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This chapter discusses best practices related to vaccine timing 

and spacing, dosing, adverse reactions, and contraindications 

and precautions for routinely recommended vaccines in the 

United States. A more thorough discussion of issues common to 

the use of multiple vaccines and non-routinely recommended 

vaccines (e.g., rabies, smallpox) can be found in the General Best 

Practice Guidelines for Immunization: Best Practices Guidance of 

the Advisory Committee on Immunization Practices. Information 

about recommended travel vaccines (e.g., yellow fever, typhoid) 

can be found in CDC’s Yellow Book.

Timing and Spacing of Vaccines

Timing and spacing of vaccine doses are two of the most 

important considerations for the appropriate use of vaccines. 

Specific circumstances commonly encountered in immunization 

practice are the intervals between doses of the same vaccine, 

simultaneous and nonsimultaneous administration of different 

vaccines, and the intervals between antibody-containing blood 

products and live attenuated vaccines (particularly measles- and 

varicella-containing vaccines). 

Interval Between Doses of the Same Vaccine

Most vaccines in the immunization schedule require two or 

more doses for development of an adequate and persistent 

antibody response. Vaccinations are recommended beginning 

with the youngest age group at risk for a disease for whom 

vaccine efficacy and safety have been demonstrated. Studies 

have demonstrated that following the recommended ages 

and intervals between doses of the same antigen(s) provides 

optimal protection. As a general rule, decreasing the interval 

between doses in a multiple-dose vaccine series may interfere 

with antibody response and protection. 

For routine vaccination, vaccine doses should not be 

administered earlier than the minimum ages or at less than 

the minimum intervals. However, exceptions may occasionally 

be necessary. One exception involves administering a dose 

up to 4 days before the minimum age or interval to avoid 

missing an opportunity to vaccinate. The patient may have 

come to the office early or for an appointment not specifically 

for vaccination. In these situations, the provider can consider 

administering the vaccine earlier than the minimum age or 

interval. However, if the provider has confidence that the 

patient will return for a later visit, it is preferable to reschedule 

vaccination on or after the recommended minimum age or 

interval. If the patient is new to the provider or habitually 

misses appointments, it may be preferable to administer the 

vaccine early. These early doses administered within 4 days of 

NOTES

Elaine Miller, RN, BSN, MPH and A. Patricia Wodi, MD

https://www.cdc.gov/vaccines/pubs/pinkbook/genrec.html Aug 2021
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the minimum age or interval are considered valid. In certain 

situations, state or local requirements might mandate doses 

of selected vaccines be administered on or after specific ages, 

superseding this 4-day grace period. Doses administered 5 days 

or more before the minimum age or interval should not be 

counted as valid and should be repeated as age-appropriate. 

Other exceptions are administering doses in a vaccine series at 

shorter intervals than recommended when a person is behind 

schedule and needs to be brought up to date quickly or when 

international travel is pending. In these cases, an accelerated 

schedule using the minimum age or minimum interval 

criteria can be used. An example is an infant age 6 through 11 

months receiving 1 dose of MMR vaccine prior to international 

travel (not to be considered valid as part of the routinely 

recommended series) or administering the second dose of 

measles vaccine before age 4 years during a measles outbreak 

(considered valid as long as a minimum interval of at least 4 

weeks from the prior dose was heeded and the child was age 12 

months or older). 

In some cases, a scheduled dose of vaccine may be 

administered late. A late dose should be administered at the 

next visit. Available data indicate intervals between doses that 

are longer than those routinely recommended do not affect 

seroconversion rates or titers when the schedule is completed. 

Therefore, it is not necessary to restart a series or add doses of 

any vaccine because of an extended interval between doses. 

Simultaneous and Nonsimultaneous Vaccine 

Administration 

Simultaneous Administration of Different Vaccines

Simultaneous administration (i.e., administration of two or 

more vaccines on the same day) of all recommended vaccines is 

important because it increases the probability that an individual 

will be fully vaccinated at the appropriate age. It is also an 

important part of immunization practice when a health care 

provider is uncertain that a patient will return for additional 

doses of vaccine.

As a general rule, almost all vaccines can be administered at the 

same visit. Exceptions to this include: • PCV13 (Prevnar 13) vaccine and MenACWY-D (Menactra)

vaccine should not be administered simultaneously to

persons with functional or anatomic asplenia or HIV.

Menactra brand meningococcal conjugate vaccine is

thought to interfere with the antibody response to Prevnar

13. When both Prevnar 13 and Menactra are indicated,

Prevnar 13 should be administered first, followed by

Menactra at least 4 weeks later.

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• PCV13 (Prevnar 13) vaccine and PPSV23 (Pneumovax 23) 

vaccine should not be administered at the same visit; 

studies show a better immune response when Prevnar 

13 is administered before Pneumovax 23. When both 

Prevnar 13 and Pneumovax 23 are indicated, Prevnar 13 

should be administered first, and Pneumovax 23 should be 

administered either at least 8 weeks later or at least 1 year 

later, depending on the age and health conditions of the 

vaccine recipient. 

• Varicella (VAR [Varivax]) vaccine should not be administered 

simultaneously with smallpox vaccine. 

Combination vaccines are generally preferred over simultaneous 

administration of single-component vaccines. Combination 

vaccines contain components that can be divided into 

independently available routine vaccines and can reduce 

the number of injections needed. Considerations for using 

combination vaccines should include an assessment of the 

number of injections, availability of vaccine, likelihood of 

improved vaccination coverage, likelihood of patient return, and 

issues regarding storage and cost. Considerations should also 

include patient choice and the potential for adverse events. 

There is an increased risk of febrile seizures following the 

first dose of the combination measles, mumps, rubella, 

varicella (MMRV [ProQuad]) vaccine compared with separate 

administration of MMR vaccine (MMR-II) and VAR vaccine 

(Varivax). For the first dose, MMR and varicella vaccines should 

be administered separately for children age 12 through 47 

months unless the parent or caregiver expresses a preference 

for MMRV vaccine.

Nonsimultaneous Administration of Live Vaccines

If any combination of live, injected vaccines (MMR-II, ProQuad, 

Varivax) or live, attenuated influenza vaccine (LAIV [FluMist]) is 

not administered simultaneously, the vaccine doses should be 

separated by at least 4 weeks. This interval is intended to reduce 

or eliminate interference from the vaccine administered first 

with the vaccine administered later. If any two of these vaccines 

are administered at an interval of less than 4 weeks, then the 

vaccine administered second should be repeated in 4 weeks or 

serologic testing should be performed following MMR-II and 

ProQuad to confirm their effectiveness (serologic testing is not 

recommended following FluMist or Varivax vaccines). 

Live vaccines administered by the oral route (e.g., typhoid 

TY21a, [Vivotif], rotavirus, and adenovirus vaccines) are 

not believed to interfere with parenteral or intranasal live 

vaccines or with each other. Therefore, they may be adminis-

tered simultaneously with or at any time before or after other 

live vaccines.

NOTES
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Vaccines and Antibody-Containing Products

Antibody, in the form of immune globulin, might be 

administered simultaneously with or around the same time 

as certain vaccines; for example, as postexposure prophylaxis 

for certain diseases, such as hepatitis B, rabies, and tetanus. 

Immune response to some live attenuated vaccines can be 

affected by receipt of immune globulin, depending on the type 

of vaccine, amount of antibody, and timing of administration. 

Immune response to inactivated vaccines are generally not 

affected by antibody-containing products. Inactivated vaccines 

can be administered before, after, or at the same time as 

the antibody products. However, the presence of circulating 

antibody to a vaccine antigen might reduce or eliminate the 

immune response to that vaccine. The vaccine antigen should 

be administered at a site distant from where the immune 

globulin was injected.

Live, Attenuated Injectable Vaccines

Live, attenuated vaccines must replicate to produce an immune 

response. Antibody against injected live vaccine antigen may 

interfere with replication. If measles, mumps, and rubella (MMR 

[MMR-II]), varicella (VAR [Varivax]), or combination measles, 

mumps, rubella, and varicella (MMRV [ProQuad]) vaccines must 

be administered around the same time as antibody, the two 

must be separated by enough time to prevent the antibody 

from interfering with viral replication. If these live vaccines are 

administered first, it is necessary to wait at least 2 weeks before 

administering the antibody. If the interval between the vaccine 

and antibody is less than 2 weeks, the recipient should be 

tested for immunity or the vaccine dose should be repeated. If 

the antibody is administered first, it is necessary to wait until the 

antibody has waned before administering the vaccine. This will 

reduce the chance of interference by the antibody. 

An exception to the waiting period for antibody to wane 

before vaccination is the low dose of RhoGam or Rhophylac 

(anti-Rho(D) globulin) or any other blood product administered 

to women who do not have evidence of immunity to rubella or 

varicella during the last trimester of pregnancy or at delivery. 

Although passively acquired antibodies can interfere with 

the response to rubella vaccine, the low dose of anti-Rho(D) 

globulin has not been demonstrated to reduce the response 

to the rubella vaccine. These women should receive MMR-II, 

Varivax, or ProQuad as indicated immediately after delivery and, 

if possible, be tested 3 or more months later to ensure immunity 

to rubella and, if necessary, to measles. 

Some blood products contain negligible antibody or 

type-specific antibody which do not interfere with vaccine 

replication. These products can be administered at any time 

NOTES
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before or after administration of MMR or varicella-containing 

vaccines. Palivizumab (Synagis), used to prevent respiratory 

syncytial virus (RSV) infection in some infants and young 

children, contains antibody directed only at RSV. Washed red 

blood cells contain a negligible amount of antibody. 

Live, Attenuated Oral and Intranasal Vaccines

Rotavirus vaccines (RV1 [Rotarix] and RV5 [RotaTeq]) and LAIV 

(FluMist) are not known to be affected by the administration of 

immune globulin or blood products. They may be administered 

simultaneously with blood products or separated from them by 

any interval. 

Doses

Many factors influence the number of doses recommended in 

a vaccine series, including the type of vaccine, epidemiology of 

the disease, and host factors (e.g., age, presence of underlying 

diseases). For live, injected vaccines, the first dose administered 

at the recommended age usually provides protection. An 

additional dose is administered to provide another opportunity 

for vaccine response in the small proportion of recipients who 

do not respond to the first dose. For instance, approximately 

95% of recipients respond to a single dose of measles vaccine. 

The second dose is administered to ensure that nearly 100% of 

persons are immune. Immunity following live vaccines is longlasting, and booster doses are usually not necessary. 

For inactivated vaccines, the first dose administered at the 

recommended age usually does not provide protection 

(hepatitis A vaccine is an exception). A protective immune 

response may not develop until after dose 2 or 3. For inactivated 

vaccines, antibody titers may decrease below protective levels 

after a few years. This phenomenon is most notable with 

pertussis vaccine. Tetanus and diphtheria vaccine-induced 

immunity also wanes. For these vaccines, a booster dose is 

administered to raise antibody back to protective levels. 

Not all inactivated vaccines require boosting throughout 

the lifetime. For example, additional doses of Haemophilus 

influenzae type b vaccine are not required after completion of 

the infant primary series and booster dose because H. influenzae

type b disease is rare in persons older than age 5 years. Hepatitis 

B vaccine does not require boosting in immunocompetent 

persons because of immunologic memory of the vaccine 

and the long incubation period for hepatitis B. Immunologic 

memory produces an “autoboost,” which means exposure to the 

virus causes the established immune memory to respond faster 

than the virus can cause disease.

NOTES
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Adverse Reactions Following Vaccination

An adverse reaction or side effect is an untoward effect caused 

by a vaccine. An adverse reaction is different from a vaccine 

adverse event. Vaccine adverse event refers to any medical 

event that occurs following vaccination. An adverse event could 

be a true adverse reaction or a coincidental event, with further 

investigation needed to distinguish between them. Health care 

providers are required by law to report certain adverse events 

after vaccination. Details on reporting adverse events after 

vaccination can be found at https://vaers.hhs.gov/

Allergic reactions may be caused by the vaccine antigen itself 

or some other vaccine component, such as cell culture material 

or a stabilizer, preservative, or antibiotic used to inhibit bacterial 

growth. Severe allergic reactions (e.g., anaphylaxis) may be 

life-threatening but fortunately are rare. The risk of an allergic 

reaction can be decreased by effective screening prior to 

vaccination. All providers who administer vaccines must have an 

emergency protocol, supplies, and training to treat anaphylaxis. 

Local adverse reactions (e.g., pain, swelling, and redness at 

the injection site) are the most common adverse reactions 

following vaccination. They generally occur within a few 

hours of the injection and are usually mild and self-limited. 

Local reactions may occur with up to 80% of vaccine doses, 

depending on the type of vaccine. On rare occasions, local 

reactions may be severe. These reactions, referred to as Arthus 

reactions, are most frequently seen with diphtheria and 

tetanus toxoids. Arthus reactions are not allergic reactions. 

They are believed to be due to high titers of antibody, usually 

caused by too many doses of toxoid. 

Systemic adverse reactions (e.g., fever, myalgia, rash, headache) 

may occur following vaccination. Adverse reactions such 

as fever or rash following live, attenuated vaccines may be 

similar to a mild form of the natural disease, with symptoms 

produced from viral replication. Systemic adverse reactions 

are usually mild and occur 3 through 21 days after the vaccine 

was administered. Systemic adverse reactions from live 

attenuated vaccines are seen at longer intervals following 

vaccine administration because they are caused by replication 

of vaccine virus in the body, which occurs over several days. 

FluMist may cause upper respiratory symptoms rather than 

influenza-like symptoms since it replicates in the mucous 

membranes of the nose and throat and not in the lungs. 

Systemic adverse reactions were relatively frequent with 

diphtheria-tetanus-whole-cell-pertussis (DTP) vaccine, which 

contained a whole-cell pertussis component. Systemic adverse 

events are less common with acellular pertussis vaccine.

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Contraindications and Precautions 

to Vaccination

Contraindications and precautions to vaccination generally 

dictate circumstances when vaccines should not be 

administered. Some contraindications and precautions are 

temporary, and the vaccine can be administered later. 

Contraindications

A contraindication is a health condition in the recipient that 

increases the likelihood of a serious adverse reaction to a 

vaccine. For instance, administering MMR-II vaccine to a person 

with a true anaphylactic allergy to gelatin could cause serious 

illness or death in the recipient. In general, vaccines should not 

be administered when a contraindication is present. 

Medical conditions that are contraindications to 

vaccination include:

• A severe allergic reaction (e.g., anaphylaxis) to a vaccine 

component is a contraindication to any vaccine containing 

that component, and a severe allergy following a dose 

of vaccine is a contraindication to subsequent doses of 

that vaccine.

• Severe immunosuppression is a contraindication to live, 

attenuated vaccines. 

• A history of intussusception is a contraindication to 

rotavirus vaccination.

• Encephalopathy not due to another identifiable cause 

and occurring within 7 days of pertussis vaccination is 

a contraindication to subsequent doses of pertussiscontaining vaccine.

Use of aerosolized steroids, such as inhalers for asthma, is 

not a contraindication to vaccination; nor are alternate-day, 

rapidly tapering, and short (less than 14 days) high-dose 

schedules, topical formulations, and physiologic replacement 

steroid dose schedules. 

Precautions 

A precaution is a health condition in the recipient that might 

increase the chance or severity of a serious adverse reaction, 

might compromise the ability of the vaccine to produce 

immunity (such as administering measles vaccine to a person 

with passive immunity to measles from a blood transfusion), or 

might cause diagnostic confusion. Injury could result, but the 

chance of this happening is less than with a contraindication. 

In general, vaccines should be deferred when a precaution is 

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present. However, situations may arise when the benefit of 

protection from the vaccine outweighs the risk of an adverse 

reaction, and a provider may decide to administer the vaccine. 

Medical conditions that are precautions to vaccination include:

• Moderate or severe acute illness, with or without fever, is a 

precaution for all vaccines.

• Guillain-Barré syndrome (GBS) occurring 6 weeks or less 

after a previous dose of a tetanus toxoid-containing vaccine 

is a precaution for tetanus toxoid-containing vaccines.

• GBS occurring 6 weeks or less after a previous dose of 

influenza vaccine is a precaution for influenza vaccines.

• History of thrombocytopenia or thrombocytopenic purpura 

is a precaution for MMR vaccine.

• Chronic gastrointestinal disease, or altered 

immunocompetence other than SCID are precautions 

for rotavirus vaccine. Spina bifida or bladder exstrophy are 

precautions for Rotarix (RV1) but not for RotaTeq 

RV5 vaccine.

• Recent receipt of antibody-containing blood products is a 

precaution for MMR- and varicella-containing vaccines.

• History of Arthus-type hypersensitivity reaction after a 

previous dose of diphtheria toxoid or tetanus toxoid vaccine 

is a precaution to these vaccines; vaccination should be 

deferred until at least 10 years have elapsed since the last 

tetanus-toxoid-containing vaccine.

• Progressive neurologic disorder, including infantile spasms, 

uncontrolled epilepsy, or progressive encephalopathy is a 

precaution for DTaP and Tdap vaccination; individual clinical 

decision-making should be used to guide revaccination 

until neurologic status has been clarified and stabilized.

Family History of Adverse Events

With few exceptions, family medical history is not a 

contraindication or precaution to vaccines. A family history 

of immunosuppression in first-degree relatives (i.e., parents 

or siblings) is a contraindication to MMR and varicellacontaining vaccines unless the potential vaccine recipient’s 

immunocompetence has been verified either clinically or by a 

laboratory. A family history of seizures is a precaution for MMRV 

vaccination. 

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Contraindications and Precautions in Persons 

with Specific Health Conditions 

Persons with a History of Allergic Reactions

A severe allergic reaction (e.g., anaphylaxis) following a dose 

of vaccine is a contraindication for a subsequent dose of that 

vaccine. Anaphylactic reactions are mediated by IgE, occur 

within minutes or hours of receiving the vaccine, and require 

emergency medical attention. Anaphylaxis involves two or 

more organ systems (dermatologic, cardiovascular, respiratory, 

and/or gastrointestinal) simultaneously. Symptoms and signs 

of anaphylactic reactions include generalized urticaria (hives), 

swelling of the mouth and throat, difficulty breathing, wheezing, 

hypotension, or shock. Anaphylaxis after vaccination occurs 

rarely and can often be prevented by appropriate screening. 

Persons may be allergic to a vaccine antigen or to a vaccine 

component such as an animal protein, antibiotic, preservative, 

or stabilizer. The most common animal protein allergen is 

egg protein found in influenza vaccines prepared using 

embryonated chicken eggs. Asking persons whether they can 

eat eggs without adverse effects is a reasonable way to screen 

for those who might be at risk if they receive egg-containing 

influenza vaccines. Persons with a history of egg allergy who 

have experienced only hives after exposure to egg should 

receive influenza vaccine. Influenza vaccine may also be 

administered to persons who report having had reactions to 

egg involving symptoms other than hives (such as swelling of 

the throat and mouth, difficulty breathing, lightheadedness, 

or recurrent emesis) or who required epinephrine or another 

emergency medical intervention. If egg-containing influenza 

vaccine is administered to persons who report having had 

reactions to egg involving symptoms other than hives, it 

should be administered in an inpatient or outpatient medical 

setting and supervised by a health care provider able to 

recognize and manage severe allergic conditions. A previous 

severe allergic reaction to influenza vaccine, regardless of the 

component suspected of being responsible for the reaction, is a 

contraindication to future receipt of the vaccine.

Studies show that children who have a history of severe allergy 

to eggs rarely have reactions to MMR-II and ProQuad vaccine. 

This is probably because measles and mumps vaccine viruses 

are both grown in chick embryo fibroblasts, not actually 

in eggs. It appears gelatin, not egg, might be the cause of 

allergic reactions to MMR-II. Children with egg allergies may be 

vaccinated with MMR-II or ProQuad without prior skin testing. 

Certain vaccines contain trace amounts of neomycin. Persons 

who have experienced an anaphylactic reaction to neomycin 

should not receive these vaccines. Most often, neomycin allergy 

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presents as contact dermatitis, a manifestation of a delayedtype (cell-mediated) immune response, rather than anaphylaxis. 

A history of delayed-type reactions is not a contraindication for 

administration of neomycin-containing vaccines. 

Latex, which is sap from the commercial rubber tree, contains 

naturally occurring impurities (e.g., plant proteins and peptides), 

which are believed to be responsible for allergic reactions. The 

most common type of latex sensitivity is contact-type (type 4) 

allergy, usually resulting from prolonged contact with latexcontaining gloves. Among patients with diabetes, latex allergies 

associated with injection procedures have been described. 

Latex-related allergic reactions after vaccination are rare. If 

a person reports a severe allergic reaction to latex, vaccines 

supplied in vials or syringes containing natural rubber should 

not be administered unless the benefit of vaccination clearly 

outweighs the risk of an allergic reaction to the vaccine. For 

latex allergies other than anaphylactic allergies (e.g., a history 

of contact allergy to latex gloves), vaccines supplied in vials or 

syringes containing latex can be administered.

Pregnancy

Inactivated influenza and Tdap vaccines are recommended 

during pregnancy.

Live, attenuated viral vaccines (e.g., MMR-II, Varivax, FluMist) are 

contraindicated during pregnancy because of the theoretical 

risk of virus transmission to the fetus. Sexually active women 

who receive MMR-II or Varivax should be instructed to practice 

careful contraception for 1 month following receipt of either 

vaccine. On theoretical grounds, inactivated poliovirus (IPV) 

vaccine should not be administered during pregnancy; however, 

it may be administered if the risk of exposure (e.g., during 

travel to endemic disease areas) is imminent and immediate 

protection is needed. HPV vaccine should not be administered 

to pregnant women. There is no recommendation to administer 

H. influenzae type b vaccine (ActHIB, Hiberix, PedvaxHIB), 

pneumococcal conjugate vaccine (Prevnar 13), or serogroup 

B meningococcal vaccine (Bexsero, Trumenba) to a pregnant 

woman. Hepatitis A vaccine (Havrix, Vaqta), hepatitis B vaccine 

(Engerix-B, Recombivax HB), and meningococcal conjugate 

vaccine (Menactra, Menveo) can be administered to a pregnant 

woman in some circumstances. Data on use of HepB-CpG 

(Heplisav-B), MenACWY-TT (MenQuadfi), and the pneumococcal 

polysaccharide (PPSV23 [Pneumovax 23]) vaccines during 

pregnancy are limited. For more detailed information about 

vaccinations during pregnancy see https://www.cdc.gov/

vaccines/pregnancy/hcp-toolkit/guidelines.html

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Immunosuppression

Live, attenuated vaccines can cause severe or fatal reactions in 

immunosuppressed persons due to uncontrolled replication 

of the vaccine virus. Live vaccines should usually not be 

administered to severely immunosuppressed persons with 

congenital immunodeficiency, leukemia, lymphoma, or 

generalized malignancy. However, persons with isolated B-cell 

deficiency may receive varicella vaccine. Generally, the provider 

treating an immunosuppressed patient should determine the 

severity of that patient’s immunosuppression. 

Certain drugs can also cause immunosuppression. For 

instance, persons receiving cancer treatment with alkylating 

agents, antimetabolites, or radiation therapy should not 

receive live vaccines. Live vaccines can be administered after 

chemotherapy or radiation therapy has been discontinued for 

at least 3 months. In addition, persons receiving large doses of 

corticosteroids should not receive live vaccines. This includes 

persons receiving 20 milligrams or more of prednisone daily 

or 2 milligrams or more of prednisone per kilogram of body 

weight per day for 14 days or longer. 

The safety and efficacy of live, attenuated vaccines administered 

concurrently with recombinant human immune mediators and 

immune modulators are not known. There is evidence that use 

of therapeutic monoclonal antibodies, especially the anti-tumor 

necrosis factor (TNF) agents (e.g., adalimumab, infliximab, 

etanercept, golimumab, and certolizumab pegol), may lead to 

reactivation of latent tuberculosis infection and disease. These 

agents might also predispose persons to other opportunistic 

infections. Because these drugs vary dramatically in the scope

 and number of immune-system-targeted components, it is 

prudent to avoid administering live, attenuated vaccines while 

patients are taking these drugs. For vaccination against seasonal 

influenza, inactivated injectable alternatives are available. 

The time health care providers should wait to administer a 

live-virus vaccine after immune modulator drugs have been 

discontinued is not specified by the Advisory Committee on 

Immunization Practices (ACIP) or other authoritative guidelines. 

No basis exists for interpreting laboratory studies of immune 

parameters with vaccines’ safety or efficacy. Lymphocytedepleting agents such as alemtuzumab and rituximab may 

cause prolonged immunosuppression. Both inactivated and live 

vaccines should be withheld at least 6 months following therapy 

with anti-B cell antibodies. Some experts recommend longer 

than 6 months following anti-B cell antibodies. The optimal time 

for restarting immunosuppressive therapy after vaccination with 

live vaccines has not been studied, but the Infectious Diseases 

Society of America (IDSA) recommends waiting at least 1 month.

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Consultation with the prescribing physician (and possibly a 

hospital pharmacist) is recommended for management of 

individual patients and guidance in estimating a patient’s 

degree of immunosuppression. Inactivated vaccines cannot 

replicate, so they are safe to use in immunosuppressed persons. 

Certain vaccines are recommended or specifically encouraged 

because immunosuppression is a risk factor for complications 

from certain vaccine-preventable diseases (i.e., influenza, 

invasive pneumococcal disease, invasive meningococcal 

disease, invasive H. influenzae type b disease, and hepatitis 

B). However, because a relatively functional immune system 

is required to develop an immune response to a vaccine, the 

immune response may be poor, depending on the degree of 

immunosuppression present.

HIV Infection

Persons infected with human immunodeficiency 

virus (HIV) may not manifest disease, or they may be 

severely immunosuppressed. In general, the same 

vaccination recommendations apply as for other types 

of immunosuppression. Live-virus vaccines are usually 

contraindicated in those with severe immunosuppression, but 

inactivated vaccines may be administered if indicated.

For persons infected with HIV: • Varivax can be considered for persons who are not 

severely immunocompromised, since varicella infection 

can be severe for HIV-positive persons and is often 

associated with complications.

• MMR-II vaccine should be administered to persons who 

are not severely immunocompromised. 

• FluMist should not be administered, but age-appropriate 

inactivated or recombinant influenza vaccine should 

be administered.

Hematopoietic Cell Transplant Recipients

Hematopoietic cell transplant (HCT) results in 

immunosuppression due to ablative therapy administered 

before the transplant and therapies to prevent or treat graftversus-host disease. In addition, HCT recipients are at increased 

risk for vaccine-preventable diseases because antibody titers 

decline 1 to 4 years after HCT if the recipient is not revaccinated. 

HCT recipients at increased risk should be routinely vaccinated 

after HCT against tetanus, poliovirus, measles, mumps, rubella, 

Streptococcus pneumoniae, and H. influenzae type b, regardless 

of the source of the transplanted cells. Specifically: • MMR and varicella-containing vaccines should be 

administered 24 months after transplantation if the HCT 

recipient is presumed to be immunocompetent.

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• Revaccination with inactivated vaccines, including influenza 

vaccine, should begin 6 months after HCT. However, 

influenza vaccine may be administered as early as 4 months 

after HCT, if needed.

• Three doses of Prevnar 13 should be administered 3-6 

months after HCT, followed by a dose of PPSV23.

• A dose of MenACWY should also be administered 6 months 

after HCT.

Invalid Contraindications and Precautions 

to Vaccination

Sometimes certain conditions or circumstances are inappropriately considered to be contraindications or precautions to 

vaccination. Such conditions or circumstances are known as 

invalid contraindications and these misperceptions result in 

missed opportunities to administer needed vaccines. Some 

of the most common invalid contraindications are mild 

illnesses, pregnancy, breastfeeding, allergies that are not 

anaphylactic in nature, and certain aspects of the patient’s 

family history. 

Mild Illness

Children with a mild acute illness, such as a low-grade fever, an 

upper respiratory infection (URI), otitis media, or mild diarrhea, 

should be vaccinated on schedule. 

Low-grade fever is not a contraindication to vaccination. 

Measuring temperature is not necessary before vaccination if 

the patient does not appear ill and does not report currently 

being ill. ACIP has not defined a body temperature above which 

vaccines should not be administered. The decision to vaccinate 

should be based on the overall evaluation of the person rather 

than an arbitrary body temperature. 

Nonanaphylactic Allergy

If an allergy to a vaccine component is not severe (e.g., is 

not anaphylaxis), it is not a contraindication to that vaccine. 

Only a severe allergic reaction (e.g., anaphylaxis) to a vaccine 

component is a true contraindication to vaccination. 

Allergy to Products Not Present in Vaccines

There is no contraindication or precaution for persons with 

nonspecific allergies, duck or feather allergies, or penicillin 

allergy, or for persons who have relatives with allergies or 

those taking allergy shots. Anyone with these allergies can and 

should be vaccinated. No vaccine available in the United States 

contains duck antigen or penicillin.

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Antimicrobial Therapy

Antimicrobials do not influence the immune response to most 

vaccines. However, antiviral drugs may affect vaccine replication 

in some circumstances. FluMist should not be administered 

until 48 hours after cessation of oseltamivir and zanamivir, 5 

days after cessation of peramivir, and 17 days after baloxavir. If 

possible, antiviral drugs (acyclovir, famciclovir) that are active 

against herpesviruses should be discontinued 24 hours before 

administration of a varicella-containing vaccine. 

Breastfeeding

Breastfeeding does not decrease the response to any routinely 

recommended childhood vaccine and is not a contraindication 

to vaccination; however, breastfeeding is a precaution for yellow 

fever vaccine. Breastfeeding also does not extend or improve 

the passive immunity to vaccine-preventable disease that is 

provided by maternal antibody.

Household Contacts of Pregnant or 

Immunosuppressed Persons

Being a household contact of a pregnant woman or 

immunosuppressed person is usually not a contraindication to 

vaccination. In fact, it is critical that healthy household contacts 

of pregnant women and immunosuppressed persons be 

vaccinated. Vaccination of healthy contacts reduces the chance 

that pregnant women and immunosuppressed persons will be 

exposed to vaccine-preventable diseases.

Most routinely recommended vaccines, including live 

vaccines (MMR-II, Varivax, RotaTeq/Rotarix, and FluMist), can 

be administered to persons who are household contacts 

of pregnant or immunosuppressed persons. If a varicella 

vaccine recipient has a rash after vaccination, direct 

contact with susceptible household contacts with altered 

immunocompetence should be avoided until the rash resolves. 

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. FluMist should 

not be administered to close contacts and caregivers of 

severely immunosuppressed persons who require a protected 

environment.

Preterm Birth

Vaccines should be started on schedule based on the child’s 

chronological age. Preterm infants have been shown to respond 

adequately to vaccines used in infancy. 

Studies demonstrate that decreased seroprotection rates might 

occur among infants with low birth weight (less than 2,000 

grams) after administration of hepatitis B vaccine at birth. 

NOTES
General Best Practice Guidance for Immunization 

23

2

However, by the chronological age of 1 month, all preterm 

infants, regardless of initial birth weight or gestational age, are 

likely to respond as adequately as older and larger infants. 

Tuberculin Skin Test 

Persons who need a tuberculin skin test (TST) can and should 

be vaccinated. All vaccines can be administered on the same 

day as a TST or at any time after a TST is administered. For most 

vaccines, there are no TST timing restrictions. 

MMR-containing vaccine may decrease the response to a TST, 

potentially causing a false-negative response in someone who 

has a tuberculosis infection. MMR-II can be administered the 

same day as a TST, but if MMR-II has been administered and 1 or 

more days have elapsed, it is recommended in most situations 

to wait at least 4 weeks before administering a routine TST. 

There is no information available on the effect of varicellacontaining vaccine or FluMist on a TST. Until such information 

is available, it is prudent to apply the same rules for spacing 

measles-containing vaccine and TST to varicella-containing 

vaccine and FluMist. 

An interferon-gamma release assay (IGRA) tuberculosis test may 

be affected by live vaccines, so it is prudent to apply the same 

spacing rules as for TST and live vaccines. 

Screening for Contraindications and Precautions 

to Vaccination

The key to preventing serious adverse reactions after 

vaccination is effective screening. Every patient should 

be screened for contraindications and precautions before 

administering any vaccine dose. Effective screening can be 

accomplished by asking a few questions: 

Is the patient sick today?

There is no evidence that acute illness reduces vaccine efficacy 

or increases vaccine adverse events. However, as a precaution, 

if there is a moderate or severe acute illness, all vaccines should 

be deferred until the illness has improved. Mild illnesses (such 

as otitis media, URIs, and diarrhea) are not contraindications or 

precautions to vaccination and recommended vaccines should 

be administered on time. 

Does the patient have allergies to medications, food, a 

vaccine component, or latex?

It may be more efficient to inquire about allergies in a generic 

way (i.e., allergies to any food or medication) rather than to 

inquire about allergies to specific vaccine components. Most 

persons will not be familiar with minor components of vaccines, 

but they should know if they or their child have had an allergic 

NOTES
24

General Best Practice Guidance for Immunization 

 2

reaction to a food or medication that was severe enough to 

require medical attention. If a person reports anaphylaxis after 

eating eggs, a specific protocol should be followed that includes 

determining the symptoms experienced. For information on 

egg allergies and influenza vaccination, please refer to the most 

recent ACIP influenza vaccination recommendations.

Has the patient experienced any reaction after 

receiving a vaccination?

A history of severe allergic reaction such as urticaria, wheezing 

or difficulty breathing, or circulatory collapse or shock (not 

fainting) following a previous dose of vaccine or to a vaccine 

component is a contraindication to further doses. A local 

adverse reaction (redness or swelling at the injection site) is not 

a contraindication to subsequent doses. 

Some reactions after vaccination (e.g., Arthus reactions after a 

previous dose of diphtheria toxoid-containing or tetanus toxoidcontaining vaccine) are considered as precautions to receiving 

further vaccine doses. ACIP recommends for persons with a 

history of Arthus-type hypersensitivity reactions after a previous 

dose of tetanus or diphtheria toxoid-containing vaccines should 

defer vaccination until at least 10 years have elapsed since the 

last tetanus toxoid-containing vaccine. Usually vaccines are 

deferred when a precaution is present. However, situations 

may arise when the benefit outweighs the risk (e.g., during a 

community pertussis outbreak). 

Has the patient experienced a brain or other nervous 

system problem including seizures?

DTaP and Tdap are contraindicated for persons who have a 

history of encephalopathy not attributed to an identifiable 

cause within 7 days following DTaP, DTP, or Tdap vaccination. 

An unstable or progressive neurologic problem is a precaution 

for the use of DTaP and Tdap. Children with stable neurologic 

disorders (including seizures) unrelated to vaccination may be 

vaccinated as usual. 

A history of GBS is a precaution for tetanus toxoid-containing 

and influenza vaccines, if it occurred within 6 weeks following a 

dose of the specific vaccine.

A personal or family history of febrile or afebrile seizures is a 

precaution for ProQuad vaccine. Simultaneous administration 

of MMR-II and Varivax is not associated with an increased risk 

of fever or seizures and is, therefore, preferred to ProQuad in 

children age 12 through 47 months.

Does the patient have a long-term health problem with 

heart, lung, kidney, or metabolic disease (e.g., diabetes), 

asthma, a blood disorder, no spleen, complement 

NOTES
General Best Practice Guidance for Immunization 

25

2

component deficiency, a cochlear implant, or a CSF leak? 

Is the patient on long-term aspirin therapy? 

These conditions are contraindications or precautions to LAIV. 

Age-appropriate inactivated or recombinant influenza vaccine is 

preferred for patients with these conditions. 

Does the patient have cancer, leukemia, HIV/AIDS, 

or any other immune system problem?

Live virus vaccines (e.g., MMR-II, Varivax, MMRV, Rotarix and 

RotaTeq, and FluMist) are usually contraindicated in severely 

immunocompromised persons. However, there are exceptions. 

For example, MMR-II and Varivax are recommended for 

HIV-infected children who do not have evidence of severe 

immunosuppression. 

Does the patient have a parent or sibling with an 

immune system problem?

MMR, VAR, and MMRV vaccines should not be given to a 

person with a family history of congenital or hereditary 

immunodeficiency in first-degree relatives (i.e., parents, 

siblings) unless the immune competence of the potential 

vaccine recipient has been clinically substantiated or verified 

by a laboratory.

Has the patient taken medications that affect the 

immune system, such as prednisone, other steroids, or 

anticancer drugs; drugs for the treatment of rheumatoid 

arthritis, Crohn’s disease, or psoriasis; or has the patient 

had radiation treatment? 

Live-virus vaccines (e.g., MMR-II, Varivax, FluMist) should be 

postponed until after chemotherapy or long-term, high-dose 

steroid therapy has ended. 

Has the patient received a transfusion of blood or blood 

products, immune (gamma) globulin, or an antiviral drug 

in the past year?

Certain live-virus vaccines (i.e., MMR-II, ProQuad, and Varivax) 

may need to be deferred following administration of blood 

products, depending on the type of blood product and the 

interval since the blood product was administered. 

Is the person pregnant or is there a chance she could 

become pregnant during the next month?

Live-virus vaccines (e.g., MMR-II, Varivax, FluMist) are 

contraindicated during pregnancy because of the theoretical 

risk of virus transmission to the fetus. Sexually active young 

women who receive MMR-II or Varivax should be instructed to 

practice careful contraception for 1 month following receipt of 

either vaccine. On theoretical grounds, inactivated poliovirus 

vaccine should not be administered during pregnancy; however, 

NOTES
26

General Best Practice Guidance for Immunization 

 2

it may be administered if the risk of exposure (e.g., during 

travel to endemic disease areas) is imminent and immediate 

protection is needed. HPV vaccine should not be administered 

to pregnant women. There is no recommendation to administer 

H. influenzae type b vaccine (ActHIB, Hiberix, PedvaxHIB), 

pneumococcal conjugate vaccine (Prevnar 13), or serogroup 

B meningococcal vaccine (Bexsero, Trumenba) to a pregnant 

woman. Hepatitis A vaccine (Havrix, Vaqta), hepatitis B vaccine 

(Engerix-B, Recombivax HB), and meningococcal conjugate 

vaccine (Menactra, Menveo), should be administered to 

pregnant women if routinely recommended or indicated. Data 

on use of HepB-CpG (Heplisav-B), MenACWY-TT (MenQuadfi), 

and the pneumococcal polysaccharide vaccine (Pneumovax 23) 

during pregnancy are limited.

Has the patient received vaccinations in the past 

4 weeks?

A person who received either Flumist or a live, injectable 

vaccine (e.g., MMR-II, Varivax) in the past 4 weeks should wait 28 

days before receiving another live vaccine. Inactivated vaccines 

may be administered at the same time or at any time before or 

after a live vaccine. 

Has the patient (if the patient is a baby) ever had 

intussusception?

Intussusception is a contraindication for the rotavirus vaccine

NOTES
General Best Practice Guidance for Immunization 

27

2

Acknowledgements

The editors would like to acknowledge Maria Cano, Jennifer 

Hamborsky, Andrew Kroger, and Valerie Morelli for their 

contributions to this chapter. 

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NOTES