Brett Petersen, MD, MPH

United States Public Health Service

Poxvirus and Rabies Branch 

Centers for Disease Control and Prevention

ACIP Meeting

November 3 , 2021

National Center for Emerging and Zoonotic Infectious Diseases

Division of High Consequence Pathogens and Pathology

Clinical guidance for the use of 

JYNNEOS
Outline

▪ Contraindications and precautions / warnings

▪ Guidance for minimizing the risk of occupational exposure

▪ Titer testing and starting work in laboratories
ACAM2000 JYNNEOS®

Vaccine virus Replication-competent vaccinia virus Replication-deficient Modified 

vaccinia Ankara

“Take” “Take” occurs No “take” after vaccination

Inadvertent inoculation 

and autoinoculation

Risk exists No risk

Serious adverse event Risk exists Fewer expected

Cardiac adverse events Myopericarditis in 5.7 per 1,000 

primary vaccinees 

Risk believed to be lower than that 

for ACAM2000

Effectiveness FDA assessed by comparing 

immunologic response and “take” 

rates to Dryvax*

FDA assessed by comparing 

immunologic response to 

ACAM2000 & animal studies

Administration Percutaneously by multiple puncture 

technique in single dose

Subcutaneously in 2 doses, 28 

days apart

ACAM2000 and JYNNEOS®

*Both ACAM2000 and Dryvax are derived from the NYC Board of Health strain of vaccinia; ACAM2000 is a “second generation” smallpox 

vaccine derived from a clone of Dryvax, purified, and produced using modern cell culture technology. 
Proposed recommendations for JYNNEOS® compared 

to ACAM2000

ACAM2000 JYNNEOS®

Population recommended Persons at occupational risk for orthopoxviruses (i.e., research laboratory 

personnel, diagnostic laboratorians, response team members)

Populations offered Persons who administer ACAM2000 or care for patients with infection or 

after vaccination with replication competent virus

Populations for whom 

booster is recommended at 

specific intervals

Persons who are at continued or sustained risk for orthopoxviruses [Note: 

Response teams are not at continued risk and will receive boosters only at the 

time of a smallpox/monkeypox event]

Frequency of boosters: 

Those working with smallpox 

and monkeypox

Every 3 years (had previously been 

every year)

Every 2 years

Frequency of boosters: 

Those working with less 

virulent orthopoxviruses

At least every 10 years
Severe Vaccinia Virus Complications

Uncontrolled Viral Replication

▪ Progressive vaccinia

▪ Eczema vaccinatum

Eczema vaccinatum

Progressive vaccinia
Severe Vaccinia Virus Complications

Inadvertent Transmission

▪ Fetal vaccinia

▪ Autoinoculation / inadvertent 

inoculation

• Ocular infections

Fetal vaccinia Ocular vaccinia
Severe Vaccinia Virus Complications

Uncertain Etiology

▪ Postvaccinial encephalitis

▪ Myopericarditis
Contraindication ACAM2000 

Primary 

Vaccinees

ACAM2000 

Revaccinees

ACAM2000 

Household 

Contacts1

JYNNEOS

History or presence of atopic dermatitis X X X

Other active exfoliative skin conditions2 X X X

Conditions associated with immunosuppression3 X X X

Pregnancy4 X X X

Aged <1 year5 X X X

Breastfeeding6 X X

Serious vaccine component allergy X X X

Known underlying heart disease (e.g., coronary 

artery disease or cardiomyopathy)

X X

Three or more known major cardiac risk factors7 X

Proposed ACIP Contraindications for ACAM2000 and JYNNEOS
1. Household contacts

▪ Household contacts include persons with prolonged intimate 

contact with the potential vaccinee (e.g., sexual contacts) 

and others who might have direct contact with the 

vaccination site or with potentially contaminated materials 

(e.g., dressings or clothing) 

▪ JYNNEOS is a replication-deficient vaccine and therefore 

should not present a risk of transmission to household 

contacts
2. Atopic dermatitis / eczema and other active 

exfoliative skin conditions

▪ Conditions include eczema, burns, impetigo, varicella-zoster, 

herpes, severe acne, severe diaper dermatitis with extensive 

areas of denuded skin, psoriasis, or Darier disease (keratosis 

follicularis)

▪ Studies evaluating JYNNEOS in persons with atopic dermatitis 

have demonstrated immunogenicity in eliciting a neutralizing 

antibody response and did not reveal any significant safety 

concerns
3. Conditions associated with immunosuppression

▪ Conditions include human immunodeficiency virus/acquired immune 

deficiency syndrome infection, leukemia, lymphoma, generalized 

malignancy, solid organ transplantation, therapy with alkylating 

agents, antimetabolites, radiation, tumor necrosis factor inhibitors, 

high-dose corticosteroids, being a recipient with hematopoietic stem 

cell transplant <24 months post-transplant or ≥24 months but with 

graft-versus-host disease or disease relapse, or having autoimmune 

disease with immunodeficiency as a clinical component

▪ Immunocompromised persons, including those receiving 

immunosuppressive therapy, may have a diminished immune 

response to JYNNEOS because of their immunocompromised status
4. Pregnancy 

▪ Available human data on JYNNEOS administered to pregnant 

women are insufficient to inform vaccine-associated risks in 

pregnancy

▪ However, animal models, including rats and rabbits, have 

shown no evidence of harm to a developing fetus
5. Aged <1 year

▪ Vaccination of infants aged <1 year is contraindicated for 

ACAM2000

▪ JYNNEOS is not licensed for persons <18 years and has not 

been rigorously evaluated in this population

▪ Caution should be used when considering the administration 

of ACAM2000 or JYNNEOS to children and adolescents aged 

<18 years
6. Breastfeeding

▪ The safety and efficacy of JYNNEOS has not been evaluated in 

breastfeeding women

▪ It is not known whether JYNNEOS is excreted in human milk and 

data are not available to assess the impact of JYNNEOS on milk 

production or the safety of JYNNEOS in breastfed infants

▪ However, JYNNEOS vaccine is replication deficient and therefore 

should not present a risk of transmission to breastfeeding infants

▪ Caution should be used when considering the administration of 

JYNNEOS to breastfeeding women
7. Three or more known major cardiac risk factors 

▪ Major cardiac risk factors include hypertension, diabetes, 

hypercholesterolemia, heart disease at age 50 years in a firstdegree relative, and smoking

▪ Clinical studies have not detected an increased risk of 

myopericarditis in recipients of JYNNEOS

▪ Persons with underlying heart disease or ≥3 major cardiac risk 

factors should be counseled on the theoretical risk of 

myopericarditis given the uncertain etiology of myopericarditis 

associated with replication-competent smallpox vaccines
Guidance for Minimizing the Risk of Occupational 

Exposure

▪ Many persons with contraindications to vaccination with 

ACAM2000 (e.g., atopic dermatitis, immunocompromising 

conditions, breastfeeding, or pregnancy) may receive vaccination 

with JYNNEOS

▪ However, such persons may be at increased risk for severe 

disease if an occupational infection occurs despite vaccination

▪ Persons with immunocompromising conditions may be less likely 

to mount an effective response after any vaccination, including 

after JYNNEOS even though JYNNEOS can be safely administered 

to such persons
Guidance for Minimizing the Risk of Occupational 

Exposure

▪ Persons who are pregnant, immunocompromised, with atopic 

dermatitis, or breastfeeding may receive JYNNEOS when it is 

considered imperative to provide protection against 

orthopoxvirus infections and after careful consideration of the 

risk/benefit ratio

▪ To find more information about the risk for severe outcomes if 

orthopoxvirus infections are acquired, please see [Smallpox 

Vaccination and Adverse Reactions: Guidance for Clinicians, 

2003. MMWR 2003, 52(RR04);1-28]
Titer Testing

▪ As a replication-deficient vaccine, JYNNEOS does not produce a vaccine 

site lesion (also known as a “take”) that can be used as a marker of 

successful vaccination

▪ Routine titer testing is not recommended following vaccination with 

JYNNEOS to confirm successful administration of vaccine given that high 

rates of seroconversion were demonstrated in clinical trials

▪ However, titer testing could be considered on a case-by-case basis after 

consultation with public health authorities for select persons with 

immunocompromising conditions or those working with more virulent 

orthopoxviruses (e.g., variola virus and monkeypox virus) to confirm an 

immune response has been achieved
Titer Testing

▪ A correlate of protection has not been established and there 

is no known antibody titer level that will ensure protection

▪ Titer results should be interpreted with caution in such cases 

to avoid providing a false sense of security
Starting Work in Laboratories

▪ A person can be considered fully immunized 2 weeks 

following administration of the second dose of JYNNEOS 

when clinical studies have demonstrated maximal antibody 

titers 
Brett W. Petersen, MD, MPH

1600 Clifton Road NE, Mail Stop H24-12

Atlanta, GA 30333

Phone: 404-639-5464

E-Mail: bpetersen@cdc.gov

For more information please contact Centers for Disease 

Control and Prevention

Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348

E-mail: cdcinfo@cdc.gov Web: http://www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily 

represent the official position of the Centers for Disease Control and Prevention.

National Center for Emerging and Zoonotic Infectious Diseases

Division of High-Consequence Pathogens and Pathology

Questions?
ACAM2000 Package Insert 

Contraindications, Warnings, and Precautions

▪ Contraindication

• Individuals with severe immunodeficiency who are not expected to benefit from the 

vaccine. These individuals may include persons who are undergoing bone marrow 

transplantation or persons with primary or acquired immunodeficiency states who require 

isolation

▪ Black Box Warning

• Myocarditis and pericarditis (suspect cases observed at a rate of 5.7 per 1000 primary 

vaccinees (95% CI: 1.9-13.3)), encephalitis, encephalomyelitis, encephalopathy, progressive 

vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major 

(including STEVENS-JOHNSON SYNDROME), eczema vaccinatum resulting in permanent 

sequelae or death, ocular complications, blindness and fetal death, have occurred 

following either primary vaccination or revaccination with live vaccinia virus smallpox 

vaccines. These risks are increased in certain individuals and may result in severe disability, 

permanent neurological sequelae and/or death [see Warnings and Precautions]

https://www.fda.gov/media/75792/download
ACAM2000 Package Insert 

Contraindications, Warnings, and Precautions

▪ Warnings and Precautions

• Myocarditis and/or pericarditis, ischemic heart disease and non-ischemic dilated cardiomyopathy

• Encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia (vaccinia necrosum), generalized 

vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson syndrome), 

eczema vaccinatum, fetal vaccinia and fetal death

• Ocular vaccinia and blindness

• These risks, including risks of severe disability and/or death, are increased in vaccinees with:

o Cardiac disease 

o Eye disease treated with topical steroids

o Congenital or acquired immune deficiency disorders

o History or presence of eczema and other skin conditions

o Infants < 12 months of age

o Pregnancy

• ACAM2000 is a live vaccinia virus that can be transmitted to persons who have close contact with the vaccinee 

and the risks in contacts are the same as those stated for vaccinees

https://www.fda.gov/media/75792/download
JYNNEOS Package Insert 

Warnings and Precautions

▪ Severe Allergic Reactions

• Appropriate medical treatment must be available to manage possible anaphylactic reactions following 

administration of JYNNEOS

• Persons who experienced a severe allergic reaction following a previous dose of JYNNEOS or following 

exposure to any component of JYNNEOS may be at increased risk for severe allergic reactions after 

JYNNEOS

• The risk for a severe allergic reaction should be weighed against the risk for disease due to smallpox or 

monkeypox

▪ Altered Immunocompetence

• Immunocompromised persons, including those receiving immunosuppressive therapy, may have a 

diminished immune response to JYNNEOS

▪ Limitations of Vaccine Effectiveness

• Vaccination with JYNNEOS may not protect all recipients

https://www.fda.gov/vaccines-blood-biologics/jynneos