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State of California—Health and Human Services Agency
California Department of Public Health

July 27, 2022

California Local Health Jurisdictions (LHJs)

Prioritizing inventory of JYNNEOS smallpox and monkeypox vaccine

Smallpox and Monkeypox Vaccine, Live, Non-Replicating (trade name JYNNEOS) is approved by FDA for the prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. JYNNEOS is licensed for a 2-dose series given at an interval of 28 days, based on a comparable immune response to replicating vaccinia vaccine (trade name ACAM2000) for participants in a pivotal randomized clinical trial.[1]


During the summer of 2022 supplies of JYNNEOS are expected to be insufficient to protect all persons who are at high risk of contracting monkeypox during the current outbreak. While supplies remain scarce, vaccinators in California may offer first doses of JYNNEOS to additional persons at risk rather than retain inventory as second doses for immunocompetent persons, even if second doses are consequently administered at an interval greater than 28 days.


Persons with moderate to severe immunosuppression, including those with CD4 cell counts below 200/mm3, should receive second doses of JYNNEOS at an interval of 28 days, when possible, due to their potentially diminished responses to vaccination.


Second doses can be offered as more doses of JYNNEOS become available to better meet the priority high risk populations.

Rationale for the interim guidance:

  • During the eradication of smallpox, a first dose of vaccines protected against smallpox soon after administration: Replicating first-generation vaccinia vaccines, when given

    • within 4 days from exposure to smallpox virus have prevented onset of smallpox disease. 

    • between 4–14 days after exposure may have reduced the symptoms of smallpox disease.

  • In the pivotal clinical trial1, measurements of immunity 14 days after vaccination were similar after a first dose of either JYNNEOS or ACAM2000, including

    • Levels of seroconversion

    • Average levels (GMTs) of neutralizing antibody

      • GMTs of neutralizing antibody 14 days after a first dose of JYNNEOS in the trial approximated threshold levels associated with protection against smallpox disease estimated in two small studies conducted during the eradication of smallpox in the 1970's.[2],[3]

      • In persons with HIV infection and a history of CD4 cell counts below 200/mm3, GMTs of neutralizing antibody after 2 doses, but not 1 dose, exceeded the protective levels estimated in historical studies.[4]

  • One dose of JYNNEOS protected macaques exposed to lethal levels of monkeypox virus four or more days after vaccination.[5]

  • Increasing the number of first doses might provide at least partial protection to more individuals at risk during the current outbreak.

  • Increasing the interval between doses is not expected to reduce (and might increase) the eventual level of immunity after a second dose, with a potential tradeoff of increasing the interval at risk of exposure.


CDPH has also considered the gaps in data and evidence for a standard interval between doses. CDPH will monitor emerging data in its ongoing evaluation of the current policy.