Mpox infection triggers stronger, longer-term protection than vaccination, study suggests
November 11, 2025
New research published in The Lancet Infectious Diseases shows that natural mpox infection provides stronger and longer-lasting immunity—up to two years—compared with vaccination using Jynneos, whose protection declines over time. Researchers from Belgium and the Netherlands found that post-infection antibody levels were significantly higher than those generated by vaccination, highlighting the need for targeted booster campaigns to sustain population immunity. The study also confirmed no long-term viral shedding in recovered patients. Experts emphasize the importance of next-generation vaccines focused on antigens that trigger durable, cross-protective immune responses, particularly for low-resource regions facing repeated outbreaks.
A new study in The Lancet Infectious Diseases offers critical insights into mpox immunity, revealing that infection confers stronger, longer-lasting protection than vaccination. Researchers from Belgium and the Netherlands tracked adults with confirmed mpox infection and recipients of the Jynneos vaccine over a two-year period. Their findings show that natural infection induces robust antibody responses that remain detectable for up to 24 months, while vaccine-induced immunity wanes substantially after one year, particularly among those who never received prior smallpox vaccination.
The trial followed 237 infected participants and 210 vaccinated adults, with the majority being men around 40 years old. By the eighth month, Jynneos recipients who had not previously been vaccinated against smallpox displayed much lower antibody concentrations than post-infection participants, and neutralizing antibodies were found in only 4 percent of vaccinated individuals. In contrast, individuals with prior mpox infection maintained high antibody levels and showed no detectable viral shedding in saliva, semen, or anorectal samples, indicating complete viral clearance.
These results reinforce the need for booster campaigns among vaccinated populations, especially those at highest risk. The authors urge further research into booster timing, immune memory, and optimal vaccination strategies to sustain population-level protection.
In an accompanying commentary, scientists from the Icahn School of Medicine at Mount Sinai noted that next-generation vaccines should focus on key orthopoxvirus antigens that elicit long-lasting and cross-reactive immunity. Incorporating these into prime-boost vaccine platforms could increase both durability and safety, enabling equitable access across all regions, including Latin America and Africa.
Access to the full article and accompanying commentary in The Lancet Infectious Diseases requires journal membership or institutional access. However, the findings signal a pivotal step in shaping future vaccine design and immunization strategies for mpox and related orthopoxviruses.