immediate-type reactions, including anaphylaxis, to vaccines. J 

Allergy Clin Immunol. 1996;98(6 Pt 1):1058-1061. DOI: 10.1016/S0091-

6749(96)80191-6

23. Sakaguchi M, Ogura H, Inouye S. IgE antibody to gelatin in children with 

immediate-type reactions to measles and mumps vaccines. J Allergy Clin 

Immunol. 1995;96(4):563-565. DOI: 10.1016/S0091-6749(95)70304-7

24. Sakaguchi M, Yamanaka T, Ikeda K, et al. IgE-mediated systemic reactions to 

gelatin included in the varicella vaccine. J Allergy Clin Immunol. 

1997;99(2):263-264. DOI: 10.1016/S0091-6749(97)70108-8

25. Rietschel RL, Bernier R. Neomycin sensitivity and the MMR vaccine.JAMA.

1981;245(6):571. DOI: 10.1001/jama.1981.03310310017008

26. Elliman D, Dhanraj B. Safe MMR vaccination despite neomycinallergy.

Lancet. 1991;337(8737):365. DOI: 10.1016/0140-6736(91)90995-2

27. Kwittken PL, Rosen S, Sweinberg SK. MMR vaccine and neomycin allergy. 

Am J Dis Child. 1993;147(2):128-129. DOI: 

10.1001/archpedi.1993.02160260018005

28. Aberer W. Vaccination despite thimerosal sensitivity. ContactDermatitis.

1991;24(1):6-10. DOI: 10.1111/j.1600-0536.1991.tb01621.x

29. Cox NH, Forsyth A. Thiomersal allergy and vaccination reactions. Contact 

Dermatitis. 1988;18(4):229-233. DOI: 10.1111/j.1600-0536.1988.tb02809.x

30. Kirkland LR. Ocular sensitivity to thimerosal: a problem with hepatitis B 

vaccine? South Med J. 1990;83(5):497-499.

31. Zheng W, Dreskin SC. Thimerosal in influenza vaccine: an immediate 

hypersensitivity reaction. Ann Allergy Asthma Immunol. 2007;99(6):574-

575. DOI: 10.1016/s1081-1206(10)60391-2

32. Wantke F, Demmer CM, Götz M, Jarisch R. Contact dermatitis from 

thimerosal. Contact Dermatitis. 1994;30(2):115. DOI: 10.1111/j.1600-

0536.1994.tb00580.x
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 89

33. Moller H. All these positive tests to thimerosal. ContactDermatitis.

1994;31(4):209-213. DOI: 10.1111/j.1600-0536.1994.tb01989.x

34. Russell M, Pool V, Kelso JM, Tomazic-Jezic VJ. Vaccination of persons 

allergic to latex: a review of safety data in the Vaccine Adverse Event 

Reporting System (VAERS). Vaccine. 2004;23(5):664-667. DOI: 

10.1016/j.vaccine.2004.06.042

35. Lear JT, English JS. Anaphylaxis after hepatitis B vaccination.Lancet.

1995;345(8959):1249. DOI: 10.1016/S0140-6736(95)92039-0

36. Slater JE. Latex allergy. J Allergy Clin Immunol. 1994;94(2 Pt 1):139-149; 

quiz 150. DOI: 10.1053/ai.1994.v94.a55437

37. Adapted from: Simons FER. Anaphylaxis. J Allergy Clin Immunol. 

2010;125:S161.
General Best Practice Guidelines for Immunization: Vaccine Administration 90

6. Vaccine Administration

Infection Control and Sterile Technique

General Precautions

Persons administering vaccinations should follow appropriate precautions to minimize 

risk for disease exposure and spread. Hands should be cleansed with an alcohol-based 

waterless antiseptic hand rub or washed with soap and water before preparing vaccines for 

administration and between each patient contact (1). Occupational Safety and Health 

Administration (OSHA) regulations do not require gloves to be worn when administering 

vaccinations, unless persons administering vaccinations have open lesions on their hands 

or are likely to come into contact with a patient’s body fluids (2). If worn, gloves should be 

changed between patients.

Vaccine Administration: Preparation and Timely Disposal

Vaccines should be drawn up in a designated clean medication area that is not adjacent to 

areas where potentially contaminated items are placed. Multi-dose vials to be used for 

more than one patient should not be kept or accessed in the immediate patient treatment 

area. This is to prevent inadvertent contamination of the vial through direct or indirect 

contact with potentially contaminated surfaces or equipment that could then lead to 

infections in subsequent patients (3). Smallpox vaccine is accessed by dipping a 

bifurcated needle directly into the vaccine vial. The vaccine adheres to the sides of the 

bifurcated needle, and is administered via skin puncture. The vial must be accessed in the 

immediate patient area to reduce environmental contamination by vaccine virus. To 

prevent contamination of the vial, make sure the patient area is clean and free of 

potentially contaminated equipment.

Different single-components of combination vaccines should never be mixed in the same 

syringe by an end-user unless specifically licensed for such use (4). Single-dose vials and 

manufacturer-filled syringes are designed for single-dose administration and should be 

discarded if vaccine has been withdrawn or reconstituted and subsequently not used 

within the time frame specified by the manufacturer. Syringes that are prefilled by the 

manufacturer and activated (i.e., syringe cap removed or needle attached) but unused 

should be discarded at the end of the clinic day. For non-live vaccines, manufacturers 
General Best Practice Guidelines for Immunization: Vaccine Administration 91

typically recommend use within the same day that a vaccine is withdrawn or reconstituted. 

For live vaccines that require reconstitution, manufacturers typically recommend the 

vaccine be used as soon as possible after reconstitution and be discarded if not used within 

30 minutes after reconstitution. For example, varicella vaccine should be discarded if not 

used within 30 minutes after reconstitution, whereas MMR vaccine, once reconstituted, 

must be kept in a dark place at 36°F to 46°F (2°C to 8°C) and should be discarded within 8 

hours if not used. When in doubt about the appropriate handling of a vaccine, vaccination 

providers should contact that vaccine’s manufacturer.

ACIP discourages the routine practice of providers’ prefilling syringes for several reasons. 

Because the majority of vaccines have a similar appearance after being drawn into a 

syringe, prefilling might result in administration errors. Because unused prefilled syringes 

also typically must be discarded if not used within the same day that they are filled, 

vaccine wastage might occur. The FDA does not license administration syringes for 

vaccine storage.

In certain circumstances in which a single vaccine type is being used (e.g., in preparation 

for a community influenza vaccination campaign), filling a small number (10 or fewer) of 

syringes may be considered (5). The doses should be administered as soon as possible 

after filling, by the same person who filled the syringes. Unused syringes that are prefilled 

by the manufacturer and activated (i.e., syringe cap removed or needle attached) should be 

discarded at the end of the clinic day. Vaccine from two or more vials should never be 

combined to make one or more doses. This can lead to violation of expiration dates and 

product contamination (6,7).

Health Care Provider Exposure to Vaccine Components

Providers are sometimes concerned when they have the same contraindications or 

precautions as their patients from whom they withhold or defer vaccine. For 

administration of routinely recommended vaccines, there is no evidence of risk of 

exposure of vaccine components to the health care provider, so conditions in the provider 

labeled as contraindications and precautions to a vaccine components are not a reason to 

withdraw from this function of administering the vaccine to someone else. Historic 

concerns about exposure to vaccine components are limited to non-parenteral vaccines in 

which some degree of environmental exposure is unavoidable (5, 8), or situations in which 
General Best Practice Guidelines for Immunization: Vaccine Administration 92

self-inoculation is likely due to the nature of the vaccine microbe [e.g. reduced attenuation 

of smallpox vaccine virus (9)]. Persons administering ACAM 2000 smallpox vaccine to 

laboratory and health care personnel at risk for occupational exposure to orthopoxviruses 

can decrease the risk for inadvertent infection through recommended infection prevention 

measures. However, because of a theoretical risk for infection, vaccination with 

ACAM2000 can be offered to health care personnel administering this vaccine, provided 

individual persons have no specified contraindications to vaccination (10).

Safe Use of Needles and Syringes

Needles and syringes used for vaccine injections must be sterile and disposable. A separate 

needle and syringe should be used for each injection. Changing needles between drawing 

vaccine from a vial and injecting it into a recipient is not necessary unless the needle has 

been damaged or contaminated (11).

Bloodborne diseases (e.g., hepatitis B, hepatitis C, human immunodeficiency virus [HIV]) 

are occupational hazards for clinicians and other health-care providers. The Needlestick 

Safety and Prevention Act (2) was enacted in 2000 to reduce the incidence of needlestick 

injury and the consequent risk for bloodborne diseases acquired from patients. The act 

directed OSHA to strengthen its existing bloodborne pathogen standards. The revised 

standards became effective in 2001 (2). These federal regulations require the use of 

engineering and work practice controls to eliminate or minimize employee exposure to 

bloodborne pathogens. Engineering controls means controls (e.g., sharps disposal 

containers, self-sheathing needles, safer medical devices, such as sharps with engineered 

sharps injury protections and needleless systems) that isolate or remove the bloodborne 

pathogens hazard from the workplace). Needle-shielding or needle-free devices that might 

satisfy the occupational safety regulations for administering injectable vaccines are 

available in the United States (12-13). The regulations also require maintenance of records 

documenting injuries caused by needles and other medical sharp objects and that 

nonmanagerial employees be involved in the evaluation and selection of safety-engineered 

devices before they are procured. Additional information about implementation and 

enforcement of these regulations is available from OSHA.
General Best Practice Guidelines for Immunization: Vaccine Administration 93

To prevent inadvertent needlestick injury or reuse, safety mechanisms should be deployed 

after use and needles and syringes should be discarded immediately in labeled, punctureproof containers located in the same room where the vaccine is administered (5). Used 

needles should never be recapped. 

Route of Administration

Injectable Route

Routes of administration are recommended by the manufacturer for each immunobiologic 

(Table 6-1). With the exceptions of bacille Calmette-Guérin (BCG) vaccine and smallpox 

vaccine [ACAM2000] (both administered by the percutaneous route), injectable vaccines 

are administered by the intramuscular or subcutaneous route. The smallpox/monkeypox 

vaccine (Jynneos) is primarily administered by the subcutaneous route but in some 

circumstances is administered by the intradermal route. Deviation from the recommended 

route of administration might reduce vaccine efficacy (14-15) or increase the risk for local 

adverse reactions (16-18). 

The method of administration of injectable vaccines is determined, in part, by the 

inclusion of adjuvants in some vaccines. An adjuvant is a vaccine component distinct from 

the antigen that enhances the immune response to the antigen, but might also increase 

risk of adverse reactions. To decrease risk of local adverse events, non-live vaccines 

containing an adjuvant should be injected into a muscle. Administering a vaccine 

containing an adjuvant either subcutaneously or intradermally can cause local irritation, 

induration, skin discoloration, inflammation, and granuloma formation.

Intramuscular Injections

Needle Length

Injectable immunobiologics should be administered where local, neural, vascular, or tissue 

injury is unlikely. Use of longer needles has been associated with less redness or swelling 

than occurs with shorter needles because of injection into deeper muscle mass (16). 

Appropriate needle length depends on age and body mass. Injection technique is the most 

important parameter to ensure efficient intramuscular vaccine delivery.
General Best Practice Guidelines for Immunization: Vaccine Administration 94

For all intramuscular injections, the needle should be long enough to reach the muscle 

mass and prevent vaccine from seeping into subcutaneous tissue, but not so long as to 

involve underlying nerves, blood vessels, or bone (15,19-22). Vaccinators should be 

familiar with the anatomy of the area into which they are injecting vaccine. 

Intramuscular injections are administered at a 90-degree angle to the skin, preferably into 

the anterolateral aspect of the thigh or the deltoid muscle of the upper arm, depending on 

the age of the patient (Table 6-2).

The needle gauge for intramuscular injection is 22-25 gauge. A decision on needle length 

and site of injection must be made for each person on the basis of the size of the muscle, 

the thickness of adipose tissue at the injection site, the volume of the material to be 

administered, injection technique, and the depth below the muscle surface into which the 

material is to be injected (Figure 1). Some experts allow intramuscular injection with a 5⁄8-

inch needle but ONLY if the skin is stretched flat (21). If the subcutaneous and muscle 

tissue are bunched to minimize the chance of striking bone (19), a 1-inch needle or larger 

is required to ensure intramuscular administration. Aspiration before injection of vaccines 

or toxoids (i.e., pulling back on the syringe plunger after needle insertion but before 

injection) is not necessary because no large blood vessels are present at the recommended 

injection sites, and a process that includes aspiration might be more painful for infants 

(22).

Infants (Aged <12 Months)

For the majority of infants, the anterolateral aspect of the thigh is the recommended site 

for injection because it provides comparatively larger muscle mass than the deltoid 

(Figure 2) (23). In certain circumstances (e.g., physical obstruction to other sites and no 

reasonable indication to defer doses), the gluteal muscle can be used. If the gluteal muscle 

must be used, care should be taken to define the anatomic landmarks.(a) For the majority of 

infants, a 1-inch needle is sufficient to penetrate the thigh muscle.

Toddlers (Aged 12 Months-2 Years)

For toddlers, the anterolateral thigh muscle is preferred, and when this site is used, the 

needle should be at least 1 inch long. The deltoid muscle can be used if the muscle mass is 

adequate. If 2 vaccines are to be administered in a single limb, they should be spaced an 

inch apart (4, 24).
General Best Practice Guidelines for Immunization: Vaccine Administration 95

Children (Aged 3-10 Years)

The deltoid muscle is preferred for children aged 3-10 years (25); the needle length for 

deltoid site injections can range from 5⁄8 to 1 inch on the basis of technique. The 

anterolateral thigh can also be used (25). In this case the needle length should be 1 inch to 

1.25 inches. Knowledge of body mass can be useful for estimating the appropriate needle 

length (26).

Young Adolescents (Aged 11-18 years)

The deltoid muscle is preferred for adolescents 11-18 years of age. The anterolateral thigh 

can also be used. For injection into the anterolateral thigh, most adolescents will require a 

1-1.5-inch needle to ensure intramuscular administration (27).

Adults (Aged ≥19 Years)

For adults, the deltoid muscle is recommended for routine intramuscular vaccinations 

(23) (Figure 3). The anterolateral thigh also can be used. When injecting into the deltoid 

muscle, for adults a measurement of body mass/weight is allowable prior to vaccination, 

understanding that resources to measure body mass/weight are not available in all clinical 

settings. For men and women who weigh <130 lbs (<60 kg), a 5⁄8-inch needle is sufficient 

to ensure intramuscular injection in the deltoid muscle if the injection is made at a 90-

degree angle and the tissue is not bunched. For men and women who weigh 130-152 lbs 

(60-70 kg), a 1-inch needle is sufficient. For women who weigh 152-200 lbs (70-90 kg) and 

men who weigh 152-260 lbs (70-118 kg), a 1- to 1.5-inch needle is recommended. For 

women who weigh >200 lbs (>90 kg) or men who weigh >260 lbs (>118 kg), a 1.5-inch 

needle is recommended (table 6-2) (20). For injection into the anterolateral thigh muscle, 

a 1.5-inch needle should be used, although a 1-inch needle may be used if the skin is 

stretched tightly and subcutaneous tissues are not bunched.

Subcutaneous Injections

Subcutaneous injections are administered at a 45-degree angle, usually into the thigh for 

infants aged <12 months and in the upper-outer triceps area of persons aged ≥12 months. 

Subcutaneous injections may be administered into the upper-outer triceps area of an 

infant if necessary. A 5⁄8-inch, 23- to 25-gauge needle should be inserted into the 

subcutaneous tissue (Figures 4 and 5) (4).
General Best Practice Guidelines for Immunization: Vaccine Administration 96

Oral Route

Rotavirus, adenovirus, cholera vaccine, and oral typhoid vaccines are the only vaccines 

administered orally in the United States. Oral typhoid capsules should be administered as 

directed by the manufacturer. The capsules should not be opened or mixed with any other 

substance. Rotavirus vaccines are licensed for infants. There are 2 brands of rotavirus 

vaccine, and they have different types of applicators. Providers should consult package 

inserts for details.

Intranasal Route

Live attenuated influenza vaccine is approved for healthy nonpregnant persons aged 2-49 

years and is the only vaccine administered by the intranasal route. The administration 

device is a nasal sprayer with a dose-divider clip that allows introduction of one 0.1-mL 

spray into each naris. The tip should be inserted slightly into the naris before 

administration. Even if the person coughs or sneezes immediately after administration or 

the dose is expelled any other way, the vaccine dose need not be repeated (5).

Severely immunosuppressed persons (i.e., those who require care in a protected 

environment, e.g., bone marrow transplant recipients, individuals with severe combined 

immunodeficiency diseases) should not administer LAIV. It would be uncommon for 

persons with these conditions to be in a role administering vaccines. Other persons at 

increased risk for influenza complications can administer LAIV. These include persons 

with underlying medical conditions placing them at higher risk or who are likely to be at 

risk, including pregnant women, persons with asthma, and persons aged ≥50 years (2).

Multiple Injections

If multiple vaccines are administered at a single visit, administer each preparation at a 

different anatomic site (28). The location of all injection sites with the corresponding 

vaccine injected should be documented in each patient’s medical record. Health-care 

practices should consider using a vaccination site map so that all persons administering 

vaccines routinely use a particular anatomic site for each particular vaccine.

For infants and younger children, if more than 2 vaccines are injected in a single limb, the 

thigh is the preferred site because of the greater muscle mass; the injections should be 

sufficiently separated (separate anatomic sites [i.e. ≥1 inch] if possible) so that any local 
General Best Practice Guidelines for Immunization: Vaccine Administration 97

reactions can be differentiated (13,29). For older children and adults, the deltoid muscle 

can be used for more than one intramuscular injection.

If a vaccine and an immune globulin preparation are administered simultaneously (e.g., 

Td/Tdap and tetanus immune globulin [TIG], hepatitis B and hepatitis B immunoglobulin 

[HBIG]), separate limbs should be used for each injection (29-30).

Jet Injections

Jet injectors are needle-free devices that pressurize liquid medication, forcing it through a 

nozzle orifice into a narrow stream capable of penetrating skin to deliver a drug or vaccine 

into intradermal, subcutaneous, or intramuscular tissues (32-33). Immune responses 

generated by jet injectors against both attenuated and non-live viral and bacterial antigens 

are usually equivalent to, and occasionally greater than, immune responses induced by 

needle injection. However, local reactions or injuries (e.g., skin laceration, transient 

neuropathy, hematoma) are sometimes more frequent on delivery of vaccine by jet 

injectors compared with needle injection, depending on the inherent irritability of the 

vaccine and operator technique (33).

Multiple use jet injectors using the same nozzle for consecutive injections without 

intervening sterilization were used in mass vaccination campaigns from the 1950s through 

the 1990s (33); however, these were found to be unsafe because of the possibility of 

bloodborne pathogen transmission (34-37) and should not be used. A new generation of 

jet injectors with disposable cartridges and syringes has been developed since the 1990s. 

With a new, sterile dose chamber and nozzle for each patient and correct use, these 

devices do not have the same safety concerns as multiple-use nozzle jet injectors. Several 

of the newer devices have been approved by FDA for use with specific vaccines (33). Jet 

injectors prevent needlestick injuries to health-care providers (2) and can overcome 

improper, unsterile reuse and other drawbacks of needles and syringes in developing 

countries (9, 38-39).
General Best Practice Guidelines for Immunization: Vaccine Administration 98

Methods for Alleviating Discomfort and Pain Associated 

with Vaccination

Comfort measures, such as distraction (e.g., playing music or pretending to blow away the 

pain), cooling of the injection site(s), topical analgesia, ingestion of sweet liquids, 

breastfeeding, swaddling, and slow, lateral swaying can help infants or children cope with 

the discomfort associated with vaccination (40-42). Pretreatment (30-60 minutes before 

injection) with a 5% topical lidocaine-prilocaine emulsion might decrease the pain of 

vaccination by causing superficial anesthesia (43-44). Evidence indicates that this cream 

does not interfere with the immune response to MMR (45). There is no evidence the cream 

interferes with other vaccines (46-49). 

Topical lidocaine-prilocaine emulsion should not be used on infants aged <12 months who 

are receiving treatment with methemoglobin-inducing agents (e.g., acetaminophen, amyl 

nitrate, nitroprusside, dapsone) because of the possible development of 

methemoglobinemia (50). Use of a topical refrigerant (vapocoolant) spray immediately 

before vaccination can reduce the short-term pain associated with injections and can be as 

effective as lidocaine-prilocaine cream (51). 

Evidence does not support use of antipyretics before or at the time of vaccination; 

however, they can be used for the treatment of fever and local discomfort that might occur 

following vaccination. Studies of children with previous febrile seizures have not 

demonstrated antipyretics to be effective in the prevention of febrile seizures (48).

Clinical Implications of Nonstandard Vaccination 

Practices

Best practice guidance for route, site, and dosage of immunobiologics is derived from data 

from clinical trials, practical experience, normal intervals of health care visits, and 

theoretical considerations. ACIP discourages variations from the recommended route, site, 

volume, or number of doses of any vaccine.

Variation from the recommended route and site can result in inadequate protection. In 

adults (but not in infants) (52), the immunogenicity of hepatitis B is substantially lower 

when the gluteal rather than the deltoid site is used for administration (8). Hepatitis B 

administered intradermally might result in a lower seroconversion rate and final titer of 
General Best Practice Guidelines for Immunization: Vaccine Administration 99

hepatitis B surface antibody than when administered by the deltoid intramuscular route 

(53-54). Hepatitis B administered by any route other than intramuscular, or in adults at 

any site other than the deltoid or anterolateral thigh, should not be counted as valid and 

should be repeated (9). Similarly, doses of rabies vaccine administered in the gluteal site 

should not be counted as valid doses and should be repeated (54). Hepatitis A vaccine and 

meningococcal conjugate vaccine do not need to be repeated if administered by the 

subcutaneous route (55-56). However, for DTaP, Hib, and PCV13, there is no evidence 

related to immunogenicity of these 3 vaccines given subcutaneously. Providers should 

address circumstances in which dose(s) of these vaccines have been administered 

subcutaneously on a case-by-case basis. 

Inactivated influenza vaccine is immunogenic when administered in a lower-thanstandard dose by the intradermal route to healthy adult volunteers. Intradermal injection 

produced antibody responses similar to intramuscular injection in vaccinees aged 18-60 

years (57). However, the immunogenicity for persons aged ≥65 years is inadequate, and 

varying the recommended route and dose either with the intradermal product licensed 

through 64 years of age or with other influenza vaccines is not recommended (24).

Live, attenuated injectable vaccines (e.g., MMR, varicella, yellow fever) and certain nonlive vaccines (e.g., meningococcal polysaccharide) are recommended by the manufacturers 

to be administered by subcutaneous injection. PPSV23and IPV are recommended by the 

manufacturer to be administered by the subcutaneous or intramuscular route. Response 

to vaccines recommended by the subcutaneous route is unlikely to be affected if the 

vaccines are administered by the intramuscular rather than subcutaneous route. 

Repeating doses of vaccine administered by the intramuscular route when recommended 

to be by the subcutaneous route is not necessary (10).

Administering volumes smaller than recommended (e.g., inappropriately divided doses) 

might result in inadequate protection. Using reduced doses administered at multiple 

vaccination visits that equal a full dose or using smaller divided doses is not recommended 

(4). Any vaccination using less than the standard dose should not be counted, and the 

person should be revaccinated according to age unless serologic testing indicates that an 

adequate response has developed. However, if 2 half-volume formulations of vaccine have 

already been administered on the same clinic day to a patient recommended for the full 

volume formulation, these 2 doses can count as one full dose. If less than a full 
General Best Practice Guidelines for Immunization: Vaccine Administration 100

recommended dose of a vaccine is administered because of syringe, applicator, or needle 

leakage, the dose should be repeated (5). Using larger-than-recommended dosages can be 

hazardous because of excessive local or systemic concentrations of antigens or other 

vaccine constituents.

(a) If the gluteal muscle is chosen, injection should be administered lateral and superior to a line between the posterior superior iliac 

spine and the greater trochanter or in the ventrogluteal site, the center of a triangle bounded by the anterior superior iliac spine, the 

tubercle of the iliac crest, and the upper border of the greater trochanter.
General Best Practice Guidelines for Immunization: Vaccine Administration 101

TABLE 6-1. Dose and route of administration for selected vaccines

Vaccine Dose Route

DEN4CYD 0.5 mL Subcut

DTaP, DT, Td, Tdap 0.5 mL IM

DTaP-HepB-IPV 0.5 mL IM

DTaP/Hib 0.5 mL IM

DTaP-IPV/Hib 0.5 mL IM

DTaP-IPV 0.5 mL IM

Hib 0.5 mL IM

Hib-MenCY 0.5 mL IM

HepA ≤18 years: 0.5 mL

≥19 years: 1.0 mL

IM 

HepB ≤19 years: 0.5 mL(a)

≥20 years: 1.0 mL

IM 

HepA-HepB ≥18 years: 1.0 mL IM

LAIV 0.2 mL divided dose between 

nares

Intranasal spray

IIV 6-35 months: 0.25 mL or 0.5 mL

≥3 years: 0.5 mL(b)

IM 

MenB 0.5 mL IM

MMR 0.5 mL Subcut

MMRV 0.5 mL Subcut

MenACWY 0.5 mL IM

MPSV4 0.5 mL Subcut

PCV13 0.5 mL IM

PCV15 0.5 mL IM

PCV20 0.5 mL IM

PPSV23 0.5 mL IM or Subcut

HPV 0.5 mL IM

IPV 0.5 mL IM or Subcut

Rotavirus (RV1 or RV5) (1.0 mL or 2.0 mL) Oral

Varicella 0.5 mL Subcut

RZV 0.5 mL(c) IM

Abbreviations: DEN4CYD = dengue vaccine; DT = diphtheria and tetanus toxoids; DTaP = diphtheria and tetanus 

toxoids and acellular pertussis; HepA = hepatitis A; HepB = hepatitis B; Hib = Haemophilus influenzae type b; HPV = 

human papillomavirus; IIV = inactivated influenza vaccine; IM = intramuscular; IPV = inactivated poliovirus; LAIV = 
General Best Practice Guidelines for Immunization: Vaccine Administration 102

TABLE 6-1. Dose and route of administration for selected vaccines

Vaccine Dose Route

live, attenuated influenza vaccine; MenACWY = quadrivalent meningococcal conjugate vaccine; MenCY = bivalent 

meningococcal conjugate vaccine component; MMR = measles, mumps, and rubella; MMRV = measles, mumps, 

rubella, and varicella; MPSV4 = quadrivalent meningococcal polysaccharide vaccine; PCV13 = pneumococcal 

conjugate vaccine; PPSV23= pneumococcal polysaccharide vaccine; RV1 = live, attenuated monovalent rotavirus 

vaccine; RV5 = live, reassortment pentavalent rotavirus vaccine; RZV = recombinant adjuvanted zoster vaccine; 

Subcut = subcutaneous; Td = tetanus and diphtheria toxoids; Tdap = tetanus toxoid, reduced diphtheria toxoid, and 

acellular pertussis.

Source: Adapted from Immunization Action Coalition: http://www.immunize.org.

(a) Persons aged 11-15 years may be administered Recombivax HB (Merck), 1.0 mL (adult formulation) on a 2-dose schedule.

(b) Note that prefilled syringes of High-Dose Fluzone have a volume of 0.7 cc and the recommended volume of administration is 

0.7 ccs.

Do not withdraw more than 0.5 mL from the reconstituted product, even if some product is left in the vial.
General Best Practice Guidelines for Immunization: Vaccine Administration 103

TABLE 6-2. Needle length and injection site of IM injections for children 

aged ≤18 years (by age) and adults aged ≥19 years (by sex and weight)

Age group Needle length Injection site

Children (birth-18 years)

Neonates(a) 5/8 inch (16 mm)(b) Anterolateral thigh

Infants, 1-12 months 1 inch (25 mm) Anterolateral thigh

Toddlers, 1-2 years 1-1.25 inch (25-32

mm)

Anterolateral thigh(c)

5/8(b)-1 inch (16-25 

mm)

Deltoid muscle of arm

Children, 3-10 years 5/8(b)-1 inch (16-25 

mm)

Deltoid muscle of arm(c)

1-1.25 inches (25-32 

mm)

Anterolateral thigh

Children, 11-18 years

5/8(b)-1 inch (16-25 

mm)

Deltoid muscle of arm(c)

1-1.5 inches (25-38 

mm)

Anterolateral thigh

Adults (≥19 years)

Men and women, <60 kg (130 lbs) 1 inch (25 mm) (d) Deltoid muscle of arm

Men and women, 60-70 kg (130-

152 lbs)

1 inch (25 mm)

Men, 70-118 kg (152-260 lbs) 1-1.5 inches (25-38 

mm)

Women, 70-90 kg (152-200 lbs)

Men, >118 kg (260 lbs) 1.5 inches (38 mm)

Women, >90 kg (200 lbs)

Men and women, any weight 1.5 inches (38 mm)(e) Anterolateral thigh
General Best Practice Guidelines for Immunization: Vaccine Administration 104

Abbreviation: IM = intramuscular.

Source: (14).

(a) First 28 days of life.

(b) If skin is stretched tightly and subcutaneous tissues are not bunched.

(c) Preferred site.

(d) Some experts recommend a 5/8-inch needle for men and women who weigh <60 kg, if used, skin must be 

stretched tightly (do not bunch subcutaneous tissue).

(e) Some experts recommend a 1-inch needle if the skin is stretched tightly and subcutaneous tissues are not 

bunched.
General Best Practice Guidelines for Immunization: Vaccine Administration 105

Figure 1. Intramuscular needle insertion

Source: Adapted from California Immunization Branch.

Alternate Text: This drawing shows intramuscular needle insertion into a crosssection of skin. The needle is inserted at a 90-degree angle and penetrates the dermis, 

fatty tissue (subcutaneous), and muscle tissue.
General Best Practice Guidelines for Immunization: Vaccine Administration 106

Figure 2. Intramuscular/subcutaneous site of administration: anterolateral 

thigh

Source: Adapted from Minnesota Department of Health.

Alternate Text: This drawing shows a mother holding an infant. The anterolateral 

aspect of the infant’s thigh is shaded, showing the proper site for 

intramuscular/subcutaneous vaccine administration.
General Best Practice Guidelines for Immunization: Vaccine Administration 107

Figure 3. Intramuscular site of administration: deltoid

Source: Adapted from Minnesota Department of Health and Immunize.org.

Alternate Text: This line drawing is a side view of an adult. The deltoid muscle of the 

arm is shaded, showing the proper site for intramuscular vaccine administration.
General Best Practice Guidelines for Immunization: Vaccine Administration 108

Figure 4. Subcutaneous site of administration: triceps

Source: Adapted from the Minnesota Department of Health.

Alternate Text: This line drawing is a rear/dorsal view of an adult. The triceps muscle 

of the arm is shaded, showing the proper site for subcutaneous vaccine administration.
General Best Practice Guidelines for Immunization: Vaccine Administration 109

Figure 5. Subcutaneous needle insertion

Source: Adapted from California Immunization Branch.

Alternate Text: This drawing shows subcutaneous needle insertion into a crosssection of skin. The needle is inserted at a 45-degree angle and penetrates the dermis 

and fatty tissue (subcutaneous) but not the muscle tissue.
General Best Practice Guidelines for Immunization: Vaccine Administration 110

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0939
General Best Practice Guidelines for Immunization: Vaccine Administration 116

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General Best Practice Guidelines for Immunization: Storage and Handling of Immunobiologics 117

7. Storage and Handling of Immunobiologics

Updates

Most of the 2011 language was removed because this content is now codified and 

continually updated in the CDC’s Vaccine Storage and Handling Toolkit, available at 

www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html. This content included 

Storage Units, Monitoring Storage Temperature, Vaccine Inventory, and Vaccine 

Transport.

General Principles

Failure to adhere to recommended specifications for storage and handling of 

immunobiologics can reduce or destroy their potency, resulting in inadequate or no 

immune response in the recipient 

(www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html). Recommendations in the 

product package inserts, including methods for reconstitution of the vaccine, should be 

followed carefully. Maintenance of vaccine quality is the shared responsibility of all 

handlers of vaccines from the time a vaccine is manufactured until administration. All 

vaccines should be inspected on delivery and monitored during storage to ensure that the 

recommended storage temperatures are maintained. Vaccines should continue to be 

stored at recommended temperatures immediately upon receipt until use. Inadequate 

vaccine storage also can result in significant costs to replace vaccine inventory 

(www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html).

Storage Temperature

Vaccines licensed for refrigerator storage should be stored at 2°C-8°C (36°F-46°F). Liquid 

vaccines containing an aluminum adjuvant permanently lose potency when exposed to 

freezing temperatures. Non-live vaccines that are stored in a liquid state (i.e., nonlyophilized [freeze-dried]) but that do not contain aluminum adjuvants should also 

generally be kept at refrigerator temperature, although whether or not they lose potency 

when frozen is not known. 
General Best Practice Guidelines for Immunization: Storage and Handling of Immunobiologics 118

Non-live lyophilized vaccines generally do not need to be frozen, but lyophilized varicellacontaining vaccines that are recommended to be stored frozen lose potency when exposed 

to higher temperatures because the viruses degrade more quickly at storage temperatures 

that are warmer than recommended (Table 7-1). These varicella-containing vaccines also 

can be prone to losses in sterility if kept too cold, due to increased gas permeability of the 

rubber vaccine vial (observed with use of dry ice at temperatures below -50°C or -58°F 

[personal communication, manufacturer]).

Expiration Dates and Windows

All vaccines have an expiration date determined by the manufacturer that must be 

observed. Providers should record the vaccine expiration dates and lot numbers on a stock 

or inventory record for each vaccine vial when a shipment is received. When vaccines are 

removed from storage, clinicians and other health-care providers should note whether an 

expiration window exists for vaccine stored at room temperature or at an intermediate 

temperature. For example, single-component varicella vaccine that is stored frozen must 

be discarded after 72 hours of storage at refrigerator temperature. Vaccine transport 

between the storage site and the administration clinic is discouraged unless the cold chain 

is maintained, and vaccine transport by the patient is particularly discouraged. An 

expiration window also applies to vaccines that have been reconstituted. For example, 

after reconstitution, MMR vaccine should be kept at refrigerator temperature and must be 

administered within 8 hours. Doses of expired vaccines that are administered 

inadvertently generally should not be counted as valid and should be repeated. Non-live 

vaccines should generally be repeated as soon as possible. Recombinant zoster vaccine 

(RZV) should be administered 28 days after the invalid dose, to reduce the burden of 

adverse reactions which occurs with this vaccine. Live vaccines should be repeated after a 

28-day interval from the invalid dose to reduce the risk for interference from interferon on 

the subsequent doses. For rotavirus vaccines, the repeat dose should be administered after 

a 28-day interval from the invalid dose or at the maximum age for the vaccine dose 

(whichever is earlier). Additional information about expiration dates is available at

https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html. 
General Best Practice Guidelines for Immunization: Storage and Handling of Immunobiologics 119

Response to Out-of-Range Temperature Reading

An out-of-range temperature reading should prompt immediate action. A plan should be 

developed ahead of time to address various types of emergencies that might require 

removal of vaccine from the original storage unit. Transfer of vaccines to a predesignated 

alternative emergency storage site might be necessary if a temperature problem cannot be 

resolved immediately (e.g., plugging in an unplugged unit or closing a door that has been 

left open). It is critical to avoid freezing vaccine during transport (improperly packing 

vaccine with ice can damage vaccines). Vaccine should be marked “do not use” and moved 

to the alternate site after verifying that the alternate unit is at the proper temperature. 

Determinations of vaccine viability in practice include consideration of both time and 

magnitude of temperature excursions and should be made in consultation with state/local 

public health departments or the vaccine manufacturer, as one or both of these groups 

may have additional information based on a broad international perspective. Damage to 

the immunogenicity of a vaccine exposed to temperatures outside of the recommended 

range might not be apparent visually. As a general rule, vaccines that have been stored at 

inappropriate temperatures should not be administered unless public health authorities or 

the manufacturer determine it is safe and effective to do so. If such vaccines already have 

been administered, vaccine exposed to inappropriate temperatures that is inadvertently 

administered should generally be repeated. Non-live vaccines should generally be repeated 

as soon as possible. Recombinant zoster vaccine (RZV) is neither live nor inactivated: the 

repeat dose of RZV should be administered 28 days after the invalid dose, to reduce the 

burden of adverse reactions which occurs with this vaccine. Live vaccines should be 

repeated after a 28-day interval from the invalid dose to reduce the risk for interference 

from interferon on the subsequent doses. For rotavirus vaccines, the repeat dose should be 

administered after a 28-day interval from the invalid dose or at the maximum age for the 

vaccine dose (whichever is earlier). Clinicians should consult promptly with state or local 

health departments in these situations. Consultation with CDC is available when 

necessary.
General Best Practice Guidelines for Immunization: Storage and Handling of Immunobiologics 120

TABLE 7-1. Vaccine storage temperature recommendations

Nonlyophilized, aluminum-adjuvanted vaccines

Vaccines Vaccine storage 

temperature

Diluent storage temperature

Diphtheria-tetanuscontaining vaccines 

(DT, Td) or pertussiscontaining vaccines 

(DTaP, Tdap)

2°C-8°C (36°F-46°F)

Do not freeze

No diluent(a)

HepA and HepB 2°C-8°C (36°F-46°F)

Do not freeze

No diluent

MenB(b) 2°C-8°C (36°F-46°F)

Do not freeze

No diluent

PCV13 2°C-8°C (36°F-46°F)

Do not freeze

No diluent

PCV15 2°C-8°C (36°F-46°F)

Do not freeze

No diluent

PCV20 2°C-8°C (36°F-46°F)

Do not freeze

No diluent

HPV(b) 2°C-8°C (36°F-46°F)

Do not freeze

No diluent

Nonlyophilized, nonaluminum-adjuvanted vaccines

Vaccines Vaccine storage 

temperature

Diluent storage temperature

PRP-OMP Hib 2°C-8°C (36°F-46°F) No diluent

IPV(b) 2°C-8°C (36°F-46°F) No diluent

MenACWY(b),(c) 2°C-8°C (36°F-46°F) No diluent

PPSV 2°C-8°C (36°F-46°F) No diluent

IIV(b) 2°C-8°C (36°F-46°F) No diluent

RZV(b) 2°C-8°C (36°F-46°F)

Do not freeze

2°C-8°C (36°F-46°F)

Do not freeze
General Best Practice Guidelines for Immunization: Storage and Handling of Immunobiologics 121

Lyophilized (non-varicella) vaccines

Vaccines Vaccine storage 

temperature

Diluent storage temperature

PRP-T Hib(b) 2°C-8°C (36°F-46°F) (d) 2°C-8°C (35°F-46°F) Do not freeze

MMR(b) -50°C-8°C (-58°F46°F) (d)2°C-25°C (35°F-77°F)

Can be refrigerated or stored at 

room temperature

DEN4CYD 2°C-8°C (36°F-46°F) 

Do not freeze

2°C-8°C (36°F-46 °F) Do not freeze

Varicella-containing vaccines

Vaccines Vaccine storage 

temperature

Diluent storage temperature

MMRV(b) -50°C to -15°C (-58°F5°F)2°C-25°C (35°F-77°F)

Can be refrigerated or stored at 

room temperature

Varicella(b) -50°C to -15°C (-58°F5°F)2°C-25°C (35°F-77°F)

Can be refrigerated or stored at 

room temperature

Noninjectable vaccines

Vaccines Vaccine storage 

temperature

Diluent storage temperature

RV5 vaccine(b) 2°C-8°C (36°F-46°F)

Do not freeze

No diluent

RV1 vaccine(b) 2°C-8°C (36°F-46°F)

Do not freeze

The diluent may be stored at a 

controlled room temperature 20°C25°C (68°F-77°F).

Do not freeze

LAIV(b) 2°C-8°C (36°F-46°F) No diluent

Abbreviations: DEN4CYD = dengue vaccine; DT = diphtheria and tetanus toxoids; DTaP = diphtheria and 

tetanus toxoids and acellular pertussis; HepA = hepatitis A; HepB = hepatitis B; Hib = Haemophilus influenzae 

type b; HPV = human papillomavirus; IIV = inactivated influenza vaccine; IPV = inactivated poliovirus; LAIV = 

live, attenuated influenza vaccine; MenACWY = quadrivalent meningococcal conjugate vaccine; MenB = Serogroup 

B meningococcal vaccine; MMR = measles, mumps, and rubella; MMRV = measles, mumps, rubella, and varicella; 

MPSV4 q adri alent
General Best Practice Guidelines for Immunization: Storage and Handling of Immunobiologics 122

REFERENCES

1. Kroger A, Atkinson W, Pickering L. General immunization practices. In: 

Plotkin S, Orenstein W, Offit P, eds. Vaccines. 6th ed. China: Elsevier 

Saunders; 2013:88-111.

2. CDC. Guidelines for maintaining and managing the vaccine cold chain.

MMWR Morb Mortal Wkly Rep. 2003;52(42):1023-1025.

meningococcal polysaccharide vaccine; PCV13 = pneumococcal conjugate vaccine; PPSV23= pneumococcal 

polysaccharide vaccine; PRP-OMP = polyribosylribitol phosphate-meningococcal outer membrane protein 

conjugate; PRP-T = polyribosylribitol phosphate polysaccharide conjugated to a tetanus toxoid; PRP-T Hib = 

polyribosylphosphate tetanus-toxoid conjugate Hib vaccine; PRP-T Hib-MenCY = polyribosylphosphate-tetanustoxoid Hib vaccine with a bivalent Meningococcal vaccine; RV = rotavirus; RV1 = live, attenuated monovalent 

rotavirus vaccine; RV5 = live, reassortment pentavalent rotavirus vaccine; Td = tetanus and diphtheria toxoids; 

Tdap = tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis.

Sources: (1,2).

(a) DTaP-Daptacel is sometimes used as a diluent for ActHib.

(b) Protect from light.

(c) There are 2 meningococcal conjugate vaccines; Menactra is nonlyophilized, and Menveo is lyophilized. Both 

powder and diluent should be stored at 35°F-46°F.

(d) The lyophilized pellet may be stored at freezer temperature; the reconstituted vaccine should be stored at 

refrigerator temperature.
General Best Practice Guidelines for Immunization: Altered Immunocompetence 123

8. Altered Immunocompetence

Updates

This section incorporates general content from the Infectious Diseases Society of America 

policy statement, 2013 IDSA Clinical Practice Guideline for Vaccination of the 

Immunocompromised Host (1), to which CDC provided input in November 2011. The 

evidence supporting this guidance is based on expert opinion and arrived at by consensus.

 

General Principles

Altered immunocompetence, a term often used synonymously with immunosuppression, 

immunodeficiency, and immunocompromise, can be classified as primary or secondary. 

Primary immunodeficiencies generally are inherited and include conditions defined by an 

inherent absence or quantitative deficiency of cellular, humoral, or both components that 

provide immunity. Examples include congenital immunodeficiency diseases such as Xlinked agammaglobulinemia, SCID, and chronic granulomatous disease. Secondary 

immunodeficiency is acquired and is defined by loss or qualitative deficiency in cellular or 

humoral immune components that occurs as a result of a disease process or its therapy. 

Examples of secondary immunodeficiency include HIV infection, hematopoietic 

malignancies, treatment with radiation, and treatment with immunosuppressive drugs.

The degree to which immunosuppressive drugs cause clinically significant 

immunodeficiency generally is dose related and varies by drug. Primary and secondary 

immunodeficiencies might include a combination of deficits in both cellular and humoral 

immunity. Certain conditions like asplenia and chronic renal disease also can cause 

altered immunocompetence.

Determination of altered immunocompetence is important to the vaccine provider 

because incidence or severity of some vaccine-preventable diseases is higher in persons 

with altered immunocompetence; therefore, certain vaccines (e.g., inactivated influenza 

vaccine, pneumococcal vaccines) are recommended specifically for persons with these 

diseases (2,3). Administration of live vaccines might need to be deferred until immune 

function has improved. This is primarily a safety concern, because persons who have 

altered immunocompetence and receive live vaccines might be at increased risk for an 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 124

adverse reaction because of uninhibited growth of the attenuated live virus or bacteria. 

Vaccines might be less effective during the period of altered immunocompetence. Non-live 

vaccines might best be deferred during a period of altered immunocompetence; in this 

circumstance, the concern is with effectiveness and not safety. Additionally, if a non-live 

vaccine is administered during the period of altered immunocompetence, it might need to 

be repeated after immune function has improved.

The degree of altered immunocompetence in a patient should be determined by a 

physician. The challenge for clinicians and other health-care providers is assessing the 

safety and effectiveness of vaccines for conditions associated with primary or secondary 

immunodeficiency, especially when new therapeutic modalities are being used and 

information about the safety and effectiveness of vaccines has not been characterized fully 

in persons receiving these drugs (Table 8-1). Laboratory studies can be useful for assessing 

the effects of a disease or drug on the immune system. Tests useful to assess humoral 

immunity include immunoglobulin (and immunoglobulin subset) levels and specific 

antibody levels (e.g., tetanus and diphtheria). Tests that demonstrate the status of cellular 

immunity include lymphocyte numbers (i.e., a complete blood count with differential), a 

test that delineates concentrations and proportions of lymphocyte subsets (i.e., B and T 

lymphocytes, CD4+ B lymphocytes versus CD8+ T lymphocytes), and tests that measure 

T-cell proliferation or function in response to specific or nonspecific stimuli (e.g., 

lymphocyte proliferation assays) (4,5). The ability to characterize a drug or disease 

condition as affecting cellular or humoral immunity is only the first step; using this 

information to draw inferences about whether particular vaccines are indicated or whether 

caution is advised with use of live or non-live vaccines is more complicated and might 

require consultation with an infectious diseases or immunology specialist.

 

Altered Immunocompetence as an Indication to Receive a 

Vaccine Outside of Routinely Recommended Age Groups

This section describes situations in which vaccines are recommended outside of the 

routine-age-based recommendation because the risk for vaccine-preventable disease is 

increased due to altered immunocompetence. 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 125

Persons with altered immunocompetence generally are recommended to receive 

polysaccharide-based vaccines (PCV13, PPSV23, and Hib), on the basis of increased risk 

for disease if the vaccine is withheld. For certain specific categories of altered 

immunocompetence, patients are also recommended to receive polysaccharide based 

vaccines (MenACWY, Hib-MenCY, and MPSV4).

Pneumococcal Vaccines

Two types of vaccine against invasive pneumococcal disease are available in the United 

States: PCV13 and PPSV23. PCV13 is recommended routinely for all children beginning at 

age 2 months through age 59 months and for adults aged 65 years or older. PCV13 is also 

recommended for children, adolescents, and adults with conditions that place them at 

high risk for invasive disease from Streptococcus pneumoniae. PCV13 is recommended for 

persons aged 6-64 years who have not previously received PCV13 and have congenital 

immunodeficiency disorders (including B- or T-lymphocyte deficiency, complement 

deficiencies, and phagocytic disorders), anatomic or functional asplenia (including sickle 

cell disease and other hemoglobinopathies), HIV infection, cochlear implant, 

cerebrospinal fluid leak, chronic renal failure, nephrotic syndrome, iatrogenic 

immunosuppression, or other immunocompromising conditions.

PPSV23 is licensed for use in persons aged ≥2 years and recommended routinely for 

adults aged 65 years and older. PPSV23 is also recommended for persons age 2 through 64 

years with congenital immunodeficiency disorders, anatomical and functional asplenia, 

HIV infection, cochlear implant, cerebrospinal fluid leak, and iatrogenic 

immunosuppression. Complete recommendations on use of PCV13 and PPSV23 are 

available in the Recommended Immunization Schedules for Persons Aged 0 Through 18 

Years and the Recommended Adult Immunization Schedule (2,6).

Meningococcal Vaccines

Three types of meningococcal vaccines are licensed in the United States: meningococcal 

conjugate (MenACWY and Hib-MenCY), meningococcal polysaccharide (MPSV4), and 

serogroup B meningococcal (MenB) vaccines. 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 126

Persons with functional or anatomic asplenia (including sickle cell disease), HIV infection

and persistent complement component deficiency (including persons taking eculizumab 

[Soliris]) (7) are at increased risk for meningococcal disease and should receive 

MenACWY vaccine. Persons with functional or anatomic asplenia (including sickle cell 

disease) and persistent complement component deficiency (including persons taking 

eculizumab [Soliris]) should receive MenB vaccine. For children 2 months through 23 

months of age, an age-appropriate series of meningococcal conjugate vaccine should be 

administered. If MenACWY-D (Menactra) is administered to a child with asplenia or HIV, 

it should be after 2 years of age and at least 4 weeks after the completion of all PCV13 

doses. A 2-dose primary series of either MenACWY-CRM (Menveo) or MenACWY-D 

(Menactra) should be administered to persons 2 years of age or older with asplenia or 

complement deficiency. Following the primary series of vaccine, a 3-year interval to the 

next dose is recommended for persons who received their previous dose at younger than 7 

years. A 5-year interval is recommended for persons who received their previous dose at 

age 7 years or older. Although MPSV4 is the only meningococcal vaccine licensed for 

persons older than 55 years of age, adults 56 years and older with asplenia or complement 

deficiency should be vaccinated with MenACWY-CRM or MenACWY-D rather than 

MPSV4 (8). Meningococcal serogroup B vaccines are licensed for persons 10-25 years of 

age and are recommended for persons 10 years of age or older for persons with high-risk 

conditions like functional or anatomic asplenia or persistent complement component 

deficiency. There are presently no recommendations for booster doses of either MenB 

vaccine (9,10). Complete recommendations for use of meningococcal vaccines are 

available in the Recommended Immunization Schedules for Persons Aged 0 Through 18 

Years and the Recommended Adult Schedule (2,6).

Hib Vaccines

Hib conjugate vaccines are available in single or combined antigen preparations. Hib 

vaccine is recommended routinely for all children through age 59 months. 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 127

Children 12 through 59 months who are at high risk for invasive Hib disease (i.e., 

recipients of chemotherapy or radiation for malignant neoplasms, or those with functional 

or anatomic asplenia, HIV infection, immunoglobulin deficiency, or early complement 

component deficiency) and who are unvaccinated or received only one dose of Hib vaccine 

before 12 months of age should receive 2 additional doses of Hib vaccine; those who 

received 2 or more doses of Hib before 12 months of age should receive one additional 

dose. 

A child younger than 5 years of age receiving chemotherapy or radiation therapy should 

have Hib doses repeated if the doses were received during therapy or within 14 days of 

starting therapy; repeat doses should be started at least 3 months after completion of 

therapy. Recipients of hematopoietic cell transplants should be revaccinated with 3 doses 

of Hib vaccine, starting 6-12 months after successful transplant, regardless of vaccination 

history or age. 

Children 5-18 years of age with HIV who are unimmunized(a) should receive a dose of Hib 

vaccine; Hib vaccination is not recommended in HIV-infected adults. Unimmunized(a) 

asplenic patients older than 59 months of age or adults should receive a dose of Hib 

vaccine. Anyone 15 months of age or older who is undergoing a splenectomy and is 

unimmunized(a) should receive a dose of Hib vaccine (11). Complete recommendations for 

use of Hib vaccine are available in the Recommended Immunization Schedules for 

Persons Aged 0 Through 18 Years and the Recommended Adult Immunization 

Schedule (2,6).

Zoster (Shingrix) Vaccine

Zoster (Shingrix) vaccine is recommended for persons 19 years old and older who have 

altered immunocompetence.

 

Vaccination of Contacts of Persons with Altered 

Immunocompetence

Household contacts and other close contacts of persons with altered immunocompetence 

should receive all age- and exposure-appropriate vaccines, with the exception of smallpox 

vaccine (12,13). 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 128

Receipt of vaccines will prevent the vaccine-preventable disease, so there can be no 

potential transmission to the contact with altered immunocompetence. The live MMR, 

varicella, and rotavirus vaccines should be administered to susceptible household contacts 

and other close contacts of immunocompromised patients when indicated. No specific 

precautions are needed unless the varicella vaccine recipient has a rash after vaccination, 

in which case direct contact with susceptible household contacts with altered 

immunocompetence should be avoided until the rash resolves (14,15). All members of the 

household should wash their hands after changing the diaper of an infant who received 

rotavirus vaccine. 

This minimizes rotavirus transmission, as shedding may occur up to one month after the 

last dose (16,17). Household and other close contacts of persons with altered 

immunocompetence should receive annual influenza vaccination. Introduction of low 

levels of vaccine viruses into the environment likely is unavoidable when administering 

LAIV. LAIV vaccine viruses are cold-adapted, so they can replicate in the nose and 

generate an immune response without entering the lungs (i.e., they are temperature 

sensitive and replicate poorly at core body temperatures). No instances have been 

reported of illness caused by attenuated vaccine virus infections among health-care 

providers or immunocompromised patients. LAIV may be administered to healthy 

household and other close contacts of persons with altered immunocompetence unless the 

person with altered immunocompetence is in a protective environment, typically defined 

as a specialized patient-care area with a positive airflow relative to the corridor, highefficiency particulate air filtration, and frequent air changes (3). No preference exists for 

inactivated influenza vaccine use by health-care workers or other persons who have close 

contact with persons with lesser degrees of immunosuppression (e.g., persons with 

diabetes, persons with asthma taking high-dose corticosteroids, or persons infected with 

HIV), and no preference exists for inactivated influenza vaccine use by health-care 

workers or other healthy persons aged 5-49 years in close contact with all other groups at 

high risk.
General Best Practice Guidelines for Immunization: Altered Immunocompetence 129

Non-live Vaccines: Safety

All non-live vaccines can be administered safely to persons with altered 

immunocompetence, whether the vaccine is a killed whole-organism or a recombinant, 

subunit, split-virus, toxoid, polysaccharide, or polysaccharide protein-conjugate vaccine.

 

Non-live Vaccines: Effectiveness

Except for inactivated influenza vaccine, vaccination during chemotherapy or radiation 

therapy should be avoided if possible because antibody response might be suboptimal. 

Patients vaccinated within a 14-day period before starting immunosuppressive therapy or 

while receiving immunosuppressive therapy should be considered unimmunized and 

should be revaccinated at least 3 months after therapy is discontinued if immune 

competence has been restored. Patients who have quantitative B-cell deficiencies and are 

receiving immunoglobulin therapy should not receive either non-live or live vaccines while 

receiving the immunoglobulin therapy because of concerns about effectiveness of the 

vaccines. Patients on chemotherapy with anti-B cell antibodies (e.g., rituximab) should 

wait at least 6 months after therapy before being vaccinated with non-live vaccines. Some

experts recommended longer than 6 months for some anti-B cell antibodies. For other 

forms of altered immunocompetence, if non-live vaccines are indicated, the usual 

schedules are recommended. However, the effectiveness of such vaccinations might be 

suboptimal (1).

Live, Attenuated Viral and Bacterial Vaccines: 

Effectiveness

The same rationale regarding effectiveness that exists with non-live vaccines also exists 

with live vaccines.

 

Live, Attenuated Viral and Bacterial Vaccines: Safety

Severe complications have followed vaccination with certain live, attenuated viral and live, 

attenuated bacterial vaccines among persons with altered immunocompetence (18-26). 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 130

Persons with most forms of altered immunocompetence should not receive live vaccines 

(MMR, varicella, MMRV, LAIV, yellow fever, Ty21a oral typhoid, BCG, smallpox, and 

rotavirus). However, exceptions exist, and are discussed in this section.

Patients with any defect in phagocytic function (e.g., chronic granulomatous disease, 

leukocyte adhesion deficiency, myeloperoxidase deficiency, Chediak-Higashi syndrome) 

should NOT receive live bacterial vaccines. Patients with a specific type of defect in 

phagocytic function—chronic granulomatous disease—should receive recommended live 

attenuated viral vaccines in addition to non-live vaccines but should NOT receive live 

bacterial vaccines. 

Patients with defects in phagocytic function that are undefined or known to be 

accompanied by defects in T-cell and natural killer cell function (e.g., leukocyte adhesion 

deficiency, myeloperoxidase deficiency, Chediak-Higashi syndrome) should NOT receive 

live attenuated viral or bacterial vaccines. These conditions include specific deficits in Tcell and natural killer cell function, reducing the response to live viral vaccine antigens to 

an extent not seen in chronic granulomatous disease (1). Children with deficiencies in 

complement should receive recommended live, attenuated viral and live, attenuated 

bacterial vaccines. Children with asplenia should not receive LAIV, but can receive 

recommended live, attenuated viral and live, attenuated bacterial vaccines.

Persons with severe cell-mediated immunodeficiency should not receive live, attenuated 

viral or bacterial vaccines. Patients with defects of the interferon-gamma/interleukin-12 

axis should not receive live bacterial vaccines. Patients with deficiencies of interferongamma or interferon-alpha should not receive live viral or live bacterial vaccine. These 

defects involve a deficiency in cytokine production which affects the immune response to a 

wide scope of antigens, both bacterial and viral (1). Two factors support vaccination of 

HIV-exposed or HIV-infected infants with rotavirus vaccines: 1) the HIV diagnosis might 

not be established in infants born to HIV-infected mothers before the age of the first 

rotavirus vaccine dose (only 1.5%-3% of HIV-exposed infants in the United States will be 

determined to be HIV-infected), and 2) the vaccine strains of rotavirus are considerably 

attenuated. Patients taking exogenous interferon as therapy should not receive live 

bacterial or live viral vaccines.
General Best Practice Guidelines for Immunization: Altered Immunocompetence 131

Children with HIV infection are at increased risk for complications from varicella and 

herpes zoster infection compared with immunocompetent children (27, 28). Limited data 

among HIV-infected children younger than 8 years (specifically, those individuals with 

CDC class N, A, or B with age-specific CD4+ T-lymphocyte percentages of ≥15%) indicate 

that single-component varicella vaccine is immunogenic, effective, and safe (14,28). Data 

on use of varicella vaccine in HIV-infected adolescents and adults are lacking. However, 

on the basis of expert opinion, the safety of varicella vaccine in HIV-infected persons older 

than 8 years with comparable levels of immune function (CD4+T-lymphocyte count 

greater than 200 cells/mm3) is likely to be similar to that of children aged younger than 8 

years (14). 

Varicella vaccine should be considered for persons who meet these criteria. Eligible HIVinfected persons 12 months of age or older should receive 2 doses of single-component 

varicella vaccine with a 3-month interval between doses (14,28). MMRV vaccine should 

not be administered to any HIV-infected person.

Persons with HIV infection are at increased risk for severe complications if infected with 

measles. No severe or unusual adverse events have been reported after measles 

vaccination among HIV-infected persons who did not have evidence of severe 

immunosuppression (29-32). Two doses of MMR vaccine are recommended for all HIVinfected individuals aged ≥12 months who do not have evidence of current severe 

immunosuppression (i.e., individuals aged ≤5 years must have CD4+T lymphocyte 

[CD4+] percentages ≥15% for ≥6 months, and individuals aged >5 years must have 

CD4+percentages ≥15% and CD4+≥200 lymphocytes/mm3 for ≥6 months) and do not 

have current evidence of measles, rubella, and mumps immunity. In cases when only 

CD4+cell counts or only CD4+percentages are available for those >5 years, the assessment 

of severe immunosuppression can be based on the CD4+values (count or percentage) that 

are available. In cases when CD4+percentages are not available for those aged ≤5 years, 

the assessment of severe immunosuppression can be based on age-specific CD4+counts at 

the time CD4+counts were measured; i.e., absence of severe immunosuppression is 

defined as ≥6 months above age-specific CD4+count criteria: CD4+count >750 

lymphocytes/mm3 while aged ≤12 months and CD4+count ≥500 lymphocytes/mm3 while 

aged 1 through 5 years (33). 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 132

Similarly, repeat doses of MMR vaccination are recommended for individuals with 

perinatal HIV infection who were vaccinated prior to establishment of effective 

combination antiretroviral therapy (cART). They should receive 2 appropriately spaced 

doses of MMR vaccine once effective cART has been established (individuals aged ≤5 

years must have CD4+percentages ≥15% for ≥6 months; individuals aged >5 years must 

have CD4+percentages ≥15% and CD4+≥200 lymphocytes/mm3 for ≥6 months) unless 

they have other acceptable current evidence of measles, rubella, and mumps immunity.

HIV-infected persons who are receiving regular doses of IGIV are unlikely to respond to 

varicella vaccine or MMR vaccine because of the continued presence of passively acquired 

antibody. 

However, because of the potential benefit, MMR and varicella vaccines should be 

considered approximately 14 days before the next scheduled dose of IGIV (if not otherwise 

contraindicated), although an optimal immune response might not occur depending on 

the presence of neutralizing antibodies against the vaccine virus. Vaccination should be 

repeated (if not otherwise contraindicated) after the recommended interval (see Table 3-6 

in the Timing and Spacing of Immunobiologics of this document). In most cases, this is 

after the therapy has been discontinued.

Patients with leukemia, lymphoma, or other malignancies whose disease is in remission, 

who have restored immunocompetence, and whose chemotherapy has been discontinued 

for at least 3 months can receive live-virus vaccines. Persons with impaired humoral 

immunity (e.g., hypogammaglobulinemia or dysgammaglobulinemia) may be vaccinated 

with varicella vaccine (14). However, most persons with these disorders also receive 

periodic doses of IGIV. Appropriate spacing should be maintained between administration 

of IGIV and varicella vaccine in an attempt to prevent an inadequate response to 

vaccination caused by the presence of neutralizing antibodies from the IGIV.

Zoster incidence is higher in persons with altered immunocompetence (34). Adults with 

most types of altered immunocompetence are expected to maintain residual immunity to 

varicella-zoster virus because of chronic latent infection that protects against primary 

varicella but provides incomplete protection against zoster. Zoster vaccine is not 

recommended in persons with primary or acquired immunodeficiency (e.g., lymphoma, 

leukemia, tumors involving bone marrow, and patients receiving chemotherapy) and some 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 133

HIV infected patients (34). Zoster vaccine may be administered to certain persons age 50 

or older with altered immunocompetence, such as persons receiving low dosages of 

immunosuppressive medications, those with isolated B-cell deficiencies (i.e., impaired 

humoral immunity), or those with HIV infection who have CD4+ T-lymphocyte counts 

>200 cells/mm3.

Recipients of Hematopoietic Cell Transplants

A hematopoietic stem cell transplant (HSCT) results in immunosuppression because of 

the hematopoietic ablative therapy administered before the transplant, drugs used to 

prevent or treat graft-versus-host disease, and, in some cases, from the underlying disease 

process necessitating transplantation (35-37). HSCT involves ablation of the bone marrow 

followed by reimplantation of the person’s own stem cells or stem cells from a donor. The 

ablation caused by the HSCT will also gradually remove immune memory from previous 

vaccination. Antibody titers to vaccine-preventable diseases (e.g., tetanus, poliovirus, 

measles, mumps, rubella, and encapsulated bacteria) decrease 1-4 years after autologous 

or allogeneic HSCT if the recipient is not revaccinated. HSCT recipients of all ages are at 

increased risk for certain vaccine-preventable diseases, including diseases caused by 

encapsulated bacteria (e.g., pneumococcal and Hib infections). As a result, HSCT 

recipients who received vaccines prior to their HSCT should receive repeat doses routinely 

after HSCT, regardless of the source of the transplanted stem cells (35-37). Revaccination 

doses following HSCT are indicated with pneumococcal vaccines, DTaP vaccine, Tdap 

vaccine, Hib vaccine, hepatitis A vaccine, hepatitis B vaccine, IPV, inactivated influenza 

vaccines, meningococcal conjugate vaccine (for individuals 11 through 18 years or at highrisk), serogroup B meningococcal vaccine (for individuals 16 through 23 years or at highrisk), and human papillomavirus (HPV) vaccines (for individuals aged 9-26 years, or 27 

through 45 years of age based on shared clinical decision-making) (1, 35). Recombinant 

zoster vaccine may be re-administered 6-12 months after an allogeneic HSCT, and may be 

re-administered 3-12 months after an autologous HSCT. For more specificity on the 

precise timing of re-administration of RZV, note that this should optimally occur 2 

months prior to cessation of prophylactic antiviral therapy (acyclovir, famciclovir, and 

valacyclovir). Varicella and MMR vaccines may be re-administered after HSCT if 24 

months have passed since HSCT, the patient does NOT have graft-vs-host disease, and is 

considered immunocompetent. 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 134

Yellow fever vaccine, rabies vaccine, tick-borne encephalitis vaccine, and Japanese 

encephalitis vaccine are not routinely administered vaccines, so their use post-HSCT will 

be driven by a disease-specific risk such as exposure or travel. If someone has received 

yellow fever vaccine prior to an HSCT, another dose should be re-administered post-HSCT

(38). BCG, LAIV, typhoid vaccine, and rotavirus vaccine are not recommended after 

HSCT. Most non-live vaccines should be re-initiated 6 months after the HSCT (37). 

Inactivated influenza vaccine should be administered beginning at least 6 months after 

HSCT and annually thereafter for the life of the patient. A dose of inactivated influenza 

vaccine can be given as early as 4 months after HSCT, but a second dose should be 

considered in this situation (37). A second dose is recommended routinely for all children

younger than 9 years receiving influenza vaccine for the first time. Revaccination of HCST 

patients with pneumococcal vaccines is recommended regardless of whether doses were 

administered prior to HSCT. For those HSCT recipients that were vaccinated prior to 

HSCT with PCV7, PCV13, PCV15, or PCV20, sequential administration of 4 doses of 

PCV20 is recommended, beginning 3-6 months after the transplant. The first three doses 

should be separated by 4 weeks and the fourth dose of PCV20 should be administered 6 

months after the third dose or 1 year after the HSCT, whichever is later. As an alternative 

to PCV20, three doses of PCV15 separated by 4 weeks, followed by PPSV23 one year after 

the last dose of PCV15 (and at least 4 weeks after the third dose of PCV15) may be 

administered. If the patient has graft-versus-host disease, substitute a fourth dose of 

PCV15 for PPSV23. For doses of pneumococcal conjugate vaccine administered after 

HSCT consisting of PCV13 or PCV15, these doses count as post-HSCT doses, so one always 

has the option to transition FROM PCV15 to PCV20 for the post-HSCT dosing regimen. A 

3-dose regimen of Hib vaccine should be administered beginning 6 months after 

transplant; at least 1 month should separate the doses (37). The revaccination schedule for 

pertussis-containing vaccines includes 3 doses of DTaP for patients <7 years (14). For

patients ≥7 years, providers have 3 options for revaccination: 1) 3 doses of DTaP; 2) one 

dose of Tdap and 2 doses of DT; or 3) one dose of Tdap and 2 doses of Td (1).

Providers need to make a clinical judgment whether they will follow the revaccination 

schedules described above in circumstances where particular vaccines were NOT 

administered prior to the HSCT. In this circumstance, providers may just vaccinate 

according to routine recommendations for post-HSCT vaccination. For instance, there are 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 135

specific recommendations for Hib and pertussis-containing vaccines. Use of the 3-dose 

Hib schedule following HSCT is supported for both patients that received Hib prior to 

HSCT and those who did not receive Hib prior to HSCT (6, 11). For children >6 years who 

did not receive previous doses of pertussis-containing vaccine prior to the HSCT, the 

preferred schedule following HSCT is a dose of Tdap followed by 2 doses of Td (personal 

communication, subject matter experts). 

This is identical to one of the alternative regimens for revaccination doses, described 

above.

Conditions or Drugs that Might Cause 

Immunodeficiencies

Asplenia and use of corticosteroids or certain drugs have the potential to be 

immunosuppressive and are presumed to cause some degree of altered 

immunocompetence.

Anatomic or Functional Asplenia

Persons with anatomic asplenia (e.g., surgical removal or congenital absence of the spleen) 

or functional asplenia (as occurs in persons with sickle cell disease) are at increased risk 

for infection by encapsulated bacteria, especially S. pneumoniae (pneumococcus), N. 

meningitidis (meningococcus), and Hib (7-8, 39). 

Children should receive an age-appropriate series of PCV13. Unvaccinated children 2-5 

years should receive 2 doses of PCV13. Children ≥6 years should receive a dose of PCV13 if 

they have not previously received a dose of PCV13. Persons aged ≥2 years should receive 2 

doses of PPSV23 separated by 5 years, beginning 8 or more weeks after completing all 

recommended doses of PCV13 (6-7, 40-41). In circumstances where both PCV13 and 

PPSV23 are indicated, doses of PCV13 should be administered first followed by PPSV23 8 

weeks after the last dose of PCV13.

Meningococcal conjugate (MenACWY) and serogroup B (MenB) vaccines are 

recommended for persons with anatomic or functional asplenia (including sickle cell 

disease). For children 2-23 months of age, a series of MenACWY-CRM (Menveo) or HibMenCY (MenHibrix) should be administered. For persons ≥2 years of age, a 2-dose 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 136

primary series of either MenACWY-CRM or MenACWY-D (Menactra) should be 

administered. If a person with functional or anatomic asplenia is catching up on 

pneumococcal conjugate vaccine (PCV13), and the provider only carries MenACWY-D, 

indicated doses of PCV13 should be completed first and MenACWY-D should be given 4 

weeks after the PCV13 series is completed. Following the primary series of vaccine, a 3-

year interval to the next dose is recommended for asplenic children who received their last 

previous dose at age younger than 7 years. A 5-year interval for asplenic persons is 

recommended for persons who received their last previous dose at age 7 years or older. 

Meningococcal B (MenB) vaccine should be administered as either a 2-dose series of 

MenB-4C (Bexsero) or a 3-dose series of MenB-FHbp (Trumenba). The same vaccine 

product must be used for all doses. Based on available data and expert opinion, MenB-4C 

or MenB-FHbp may be administered concomitantly with MenACWY vaccines, but at a 

different anatomic site, if feasible. There are presently no recommendations for booster 

doses of either MenB vaccine.

Hib vaccine is recommended routinely for all children through age 59 months. Children 

12-59 months with functional or anatomic asplenia and who are unvaccinated or who 

received only one dose of Hib disease before 12 months of age should receive 2 doses of 

Hib vaccine; those who received 2 or more doses of Hib before 12 months of age should 

receive one additional dose. Unimmunized(a) asplenic patients older than 59 months of 

age should receive one dose of Hib vaccine. Anyone ≥15 months of age who is undergoing 

a splenectomy and is unimmunized(a) should receive one dose of Hib vaccine.

Pneumococcal, meningococcal, and Hib vaccinations should be administered at least 14 

days before elective splenectomy, if possible. If the vaccinations are not administered 

before surgery, they should be administered after the procedure as soon as the patient’s 

condition is stable.

Corticosteroids

The amount of systemically absorbed corticosteroids and the duration of administration 

needed to suppress the immune system of an otherwise immunocompetent person are not 

well defined. Although the immunosuppressive effects of steroid treatment vary, the 

majority of clinicians consider a dose equivalent to either ≥2 mg/kg of body weight or ≥20 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 137

mg/day of prednisone or equivalent for persons who weigh >10 kg when administered for 

≥14 consecutive days as sufficiently immunosuppressive to raise concern about the safety 

of vaccination with live-virus vaccines (37). This dosage is referred to as “high-dose 

corticosteroids”. Corticosteroids used in greater than physiologic doses also can reduce the 

immune response to vaccines. 

Vaccination providers should defer live-virus vaccination for at least 1 month after 

discontinuation of high-dose systemically absorbed corticosteroid therapy administered 

for ≥14 days. Following vaccination, the decision needs to be made when to restart 

immunosuppressive therapy. There are no specific recommendations about when to 

restart immunosuppressive medicines. However, when initiating immunosuppressive 

therapy, providers should wait 4 weeks after a live vaccine and 2 weeks after a non-live

vaccine. However, if patients require therapy for chronic inflammatory conditions, this 

therapy should not be delayed because of past administration of vaccines (1).

Corticosteroid therapy usually is not a contraindication to administering live-virus vaccine 

when administration is 1) short term (i.e., <14 days); 2) a low to moderate dose (i.e., <20 

mg of prednisone or equivalent per day or <2mg/kg body weight per day for a young 

child); 3) long-term, alternate-day treatment with short-acting preparations; 4) 

maintenance physiologic doses (replacement therapy); or 5) topical (skin or eyes), inhaled, 

or by intra-articular, bursal, or tendon injection (37). No evidence of an increased risk for 

more severe reactions to live, attenuated viral vaccines has been reported among persons 

receiving corticosteroid therapy by aerosol, and such therapy is not a reason to delay 

vaccination.

Other Immunosuppressive Drugs

When feasible, clinicians should administer all indicated vaccines before initiation of 

chemotherapy, before treatment with other immunosuppressive drugs, and before 

radiation or splenectomy. Persons receiving chemotherapy or radiation for leukemia and 

other hematopoietic malignancies, or for solid tumors, should be assumed to have altered 

immunocompetence. Live, attenuated vaccines should not be administered for at least 3 

months after such immunosuppressive therapy. Non-live vaccines administered during 

chemotherapy should be readministered after immune competence is regained. Children 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 138

vaccinated before receiving chemotherapy for leukemia, lymphoma, other malignancies, 

or radiation generally are thought to retain immune memory after treatment, although 

revaccination with the common childhood vaccines after chemotherapy for acute 

lymphoblastic leukemia might be indicated (42). 

In general, revaccination of a person after chemotherapy or radiation therapy is 

considered unnecessary if the previous vaccination occurred before therapy and not 

during therapy, with the exception of recipients of HSCT, who should be revaccinated as 

recommended previously. Determination of the level of immune memory and the need for 

revaccination should be made by the treating physician.

Certain immunosuppressive medications are administered to prevent solid organ 

transplant rejection. Live vaccines should be withheld for 2 months following 

discontinuation of anti-rejection therapies in patients with a solid organ transplant. 

Other immunosuppressive medications include human immune mediators like 

interleukins and colony-stimulating factors, immune modulators, and medicines like 

tumor necrosis factor-alpha inhibitors and anti-B cell agents. Non-live and live vaccines 

should be administered 2 or more weeks before initiating such therapies. Live vaccines 

should be withheld 3 months following such therapies, and both non-live and live vaccines 

should be withheld at least 6 months following therapy with anti-B cell agents. Some 

experts recommend longer than 6 months following anti-B cell agents. 

Anti-B cell agents suppress antibody-producing cells for a prolonged duration, hence the 

longer interval recommended before administering vaccines (17).

Zoster vaccine is an exception and should be withheld 1 month following anti-B cell 

agents. After vaccination, anti-B cell agents can be resumed 1 month later.

(a) Patients who have not received a primary series and booster dose or at least 1 dose of Hib vaccine after 14 months of age are 

considered unimmunized.
General Best Practice Guidelines for Immunization: Altered Immunocompetence 139

Table 8-1. Vaccination of persons with primary and secondary immunodeficiencies

Category Specific types Contraindications(a) Risk-specific 

recommended 

vaccines(a)

Effectiveness 

and 

comments

Primary: Blymphocyte 

(humoral)

Severe antibody 

deficiencies (e.g., Xlinked 

agammaglobulinemia 

and common variable 

immunodeficiency)

OPV(b)

Smallpox©

LAIV

BCG

Ty21a (live typhoid)

Yellow fever

MMR

MMRV

DEN4CYD

Pneumococcal

Hib (children 

12–59 months of 

age)(d)

Recombinant 

zoster vaccine(e)

The 

effectiveness 

of any 

vaccine is 

uncertain if 

it depends 

only on the 

humoral 

response 

(e.g., 

PPSV23)

IGIV 

interferes 

with the 

immune 

response to 

measles 

vaccine and 

possibly 

varicella 

vaccine

Less severe antibody 

deficiencies (e.g., 

selective IgA 

deficiency and IgG 

subclass deficiency)

OPV(b)

BCG

DEN4CYD

Yellow fever(f)

Other live vaccines 

appear to be safe

Pneumococcal

Hib (children 

12–59 months of 

age)(d)

Recombinant 

zoster(e)

All vaccines 

likely 

effective; 

immune 

response 

might be 

attenuated

Primary: Tlymphocyte 

(cellmediated 

Complete defects 

(e.g., SCID disease, 

complete DiGeorge 

syndrome)

All live vaccines(g), (h), 

(i)

Pneumococcal

Hib (children 

12–59 months of 

age)(d)

Vaccines 

unlikely to 

be effective
General Best Practice Guidelines for Immunization: Altered Immunocompetence 140

and 

humoral)

Recombinant 

zoster(e)

Partial defects (e.g., 

most patients with 

DiGeorge syndrome, 

Wiskott-Aldrich 

syndrome, ataxiatelangiectasia)

All live vaccines(g),(h),(i) Pneumococcal 

Meningococcal 

Hib (children 12-

59 months of 

age)(d)

Recombinant 

zoster(e)

Effectiveness 

of any 

vaccine 

depends on 

degree of 

immune 

suppression

Interferon-alpha 

deficiencies, 

interferon-gamma 

deficiencies

All live vaccines(g), (h) Recombinant 

zoster(e)

Interferongamma/interleukin12 axis deficienciesLive bacterial 

vaccines(g)

Recombinant 

zoster(e)

Primary: 

phagocytic 

function

Chronic 

granulomatous 

disease

Live bacterial 

vaccines(g)

Recombinant 

zoster(e)

Live viral 

vaccines 

likely safe 

and effective

Phagocytic 

deficiencies that are 

undefined or 

accompanied by 

defects in T-cell and 

NK cell dysfunction 

(such as a ChediakHigashi syndrome, 

Leukocyte Adhesion 

Deficiency [LAD], 

and myeloperoxidase 

deficiency)

Live 

vaccines(g),(h)

Pneumococcal

Recombinant 

zoster(e)

All non-live 

vaccines safe 

and likely 

effective

Primary: 

complement

Persistent 

complement, 

properdin, or Factor 

B deficiency

None Pneumococcal

Meningococcal

Hib (children 12-

59 months of 

age)(d)

All routine 

vaccines 

likely 

effective
General Best Practice Guidelines for Immunization: Altered Immunocompetence 141

Secondary HIV/AIDS OPV(b)

Smallpox BCG

LAIV

Ty21a 

MMRV

DEN4-CYD

Withhold MMR, and 

varicella in severely 

immunocompro 

mised persons

Yellow fever vaccine 

might have a 

contraindication or a 

precaution depending 

on clinical parameters 

of immune function(j)

Pneumococcal 

Hib(d),(k) 

HepB

MenACWY

Recombinant 

zoster(e)

MMR and 

Varicella 

vaccine in 

those with 

mild 

immunosup

pression, 

rotavirus, 

and all nonlive vaccines, 

including 

inactivated 

influenza as 

per routine 

vaccination 

schedule, 

might be 

effective(l)

Generalized 

malignant neoplasm, 

transplantation, 

immunosuppressive 

or radiation therapy

Live viral and 

bacterial, depending 

on immune 

status(g),(h),(m)

Pneumococcal 

Hib(m)

Recombinant 

zoster(e)

Effectiveness 

of any 

vaccine 

depends on 

degree of 

immune 

suppression

Taking eculizumab 

(Solaris), and/or 

ravulizumab 

(Ultomiris)

None Meningococcal

Asplenia LAIV Pneumococcal 

Meningococcal 

Hib(d),(o)

Chronic renal disease None Pneumococcal 

HepB(p)

All routine 

vaccines 

likely 

effective
General Best Practice Guidelines for Immunization: Altered Immunocompetence 142

Abbreviations: AIDS = acquired immunodeficiency syndrome; BCG = bacille Calmette-Guérin; HepB = hepatitis B; Hib = 

Haemophilus influenzae type b; HIV = human immunodeficiency virus; IG = immunoglobulin; IGIV = immune globulin 

intravenous; IgA = immune globulin A; IgG = immune globulin G; LAIV = live, attenuated influenza vaccine; MenACWY = 

quadrivalent meningococcal conjugate vaccine; MMR = measles, mumps, and rubella; MMRV = measles, mumps, rubella, 

and varicella; OPV = oral poliovirus vaccine (live); PPSV23= pneumococcal polysaccharide vaccine; SCID = severe combined 

immunodeficiency; Ty21a = live oral typhoid vaccine.

Source: (43).

(a) Other vaccines that are universally or routinely recommended should be given if not contraindicated. An exception is 

patients with B-cell deficiencies receiving immunoglobulins, who should not receive either live or non-live vaccines, due 

to safety (live vaccines) and efficacy (live and non-live vaccines) concerns.

(b) OPV is no longer available in the United States.

(c) This table refers to contraindications for nonemergency vaccination (i.e., the ACIP recommendations); emergency 

response recommendations are addressed in the clinical guidance for smallpox vaccine use in an emergency.

(d) Children 12-59 months: if unimmunized or received zero or only 1 dose, and that dose was administered before 12 months 

of age, should receive 2 Hib doses, 8 weeks apart; if received 2 or more doses before age 12 months, and none after 12 

months, should receive 1 Hib dose 8 weeks after the last dose; if completed a primary series and received a booster dose at 

age 12 months or older, no additional Hib doses are recommended.

(e) 19 years and older only.

(f) There are no data to support IgA deficiency as a contraindication for yellow fever vaccine.

(g) Live bacterial vaccines: BCG and oral Ty21a Salmonella Typhi vaccine.

(h) Live viral vaccines: MMR, MMRV, OPV, LAIV, yellow fever, rotavirus, varicella, and vaccinia (smallpox). Nonemergency 

smallpox vaccination is not recommended for children younger than 18 years or the general public.

(i) Regarding T-lymphocyte immunodeficiency as a contraindication for rotavirus vaccine, data exist only for SCID.

(j) Symptomatic HIV infection or CD4+ T-lymphocyte count of <200/mm3 or <15% of total lymphocytes for children aged 

<6 years is a contraindication to yellow fever vaccine administration. Asymptomatic HIV infection with CD4+ Tlymphocyte count of 200-499/mm3 for persons aged ≥6 years or 15%-24% of total lymphocytes for children aged <6 years 

is a precaution for yellow fever vaccine administration. Details of yellow fever vaccine recommendations are available from 

CDC (44)

(k) Patients 5-18 years of age who have not received a Hib primary series and a booster dose or at least one Hib dose after 14 

months of age.

(l) HIV-infected children should be considered for varicella vaccine if CD4+ T-lymphocyte count is ≥15% and should receive 

MMR vaccine if they are aged ≥12 months and do not have 1) evidence of current severe immunosuppression (i.e., 
General Best Practice Guidelines for Immunization: Altered Immunocompetence 143

individuals aged ≤5 years must have CD4+T lymphocyte [CD4] percentages ≥15% for ≥6 months; and individuals aged >5 

years must have CD4+percentages ≥15% and CD4+≥200 lymphocytes/mm3 for

≥6 months) and 2) other current evidence of measles, rubella, and mumps immunity. In cases when only CD4+cell counts 

or only CD4+percentages are available for those older than age 5 years, the assessment of severe immunosuppression can 

be based on the CD4+values (count or percentage) that are available. In cases when CD4+percentages are not available for 

those aged ≤5 years, the assessment of severe immunosuppression can be based on age-specific CD4+counts at the time 

CD4+counts were measured; i.e., absence of severe immunosuppression is defined as ≥6 months above age-specific 

CD4+count criteria: CD4+count >750 lymphocytes/mm3 while aged ≤12 months and CD4+count ≥500 lymphocytes/mm3 

while aged 1 through 5 years (33).

(m) Withholding non-live vaccines also is recommended with some forms of immunosuppressive therapy, like anti-CD20 

antibodies, induction or consolidation chemotherapy, or patients with major antibody deficiencies receiving 

immunoglobulins. Inactivated influenza vaccine is an exception, but consideration should be given to repeating doses of 

any non-live vaccine administered during these therapies.

(n) Persons younger than 60 months undergoing chemotherapy or radiation therapy who have not received a Hib primary 

series and a booster dose or at least one Hib dose after 14 months of age; HSCT patients of any ages, regardless of Hib 

vaccine history.

(o) Persons older than 59 months who are asplenic and persons 15 months or older who are undergoing elective 

splenectomy who have not received a Hib primary series and a booster dose or at least one Hib dose after 14 months of 

age.

(p) Hepatitis B vaccine is recommended for all persons birth through 59 years of age. Hepatitis B vaccine is also recommended 

for patients with chronic renal disease in all age groups (including 60 years old and older) based on the risk from dialysisbased bloodborne transmission.
General Best Practice Guidelines for Immunization: Altered Immunocompetence 144

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General Best Practice Guidelines for Immunization: Special Situations 149

9. Special Situations

Updates

Major revisions to this section of the best practices guidance include the timing of 

intramuscular administration and the timing of clotting factor deficiency replacement.

 

Concurrent Administration of Antimicrobial Agents and 

Vaccines 

With a few exceptions, use of an antimicrobial agent does not interfere with the 

effectiveness of vaccination. Antibacterial agents have no effect on non-live vaccines. They 

also have no effect on response to live, attenuated vaccines, except live oral Ty21a typhoid 

vaccine and BCG vaccines. Ty21a typhoid vaccine should not be administered to persons 

receiving antimicrobial agents until 72 hours after the last dose of antimicrobial (1). If 

feasible, to avoid a possible reduction in vaccine effectiveness, antibacterial drugs should 

not be started or resumed until 1 week after the last dose of Ty21a. Antimicrobial or 

immunosuppressive agents may interfere with the immune response to BCG and should 

only be used under medical supervision (for additional information, see 

www.merck.com/product/usa/pi_circulars/b/bcg/bcg_pi.pdf).

Antiviral drugs used for treatment or prophylaxis of influenza virus infections have no 

effect on the response to inactivated influenza vaccine (2). However, live, attenuated 

influenza vaccine should not be administered until 48 hours after cessation of therapy 

with antiviral influenza drugs. If feasible, to avoid possible reduction in vaccine 

effectiveness, antiviral medication should not be administered for 14 days after LAIV 

administration (2). If influenza antiviral medications are administered within 2 weeks 

after receipt of LAIV, the LAIV dose should be repeated 48 or more hours after the last 

dose of zanamivir or oseltamivir. The LAIV dose should be repeated 5 days after peramivir 

and 17 days after baloxavir. Alternatively, persons receiving antiviral drugs within the 

period 2 days before to 14 days after vaccination with LAIV may be revaccinated with 

another approved vaccine formulation (e.g., IIV or recombinant influenza vaccine). 

Antiviral drugs active against herpesviruses (e.g., acyclovir or valacyclovir) might reduce 

the efficacy of vaccines containing live, attenuated varicella zoster virus (i.e., Varivax and 
General Best Practice Guidelines for Immunization: Special Situations 150

ProQuad) (3,4). These drugs should be discontinued at least 24 hours before 

administration, if possible. If clinically appropriate, delay use or resumption of antiviral 

therapy for 14 days after vaccination. No data exist to suggest that commonly used 

antiviral drugs have an effect on rotavirus vaccine or MMR.

Administration of Live Vaccines and Tuberculin Skin 

Tests (TSTs) and Interferon-gamma Release Assays 

(IGRAs)

Measles illness, severe acute or chronic infections, HIV infection, and malnutrition can 

create a relatively anergic state during which the TST might have a false-negative reaction 

(5-7). Although live, attenuated measles vaccine theoretically can suppress TST reactivity, 

the degree of suppression is likely less than that occurring from acute infection from wildtype measles virus. Screening children for tuberculosis exposure is accomplished by 

medical history rather than TST testing; universal TST screening of all children is no 

longer recommended, though TST screening is sometimes indicated (e.g., for persons at 

increased risk for tuberculosis exposure based on medical history, or for employees for 

occupational health reasons).

In a general screening situation, a provider may find that: both TST and live vaccine are 

recommended; live vaccine is recommended, and TST has already been administered 

more than one day previous; or TST is indicated, and the live vaccine has already been 

administered more than one day previous. TST may be administered simultaneously with 

live vaccines, and this is the preferred scenario. If live vaccine is indicated, and TST has 

been administered more than one day previous, the live vaccine can be administered at 

any interval after the TST. If TST is recommended, and the live vaccine has already been 

administered more than one day previous, providers should ensure a 28 day interval, in 

other words defer the TST for 28 days after vaccination. A delay in performing the TST 

removes the concern of any theoretical transient suppression of TST reactivity. Some 

providers choose to perform TST screening and then delay the vaccine until the patient 

returns to have the TST read. This option is less favored compared with simultaneous 

TST/live vaccination, because it delays receipt of the measles-containing vaccine.

While the above rationale is based on measles suppression of TST response, because of 

similar concerns about smallpox vaccine and TST suppression, a TST should not be 

performed until 4 weeks after smallpox vaccination (8). No data exist regarding the 
General Best Practice Guidelines for Immunization: Special Situations 151

potential degree of TST suppression that might be associated with other live, attenuated 

virus vaccines (e.g., varicella or yellow fever). However, in the absence of data, following 

guidelines for measles-containing vaccine when scheduling TST screening and 

administering other live, attenuated virus vaccines is prudent. 

If the opportunity to vaccinate might be missed, vaccination should not be delayed only 

because of these theoretical considerations. TST can be repeated 4 weeks after vaccination 

if it is negative and concern for TB infection persists.

Interferon gamma release assays (IGRAs), such as the QuantiFERON-TB Gold In-Tube 

test and the T-Spot TB test, are blood-test alternatives to the TST for 

detecting Mycobacterium tuberculosis infection. The IGRA requires only a single visit to 

complete and may be less effected by previous BCG vaccination (9). The same timing 

guidelines that apply to the interval between a live vaccine and TST apply to IGRA (i.e., 28 

days between live vaccine and IGRA if they do not occur on the same day), because IGRA 

(like TST) might be suppressed through immunologic mechanisms. The potential for a 

previous TST to cause boosting of future TST results should be considered in adults who 

have a negative initial TST (9). Two-step testing, in which TST is repeated in a short time 

frame (e.g., 1 to 3 weeks) after an initial negative TST, can illicit boosting and identify 

persons whose immune response may have waned with time since infection or BCG 

vaccination. For people undergoing serial screening for infection, for instance health care 

personnel who are tested yearly, differentiation of positive tests due boosting versus new 

infection is important (9). The 2-step test, in which the test is given twice in a short time 

frame, reduces the chance of these false negatives, which are important to identify among 

adults who may have had or plan to have repeat testing anyway—for example, healthcare 

personnel who are tested yearly (9). Because this test consists of 2 TSTs separated by an 

interval of 1-3 weeks, there is a greater window of time during which live vaccine 

replication could suppress reactivity. If a live vaccine is administered, the first dose of a 2-

step TST should be delayed for 4 weeks, and if additional doses of live vaccines are 

indicated thereafter, they should be delayed until the second TST is measured.

TST or IGRA reactivity in the absence of active tuberculosis is not a contraindication to 

administration of any vaccine, including live, attenuated virus vaccines.
General Best Practice Guidelines for Immunization: Special Situations 152

Note that TST screening of an asymptomatic individual is clinically different than testing a 

person suspected to have active tuberculosis. If a person is suspected to have active 

tuberculosis, MMR vaccine is typically not administered. Active tuberculosis should be 

considered severe acute illness, and moderate or severe acute illness is a precaution for 

vaccination.

Although no studies have reported on the effects of MMR vaccine on persons with active 

untreated tuberculosis, a theoretical basis exists for concern that measles vaccine might 

exacerbate active tuberculosis (10). As a result, before administering MMR to persons with 

untreated active tuberculosis, initiating antituberculosis therapy is advisable (10).

Considering whether concurrent immunosuppression (e.g., immunosuppression caused by 

HIV infection) is present before administering live, attenuated vaccines also is necessary, 

because immunosuppression is a contraindication to MMR vaccine.

Vaccination of Preterm Infants

In the majority of cases, preterm infants (infants born before 37 weeks’ gestation), 

regardless of birth weight, should be vaccinated at the same chronological age and 

according to the same schedule and using the same precautions as for full-term infants 

and children. Birth weight and size are not factors in deciding whether to vaccinate a 

clinically stable preterm infant (11-15), except for hepatitis B vaccination. The full 

recommended dose of each vaccine should be used. Divided or reduced doses are not 

recommended.

Decreased seroconversion rates might occur among certain preterm infants (i.e., those 

with low birth weights [<2,000 g]) after administration of hepatitis B vaccine at birth (16). 

However, by the chronological age of 1 month, all preterm infants, regardless of initial 

birth weight, are likely to respond as adequately as larger infants (17-19). Infants weighing 

<2,000 g born to HBsAg-negative mothers should receive the first dose of the hepatitis B 

vaccine series at chronological age 1 month or hospital discharge, if hospital discharge 

occurs when the infant is younger than one month of age. Preterm low-birth-weight–

infants born to HBsAg-positive mothers should receive immunoprophylaxis with hepatitis 

B vaccine within 12 hours after birth. The initial vaccine dose should not be counted 

toward completion of the hepatitis B series, and 3 additional doses of hepatitis B vaccine 
General Best Practice Guidelines for Immunization: Special Situations 153

should be administered, beginning when the infant is aged 1 month. For mothers with 

unknown HBsAg status, hepatitis B vaccine is recommended within 12 hours of birth 

regardless of low-birth-weight status.

In addition to hepatitis B vaccines, hepatitis B Immunoglobulin (HBIG) is recommended 

for infants whose mothers are HBsAg positive or unknown. 

If the mother is HBsAg positive, HBIG must be given within 12 hours of birth. If the 

mother’s HBsAg status is unknown, providers should first attempt to determine the 

mother’s status. Regardless, if the infant is preterm or low birth weight, HBIG must be 

given within 12 hours of birth. If the infant is neither preterm nor low birth weight, 

providers have up to 7 days from birth to determine if the mother is HBsAg negative; 

because the protective efficacy of HBIG declines the longer that administration is delayed, 

if results are unlikely to be known by day 7 of life, HBIG should be given no later than day 

7 if not earlier. If the mother is determined to be HBsAg positive, HBIG should be 

administered as soon as possible (20).

If a child aged at least 6 weeks has been in the hospital since birth, deferral of rotavirus 

vaccine is recommended until the time of discharge. If an infant were to be vaccinated 

with rotavirus vaccine while still needing care in the NICU or nursery, at least a theoretic 

risk exists for vaccine virus being transmitted to infants in the same unit who are acutely 

ill and to preterm infants who are not age-eligible for vaccine (21). The rotavirus vaccine 

series should not be initiated for infants aged ≥15 weeks, 0 days.

Breastfeeding and Vaccination

With 2 exceptions, neither non-live nor live-virus vaccines administered to a lactating 

woman affect the safety of breastfeeding for women or their infants. Although live viruses 

in vaccines can replicate in the mother, the majority of live viruses in vaccines have been 

demonstrated not to be excreted in human milk. Varicella vaccine virus has not been 

found in human milk (22). Although rubella vaccine virus has been excreted in human 

milk, the virus usually does not infect the infant. If infection does occur, it is well tolerated 

because the virus is attenuated (23). Non-live vaccines pose no risk for mothers who are 

breastfeeding or for their infants. Breastfeeding is a contraindication for smallpox 

vaccination of the mother because of the theoretical risk for contact transmission from 
General Best Practice Guidelines for Immunization: Special Situations 154

mother to infant. Yellow fever vaccine should be avoided in breastfeeding women, because 

2 cases (one confirmed, one probable) of yellow-fever vaccine associated acute neurotropic 

disease (YEL-AND) have been detected in infants whose mothers were vaccinated but 

were not vaccinated themselves. In both infants, vaccine virus was recovered from the 

cerebrospinal fluid of the infant, but the exact mode of transmission was not precisely 

determined because vaccine virus was not recovered from breast milk (24). 

However, when nursing mothers cannot avoid or postpone travel to areas endemic for 

yellow fever in which risk for acquisition is high, these women should be vaccinated.

Limited data indicate that breastfeeding can enhance the response to certain vaccine 

antigens (25). There are no data to suggest that passive transfer of antibodies in human 

milk can affect the efficacy of live-virus vaccines. Breastfed infants should be vaccinated 

according to the recommended schedule (26-28).

Vaccination During Pregnancy

No evidence exists of risk to the fetus from vaccinating pregnant women with non-live 

virus or bacterial vaccines (29,30). In spite of the lack of evidence of risk, HPV vaccine, a 

non-live vaccine, is not recommended during pregnancy. Live vaccines administered to a 

pregnant woman pose a theoretical risk to the fetus; therefore, live, attenuated virus and 

live bacterial vaccines generally are contraindicated during pregnancy. Women should 

avoid conception for 4 weeks after vaccination with live vaccines. However, benefits of 

vaccinating pregnant women usually outweigh potential risks when the likelihood of 

disease exposure is high, when infection would pose a risk to the mother or fetus, and 

when the vaccine is unlikely to cause harm. Recommendations for vaccination during 

pregnancy are developed using ACIP’s Guiding Principles for Development of ACIP 

Recommendations for Vaccination During Pregnancy and Breastfeeding (31).

Women who are pregnant should receive a dose of Tdap for the prevention of infant 

pertussis whether or not they have previously received Tdap. Vaccination of the mother 

generates antibodies that pass transplacentally to the fetus (32). Vaccination in the third 

trimester optimizes the duration of this antibody protection until after birth. Additionally, 

preventing pertussis in the mother reduces the risk that the infant is exposed to pertussis 
General Best Practice Guidelines for Immunization: Special Situations 155

after birth (33). Health care personnel should administer Tdap during pregnancy, 

preferably during the third trimester. If Tdap is not administered during pregnancy to 

women who have never received it, it should be administered immediately postpartum. 

Pregnant women who are not vaccinated or are only partially vaccinated against tetanus 

should complete the primary series (34). Women for whom Td is indicated but who did 

not complete the recommended 3-dose series during pregnancy should receive follow-up 

after delivery to ensure the series is completed. 

One dose of the tetanus vaccine series should be Tdap, if Tdap has not already been 

received.

Pregnant and postpartum women are at higher risk for severe illness and complications 

from influenza than women who are not pregnant (2, 35). Pregnant women have 

protective levels of anti-influenza antibodies after vaccination (36,37). Passive transfer of 

anti-influenza antibodies that might provide protection from vaccinated women to 

neonates has been reported (36, 38-41). Routine vaccination with inactivated influenza 

vaccine is recommended for all women who are or will be pregnant (in any trimester) 

during influenza season.

IPV can be administered to pregnant women who are at risk for exposure to wild-type 

poliovirus. This includes travelers to areas or countries where polio is epidemic or 

endemic; members of communities or specific population groups with disease caused by 

wild polioviruses; laboratory workers who handle specimens that might contain 

polioviruses; healthcare personnel who have close contact with patients who might be 

excreting wild polioviruses; and unvaccinated persons whose children will be receiving 

oral poliovirus vaccine (42). Hepatitis A, pneumococcal polysaccharide, meningococcal 

conjugate, and meningococcal polysaccharide vaccines should be considered for women at 

increased risk for those infections (43-45). Pregnant women who must travel to areas 

where there is a risk for acquiring yellow fever should receive yellow fever vaccine, because 

the limited theoretical risk from vaccination is outweighed substantially by the risk for 

yellow fever infection (24, 46). Hepatitis B vaccine is not contraindicated in pregnancy and 

should be given to a pregnant woman for whom it is indicated (20, 47).

Pregnancy is a contraindication for smallpox (vaccinia) vaccine and measles-, mumps-, 
General Best Practice Guidelines for Immunization: Special Situations 156

rubella-, and varicella-containing vaccines. Smallpox vaccine is the only vaccine known to 

harm a fetus when administered to a pregnant woman. In addition, smallpox vaccine 

should not be administered to a household contact of a pregnant woman (8). Women who 

are pregnant should not have close contact with anyone who has recently (within the last 

28 days) received the smallpox vaccine. Data from studies of children born to mothers 

inadvertently vaccinated with rubella vaccine during pregnancy demonstrate rubella 

antibody in unvaccinated infants. This could represent passive transfer of maternal 

antibody or a fetal antibody response to vaccine virus infection in the fetus. 

No cases of congenital rubella or varicella syndrome or abnormalities attributable to fetal 

infection have been observed among infants born to susceptible women who inadvertently 

received rubella or varicella vaccines during pregnancy (48-50). Because of the importance 

of protecting women of childbearing age against rubella and varicella, reasonable practices 

in any vaccination program include asking women if they are pregnant or might become 

pregnant in the next 4 weeks; not vaccinating women who state that they are or plan to 

become pregnant within that interval; explaining the theoretical risk for the fetus if MMR, 

varicella, or MMRV vaccine were administered to a woman who is pregnant; and 

counseling women who are vaccinated not to become pregnant during the 4 weeks after 

MMR, varicella, or MMRV vaccination (10, 48-51). MMRV is an unlikely option for a 

pregnant woman because the vaccine is only licensed through 12 years of age. Routine 

pregnancy testing of women of childbearing age before administering a live-virus vaccine 

is not recommended (3, 10). If a pregnant woman is inadvertently vaccinated or becomes 

pregnant within 4 weeks after MMR or varicella vaccination, she should be counseled 

about the theoretical basis of concern for the fetus; however, MMR or varicella vaccination 

during pregnancy should not be considered a reason to terminate pregnancy (3, 10, 50).

Persons who receive MMR vaccine do not transmit the vaccine viruses to contacts (10). 

Transmission of varicella vaccine virus to contacts is exceedingly rare (3). MMR and 

varicella vaccines should be administered when indicated to children and other household 

contacts of pregnant women (10). Infants living in households with pregnant women 

should be vaccinated with rotavirus vaccine according to the same schedule as infants in 

households without pregnant women.

Pregnant women should be evaluated for evidence of immunity to rubella and varicella 
General Best Practice Guidelines for Immunization: Special Situations 157

and be tested for the presence of HBsAg during every pregnancy (10, 20, 52). Women 

without evidence of immunity to rubella and varicella should be vaccinated immediately 

after delivery. A second dose of varicella vaccine should be administered 4-8 weeks later. A 

woman found to be HBsAg positive should be followed-up carefully to ensure that the 

infant receives HBIG and begins the hepatitis B vaccine series no later than 12 hours after 

birth and that the infant completes the recommended hepatitis B vaccine series on 

schedule (20). No known risk exists for the fetus from passive immunization of pregnant 

women with immune globulin preparations.

Persons Vaccinated Outside the United States

Clinicians have a limited ability to determine whether persons are protected on the basis of 

their country of origin and their vaccination records alone. Vaccines administered outside 

the United States generally can be accepted as valid if the schedule (i.e., minimum ages 

and intervals) is similar to that recommended in the United States. There are exceptions 

(providers should not accept documentation of these vaccines): Aimmugen, a hepatitis A 

vaccine; and Twinrix Jr., a combination vaccine containing hepatitis A and hepatitis B 

components (providers can accept the hepatitis B component but NOT the hepatitis A 

component). 

Only written documentation should be accepted as evidence of previous vaccination. There 

is one exception, influenza vaccine, for which self-report can be accepted. Written records 

are more likely to predict protection if the vaccines, dates of administration, intervals 

between doses, and age at the time of vaccination are comparable to U.S. 

recommendations. Although vaccines with inadequate potency have been produced in 

other countries (53,54), the majority of vaccines used worldwide are produced with 

adequate quality control standards and are potent. Medscape has a guide to pediatric 

vaccines used in other countries, available at 

https://emedicine.medscape.com/article/2500038-overview. Persons vaccinated outside 

of the United States can enter the country through a number of different mechanisms. 

Those seeking to immigrate to the United States may be vaccinated under the authority of 

a civil surgeon or a panel physician. Some enter the United States as refugees and are 

vaccinated under the authority of the Office of Refugee Resettlement, part of the 

Administration for Children and Families, in the Department of Health and Human 

Services.
General Best Practice Guidelines for Immunization: Special Situations 158

Adopted children’s birth countries often have vaccination schedules that differ from the 

recommended childhood vaccination schedule in the United States. Differences in the U.S. 

schedule and those used in other countries include the vaccines administered, the 

recommended ages of administration, and the number and timing of doses.

Data are inconclusive regarding the extent to which an internationally adopted child’s 

vaccination record reflects the child’s protection. 

A child’s record might indicate administration of MMR vaccine when only single-antigen 

measles vaccine was administered. A study of children adopted from orphanages in the 

People’s Republic of China, Russia, and countries in Eastern Europe determined that 67% 

of children with documentation of >3 doses of DTP before adoption had nonprotective 

titers to these antigens (54). 

In contrast, children adopted from these countries who received vaccination in the 

community (not only from orphanages) and had documentation of ≥1 doses of DTP 

exhibited protective titers 67% of the time (54). However, antibody testing was performed 

by using a hemagglutination assay, which tends to underestimate protection and cannot 

directly be compared with antibody concentration (55). Data are likely to remain limited

for areas other than the People’s Republic of China, Russia, and Eastern Europe. 

Healthcare providers should ensure that household contacts of international adoptees are 

vaccinated adequately, particularly for measles, hepatitis A, and hepatitis B (56). 

Healthcare providers may use one of multiple approaches if the immunogenicity of 

vaccines or the completeness of series administered to persons outside the United States is 

in question. Repeating the vaccinations is an acceptable option that usually is safe and 

prevents the need to obtain and interpret serologic tests. If avoiding unnecessary 

injections is desired, judicious use of serologic testing might help determine which 

vaccinations are needed. For some vaccines, the most readily available serologic tests 

cannot document protection against infection. This best practices document provides 

guidance on possible approaches to evaluation and revaccination for each vaccine 

recommended in the United States (Table 9-1).

DTaP Vaccine
General Best Practice Guidelines for Immunization: Special Situations 159

Vaccination providers can revaccinate children younger than 7 years of age with DTaP 

vaccine without regard to recorded doses; however, data indicate increased rates of local 

adverse reactions after the fourth and fifth doses of DTaP (57). If a revaccination approach 

is adopted and a severe local reaction occurs, serologic testing for specific IgG antibody to 

tetanus and diphtheria toxins can be measured before administering additional doses. 

Protective concentration(a) indicates that additional doses are unnecessary and subsequent 

vaccination should occur as age appropriate. No established serologic correlates exist for 

protection against pertussis.

For a child whose record indicates receipt of ≥3 doses of DTP or DTaP, serologic testing 

for specific IgG antibody to both diphtheria and tetanus toxin before additional doses is a 

reasonable approach. If a protective concentration is present, recorded doses are 

considered valid, and the vaccination series should be completed as age appropriate. 

An indeterminate antibody concentration might indicate immunologic memory but 

waning antibody; serologic testing can be repeated after a booster dose if vaccination 

providers or parents want to avoid revaccination with a complete series.

Alternately, for a child whose records indicate receipt of ≥3 doses, a single booster dose 

can be administered followed by serologic testing after 1 month for specific IgG antibody

to both diphtheria and tetanus toxins. If the child has a protective concentration, the 

recorded doses are considered valid, and the vaccination series should be completed as age 

appropriate. Children with an indeterminate concentration after a booster dose should be 

revaccinated with a complete series.

Hepatitis A Vaccine

Children aged 12-23 months without documentation of hepatitis A vaccination or serologic 

evidence of immunity should be vaccinated on arrival in the United States (45). Persons 

who have received 1 dose should receive the second dose if 6-18 months have passed since 

the first dose was administered.

Hepatitis B Vaccine

Persons not known to be vaccinated for hepatitis B should receive an age-appropriate 

series of hepatitis B vaccine. A person whose records indicate receipt of a complete series 
General Best Practice Guidelines for Immunization: Special Situations 160

of vaccine is considered protected(b), and additional doses are not needed if ≥1 dose was 

administered at age ≥24 weeks. Persons who received their last hepatitis B vaccine dose at 

an age <24 weeks should receive an additional dose at age ≥24 weeks. People who have 

received no doses or a partial series of vaccine should complete the series at the 

recommended intervals and ages.

All foreign-born persons and immigrants, refugees, and internationally adopted children 

born in Asia, the Pacific Islands, Africa, and other regions of high or intermediate hepatitis 

B endemicity should be tested for HBsAg, regardless of vaccination status (58). Those 

determined to be HBsAg positive should be monitored for development of liver disease. 

Household members of HBsAg-positive children or adults should be vaccinated if they are 

not already immune.

Hib Vaccine 

Interpretation of a serologic test to verify whether children who were vaccinated >2 

months previously are protected against Hib bacteria can be difficult. Because the number 

of vaccinations needed for protection decreases with age and because adverse events are 

rare (59), age-appropriate vaccination should be provided. Hib vaccination is not 

recommended routinely for persons aged ≥5 years (59).

Meningococcal Vaccine

Quadrivalent meningococcal conjugate vaccines are not routinely used in other countries 

in adolescents (the United Kingdom is the exception). Unless patients have documented 

receipt they should be considered unvaccinated and receive the age-appropriate doses.

MMR Vaccine

The simplest approach to resolving concerns about MMR vaccination is to revaccinate 

with 1 or 2 doses of MMR vaccine, depending on age. Serious adverse events after MMR 

vaccinations are rare (10). No evidence indicates that administering MMR vaccine 
General Best Practice Guidelines for Immunization: Special Situations 161

increases the risk for adverse reactions among persons who are already immune to 

measles, mumps, or rubella as a result of previous vaccination or natural disease. Doses of 

measles-containing vaccine administered before the first birthday should not be counted 

as part of the series (10). Alternatively, serologic testing for IgG antibody to vaccine viruses 

indicated on the vaccination record can be considered. Serologic testing is widely available 

for measles and rubella IgG antibody. 

A person whose record indicates receipt of monovalent measles or measles-rubella vaccine 

on or after the first birthday and who has protective antibody against measles and rubella 

should receive 1 or 2 doses of MMR or MMRV as age appropriate to ensure protection 

against mumps and varicella (and rubella if measles vaccine alone had been 

administered). If a person whose record indicates receipt of MMR at age ≥12 months has a 

protective concentration of antibody to measles, no additional vaccination is needed 

unless a second dose is required for school entry.

Pneumococcal Vaccines

Many industrialized countries now routinely use pneumococcal vaccines. Although 

recommendations for pneumococcal polysaccharide vaccine also exist in many countries, 

the pneumococcal conjugate vaccine might not be routinely administered. PCV13 and 

PPSV23 should be administered according to age-appropriate vaccination schedules or as 

indicated by the presence of underlying medical conditions (43, 60).

Poliovirus Vaccine

The simplest approach to vaccinating with poliovirus vaccine is to revaccinate persons 

aged <18 years with IPV according to the U.S. schedule. Adverse events after IPV are rare 

(42). Children appropriately vaccinated with 3 doses of OPV in economically developing 

countries might have suboptimal seroconversion, including to type 3 poliovirus (42).

Rotavirus Vaccine
General Best Practice Guidelines for Immunization: Special Situations 162

Rotavirus vaccination should not be initiated for infants aged ≥15 weeks, 0 days. Infants 

who began the rotavirus vaccine series outside the United States but who did not complete 

the series and who are still aged ≤8 months, 0 days, should follow the routine schedule 

and receive doses to complete the series. If the brand of a previously administered dose is 

live, reassortment pentavalent rotavirus vaccine or is unknown, a complete series of 

rotavirus vaccine should be documented for series completion(b). All doses should be 

administered by age 8 months, 0 days.

Td and Tdap Vaccines

Children aged ≥7 years who are not considered fully vaccinated for pertussis should 

receive Tdap vaccine. “Fully vaccinated” means at least 5 doses of DTaP before the seventh 

birthday or at least 4 doses of DTaP before the seventh birthday if the fourth dose is given 

after the fourth birthday. One dose of Tdap is recommended after the seventh birthday. If 

additional doses of vaccine are needed, Td should be administered as age appropriate.

Varicella Vaccine

Varicella vaccine is not available in most countries. A person who lacks evidence of 

varicella immunity should be vaccinated as age appropriate (3, 59).

Zoster Vaccine

In the United States, zoster vaccination is recommended for all persons aged ≥50 years 

who have no contraindications, including persons who report a previous episode of zoster 

or who have chronic medical conditions. For persons who do not have documentation of 

receipt of zoster vaccine, the vaccine should be offered at the patient’s first clinical 

encounter with the healthcare provider. Two doses of vaccine are recommended 2-6 

months apart, each dose a 0.5-mL intramuscular dose. Zoster vaccination is not indicated 

to treat acute zoster, to prevent persons with acute zoster from developing postherpetic 

neuralgia, or to treat ongoing postherpetic neuralgia. Patients do not need to be asked 

about their history of varicella or to have serologic testing conducted to determine zoster 

immunity prior to administration of zoster vaccine.
General Best Practice Guidelines for Immunization: Special Situations 163

Vaccinating Persons with Increased Bleeding Risk

Providers often avoid giving intramuscular injections or choose alternative routes for 

persons with bleeding disorders because of the risk for hematoma formation after 

injections. In one study, hepatitis B vaccine was administered intramuscularly to 153 

persons with hemophilia. The vaccination was administered with a 23-gauge or smaller 

caliber needle, followed by application of steady pressure to the site for 1-2 minutes. The 

vaccinations resulted in a low (4%) bruising rate, and no patients required factor 

supplementation (61). Whether antigens that produce more local reactions (e.g., pertussis) 

would produce an equally low rate of bruising is unknown.

When hepatitis B or any other intramuscularly administered vaccine is indicated for a 

patient with a bleeding disorder, the vaccine should be administered intramuscularly if a 

physician familiar with the patient’s bleeding risk determines that the vaccine can be 

administered by this route with reasonable safety. If the patient receives antihemophilia or 

similar therapy, intramuscularly administered vaccinations can be scheduled shortly after 

such therapy is administered. 

A fine-gauge needle (23-gauge or smaller caliber) should be used for the vaccination, 

followed by firm pressure on the site, without rubbing, for at least 2 minutes. The patient 

or family should be given information on the risk for hematoma from the injection. 

Patients receiving anticoagulation therapy presumably have the same bleeding risk as 

patients with clotting factor disorders and should follow the same guidelines for 

intramuscular administration. If possible, vaccination could be scheduled prior to the use 

of these medications, so that the patients’ risk of bleeding is not increased by their 

therapeutic action.

(a) Enzyme immunoassay tests are available. Physicians should contact the laboratory performing the test for interpretive 

standards and limitations. Protective concentrations for antibody to diphtheria and tetanus toxins are defined as >0.1 IU/mL.

(b) A complete series may consist of two or three doses, depending on the brand of vaccine used in the country of origin.
General Best Practice Guidelines for Immunization: Special Situations 164

TABLE 9-1. Approaches to evaluation and vaccination of persons 

vaccinated outside the United States who have no (or questionable) 

vaccination records

Vaccine Recommended 

approach

Alternative approach(a)

DTaP Revaccination with DTaP, 

with serologic testing for 

specific IgG antibody to 

tetanus and diphtheria 

toxins in the event of a 

severe local reaction

Persons whose records indicate 

receipt of ≥3 doses: serologic testing 

for specific IgG antibody to 

diphtheria and tetanus toxins before 

administering additional doses (see 

text), or administer a single booster 

dose of DTaP, followed by 

serological testing after 1 month for 

specific IgG antibody to diphtheria 

and tetanus toxins with 

revaccination as appropriate (see 

text)

HepA Age-appropriate 

revaccination

Serologic testing for IgG antibodies 

to hepatitis A

HepB Age-appropriate 

revaccination and serologic 

testing for HBsAg(b)

—

Hib Age-appropriate 

revaccination

—

HPV Age-appropriate 

revaccination

—

Meningococcal 

conjugate 

(MenACWY)

Age-appropriate 

revaccination

—

MMR Revaccination with MMR Serologic testing for IgG antibodies 

to measles, mumps, and rubella

Pneumococcal 

conjugate (or in 

some cases, both 

PCV13 and 

PPSV23)

Age-appropriate 

revaccination

—
General Best Practice Guidelines for Immunization: Special Situations 165

Poliovirus Revaccination with 

inactivated poliovirus 

vaccine

—

Rotavirus Age-appropriate 

revaccination

—

Tdap Age-appropriate 

revaccination of persons 

who are candidates for 

Tdap vaccine

—

Varicella Age-appropriate 

revaccination of persons 

who lack evidence of 

varicella immunity

—

Zoster Age-appropriate 

revaccination

—

Abbreviations: DTaP = diphtheria and tetanus toxoids and acellular pertussis; HBsAg = hepatitis B surface 

antigen; HepA = hepatitis A; HepB = hepatitis B; Hib = Haemophilus influenzae type b; HPV = human 

papillomavirus; IgG = immune globulin G; MMR = measles, mumps, and rubella; PCV13 = pneumococcal conjugate 

vaccine; PPSV23= pneumococcal polysaccharide vaccine; Tdap = tetanus toxoid, reduced diphtheria toxoid, and 

acellular pertussis.

(a) There is a recommended approach for all vaccines and an alternative approach for some vaccines.

(b) In rare instances, hepatitis B vaccine can give a false-positive HBsAg result up to 18 days after vaccination; 

therefore, blood should be drawn to test for HBsAg before vaccinating (20).
General Best Practice Guidelines for Immunization: Special Situations 166

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19. Losonsky GA, Wasserman SS, Stephens I, et al. Hepatitis B vaccination of 

premature infants: a reassessment of current recommendations for delayed 

immunization. Pediatrics. 1999;103(2):E14. DOI: 10.1542/peds.103.2.e14

20. Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization 

strategy to eliminate transmission of hepatitis B virus infection in theUnited 

States: recommendations of the Advisory Committee on Immunization 

Practices (ACIP) part 1: immunization of infants, children, and adolescents. 

MMWR Recomm Rep. 2005;54(RR-16):1-31.

21. Cortese MM, Parashar UD. Prevention of rotavirus gastroenteritis among 

infants and children: recommendations of the Advisory Committee on 

Immunization Practices (ACIP). MMWR Recomm Rep. 2009;58(RR-2):1-25.

22. Bohlke K, Galil K, Jackson LA, et al. Postpartum varicella vaccination: is the 

vaccine virus excreted in breast milk? Obstet Gynecol. 2003;102(5 Pt 1):970-

977. DOI: 10.1016/S0029-7844(03)00860-3

23. Krogh V, Duffy LC, Wong D, Rosenband M, Riddlesberger KR, Ogra PL. 

Postpartum immunization with rubella virus vaccine and antibody response 

in breast-feeding infants. J Lab Clin Med. 1989;113(6):695-699.

24. Staples JE, Gershman M, Fischer M. Yellow fever vaccine: recommendations 

of the Advisory Committee on Immunization Practices (ACIP). MMWR 

Recomm Rep. 2010;59(RR-7):1-27.

25. Pickering LK, Granoff DM, Erickson JR, et al. Modulation of the immune 

system by human milk and infant formula containing nucleotides. Pediatrics. 

1998;101(2):242-249. DOI: 10.1542/peds.101.2.242

26. Kim-Farley R, Brink E, Orenstein W, Bart K. Vaccination and breastfeeding.

JAMA. 1982;248(19):2451-2452. DOI: 10.1001/jama.1982.03330190021019

27. Patriarca PA, Wright PF, John TJ. Factors affecting the immunogenicity of 

oral poliovirus vaccine in developing countries: review. Rev Infect Dis. 

1991;13(5):926-939.
General Best Practice Guidelines for Immunization: Special Situations 169

28. Hahn-Zoric M, Fulconis F, Minoli I, et al. Antibody responses to parenteral 

and oral vaccines are impaired by conventional and low protein formulas as 

compared to breast-feeding. Acta Paediatr Scand. 1990;79(12):1137-1142. 

DOI: 10.1111/j.1651-2227.1990.tb11401.x

29. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Engl J Med.

1998;338(16):1128-1137. DOI: 10.1056/nejm199804163381607

30. Grabenstein JD. Vaccines and antibodies in relation to pregnancy and 

lactation. Hospital Pharmacy. 1999;34:949-960.

31. CDC. Guiding principles for development of ACIP recommendations for 

vaccination during pregnancy and breastfeeding. MMWR Morb Mortal Wkly 

Rep. 2008;57(21):580.

32. Munoz FM, Bond NH, Maccato M, et al. Safety and immunogenicity of 

tetanus diphtheria and acellular pertussis (Tdap) immunization during 

pregnancy in mothers and infants: a randomized clinical trial. JAMA. 

2014;311(17):1760-1769. DOI: 10.1001/jama.2014.3633

33. Wendelboe AM, Njamkepo E, Bourillon A, et al. Transmission of Bordetella 

pertussis to young infants. Pediatr Infect Dis J. 2007;26(4):293-299. DOI: 

10.1097/01.inf.0000258699.64164.6d

34. Kretsinger K, Broder KR, Cortese MM, et al. Preventing tetanus, diphtheria, 

and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid 

and acellular pertussis vaccine recommendations of the Advisory Committee 

on Immunization Practices (ACIP) and recommendation of ACIP, supported 

by the Healthcare Infection Control Practices Advisory Committee (HICPAC), 

for use of Tdap among health-care personnel. MMWR Recomm Rep. 

2006;55(RR-17):1-37.

35. Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of 

influenza on acute cardiopulmonary hospitalizations in pregnant women. Am 

J Epidemiol. 1998;148(11):1094-1102. DOI: 

10.1093/oxfordjournals.aje.a009587

36. Sumaya CV, Gibbs RS. Immunization of pregnant women with influenza 

A/New Jersey/76 virus vaccine: reactogenicity and immunogenicity in mother 

and infant. J Infect Dis. 1979;140(2):141-146. DOI: 10.1093/infdis/140.2.141
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37. Munoz FM, Greisinger AJ, Wehmanen OA, et al. Safety of influenza 

vaccination during pregnancy. Am J Obstet Gynecol. 2005;192(4):1098-1106. 

DOI: 10.1016/j.ajog.2004.12.019

38. Englund JA, Mbawuike IN, Hammill H, Holleman MC, Baxter BD, Glezen 

WP. Maternal immunization with influenza or tetanus toxoid vaccine for 

passive antibody protection in young infants. J Infect Dis. 1993;168(3):647-

656. DOI: 10.1093/infdis/168.3.647

39. Puck JM, Glezen WP, Frank AL, Six HR. Protection of infants from infection 

with influenza A virus by transplacentally acquired antibody. J Infect Dis. 

1980;142(6):844-849. DOI: 10.1093/infdis/142.6.844

40. Reuman PD, Ayoub EM, Small PA. Effect of passive maternal antibody on 

influenza illness in children: a prospective study of influenza A inmotherinfant pairs. Pediatr Infect Dis J. 1987;6(4):398-403. DOI: 

10.1097/00006454-198704000-00011

41. Steinhoff MC, Omer SB, Roy E, et al. Influenza immunization in pregnancy—

antibody responses in mothers and infants. N Engl J Med. 

2010;362(17):1644-1646. DOI: 10.1056/NEJMc0912599

42. Prevots DR, Burr RK, Sutter RW, Murphy TV. Poliomyelitis prevention in the 

United States. Updated recommendations of the Advisory Committee on 

Immunization Practices (ACIP). MMWR Recomm Rep. 2000;49(RR-5):1-22; 

quiz CE21-27.

43. CDC. Prevention of pneumococcal disease: recommendations of the Advisory 

Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 

1997;46(RR-8):1-24.

44. Bilukha OO, Rosenstein N. Prevention and control of meningococcal disease. 

Recommendations of the Advisory Committee on Immunization Practices 

(ACIP). MMWR Recomm Rep. 2005;54(RR-7):1-21.

45. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or 

passive immunization: recommendations of the Advisory Committee on 

Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55(RR-7):1-23.
General Best Practice Guidelines for Immunization: Special Situations 171

46. Tsai TF, Paul R, Lynberg MC, Letson GW. Congenital yellow fever virus 

infection after immunization in pregnancy. J Infect Dis. 1993;168(6):1520-

1523. DOI: 10.1093/infdis/168.6.1520

47. Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization 

strategy to eliminate transmission of hepatitis B virus infection in theUnited 

States: recommendations of the Advisory Committee on Immunization 

Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 

2006;55(RR-16):1-33; quiz CE31-34.

48. Wilson E, Goss MA, Marin M, et al. Varicella vaccine exposure during 

pregnancy: data from 10 years of the pregnancy registry. J Infect Dis. 

2008;197 Suppl 2:S178-184. DOI: 10.1086/522136

49. CDC. Revised ACIP recommendation for avoiding pregnancy after receiving a 

rubella-containing vaccine. MMWR Morb Mortal Wkly Rep. 

2001;50(49):1117.

50. CDC. Rubella vaccination during pregnancy—United States, 1971-1988.

MMWR Morb Mortal Wkly Rep. 1989;38(17):289-293.

51. Black NA, Parsons A, Kurtz JB, McWhinney N, Lacey A, Mayon-White RT. 

Post-partum rubella immunisation: a controlled trial of two vaccines.Lancet. 

1983;2(8357):990-992. DOI: 10.1016/S0140-6736(83)90979-0

52. CDC. Control and prevention of rubella: evaluation and management of 

suspected outbreaks, rubella in pregnant women, and surveillance for 

congenital rubella syndrome. MMWR Recomm Rep. 2001;50(RR-12):1-23.

53. Murray TS, Groth ME, Weitzman C, Cappello M. Epidemiology and 

management of infectious diseases in international adoptees. Clin Microbiol 

Rev. 2005;18(3):510-520. DOI: 10.1128/cmr.18.3.510-520.2005

54. Hostetter MK. Infectious diseases in internationally adopted children: 

findings in children from China, Russia, and eastern Europe. Adv Pediatr 

Infect Dis. 1999;14:147-161.

55. Kriz B, Burian V, Sladky K, Burianova B, Mottlova O, Roth Z. Comparison of 

titration results of diphtheric antitoxic antibodies obtained by means of 

Jensen's method and the methods of tissue cultures and haemagglutination. J 

Hyg Epidemiol Microbiol Immunol. 1978;22(4):485-493.
General Best Practice Guidelines for Immunization: Special Situations 172

56. CDC. Updated recommendations from the Advisory Committee on 

Immunization Practices (ACIP) for use of hepatitis A vaccine in close contacts 

of newly arriving international adoptees. MMWR Morb Mortal Wkly Rep. 

2009;58(36):1006-1007.

57. CDC. Use of diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine as a 

five-dose series. Supplemental recommendations of the Advisory Committee 

on Immunization Practices (ACIP). MMWR Recomm Rep. 2000;49(RR-13):1-

8.

58. Weinbaum CM, Williams I, Mast EE, et al. Recommendations for 

identification and public health management of persons with chronic 

hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1-20.

59. CDC. Recommended immunization schedules for persons aged 0 through 18 

years—United States, 2011. MMWR Morb Mortal Wkly Rep.2011;60(5):1-4.

60. Nuorti JP, Whitney CG. Prevention of pneumococcal disease among infants 

and children - use of 13-valent pneumococcal conjugate vaccine and 23-valent 

pneumococcal polysaccharide vaccine - recommendations of the Advisory 

Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 

2010;59(RR-11):1-18.

61. Evans DI, Shaw A. Safety of intramuscular injection of hepatitis B vaccine in 

haemophiliacs. BMJ. 1990;300(6741):1694-1695. DOI: 

10.1136/bmj.300.6741.1694-a
General Best Practice Guidelines for Immunization: Vaccination Records 173

10. Vaccination Records

Records of Healthcare Providers

Appropriate and timely vaccination documentation helps ensure not only that persons in 

need of recommended vaccine doses receive them but also that adequately vaccinated 

patients do not receive excess doses. Curtailing the number of excess doses administered 

to patients controls costs incurred by patients, providers, insurers, vaccination programs, 

and other stakeholders. In addition, avoidance of excess doses of vaccines should decrease 

the number of adverse reactions to vaccines. Health care providers who administer 

vaccines covered by the National Vaccine Injury Compensation Program (VICP) are 

required under the National Childhood Vaccine Injury Act (1) to ensure that the 

permanent medical record of the recipient (or a permanent office log or file) indicates the 

date the vaccine was administered, the vaccine manufacturer, the vaccine lot number, and 

the name, address, and title of the person administering the vaccine. This Act applies to 

any vaccine for which there is a routine recommendation for childhood vaccination, even 

if many or most doses of the vaccine are administered to adults (e.g., influenza vaccine). In 

addition, the provider is required to record the edition date of the VIS distributed and the 

date those materials were provided. The Act considers a health-care provider to be any 

licensed health care professional, organization, or institution, whether private or public 

(including federal, state, and local departments and agencies), under whose authority a 

specified vaccine is administered. This information should be kept for all vaccines, not just 

for those required by the Act. Providers and staff members also should systematically 

update patients’ permanent medical records to reflect any documented episodes of 

adverse events after vaccination and any serologic test results related to vaccinepreventable diseases (e.g., those for rubella screening and anti-HBs).

Personal Records of Patients

Official childhood vaccination records have been adopted by every state and territory and 

the District of Columbia to encourage uniformity of records and to facilitate assessment of 

vaccination status by schools and child-care centers. 
General Best Practice Guidelines for Immunization: Vaccination Records 174

The records also are key tools in vaccination education programs aimed at increasing 

parental and patient awareness of the need for vaccines. This record can exist in electronic 

file format or in hardcopy format. A permanent vaccination record should be established 

for each newborn infant and maintained by the parent or guardian. The parent or 

guardian should be educated about the importance of keeping the record up-to-date and 

instructed to keep the record indefinitely. These records should be distributed to new 

parents and/or guardians before discharge from the hospital or birthing center. Using 

vaccination records for adolescents and adults also is encouraged. Standardized adult 

vaccination records are available at http://www.immunize.org. 

Immunization Information Systems (IISs)

IISs (formerly referred to as immunization registries) are confidential, population-based, 

computerized information systems that collect and consolidate vaccination data from 

multiple health care providers within a geographic area. IISs are a critical tool that can 

increase and sustain vaccination coverage by consolidating vaccination records from 

multiple providers, generating reminder and recall vaccination notices for each person, 

and providing official vaccination forms and vaccination coverage assessments (2). 

Providers should be aware of state and/or regional IISs and requirements for reporting.

Changing vaccination providers during the course of an individual’s vaccination series is 

common in the United States. In addition to changes in providers, the vaccination records 

of persons who have changed vaccination providers often are unavailable or incomplete or 

might not have been entered into an IIS (2). Missing or inaccurate information regarding 

vaccines received previously might preclude accurate determination of which vaccines are 

indicated at the time of a visit, resulting in administration of extra doses.

A fully operational IIS also can prevent duplicate vaccinations, forecast when the next 

dose is due, limit missed appointments, allow recall for those who missed appointments, 

determine when vaccines need to be repeated (the technical IIS term for this is 

“evaluation”), reduce vaccine waste, and reduce staff time required to produce or locate 

vaccination records or certificates. 
General Best Practice Guidelines for Immunization: Vaccination Records 175

Most IISs have additional capabilities, such as measurement of vaccination update and 

coverage, aid in tracking vaccine inventory and placing vaccine orders, recall of vaccine by 

lot number, maintenance of lifetime vaccination histories, and interoperability with other 

health information systems. The National Vaccine Advisory Committee recommends that 

vaccination providers participate in these systems when possible. Electronic health 

records should maintain interoperability with IISs as part of an effort to improve the 

quality of care, reduce health disparities, engage patients and families in their health, 

improve the coordination of care, improve population health, and ensure adequate privacy 

and security protection for personal health information (see 

www.cdc.gov/ehrmeaningfuluse/introduction.html)

One of the national Healthy People objectives for 2020 is 95% participation of children 

aged <6 years in a fully operational population-based IIS (objective 20.1) (3,4). 

Participating in an IIS means having two or more vaccinations recorded in the IIS. 2012 

IIS data indicate that approximately 86% of children aged <6 years with two or more 

vaccinations were participating in IISs (4,5).

The National Vaccine Advisory Committee recommends that public health departments 

work toward including adults in all state IISs, reduce barriers to including adult 

vaccination records in IISs, and ensure that IISs meet new standards of EHR 

interoperability to track and maintain adult vaccination records (6).

Nationally, 57.8 million U.S. adults aged 19 years or older participated in an IIS in 2012 

(4). This number reflects adults who may have had childhood vaccines entered during 

childhood and now have aged to adults. In 2013, 32% of U.S. adults had a record in the IIS 

and at least one vaccination administered during adulthood.
General Best Practice Guidelines for Immunization: Vaccination Records 176

REFERENCES

1. National Childhood Vaccine Injury Act, 42 U.S.C. Sect. 300aa-1 to300aa-34 

(1986).

2. CDC. Immunization information systems progress—United States, 2006. MMWR 

Morb Mortal Wkly Rep. 2008;57(11):289-291.

3. US Department of Health and Human Services. Immunization and infectious 

diseases. Healthy people 2010. Vol 1 (conference edition). 1st ed.Washington, 

DC: US Government Printing Office; 2000.

4. CDC. Progress in immunization information systems - United States, 2012.

MMWR Morb Mortal Wkly Rep. 2013;62(49):1005-1008.

5. Mangione-Smith R, DeCristofaro AH, Setodji CM, et al. The quality of 

ambulatory care delivered to children in the United States. N Engl J Med. 

2007;357(15):1515-1523. DOI: 10.1056/NEJMsa064637

6. National Vaccine Advisory Committee. Recommendations from the National 

Vaccine Advisory committee: standards for adult immunization practice. Public 

Health Rep. 2014;129(2):115-123.
General Best Practice Guidelines for Immunization: Vaccination Programs 177

11. Vaccination Programs

Updates

The major revision to this section is the addition of language related to Affordable Care 

Act (1) coverage of adult vaccination.

 

General Principles

Universal vaccination is a critical part of quality health care and should be accomplished 

through routine and catch-up vaccination provided in physicians’ offices, public health 

clinics, and other appropriate settings. In the United States, vaccination is considered 

primarily the responsibility of individual health care providers and health care systems 

serving patients.

Certain programs and other efforts attempt to ensure all patients receive the full schedule 

of appropriate vaccinations by removing barriers posed by access to immunizations, cost, 

or other factors. Such efforts may include school-located clinics, school-based health 

centers, back-to-school immunization clinics, public health clinics for schoolchildren, 

periodic influenza vaccination clinics, public health nurse tracking of childhood 

immunizations, and government-sponsored financing of vaccines through the Vaccines for 

Children and Section 317 program (www.cdc.gov/vaccines/hcp/admin/vfc.html).

In the United States, vaccination programs have eliminated many vaccine-preventable 

diseases and markedly reduced the incidence of others (2). Because infants and young 

children were the principal recipients of most vaccines developed during the twentieth 

century (e.g., poliovirus vaccine), many persons in the United States might believe that 

vaccinations are solely for the young; however, vaccinations are recommended for persons 

of all ages (3,4). Improved vaccination coverage can result in additional reductions in the 

incidence of vaccine-preventable diseases that affect persons throughout the life span, and 

decrease associated morbidity and mortality.
General Best Practice Guidelines for Immunization: Vaccination Programs 178

Vaccination of Children and Adolescents

Physicians and other pediatric vaccination providers should adhere to the standards for 

child and adolescent vaccination practices (5). These standards are published by the 

National Vaccine Advisory Committee and define appropriate vaccination practices for 

both public and private sectors. The standards provide guidance on practices that 

eliminate barriers to vaccination, including eliminating unnecessary prerequisites for 

receiving vaccinations, eliminating missed opportunities to vaccinate, improving 

procedures to assess vaccination needs, enhancing knowledge about vaccinations among 

parents and providers, and improving management and reporting of adverse events. In 

addition, the standards address the importance of recall and reminder systems and using 

assessments to monitor clinic or office vaccination coverage levels. Health-care providers 

should simultaneously administer as many vaccine doses as possible as indicated on 

the Recommended Immunization Schedules for Persons Aged 0 Through 18 Years (3).

While rates of childhood vaccination are generally higher than rates of adult vaccination, 

for some doses coverage rates are still low, like the birth dose of hepatitis B vaccine. 

Community health-care providers, as well as state and local public health vaccination 

programs, should coordinate with partners to identify and maximize outreach to 

populations at risk for undervaccination and vaccine-preventable diseases. For example, 

the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is a 

categorical federal grant program administered by the U.S. Department of Agriculture 

through state health departments. The program provides supplemental foods, health-care 

referrals, and nutrition education to low-income pregnant, breastfeeding, or postpartum 

women, as well as to infants and children aged

<5 years. Between 8.5 and 8.9 million people participated in this program in 2013 

(www.fns.usda.gov/pd/wic-program). In collaboration, WIC and state vaccination 

programs assess regularly the vaccination coverage levels of WIC participants and develop 

new strategies and aggressive outreach procedures in sites with coverage levels

<90%. 
General Best Practice Guidelines for Immunization: Vaccination Programs 179

Vaccination programs and private providers are encouraged to refer eligible

children to obtain WIC nutritional services, at www.fns.usda.gov/wic/immunizationscreening-and-referral-wic (6).

Adolescent-Specific Issues

Vaccinations are recommended throughout life, including during adolescence. The age 

range for adolescence is defined as 11-21 years by many professional associations, 

including the American Academy of Pediatrics and the American Medical Association 

(7,8). Definitions of these age cutoffs differ depending on the source of the definition and 

the source’s purpose for creating a definition. Vaccination of adolescents is critical for 

preventing diseases for which adolescents are at particularly high or increasing risk, such 

as meningococcal disease and human papillomavirus infection. Three vaccines 

recommended for adolescents have been licensed since 2005: MenACWY and Tdap were

licensed in 2005, and HPV was licensed in 2006. A second dose of varicella vaccine is 

recommended for persons who received 1 dose of varicella vaccine after age 12 months. In 

addition, annual seasonal influenza vaccination is recommended for persons aged >6 

months who have no contraindications. To ensure vaccine coverage, clinicians and other 

health-care providers who treat adolescents must review vaccination history on every 

occasion that an adolescent has an office visit.

National goals for vaccination coverage for adolescents aged 13-15 years were included in 

Healthy People 2020, at www.healthypeople.gov/2020/topicsobjectives/topic/immunization-and-infectious-diseases. Targets of 80% coverage were 

specified for one dose of Tdap, one dose of meningococcal conjugate vaccine, and 3 doses 

of HPV vaccine. Results of the published 2014 National Immunization Survey—Teen 

indicate that coverage rates for 13-17 years olds is 87.6% for one dose of Tdap and 79.3% 

for one dose of meningococcal vaccine. Coverage rates for 13-17 years olds for HPV vaccine 

are considerably lower—39.7% for females and 21.6% for males (9,10).

Ensuring adolescents receive routine and catch-up vaccination and achieving high levels 

of vaccination coverage present challenges. In general, adolescents do not visit health care 

providers frequently. Health care providers should promote annual preventive visits (11), 

including one specifically for adolescents aged 11 and 12 years. 
General Best Practice Guidelines for Immunization: Vaccination Programs 180

The annual visits should be used as opportunities to provide routinely recommended 

vaccine doses, additional catch-up doses needed for lapsed vaccine series, vaccines 

recommended for high-risk groups, additional doses that might have been recently 

recommended, and other recommended health-care services. Additional strategies include 

adolescent immunizations at community-based venues such as pharmacies and schools.

All vaccine doses should be administered according to ACIP vaccine-specific statements 

and with the most recent schedules for both routine and catch-up vaccination. Before 

leaving any visit for medical care, adolescents should be encouraged to schedule return 

visits for any additional vaccine doses needed. During visits that occur outside of influenza 

season, providers should discuss and recommend seasonal influenza vaccination and 

make explicit plans for vaccination, including timing and anticipated setting (e.g., health 

care provider’s office, school, or pharmacy). Catch-up vaccination with multidose 

adolescent vaccines generally can occur according to the routine dosing schedule for these 

vaccines, although in some circumstances the clinician or health care provider might use 

minimum intervals for vaccine doses. These circumstances include an outbreak that 

increases risk for disease or the likelihood that doses will be missed in the future (e.g., 

because of transportation challenges). Because of lack of efficacy data for HPV vaccine 

administration using minimum intervals, providers are encouraged, when possible, to use 

routine dosing intervals for females aged 11-26 years and males aged 11-21 years who have 

not yet received 3 HPV vaccine doses as recommended (3,4).

One of the challenges of adolescent vaccination is ensuring that current, complete 

vaccination histories are available. Insurers, covered services, or reimbursement levels can 

change, and these changes might affect reimbursement for vaccine doses and vaccination 

services directly while also causing disruptions in an adolescent’s access to vaccination 

providers or venues. In circumstances in which a vaccination record is unavailable, 

vaccination providers should attempt to obtain this information from various sources 

(e.g., parent, previous providers, or school records). More detail about how to obtain these 

records is available from CDC at www.cdc.gov/vaccines/hcp/admin/immunizrecords.html. With the exception of influenza and pneumococcal polysaccharide vaccines, 

if documentation of a vaccine dose is not available, the adolescent should be considered 

unvaccinated for that dose. 
General Best Practice Guidelines for Immunization: Vaccination Programs 181

Regardless of the venue in which an adolescent receives a dose of vaccine, that vaccine 

dose should be documented in the patient’s chart or in an office log, and the information 

should be entered into an IIS. The adolescent also should be provided with a record that 

documents the vaccination history.

Adult Vaccination

In 2013, the National Vaccine Advisory Committee published updated standards for adult 

vaccination (12). These standards are targeted to distinct groups involved in adult 

vaccination, including immunizing providers, non-immunizing providers, professional 

health-care organizations, and public health departments. All health-care providers, 

whether they provide immunizations or not, should incorporate immunization needs 

assessment into every clinical encounter, strongly recommend needed vaccine(s) and 

either administer vaccine(s) or refer patients to a provider who can immunize, stay up-todate on, and educate patients about vaccine recommendations, implement systems to 

incorporate vaccine assessment into routine clinical care, and understand how to access 

immunization information systems (i.e., immunization registries) (12).

Vaccination rates in adults are considered suboptimal (13,14). New Healthy People 

2020 goals include specific subsets of adults, including institutionalized adults aged ≥18 

years (for pneumococcal vaccines) and noninstitutionalized adults at high risk aged >18 

years (for pneumococcal vaccines) (9).

The most substantial barrier to vaccination coverage is lack of knowledge about these 

vaccines among adult patients and adult providers. Other barriers are cost (incomplete 

Medicare coverage for recommended vaccines) (15) and the lack of financing mechanisms 

for newly licensed and recommended vaccines. Effective for private health insurance plans 

drafted or updated after September 2010, coverage for all immunizations that are included 

on the immunization schedule(s) must be covered without deductibles or co-pays, when 

delivered by an in-network provider. For this reason, cost may present less of a barrier to 

adult vaccination as time passes.
General Best Practice Guidelines for Immunization: Vaccination Programs 182

A common challenge for health-care providers is vaccinating adults with unknown 

vaccination records. In general (except for influenza and pneumococcal polysaccharide 

vaccines), adults should receive a vaccine dose if the dose is recommended and no record 

of previous administration exists. If an adult has a record of military service and does not 

have records available, providers can assume that the person has received all vaccines 

recommended by the military at the time of service entry. Serologic testing might be 

helpful in clarifying immune status if questions remain, because at different times and 

depending on military assignments, there might be inter-service and individual 

differences.

Evidence-based Interventions to Increase Vaccination 

Coverage

The independent, nonfederal Task Force on Community Preventive Services, whose 

membership is appointed by CDC, provides public health decision-makers with 

recommendations on population-based interventions to promote health and prevent 

disease, injury, disability, and premature death. The recommendations are based on 

systematic reviews of the scientific literature about effectiveness and cost-effectiveness of 

these interventions. In addition, the task force identifies critical information about the 

other effects of these interventions, the applicability to specific populations and settings, 

and the potential barriers to implementation. Additional information, including updates 

of published reviews, is available from The Community Guide at 

http://www.thecommunityguide.org. 

Beginning in 1996, the task force systematically reviewed published evidence on the 

effectiveness and cost-effectiveness of population-based interventions to increase coverage 

of vaccines recommended for routine use among children, adolescents, and adults. A total 

of 197 articles were identified that evaluated a relevant intervention, met inclusion 

criteria, and were published during 1980-1997. Reviews of 17 specific interventions were 

published in 1999 (13,14,16,17). Using the results of their review, the task force made 

recommendations about the use of these interventions (15). Several interventions were 

identified and recommended on the basis of published evidence. Follow-up reviews were 

published in 2000, and a review of interventions to improve the coverage of adults at high 

risk was conducted in 2005 (15,17). 
General Best Practice Guidelines for Immunization: Vaccination Programs 183

The interventions and the recommendations are summarized in this section of this report 

(Table 11-1). Interventions designated for adults younger than 65 years at high risk for 

influenza, invasive pneumococcal disease, and hepatitis B, include provider reminder 

systems or a menu of items (combinations of strategies ) (Table 11-2). In 1997, the task 

force categorized vaccination requirements for child care, school, and college as a 

recommended strategy (14).

A 2008 update of the original task force systematic review of the evidence on the 

effectiveness of provider assessment and feedback for increasing coverage rates found that 

this strategy remains an effective intervention (18). This later update reviewed 19 new 

studies published during 1997-2007. The updated review supports the original task force 

recommendation for use of assessment and feedback based on strong evidence of 

effectiveness. The task force reviewed studies of assessment and feedback as a strategy 

that were conducted in a range of settings, including private practice, managed care, 

public health, community health settings, and academic centers. Studies have assessed the 

effectiveness of this intervention to improve coverage with MMR, DTP, DTaP, Hib, 

influenza, pneumococcal, and Td vaccines (16). The most updated information on this 

review is available at www.thecommunityguide.org/findings/vaccination-programsprovider-assessment-and-feedback. As recognized by the task force, routine assessment 

and feedback of vaccination rates obtained at the provider site is one of the most effective 

strategies for achieving high, sustainable vaccine coverage. Since 1995, all states receiving 

federal funds for vaccination programs have been required to conduct annual assessments 

of vaccination rates both in public health clinics and in private provider offices. Primarily 

to aid local and state health departments in their efforts to conduct assessments and assist 

providers, CDC has developed numerous software applications to measure vaccination 

rates in provider practices.

Other General Programmatic Issues

Programmatic challenges, evolving issues, and effective interventions related to adult and 

adolescent vaccination programs have been described by other advisory groups and expert 

groups. Additional evidence-based approaches are being developed for certain issues (e.g., 

settings for adolescent vaccination delivery) through ongoing research and evaluation. 
General Best Practice Guidelines for Immunization: Vaccination Programs 184

Among current programmatic challenges, vaccine financing is especially difficult because 

certain problems and solutions differ markedly from one state to another. Practitioners 

interested in beginning or continuing to provide vaccinations to patients are encouraged 

to consult with local and state public health vaccination programs to learn about publicly 

funded programs that might be available in their areas for patients who need vaccination 

but have insufficient health insurance coverage and no financial resources. If not already 

participating, providers who care for adolescents and children aged <19 years should 

enroll in the Vaccines for Children Program 

(www.cdc.gov/vaccines/hcp/admin/vfc.html). Through this program’s provision of ACIPrecommended, federally purchased vaccines, participating providers are able to fully 

vaccinate eligible children whose parents might not otherwise be able to afford the 

vaccinations. Interested providers are encouraged to work with insurers, state and 

specialty-specific medical organizations, vaccine manufacturers, and other stakeholders to 

address financial barriers to achieving high vaccination coverage. With availability of safe 

and effective vaccines for 18 vaccine-preventable diseases, the capacity for realizing the 

potential benefits of these products in the United States depends on reaching children, 

adolescents, and adults through dedicated, knowledgeable vaccination providers and 

efficient, strong vaccination programs at local, state, and federal levels.
General Best Practice Guidelines for Immunization: Vaccination Programs 185

TABLE 11-1. Recommendations regarding interventions to improve 

coverage of vaccines recommended for routine use among children, 

adolescents, and adults

Intervention Recommendation

Increase community demand for vaccination

Client reminder or recall systems Recommended

Requirements for entry to schools, child- care 

facilities, and colleges

Recommended

Community education alone Insufficient evidence

Community-based interventions implemented in 

combination

Recommended

Clinic-based education Insufficient evidence

Patient or family incentives Recommended

Patient or family monetary sanctions Insufficient evidence

Client-held medical records Insufficient evidence

Enhance access to vaccination services

Reducing out-of-pocket costs Recommended

Enhancing access through the U.S. Department of 

Agriculture’s Women, Infants, and Children (WIC) 

program

Recommended

Home visits, outreach, and case management 

targeted to particularly hard-to-reach populations 

to increase vaccination rates

Recommended

Enhancing access at schools Recommended

Expanding access in health-care settings Recommended as part of 

multicomponent interventions 

only

Enhancing access at organized child care centers Recommended

Focus on providers

Provider reminder or recall systems Recommended
General Best Practice Guidelines for Immunization: Vaccination Programs 186

Provider assessment and feedback Recommended

Standing orders Recommended

Provider education alone Insufficient evidence

Health-care systems-based interventions 

integrated in combination

Recommended

Immunization information systems Recommended

Source: www.thecommunityguide.org/topic/vaccination.
General Best Practice Guidelines for Immunization: Vaccination Programs 187

TABLE 11-2. Strategies to improve influenza, pneumococcal 

polysaccharide, and hepatitis B vaccine coverage among high-risk adults 

younger than 65 years

One or both of these interventions to 

improve access to vaccination services

1. Expanded access in health-care settings

2. Reducing client out-of-pocket costs

PLUS:

One or more of these provider or system 

based interventions

1. Standing orders

2. Provider reminder systems

3. Provider assessment or feedback

AND/OR:

One or both of these interventions to 

increase client demand for vaccination 

services

1. Client reminder systems

2. Client education

Source (15)
General Best Practice Guidelines for Immunization: Vaccination Programs 188

REFERENCES

1. The Patient Protection and Affordable Care Act, Pub. L. No. 111-148 (2010).

2. Roush SW, Murphy TV. Historical comparisons of morbidity and mortality for 

vaccine-preventable diseases in the United States. JAMA. 2007;298(18):2155-

2163. DOI: 10.1001/jama.298.18.2155

3. Strikas RA. Advisory committee on immunization practices recommended 

immunization schedules for persons aged 0 through 18 years—UnitedStates, 

2015. MMWR Morb Mortal Wkly Rep. 2015;64(4):93-94.

4. Kim DK, Bridges CB, Harriman KH. Advisory committee on immunization 

practices recommended immunization schedule for adults aged 19 years or 

older—United States, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(4):91-

92.

5. National Vaccine Advisory Committee. Standards for child andadolescent 

immunization practices. Pediatrics. 2003;112(4):958-963.

6. CDC. Recommendations of the Advisory Committee on Immunization 

Practices: programmatic strategies to increase vaccination coverage by age 2 

years—linkage of vaccination and WIC services. MMWR Morb Mortal Wkly 

Rep. 1996;45(10):217-218.

7. Hagan J, Shaw J, Duncan P, eds. Bright futures: guidelines for health 

supervision on infants, children and adolescents. 3rd ed. Elk Grove Village, 

IL: American Academy of Pediatrics; 2008.

8. CDC. Immunization of adolescents. Recommendations of the Advisory 

Committee on Immunization Practices, the American Academy of Pediatrics, 

the American Academy of Family Physicians, and the American Medical 

Association. MMWR Recomm Rep. 1996;45(RR-13):1-16.

9. US Department of Health and Human Services. Immunization and infectious 

diseases. Healthy People 2020 website. 

https://www.healthypeople.gov/2020/topics-objectives/topic/immunizationand-infectious-diseases. Accessed 09 March, 2017.
General Best Practice Guidelines for Immunization: Vaccination Programs 189

10. CDC. U.S. vaccination coverage reported via NIS-Teen. 2016; https:// 

www.cdc.gov/vaccines/imz-managers/coverage/teenvaxview/index.html.

Accessed 09 March 2017.

11. Mangione-Smith R, DeCristofaro AH, Setodji CM, et al. The quality of 

ambulatory care delivered to children in the United States. N Engl J Med. 

2007;357(15):1515-1523. DOI: 10.1056/NEJMsa064637

12. National Vaccine Advisory Committee. Recommendations from theNational 

Vaccine Advisory committee: standards for adult immunization practice. 

Public Health Rep. 2014;129(2):115-123.

13. Shefer A, Briss P, Rodewald L, et al. Improving immunization coverage rates: 

an evidence-based review of the literature. Epidemiol Rev. 1999;21(1):96-142.

14. CDC. Vaccine-preventable diseases: improving vaccination coverage in 

children, adolescents, and adults. A report on recommendations from the 

Task Force on Community Preventive Services. MMWR Recomm Rep. 

1999;48(RR-8):1-15.

15. Ndiaye SM, Hopkins DP, Shefer AM, et al. Interventions to improve influenza, 

pneumococcal polysaccharide, and hepatitis B vaccination coverage among 

high-risk adults: a systematic review. Am J Prev Med. 2005;28(5 Suppl):248-

279. DOI: 10.1016/j.amepre.2005.02.016

16. Briss PA, Rodewald LE, Hinman AR, et al. Reviews of evidence regarding 

interventions to improve vaccination coverage in children, adolescents, and 

adults. The Task Force on Community Preventive Services. Am J Prev Med. 

2000;18(1 Suppl):97-140. DOI: 10.1016/S0749-3797(99)00118-X

17. Task Force on Community Preventive S. Recommendations regarding 

interventions to improve vaccination coverage in children, adolescents, and 

adults12. Am J Prev Med. 2000;18(1, Supplement 1):92-96. DOI: 

10.1016/S0749-3797(99)00121-X

18. CDC. Vaccination programs: provider assessment and feedback. The 

Community Guide website. 2015; 

https://www.thecommunityguide.org/findings/vaccination-programsprovider-assessment-and-feedback. Accessed 09 March 2017.
General Best Practice Guidelines for Immunization: Vaccination Programs 190

12. Vaccine Information Sources

In addition to these general recommendations, the following sources contain specific and 

updated vaccine information.

• CDC-INFO Contact Center

The CDC-INFO contact center is supported by CDC and provides public healthrelated information, including vaccination information, for health-care providers 

and the public, 24 hours a day, 7 days a week. To contact CDC-INFO online at any 

time, visit https://wwwn.cdc.gov/dcs/ContactUs/Form. To contact CDC-INFO by 

telephone, call between 8 am to 8 pm Eastern Time Monday through Friday at 

[English and Spanish]: 800-232-4636; telephone [TTY]: 800-232-6348. 

• CDC’s National Center for Immunization and Respiratory Diseases

CDC’s National Center for Immunization and Respiratory Diseases website 

provides direct access to ACIP’s best practices for vaccination guidance, vaccination 

schedules, automated child schedulers, an adult immunization scheduler, vaccine 

safety information, publications, provider education and training, and links to other 

vaccination-related websites (www.cdc.gov/vaccines/hcp/admin/immunizrecords.html). 

• Morbidity and Mortality Weekly Report (MMWR)

Some ACIP guidance regarding vaccine use, statements of vaccine policy as they are 

developed, and reports of specific disease activity are published by CDC in the 

MMWR series and can be found at www.cdc.gov/vaccines/hcp/aciprecs/index.html. Electronic subscriptions are free 

(www.cdc.gov/mmwr/index.html). Subscriptions to print versions also are 

available from the Superintendent of Documents, U.S. Government Printing Office, 

Washington, D.C. 20402-9235 (telephone: 202-512-1800). 

• American Academy of Family Physicians (AAFP)

Information from the professional organization of family physicians is available at 

www.aafp.org/home.html.
General Best Practice Guidelines for Immunization: Vaccination Programs 191

• American Academy of Pediatrics (AAP)

Every 3 years, AAP issues the Red Book: Report of the Committee on Infectious 

Diseases, which contains a composite summary of AAP and ACIP recommendations 

concerning infectious diseases and vaccinations for infants, children, and 

adolescents (telephone: 888-227-1770; website: www.aap.org/enus/Pages/Default.aspx).

• American College of Physicians (ACP)

Produced by faculty of ACP’s Quality Improvement Programs and members of the 

ACP Adult Immunization Advisory Board, the ACP Guide to Adult Immunization 

helps internists develop systematic processes for incorporating immunization in 

their day-to- day practice (see https://www.acponline.org/).

• American Congress of Obstetricians and Gynecologists (ACOG)

The American Congress of Obstetricians and Gynecologists (ACOG), formerly the 

American College of Obstetricians and Gynecologists, is a professional association 

of physicians specializing in obstetrics and gynecology in the United States. 

Information about ACOG can be found at https://www.acog.org/. 

• American Pharmacists Association (APhA)

Founded in 1852, APhA is the largest association of pharmacists in the United 

States, with more than 62,000 practicing pharmacists, pharmaceutical scientists, 

student pharmacists, pharmacy technicians as members. Information about APhA 

educational activities can be found at www.pharmacist.com/immunization-center. 

• Group on Immunization Education of the Society of Teachers of Family 

Medicine

The Group on Immunization Education of the Society of Teachers of Family 

Medicine provides information for clinicians, including the free program Shots. 

Shots includes the childhood, adolescent, and adult schedules for iPhone, Palm, and 

Windows devices, as well as online versions (http://www.immunizationed.org/).
General Best Practice Guidelines for Immunization: Vaccination Programs 192

• Immunization Action Coalition (IAC)

IAC provides child, teen, and adult immunization information for health care 

professionals and their patients at http://www.immunize.org. Free materials 

include CDC-reviewed technical pieces, patient handouts, VISs in multiple 

languages, and the weekly immunization news and information service “IAC 

Express,” available at http://www.immunize.org/express. Information for the 

general public about vaccines and vaccine-preventable diseases is available at 

http://www.vaccineinformation.org. 

• Institute for Vaccine Safety

Located at the Johns Hopkins University School of Public Health, the Institute for 

Vaccine Safety provides information about vaccine safety concerns and objective 

and timely information to physicians and health-care providers and parents. The 

Institute for Vaccine Safety also includes links to tables that include all vaccine 

components (http://www.vaccinesafety.edu).

• State and Local Health Departments

State and local health departments provide technical advice through hotlines, email, and websites, including printed information regarding vaccines and 

immunization schedules, posters, and other educational materials (see 

www.cdc.gov/vaccines/imz- managers/awardee-imz-websites.html and 

www.cdc.gov/mmwr/international/relres.html).

• Vaccine Education Center

Located at the Children’s Hospital of Philadelphia, the Vaccine Education Center 

provides patient and provider vaccine information (www.chop.edu/centersprograms/vaccine-education-center).
General Best Practice Guidelines for Immunization: Appendix 1: Glossary 193

Appendix 1: Glossary

Adverse event. An undesirable medical condition that occurs following vaccination 

which might be truly caused by a vaccine, or it might be pure coincidence. 

Adverse reaction. An undesirable medical condition that has been demonstrated to 

be caused by a vaccine. Evidence for the causal relation is usually obtained through 

randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine 

strain from the pathogenic site, or recurrence of the condition with repeated 

vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

Adjuvant. A vaccine component distinct from the antigen that enhances the immune 

response to the antigen.

Antitoxin. A solution of antibodies against a toxin. Antitoxin can be derived from 

either human (e.g., tetanus immune globulin) or animal (usually equine) sources (e.g.,

diphtheria and botulism antitoxin). Antitoxins are used to confer passive immunity 

and for treatment.

Hyperimmune globulin (specific). Special preparations obtained from blood 

plasma from donor pools preselected for a high antibody content against a specific 

antigen (e.g., hepatitis B immune globulin, varicella-zoster immune globulin, rabies 

immune globulin, tetanus immune globulin, vaccinia immune globulin, 

cytomegalovirus immune globulin, botulism immune globulin).

Immune globulin. A sterile solution containing antibodies, which are usually 

obtained from human blood. It is obtained by cold ethanol fractionation of large pools 

of blood plasma and contains 15%-18% protein. Intended for intramuscular 

administration, immune globulin is primarily indicated for routine maintenance of 

immunity among certain immunodeficient persons and for passive protection against 

measles and hepatitis A.
General Best Practice Guidelines for Immunization: Appendix 1: Glossary 194

Immunization. The process of inducing or providing immunity by administering an 

immunobiologic. Immunization can be active or passive. Active immunization is the 

production of antibody or other immune responses through administration of a 

vaccine or toxoid. Passive immunization means the provision of temporary immunity 

by the administration of preformed antibodies. 

Immunobiologic. Antigenic substances (e.g., vaccines and toxoids) or antibodycontaining preparations (e.g., globulins and antitoxins) from human or animal donors. 

These products are used for active or passive immunization or therapy. Examples of 

immunobiologics include antitoxin, immune globulin and hyperimmune globulin, 

monoclonal antibodies, toxoids, and vaccines.

Intravenous immune globulin. A product derived from blood plasma from a donor 

pool similar to the immune globulin pool, but prepared so that it is suitable for 

intravenous use. Intravenous immune globulin is used primarily for replacement 

therapy in primary antibody-deficiency disorders, for treatment of Kawasaki disease, 

immune thrombocytopenic purpura, hypogammaglobulinemia in chronic lymphocytic 

leukemia, and certain cases of human immunodeficiency virus infection (Table 3-6).

Monoclonal antibody. An antibody product prepared from a single 

lymphocyte clone, which contains only antibody against a single antigen.

Simultaneous. In the context of vaccine timing and spacing, occurring on the 

same clinic day, at different anatomic sites, and not combined in the same syringe.

Toxoid. A modified bacterial toxin that has been made nontoxic, but retains the ability 

to stimulate the formation of antibodies to the toxin.

Vaccination. The physical act of administering any vaccine or toxoid. 

Vaccine. A suspension of live (usually attenuated) or inactivated microorganisms (e.g., 

bacteria or viruses) or fractions thereof administered to induce immunity and prevent 

infectious disease or its sequelae. Some vaccines contain highly defined antigens (e.g., 

the polysaccharide of Haemophilus influenzae type b or the surface antigen of hepatitis 

B); others have antigens that are complex or incompletely defined (e.g., Bordetella 

pertussis antigens or live, attenuated viruses).
General Best Practice Guidelines for Immunization: Appendix 2: Membership 195

Appendix 2: Membership

Advisory Committee on Immunization Practices

Membership List, October 2018

Chair: ROMERO, José R., MD, FAAP, University of Arkansas for Medical Sciences and 

Arkansas Children’s Hospital Little Rock, AR

Executive Secretary: Amanda Cohn, MD, National Center for Immunization 

and Respiratory Diseases, CDC, Atlanta, Georgia.

Members: ATMAR, Robert L., MD, Baylor College of Medicine, Houston, TX

BERNSTEIN, Henry, DO, MHCM, FAAP, Zucker School of Medicine at 

Hofstra/Northwell Cohen Children’s Medical Center, New Hyde Park, NY

EZEANOLUE, Echezona, MD, MPH, University of Nevada, Las Vegas, NV 

FREY, Sharon E., MD, Saint Louis University Medical School, Saint Louis, MO 

HUNTER, Paul, MD, City of Milwaukee Health Department Milwaukee, WI

LEE, Grace M., MD, MPH, Lucile Packard Children’s Hospital, Stanford 

University School of Medicine, Stanford, CA

MOORE, Kelly, MD, MPH, Vanderbilt University School of Medicine, Nashville, 

TN STEPHENS, David, MD, Emory University, Atlanta, GA

SZILAGYI, Peter, MD, MPH, University of California, Los Angeles (UCLA), Los Angeles, 

CA

WALTER, Emmanuel (Chip), Jr., MD, MPH, Duke University School of 

Medicine, Durham, NC
General Best Practice Guidelines for Immunization: Appendix 2: Membership 196

Ex Officio Members: Eric Deussing, MD, MPH, Department of Defense, DoD; Lori 

Hoffman-Hogg, Department of Veterans Affairs, Durham, North Carolina; Doran 

Fink, MD, PhD, Food and Drug Administration, Bethesda, Maryland; Narayan Nair, 

MD, Health Resources and Services Administration, Rockville, Maryland; Thomas 

Weiser, MD, MPH, Indian Health Service, Albuquerque, New Mexico; Tammy 

Beckham, National Vaccine Program Office, Washington, District of Columbia; John 

Beigel, MD, National Institutes of Health, Bethesda, Maryland.

Liaison Representatives: American Academy of Family Physicians, Pamela G. 

Rockwell, DO, Ann Arbor, Michigan; American Academy of Pediatrics, Yvonne 

Maldonado, MD, Stanford, California; David Kimberlin, MD, Birmingham, Alabama; 

American Academy of Physician Assistants, Marie-Michèle Léger MPH, PA-C, 

Alexandria, Virginia; American College Health Association, Susan Even, MD, Columbia, 

Missouri; American College of Nurse Midwives, Carol E. Hayes, CNM, MN, MPH, 

Atlanta, Georgia; American College of Physicians, Jason M. Goldman, MD, FACP, Boca 

Raton, FL; American Geriatrics Society, Kenneth Schmader, MD, Durham, North 

Carolina; American Medical Association, Sandra Adamson Fryhofer, MD, Atlanta, 

Georgia; American Nurses Association, Chad Rittle, DNP, Pittsburgh, Pennsylvania; 

American Osteopathic Association, Stanley Grogg, DO, Tulsa, Oklahoma; American 

Pharmacists Association, Stephan L. Foster, PharmD, Memphis, Tennessee; American 

Immunization Registry Association, Rebecca Coyle, MSEd, Washington D.C.; America’s 

Health Insurance Plans, Mark Netoskie, MD, MBA, Houston, Texas; Association of 

Immunization Managers, Chris Finley, RN, MPH, Burlington, VT; Council of State and 

Territorial Epidemiologists, Christine Hahn, MD, Boise, ID; Infectious Diseases Society 

of America, Kathleen Neuzil, MD, Seattle, Washington; National Association of City and 

County Health Officials, Jeff Duchin, MD, Seattle, WA; National Association of Pediatric 

Nurse Practitioners, Patricia Stinchfield, MPH, St Paul, Minnesota; National Foundation 

for Infectious Diseases, William Schaffner, MD, Nashville, Tennessee; National Medical 

Association, Patricia Whitley-Williams, MD, New Brunswick, New Jersey; Pediatric 

Infectious Diseases Society, Sean O’Leary, MD, MPH, Colorado; Pharmaceutical 

Research and Manufacturers of America, Cory Robertson; 
General Best Practice Guidelines for Immunization: Appendix 2: Membership 197

Society for Adolescent Medicine, Amy Middleman, MD, Oklahoma City, OK; Society for 

Healthcare Epidemiology of America, David Weber, MD, Chapel Hill, North Carolina 

Houston, Texas.

Members of the General Best Practices Work Group, January, 2023

Advisory Committee on Immunization Practices (ACIP), Lynn Bahta, RN; Sarah Long, 

MD; Pablo Sanchez, MD; ACIP Liaison and Ex-Officio Members, Marcie Drees, MD, 

Society for Health Care Epidemiology of America; Susan Farrall, Office of Infectious 

Disease and HIV/AIDS Policy; Mary-Margaret Fill, MD, Council of State and Territorial 

Epidemiologists; Michelle Fiscus, MD, Association of Immunization Managers; David 

Kim, MD, Office of Infectious Disease and HIV/AIDS Policy; Marie-Michele Leger, MPH, 

American Academy of Physician Associates; Anuja Rastogi, Food and Drug 

Administration; Charles (Chad) Rittle, American Nurses Association; Pam Rockwell, 

DO, American Academy of Family Physicians; Mark Sawyer, MD, American Academy of 

Pediatrics; CDC Staff Members, Andrew Kroger, MD, Cynthia Jorgensen, Alison Lale, 

MD, Eloisa Llata, MD, Elaine Miller, Sarah Morales, Sarah Schillie, MD, Akpobome 

Wodi, MD, Joellen Wolicki, RN; other members and consultants, Kenneth Bromberg, 

MD, SUNY Downstate Medical School, Paul Hunter, MD, University of Wisconsin, 

Susan Lett, MD, Kelly Moore, MD, Immunize.org, Walter Orenstein, MD, Emory 

University School of Medicine, Lynn Trefren, Skip Wolfe.