A new two-year study is raising concerns about how long protection from the mpox vaccine actually lasts, with implications for vaccination policy and high-risk communities worldwide.
Researchers at National Taiwan University Hospital tracked immune responses and breakthrough infections over two years among 452 men who have sex with men enrolled in Taiwan’s national mpox vaccination program. The study, published in Clinical Microbiology and Infection, offers some of the most detailed real-world evidence yet on how vaccine protection holds up over time, and the picture is not reassuring.
Antibody Protection Drops Off Quickly
Among vaccinated participants who had never received the older smallpox vaccine, fewer than 20 percent still had detectable antibodies against two key mpox markers after two years. HIV status made little difference. People with HIV who were on effective antiretroviral treatment lost antibodies at about the same rate as HIV-negative participants. For most people in the study, the vaccine simply did not produce immunity that lasted.
The picture looked different for people with other forms of immune priming. Participants born before 1979, who had received the older smallpox vaccine as children, retained antibodies at two to three times the rate of younger participants, with about half still testing positive at the two-year mark. People who had previously been infected with mpox fared even better. Statistical analysis found that prior mpox infection lowered the odds of losing antibodies by 83 to 96 percent, while prior smallpox vaccination lowered those odds by 76 to 92 percent. In other words, immunity built from infection or from decades-old smallpox vaccination held up far better than immunity from the newer mpox vaccine alone, a gap that should factor into how officials think about booster eligibility and timing.
Breakthrough infections were uncommon but revealing. Six vaccinated participants developed confirmed mpox, with a median gap of more than 828 days, nearly two and a half years, between their second vaccine dose and symptom onset. Almost all of these individuals had no detectable antibodies at the time of infection, and most had never mounted an antibody response after vaccination in the first place. That last point matters: it suggests a meaningful share of vaccinated people may never develop lasting protection from the standard two-dose series, rather than starting with strong protection that later fades.
The six breakthrough cases offered a mixed picture. Vaccinated individuals who developed mpox were less likely to have lesions outside the genital area compared to unvaccinated cases, suggesting the vaccine still softened the course of illness for most. But three of the six needed the antiviral drug tecovirimat to treat severe complications including proctitis, and two of those three also had a concurrent sexually transmitted infection. Milder disease is not the same as prevented disease, and these cases are a reminder that antiviral treatment capacity still matters even as more people get vaccinated.
Silent Infections Suggest Surveillance Gaps
Twenty participants showed a significant rise in antibodies without ever reporting symptoms, suggesting infections that went completely unnoticed. This points to a limitation in relying on symptom-based case reporting alone, and strengthens the case for using blood testing to track population-level immunity and exposure more accurately.
Researchers measured antibodies against two mpox markers at seven points over 24 months, allowing for detailed tracking of how immunity changed across different groups. The study did not measure neutralizing antibodies or cellular immune responses, so the findings reflect only one part of the immune picture. The small number of breakthrough infections also limits how confidently the findings can be broken down by subgroup, and because most participants with HIV in the study had well-controlled infection, the results may not apply to people with more advanced immune suppression.
Taken together, the findings build a case for formally evaluating booster doses for high-risk groups, particularly those vaccinated more than two years ago or who may never have responded to the vaccine at all. Other emerging research suggests a booster dose can quickly boost antibody levels even in people who did not respond to their original vaccination. With mpox continuing to circulate globally at low levels and high-risk sexual networks persisting, this study offers some of the strongest evidence yet that a completed vaccine series does not guarantee lasting protection.
Sources and further reading
Liu WD et al. Two-year durability of MVA-BN vaccine-induced antibodies and the risk of Mpox breakthrough infections among high-risk populations: a prospective, longitudinal study. Clinical Microbiology and Infection, 3 August 2026.
This article was researched and sourced by Global Biodefense editors and reported with Claude AI assistance for drafting and editing.