Breakthrough Infection, Reinfection Rare but Possible After Mpox Infection or Vaccination
June 28, 2025
New findings from CROI 2025 confirm that mpox reinfection is rare, but not impossible—even among vaccinated individuals. Two studies show that vaccine-induced immunity wanes over time, particularly in people with HIV, and that prior infection does not guarantee lifelong protection. However, the CDC continues to recommend against vaccinating people who have already recovered from mpox, citing the rarity and mild nature of reinfections. These findings underscore the need for ongoing surveillance, research into booster strategies, and nuanced guidance for vulnerable populations, especially as mpox continues to evolve and circulate in both endemic and non-endemic settings.
Two pivotal studies presented at CROI 2025 in San Francisco reveal critical insights into mpox reinfection and vaccine durability. Researchers from University College Dublin found that immunity from the Jynneos (MVA-BN) vaccine significantly wanes within two years, especially in people with HIV. In contrast, individuals with prior mpox infection retained stronger and longer-lasting antibody responses. Only 32% of vaccinated participants remained seropositive after roughly 650 days, compared to 85% of those previously infected.
A separate California Department of Public Health study identified nine confirmed or probable reinfections among over 6,400 mpox cases between 2022 and 2024—a 0.14% reinfection rate. Genome sequencing confirmed distinct clade IIb virus lineages in three of the reinfected patients. Notably, some reinfections occurred in individuals who had completed the two-dose vaccine series. Despite this, reinfections were mild, and current CDC guidance does not recommend vaccination for individuals with prior mpox infections.
These findings emphasize that although mpox reinfections and breakthrough cases are rare, immunity—whether from vaccination or natural infection—may not be uniformly durable, particularly in immunocompromised populations. This raises the need to revisit booster strategies for at-risk groups, while reinforcing that blanket re-vaccination for all previously infected individuals is not currently necessary.
Clinicians are urged to consider mpox in patients presenting with compatible symptoms, regardless of prior infection or vaccination status. Ongoing surveillance, genomic analysis, and prospective immunity studies are essential for refining public health recommendations and preventing resurgence. As mpox becomes endemic in more regions, nuanced strategies will be key—especially for vulnerable groups like people with HIV. In the evolving landscape of post-emergency mpox management, evidence-based updates must drive equitable, effective response efforts worldwide.