The U.S. Food and Drug Administration (FDA) has approved a freeze-dried formulation of JYNNEOS® (Smallpox and Mpox Vaccine, Live, Non-replicating) for the prevention of smallpox and mpox disease in adults 18 years of age and older, Bavarian Nordic A/S announced on March 31, 2025. This new formulation will enhance stockpiling capabilities against potential smallpox events or mpox outbreaks.
The approval follows the FDA's standard review of a supplemental Biologics License Application (sBLA) submitted by Bavarian Nordic in May 2024. The application was supported by clinical data demonstrating comparable immune responses and safety profiles between the freeze-dried and liquid-frozen formulations, along with additional non-clinical and manufacturing data.
Advantages of the Freeze-Dried Formulation
Unlike the current liquid-frozen formulation of JYNNEOS, which was approved by the FDA in September 2019 and requires specific cold-chain conditions, the freeze-dried version offers significant advantages in transportation, storage, and shelf life—critical factors for effective long-term stockpiling of vaccines for emergency preparedness.
"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. "As a long-term supplier of JYNNEOS to the U.S. biological preparedness, we are committed to continue supporting the government's efforts to protect its citizens against current and future public health threats."
Long-Standing Partnership with U.S. Government
Bavarian Nordic has collaborated with the U.S. government since 2003 on developing and supplying a non-replicating smallpox vaccine. This partnership aims to ensure protection for all population groups, including immunocompromised individuals who face higher risks from traditional smallpox vaccines based on replicating vaccinia virus strains.
JYNNEOS holds the distinction of being the first smallpox vaccine successfully developed under Project BioShield—a program established by the U.S. Congress in 2004 to accelerate the development and availability of medical countermeasures against biological, chemical, radiological, and nuclear threats through public-private partnerships.
The company has been supplying the liquid-frozen version of JYNNEOS to the U.S. government for stockpiling since 2010 and provided additional doses during the 2022-2023 mpox outbreak. The U.S. Biomedical Advanced Research and Development Authority (BARDA) has contracted Bavarian Nordic to develop and supply the freeze-dried version specifically for stockpiling purposes. Manufacturing under this contract began in 2024, with initial vaccine deliveries scheduled for later in 2025.
Clinical Profile and Safety Information
JYNNEOS is indicated for adults 18 years and older determined to be at high risk for smallpox and mpox infection. The vaccine's development was initially focused on ensuring smallpox vaccine availability for the entire population, particularly addressing the needs of immunocompromised individuals.
In 2021, the Advisory Committee on Immunization Practices (ACIP) under the Centers for Disease Control and Prevention (CDC) recommended JYNNEOS for pre-exposure vaccination of people at occupational risk for orthopoxvirus exposures. During the 2022 mpox outbreak, the CDC issued interim guidance enabling both pre- and post-exposure use of the vaccine, and the FDA granted an Emergency Use Authorization (EUA) for its use in people under 18 years. In October 2023, the CDC updated its guidance to recommend routine use of JYNNEOS for at-risk individuals 18 years and older.
The safety profile of JYNNEOS includes common injection site reactions such as pain, redness, swelling, induration, and itching. Systemic adverse reactions frequently reported include muscle pain, headache, fatigue, nausea, and chills. The frequencies of these reactions were generally similar among healthy adults, adults with HIV infection, and adults with atopic dermatitis.
Public Health Implications
The approval of the freeze-dried JYNNEOS formulation represents a significant advancement in public health preparedness. The improved stability and storage characteristics address key logistical challenges in maintaining vaccine stockpiles, particularly important for rapid response to potential outbreaks.
This development comes at a critical time as global health authorities continue to emphasize the importance of preparedness against potential infectious disease threats. The 2022-2023 mpox outbreak highlighted the need for readily available vaccines that can be quickly deployed to affected areas.
The freeze-dried JYNNEOS formulation is expected to play a vital role in the U.S. government's strategic national stockpile, enhancing the country's ability to respond effectively to future smallpox or mpox threats while ensuring vaccine accessibility for vulnerable populations.
