Prior Mpox Infection Results in More Durable Protection Than MVA-BN Vaccination
January 13, 2026
New findings reported in The Lancet Infectious Diseases complicate assumptions about mpox immunity. Among smallpox-naive adults, prior mpox infection produced stronger and more durable immune memory than vaccination with the MVA-BN vaccine. As breakthrough infections increase, these data suggest population-level immunity may erode faster than anticipated. While vaccination remains essential for prevention, especially during outbreaks, the results underscore the need to reassess durability, booster strategies, and how natural infection data should inform long-term mpox control planning.
Evidence emerging from a longitudinal cohort study challenges prevailing assumptions about mpox immunity in smallpox-naive populations. Research conducted at the Institute of Tropical Medicine indicates that individuals with prior mpox infection develop more robust and durable immunologic memory than those vaccinated with the MVA-BN. As breakthrough infections continue to be documented, this distinction carries significant implications for outbreak preparedness and vaccination policy.
The study followed adults with confirmed mpox infection for up to 24 months, alongside a parallel cohort vaccinated between 2022 and 2023. While long-term clinical sequelae were generally limited, visible scarring persisted in a substantial subset of patients, even as pain, fatigue, and functional impacts declined over time. Importantly, no evidence of viral persistence was detected in saliva, anorectal, or semen samples during follow-up, providing reassurance regarding long-term transmissibility.
Immunologically, the contrast was more striking. Previously infected individuals maintained higher antibody levels over time, whereas vaccinated participants, particularly those born after 1976, showed significantly reduced antibody concentrations and lower neutralizing antibody prevalence within months. Older participants benefited from residual vaccinia-derived immunity, reinforcing the protective legacy of historical smallpox vaccination and highlighting a generational vulnerability among younger cohorts.
These findings do not diminish the value of vaccination. MVA-BN remains a critical countermeasure for outbreak control, especially for those without prior exposure. However, they do raise pressing questions about the durability of vaccine-induced protection and whether current dosing strategies are sufficient to sustain immunity at the population level.
The authors appropriately note limitations, including potential participation bias and loss to follow-up. Even so, the signal is clear. If declining antibodies correspond to reduced protection, booster strategies and next-generation vaccines may be necessary. Mpox immunity should no longer be viewed as static. It is dynamic, unevenly distributed, and central to preventing future resurgence.