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Why can smallpox vaccination be risky for people with weakened immune systems?

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Smallpox vaccines, such as ACAM2000, contain live, replication-competent vaccinia virus. For individuals with weakened immune systems, this poses significant risks because their bodies may struggle to control the viral replication.1

In such cases, the vaccine can lead to severe and potentially life-threatening complications, including:

Progressive vaccinia: The development of a nonhealing, worsening sore or ulceration at the vaccination site.12
Eczema vaccinatum: A severe, widespread skin rash.1
Inflammation: Serious reactions such as myocarditis (inflammation of the heart) or pericarditis (inflammation of the lining of the heart).12
Neurological issues: Potential brain inflammation, also known as encephalitis.12

Because of these dangers, medical professionals prioritize safety by utilizing nonreplicating vaccines, such as JYNNEOS, for individuals who cannot safely receive replication-competent versions. It is ethically imperative to carefully screen patients to prevent these severe adverse outcomes.12