Infection with the mpox virus (MPXV) confers strong immunity against future infection for up to two years, compared with vaccine-conferred protection, which wanes with time and requires boosting, researchers in Belgium and the Netherlands reported late last week in The Lancet Infectious Diseases.

The investigators evaluated the long-term clinical consequences of mpox infection in adults; the continued presence of the virus in saliva, semen, and the anorectal area; and long-term antibody dynamics post-infection versus that after receipt of the Jynneos smallpox/mpox vaccine. 

The study period began in 2022, with enrollment of participants in a clinical registry with 1-month post-infection follow-up in May and a long-term follow-up study with a parallel group of adult recipients of two doses of Jynneos (or one dose if vaccinated against smallpox in childhood) from August 2022 to January 2023.

High antibody levels after infection

Of 250 infected participants, 237 were enrolled (199 prospectively and 38 retrospectively). Among 1,728 Jynneos recipients, 210 were enrolled (209 prospectively and one retrospectively). 

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

In total, 47% of 237 infected participants attended follow-up at eight months, 57% at 16 months, and 27% at 24 months. In the Jynneos group, 98% of 210 adults attended follow-up at eight months, 77% at 16 months, and 69% at 24 months. Median participant age was 40 years, and 96% were men. 

Scarring occurred in 46% of 71 mpox patients at month eight, 30% of 57 at month 16, and 32% of 63 at month 24. Other symptoms mostly resolved within a year. All saliva and anorectal swabs were negative for MPXV throughout follow-up, and all 23 semen swabs tested negative at month eight.

Also in month eight, Jynneos recipients not vaccinated against smallpox had lower binding antibody concentrations than those with mpox infection, and MPXV neutralizing antibodies were detected in 4%; intradermal vaccination elicited lower binding antibody concentrations than subcutaneous vaccination.

“Further studies are needed to determine whether booster doses can enhance the durability of immunological memory in previously vaccinated individuals,” the authors wrote. “Should booster vaccination prove beneficial, targeted revaccination campaigns will be necessary to maintain population-level protection.”

Developing next-generation vaccines

In a commentary in the same journal, Raianna Fantin, PhD, and Camila Coelho, PhD, both of the Icahn School of Medicine at Mount Sinai, said that the study 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.

“Incorporating such epitopes [part of an antigen that an antibody or T-cell receptor binds to] into next-generation prime-boost platforms has the potential to enhance both the magnitude and the longevity of antibody-mediated protection, while preserving a favorable safety profile and ensuring global production feasibility, not only in high-income countries but also in Latin America and Africa, where the effects of mpox have been particularly severe and disproportionately felt,” they concluded.