What is already known about this topic? In 2015, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure prophylaxis with ACAM2000, a replication-competent live virus Vaccinia virus vaccine, for certain U.S. persons at risk for occupational exposure to orthopoxviruses.

What is added by this report? In 2019, JYNNEOS, a replication-deficient live Vaccinia virus vaccine was licensed in the United States. On November 3, 2021, ACIP voted to recommend JYNNEOS preexposure prophylaxis as an alternative to ACAM2000 for certain persons at risk for exposure to orthopoxviruses.

What are the implications for public health practice? A second vaccine is now available for persons for whom vaccination against orthopoxvirus infections is recommended. Potential vaccinees should weigh the risks and benefits of each vaccine when deciding which to receive.

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.

Suggested citation for this article: Rao AK, Petersen BW, Whitehill F, et al. 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. MMWR Morb Mortal Wkly Rep. ePub: 27 May 2022.

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