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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
Early Release / May 27, 2022 / 71
Agam K. Rao, MD1; Brett W. Petersen, MD1; Florence Whitehill, DVM1,2; Jafar H. Razeq, PhD3; Stuart N. Isaacs, MD4; Michael J. Merchlinsky, PhD5; Doug Campos-Outcalt, MD6; Rebecca L. Morgan, PhD7; Inger Damon, MD, PhD1; Pablo J. Sánchez, MD8; Beth P. Bell, MD9
... Certain laboratorians and health care personnel can be exposed to orthopoxviruses through occupational activities. Because orthopoxvirus infections resulting from occupational exposures can be serious, the Advisory Committee on Immunization Practices (ACIP) has continued to recommend preexposure vaccination for these persons since 1980 (1), when smallpox was eradicated (2). In 2015, ACIP made recommendations for the use of ACAM2000, the only orthopoxvirus vaccine available in the United States at that time (3). During 2020–2021, ACIP considered evidence for use of JYNNEOS, a replication-deficient Vaccinia virus vaccine, as an alternative to ACAM2000. In November 2021, ACIP unanimously voted in favor of JYNNEOS as an alternative to ACAM2000 for primary vaccination and booster doses. With these recommendations for use of JYNNEOS, two vaccines (ACAM2000 and JYNNEOS) are now available and recommended for preexposure prophylaxis against orthopoxvirus infection among persons at risk for such exposures.
Orthopoxviruses are large, double-stranded DNA viruses (Genus Orthopoxvirus, Family Poxviridae) that comprise multiple species, including Variola virus, Vaccinia virus, Monkeypox virus, Cowpox virus, and newly discovered species (e.g., Akhmeta virus and Alaskapox virus) (4). Infection with an orthopoxvirus or immunization with an orthopoxvirus vaccine lends immunologic cross-protection against other viruses in the genus (3). Until 1971, children in the United States received an orthopoxvirus vaccine (to prevent smallpox) as part of their routine childhood vaccines. However, with the World Health Organization (WHO) declaration of the eradication of smallpox (the infection caused by Variola virus) in 1980 (2), recommendations for routine vaccinations ended worldwide.
A small subset of persons in the United States continues to receive orthopoxvirus vaccination (3): persons at occupational risk for exposure to orthopoxvirus infections and certain U.S. military personnel. The first group (those with occupational risk for exposure) are within the purview of ACIP and the focus of this report. Regular booster doses are recommended for persons with ongoing occupational risk for exposure to orthopoxvirus infections. Designated public health and health care worker response teams approved by public health authorities should receive booster vaccination only at the time of an event, rather than at regular intervals.* ...
Summary of Findings and Rationale for Recommendations
For the first and second questions, regarding recommendation for JYNNEOS as an alternative to ACAM2000 for primary vaccination, the systematic review identified three randomized controlled studies and 15 observational studies including a total of 5,775 subjects. After considering geometric mean titers and seroconversion data together, the Work Group had moderate (level 2) certainty that JYNNEOS provides a small increase in disease prevention compared with that provided by ACAM2000.† The Work Group estimated with low (level 3) certainty that fewer serious adverse events occur following the JYNNEOS primary series compared with ACAM2000 primary vaccination, and that fewer events of myopericarditis occur after JYNNEOS primary series than after ACAM2000 primary vaccination. Based on the results from the GRADE assessment and EtR framework,§ ACIP unanimously voted in favor of the JYNNEOS vaccine as an alternative to ACAM2000 for primary vaccination.
To address the third and fourth questions, regarding booster doses, the systematic review identified one randomized controlled trial and 17 observational studies that included a total of 6,417 subjects. After considering geometric mean titer and seroconversion rate together, the Work Group estimated with very low (level 4) certainty that a small increase in disease prevention occurs after JYNNEOS booster versus the JYNNEOS primary series only.¶ The Work Group estimated with very low (level 4) certainty that fewer serious adverse events occur after a JYNNEOS booster administered following completion of the JYNNEOS primary series compared with the JYNNEOS primary series (i.e., no booster dose). No myopericarditis events were recorded in either the intervention or comparison; for this reason, the effect was not estimable and the Work Group had very low (level 4) certainty that myopericarditis does not occur after JYNNEOS boosters because of inadequate sample size to detect rare events. The ACIP unanimously voted in favor of the JYNNEOS booster vaccine after the 2-dose JYNNEOS primary series. ACIP recommended that the JYNNEOS booster dose be administered every 2 years to persons working with more virulent orthopoxviruses and every 10 years to persons working with less virulent orthopoxviruses.
For the fifth question, regarding providing the option of transitioning to JYNNEOS for a booster dose in persons who had received primary vaccination with ACAM2000, the systematic review identified one randomized controlled trial and five observational studies that included a total of 435 subjects. A total of 82% of subjects seroconverted when given JYNNEOS booster, with very low (level 4) certainty in that estimate. The Work Group estimated, with low (level 3) certainty, fewer serious adverse events occurred after the JYNNEOS booster than after the ACAM2000 booster in persons previously vaccinated with ACAM2000** and that fewer myopericarditis events occurred after a JYNNEOS booster than after an ACAM2000 booster in persons who received ACAM2000 as the primary vaccine (very low [level 3] certainty). Based on the results from the GRADE methodology and findings within the EtR framework,†† ACIP unanimously voted in favor of recommending JYNNEOS boosters as an alternative to ACAM2000 boosters in persons who received ACAM2000 as the primary vaccine. ...
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. ...
Early Release / May 27, 2022 / 71
Agam K. Rao, MD1; Brett W. Petersen, MD1; Florence Whitehill, DVM1,2; Jafar H. Razeq, PhD3; Stuart N. Isaacs, MD4; Michael J. Merchlinsky, PhD5; Doug Campos-Outcalt, MD6; Rebecca L. Morgan, PhD7; Inger Damon, MD, PhD1; Pablo J. Sánchez, MD8; Beth P. Bell, MD9
... Certain laboratorians and health care personnel can be exposed to orthopoxviruses through occupational activities. Because orthopoxvirus infections resulting from occupational exposures can be serious, the Advisory Committee on Immunization Practices (ACIP) has continued to recommend preexposure vaccination for these persons since 1980 (1), when smallpox was eradicated (2). In 2015, ACIP made recommendations for the use of ACAM2000, the only orthopoxvirus vaccine available in the United States at that time (3). During 2020–2021, ACIP considered evidence for use of JYNNEOS, a replication-deficient Vaccinia virus vaccine, as an alternative to ACAM2000. In November 2021, ACIP unanimously voted in favor of JYNNEOS as an alternative to ACAM2000 for primary vaccination and booster doses. With these recommendations for use of JYNNEOS, two vaccines (ACAM2000 and JYNNEOS) are now available and recommended for preexposure prophylaxis against orthopoxvirus infection among persons at risk for such exposures.
Orthopoxviruses are large, double-stranded DNA viruses (Genus Orthopoxvirus, Family Poxviridae) that comprise multiple species, including Variola virus, Vaccinia virus, Monkeypox virus, Cowpox virus, and newly discovered species (e.g., Akhmeta virus and Alaskapox virus) (4). Infection with an orthopoxvirus or immunization with an orthopoxvirus vaccine lends immunologic cross-protection against other viruses in the genus (3). Until 1971, children in the United States received an orthopoxvirus vaccine (to prevent smallpox) as part of their routine childhood vaccines. However, with the World Health Organization (WHO) declaration of the eradication of smallpox (the infection caused by Variola virus) in 1980 (2), recommendations for routine vaccinations ended worldwide.
A small subset of persons in the United States continues to receive orthopoxvirus vaccination (3): persons at occupational risk for exposure to orthopoxvirus infections and certain U.S. military personnel. The first group (those with occupational risk for exposure) are within the purview of ACIP and the focus of this report. Regular booster doses are recommended for persons with ongoing occupational risk for exposure to orthopoxvirus infections. Designated public health and health care worker response teams approved by public health authorities should receive booster vaccination only at the time of an event, rather than at regular intervals.* ...
Summary of Findings and Rationale for Recommendations
For the first and second questions, regarding recommendation for JYNNEOS as an alternative to ACAM2000 for primary vaccination, the systematic review identified three randomized controlled studies and 15 observational studies including a total of 5,775 subjects. After considering geometric mean titers and seroconversion data together, the Work Group had moderate (level 2) certainty that JYNNEOS provides a small increase in disease prevention compared with that provided by ACAM2000.† The Work Group estimated with low (level 3) certainty that fewer serious adverse events occur following the JYNNEOS primary series compared with ACAM2000 primary vaccination, and that fewer events of myopericarditis occur after JYNNEOS primary series than after ACAM2000 primary vaccination. Based on the results from the GRADE assessment and EtR framework,§ ACIP unanimously voted in favor of the JYNNEOS vaccine as an alternative to ACAM2000 for primary vaccination.
To address the third and fourth questions, regarding booster doses, the systematic review identified one randomized controlled trial and 17 observational studies that included a total of 6,417 subjects. After considering geometric mean titer and seroconversion rate together, the Work Group estimated with very low (level 4) certainty that a small increase in disease prevention occurs after JYNNEOS booster versus the JYNNEOS primary series only.¶ The Work Group estimated with very low (level 4) certainty that fewer serious adverse events occur after a JYNNEOS booster administered following completion of the JYNNEOS primary series compared with the JYNNEOS primary series (i.e., no booster dose). No myopericarditis events were recorded in either the intervention or comparison; for this reason, the effect was not estimable and the Work Group had very low (level 4) certainty that myopericarditis does not occur after JYNNEOS boosters because of inadequate sample size to detect rare events. The ACIP unanimously voted in favor of the JYNNEOS booster vaccine after the 2-dose JYNNEOS primary series. ACIP recommended that the JYNNEOS booster dose be administered every 2 years to persons working with more virulent orthopoxviruses and every 10 years to persons working with less virulent orthopoxviruses.
For the fifth question, regarding providing the option of transitioning to JYNNEOS for a booster dose in persons who had received primary vaccination with ACAM2000, the systematic review identified one randomized controlled trial and five observational studies that included a total of 435 subjects. A total of 82% of subjects seroconverted when given JYNNEOS booster, with very low (level 4) certainty in that estimate. The Work Group estimated, with low (level 3) certainty, fewer serious adverse events occurred after the JYNNEOS booster than after the ACAM2000 booster in persons previously vaccinated with ACAM2000** and that fewer myopericarditis events occurred after a JYNNEOS booster than after an ACAM2000 booster in persons who received ACAM2000 as the primary vaccine (very low [level 3] certainty). Based on the results from the GRADE methodology and findings within the EtR framework,†† ACIP unanimously voted in favor of recommending JYNNEOS boosters as an alternative to ACAM2000 boosters in persons who received ACAM2000 as the primary vaccine. ...
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. ...
