Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses

Recommendations of the Advisory Committee on Immunization Practices -- United States, 2022

Agam K. Rao, MD; Brett W. Petersen, MD; Florence Whitehill, DVM; Jafar H. Razeq, PhD; Stuart N. Isaacs, MD; Michael J. Merchlinsky, PhD; Doug Campos-Outcalt, MD; Rebecca L. Morgan, PhD; Inger Damon, MD, PhD; Pablo J. Sánchez, MD; Beth P. Bell, MD


Morbidity and Mortality Weekly Report. 2022;71(22):734-742. 

In This Article

Clinical Guidance

Considerations in Choosing JYNNEOS or ACAM2000 for Primary Vaccination

JYNNEOS involves a replication-deficient virus and has fewer contraindications, no risk for inadvertent inoculation and autoinoculation, and is associated with fewer serious adverse events compared with ACAM2000 (Table 2). In addition, most health care providers have experience with and are comfortable providing vaccines by subcutaneous administration, the route by which JYNNEOS is administered. ACAM2000, on the other hand, is administered percutaneously through a multiple puncture (scarification) technique, through 15 jabs with a stainless steel bifurcated needle that has been dipped into the reconstituted vaccine, a vaccination technique that is unique to orthopoxvirus vaccinations.[3] JYNNEOS involves 2 vaccine doses 28 days apart and vaccine protection is not conferred until 2 weeks after receipt of the second dose; ACAM2000 involves 1 dose of vaccine and peak vaccine protection is conferred within 28 days.

For those working with more virulent orthopoxviruses, the frequency of booster doses also differs: ACAM2000 boosters are recommended every 3 years, whereas JYNNEOS boosters are recommended every 2 years. After successful administration of vaccine, ACAM2000 produces a take containing infectious vaccinia virus capable of transmission through autoinoculation and inadvertent inoculation of close contacts of vaccinees; JYNNEOS does not produce a take. Some persons might prefer receiving ACAM2000 because the vaccine is a derivative of Dryvax, which was used successfully in eradicating smallpox, a clear demonstration of its effectiveness in preventing disease.

A robust antibody response following a single dose of JYNNEOS has been observed in clinical trials.[9] In addition, limited data from animal model studies indicate that a single dose of JYNNEOS might provide protection for some persons against orthopoxvirus infection when administered before and closely after (1 day) viral challenge.[10,11]

Considerations for Transitioning From the use of one Orthopoxvirus Vaccine to the Other for Booster Doses

Persons who previously received ACAM2000 should decide before their next booster dose whether to receive ACAM2000 or JYNNEOS. Persons who transition to receiving JYNNEOS boosters are expected to continue receiving JYNNEOS boosters and to not revert to ACAM2000; in addition, the frequency of booster doses should correspond to the vaccine used for boosters. For example, persons who previously received ACAM2000 every 3 years because of work with more virulent orthopoxviruses might decide to change to JYNNEOS when their next booster dose is due; in these cases, subsequent JYNNEOS booster doses should be administered every 2 years.

Fewer persons are expected to transition from JYNNEOS to ACAM2000; however, if those situations arise, they should be handled on a case-by-case basis. If this transition is approved by public health authorities, vaccinees should be advised that the expectation is that they will receive ACAM2000 for all future vaccine booster doses.

Contraindications to and Precautions Associated With Vaccinations to Prevent Orthopoxvirus Infections

JYNNEOS is contraindicated in persons with a serious allergy to a vaccine component (Table 3). Primary vaccination with ACAM2000 is contraindicated in persons with the following conditions: serious allergy to a vaccine component, history of atopic dermatitis or other exfoliative skin condition,**** an immunocompromising condition (e.g., due to a disease or therapeutics),†††† pregnancy, breastfeeding, and known underlying heart disease (e.g., coronary artery disease or cardiomyopathy). ACAM2000 vaccination is also contraindicated if the vaccine recipient cannot sufficiently isolate from household contacts who have a history of atopic dermatitis or other active exfoliative skin condition, an immunocompromising condition, or who are pregnant or aged <1 year; household contacts include persons with prolonged intimate contact with the potential vaccine recipient and others who might have direct contact with the vaccination site or with potentially contaminated materials (e.g., clothing or vaccination site dressings). Availability of JYNNEOS provides opportunities for vaccinating persons in situations where ACAM2000 might be contraindicated.

Because of the documented risk for myocarditis after receipt of both ACAM2000 and mRNA COVID-19 vaccines[12] and the unknown risk for myocarditis after JYNNEOS, persons might consider waiting 4 weeks after orthopoxvirus vaccination (either JYNNEOS or ACAM2000) before receiving an mRNA COVID-19 vaccine, particularly adolescent or young adult males. However, if an orthopoxvirus vaccine is recommended for prophylaxis in the setting of an outbreak, administration of orthopoxvirus vaccine should not be delayed because of recent receipt of an mRNA COVID-19 vaccine. No minimum interval between mRNA COVID-19 vaccination and orthopoxvirus vaccination is necessary.

Vaccinations Administered to Special Populations

Persons With Atopic Dermatitis, Eczema, or Other Exfoliative Skin Conditions. Studies evaluating JYNNEOS in persons with atopic dermatitis have demonstrated immunogenicity in eliciting a neutralizing antibody response. No safety signals were revealed. However, persons with these conditions might be at increased risk for severe disease if an occupational infection occurs despite vaccination.[13]

Persons With Immunocompromising Conditions. JYNNEOS is safe to administer to persons with immunocompromising conditions. However, such persons might be at increased risk for severe disease if an occupational infection occurs, despite vaccination. In addition, persons with immunocompromising conditions might be less likely to mount an effective response after any vaccination,§§§§ including after JYNNEOS; the risk/benefit ratio should be considered along with whether it is considered imperative to vaccinate an immunocompromised person.

Pregnant Women. Available human data on JYNNEOS administered to pregnant women are insufficient to determine vaccine-associated risks in pregnancy. However, animal models, including rats and rabbits, have shown no evidence of harm to a developing fetus.

Breastfeeding Women. The safety and efficacy of JYNNEOS has not been evaluated in breastfeeding women. It is not known whether JYNNEOS is excreted in human milk. Data are not available to assess the impact of JYNNEOS on milk production or the safety of JYNNEOS in breastfed infants. However, because JYNNEOS vaccine is replication-deficient, it likely does not present a risk of transmission to breastfed infants and can be administered to women who are breastfeeding if vaccination is critical.

Children and Adolescents Aged <18 Years. Although occupational exposure to orthopoxviruses is unlikely in persons aged <18 years, it is important to note that JYNNEOS is not licensed for persons aged <18 years and has not been rigorously evaluated in this population. Public health authorities should be consulted if JYNNEOS is being considered for children and adolescents aged <18 years. Administration of ACAM2000 to infants aged <1 year is contraindicated. Caution should be used when considering the administration of ACAM2000 or JYNNEOS to children and adolescents aged <18 years.

Persons With Multiple Cardiac Risk Factors. Major cardiac risk factors include hypertension, diabetes, hypercholesterolemia, heart disease at age ≤50 years in a first-degree relative, and smoking and the presence of three or more of these factors are contraindications to primary vaccination with ACAM2000. Clinical studies have not detected an increased risk for myopericarditis in recipients of JYNNEOS. Persons with underlying heart disease or three or more major cardiac risk factors should be counseled about the theoretical risk for myopericarditis following vaccination with JYNNEOS given the uncertain etiology of myopericarditis associated with replication-competent smallpox vaccines such as ACAM2000.

Reporting of Adverse Events

Adverse events following vaccination can be reported to the Vaccine Adverse Event Reporting System (VAERS). Reporting is encouraged for any clinically significant adverse event, even if it is uncertain whether the vaccine caused the event. Information on how to submit a report to VAERS is available at or by telephone at 1–800-822-7967.

Peak Antibody Response, Confirming Effective Vaccination in Immunocompromised Persons, and Correlate of Protection After Vaccination with JYNNEOS

Peak antibody response is achieved 2 weeks after receipt of the second dose of the 2-dose JYNNEOS vaccination series.[9] Evidence of a take is often used as a marker of successful vaccination after ACAM2000.[3] Because JYNNEOS is a replication-deficient vaccine, vaccination with JYNNEOS does not produce a take; however, clinical trials have demonstrated high rates of seroconversion after the 2-dose series. Therefore, effective vaccination can be assumed for immunocompetent persons. Routine antibody titer testing (to confirm successful vaccination) following vaccination with JYNNEOS is not recommended for immunocompetent persons. If the decision is made to vaccinate immunocompromised persons, titer testing by CDC might be considered on a case-by-case basis; clinicians considering vaccinating immunocompromised persons should consult public health authorities. Because 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. An immunocompetent person is considered fully immunized 2 weeks following administration of the second dose of the 2-dose JYNNEOS vaccination series, which is when clinical studies have demonstrated maximal antibody titers. Titer testing might also be considered on a case-by-case basis after vaccination of persons working with more virulent orthopoxviruses (e.g., Variola virus and Monkeypox virus).

Minimizing Risk for Occupational Exposures

Many persons with contraindications to vaccination with ACAM2000 (e.g., atopic dermatitis, immunocompromising conditions, breastfeeding, or pregnancy) may receive vaccination with JYNNEOS. However, because the number of immunocompromised persons is increasing in the United States,[14] and these persons might be less likely to mount an effective vaccine response, infections in vaccinated persons might occur. Outcomes after an infection in a vaccinated person could be particularly severe in these populations, particularly following exposure to more virulent orthopoxviruses;[3] for this reason, vaccine recipients might consider avoiding high-risk exposures until after temporary conditions (e.g., pregnancy or transient therapy with immunocompromising therapeutics) are completed. If high-risk exposures cannot be avoided, persons who are pregnant, immunocompromised, or breastfeeding or who have atopic dermatitis may receive JYNNEOS in consultation with their health care provider and after careful consideration of the risks and benefits. Irrespective of vaccination status, all persons who work with orthopoxviruses should wear appropriate personal protective equipment.¶¶¶¶

****Examples include eczema, burns, impetigo, varicella-zoster, herpes, severe acne, severe diaper dermatitis with extensive areas of denuded skin, psoriasis, or Darier disease (keratosis follicularis).
††††Conditions include HIV; AIDS; leukemia; lymphoma; generalized malignancy; solid organ transplantation; therapy with alkylating agents, antimetabolities, radiation, tumor necrosis factor inhibitors, or high-dose corticosteroids; being a recipient of a hematopoietic stem cell transplant <24 months ago or ≥24 months ago but with graft-versus-host disease or disease relapse; or having autoimmune disease with immunodeficiency as a clinical component.