The fading shield: why losing smallpox immunity leaves us vulnerable to new outbreaks

Health · Published 19 October 2026 Swipe more like this →

In short: The 1980 eradication of smallpox was a monumental achievement, yet stopping widespread vaccinations may have weakened our collective defenses. Because these vaccines offered cross-protection, the decline in global immunization has reduced our immunity to other orthopoxviruses that continue to circulate within various animal populations around the world.

The Orthopagodoxvirus genus includes some of history's most devastating pathogens, most notably the Variola virus. While a coordinated global effort successfully eradicated smallpox by 1980, this victory came with a hidden cost. Because the smallpox vaccine also provided cross-protection against related orthopoxviruses, the widespread discontinuation of vaccination has diminished global immunological memory against the broader group.

Today, the threat is not just from known pathogens like mpox, but from the potential for zoonotic spillover. While smallpox was uniquely unable to maintain animal reservoirs, many other members of the genus—such as cowpox, mpox, and buffalopox—can infect a wide range of mammals, including rodents, cats, and cows. This diversity is driven by a large repertoire of accessory genes that help the virus inhibit host immune responses. Interestingly, the evolutionary path of these viruses involves significant genomic flux; for instance, the Modified vaccinia Ankara vaccine strain has lost roughly 15% of its ~200 kb genome, leading to a more restricted host range.

Predicting where the next outbreak might emerge is a complex challenge. Researchers are now using machine learning to combine host ecological data with viral genomic features to identify 'hotspots' for potential emergence. Current models point to high-risk regions in Southeast Asia, equatorial Africa, and the Amazon, where high potential for host species overlaps with low smallpox vaccination coverage. As mpox continues to spread beyond its historical range, identifying these unidentified reservoirs in wildlife becomes a critical priority for global health surveillance.

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