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What is the difference between ACAM2000 and JYNNEOS smallpox vaccines?

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Infographic showing estimated lives saved by childhood vaccinations worldwide from 1974 to 2024, with syringe-shaped bars for each disease. Measles tops the list at 93.71 million lives saved, followed by tetanus, whooping cough, and others, for a total of 153.84 million lives saved. — vaccine Vaccines and the estimates of lives saved over the period 1974–2024.

The primary difference between ACAM2000 and JYNNEOS lies in their ability to replicate within the human body, which significantly impacts their safety profiles.

ACAM2000: This vaccine contains a live, replication-competent vaccinia virus. Because the virus can replicate in human cells, it is effective for emergency preparedness but carries a higher risk of side effects and complications, such as myocarditis or the accidental spread of the virus to other parts of the body or other people.1
JYNNEOS: Also known as MVA-BN, this is a live, nonreplicating vaccinia-based vaccine. Because the virus cannot replicate in human cells, it offers a more favorable safety profile. It is the preferred option for individuals who cannot safely receive replication-competent vaccines, such as those with weakened immune systems or specific skin conditions.1

While both are used to prevent smallpox, JYNNEOS is also indicated for the prevention of mpox. Maintaining these vaccine stockpiles is a critical component of global public health preparedness.1