Mpox Infection Protects People Longer than Vaccination

Infection with the mpox virus (MPXV) confers stronger immunity against future infection than vaccine-conferred protection, which wanes over time and requires boosting, researchers wrote in The Lancet Infectious Diseases on November 7, 2025.

These findings suggest that MPXV infection confers long-term protection against reinfection, whereas vaccine-induced immunity can wane over time and requires boosting.

These researchers wrote that further studies are needed to determine whether booster doses can enhance the durability of immunological memory in previously vaccinated individuals.

Should booster vaccination prove beneficial, targeted revaccination campaigns will be necessary to maintain population-level protection.

In a related commentary, researchers from the Icahn School of Medicine at Mount Sinai said that the study's findings indicate that the success of next-generation vaccines against orthopoxviruses, such as mpox, will depend on antigen selection that focuses immune responses on proteins associated with long-lasting protection and cross-reactivity against multiple orthopoxviruses.

Currently, the U.S. FDA-approved JYNNEOS (MVA-BN) mpox/smallpox vaccine is offered at clinics and pharmacies in the United States.

Funding for this study was from the Research Foundation–Flanders, Department of Economy, Science and Innovation Flanders, and the Netherlands Organization for Health Research and Development.