FDA Approves Freeze-Dried Smallpox/Mpox Vaccine

On Mar. 31, 2025, the U.S. Food and Drug Administration (FDA) approved the freeze-dried formulation of Bavarian Nordic A/S’s Jynneos vaccine for smallpox and mpox (formerly monkey pox) in adults 18 years of age and older. The liquid-frozen formulation of the vaccine was approved by the FDA on Sept. 24, 2019, but that version requires temperature-controlled environments that allows them to remain frozen between production and final use. Meanwhile, the freeze-dried formulation provides certain logistical advantages such as ease of transportation, flexibility of storage conditions, extension of molecular stability, and thus and shelf life, which can facilitate long-term stockpiling.^{1 2 3 4 5 6}

The approval of the freeze-dried version of Jynneos follows a standard review by the FDA of a supplemental Biologics License Application (sBLA) submitted in May 2024 by Bavarian Nordic of Hellerup, Denmark. The review looked mainly at the results of a Phase II clinical trial involving 651 healthy participants who were each given two doses of either the liquid-frozen vaccine or the freeze-dried formulation. The trial noted no statistical differences between the two groups in immune responses and no serious adverse events, although it was observed that the freeze-dried group did experience slightly higher local reactions. The review also looked at other non-clinical and manufacturing data.^{1 2 3 5 6}

“Today’s FDA approval represents a significant milestone in our development of this next generation of Jynneos  and in our collaborative efforts with the U.S. government to strengthen public health security,” said Paul Chaplin, president and CEO of Bavarian Nordic. It will “provide additional flexibility for stockpiling against a smallpox event or mpox outbreak,” added a company press release.^{1 2 3 5 6}

Bavarian Nordic has supplied a liquid-frozen version of Jynneos to the U.S. government for stockpiling since 2010 and in response to the mpox outbreak in 2022-2023. In 2017, the U.S. Biomedical Advanced Research and Development Authority (BARDA) awarded the company a contract to develop a freeze-dried formulation of Jynneos with a longer shelf-life to replace the stockpile. In August 2023, a $120 million BARDA contract for production of a freeze-dried Jynneos was awarded to Bavarian Nordic, and this was followed up in August 2024 with a $156.8 million contract—$139.7 million of which will be used to replenish the U.S. government inventory of the vaccine, while $17 million will go toward storing vaccine doses during 2025-2027.^{1 3 7 8}

Jynneos is a Live Virus Vaccine

Both the freeze-dried and liquid-frozen formulations of the Jynneos vaccine are live virus vaccines. They are produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated (weakened), non-replicating orthopoxvirus—a modified form of the vaccinia virus that reportedly does not cause disease in humans and cannot reproduce in human cells.⁹

Side Effects of Jynneos

The most common injection site reactions to the Jynneos (also known as Imvamune or Imvanex) vaccine are pain, redness, swelling, induration (thickening and hardening of skin) and itching. The most common systemic adverse reactions include muscle pain, headache, fatigue, nausea and chills. The incidence of cardiac adverse events following vaccination with Jynneos is unknown. A study published in the journal Vaccine in 2023 noted that the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended that people with “underlying cardiac risk factors should be counseled about the theoretical risk for myopericarditis” after getting the vaccine.¹⁰

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