Vaccines · Oct 10, 2026

Age-Related Immune Response to Previous Smallpox Vaccination in Albanian Subjects and Cross-Reactivity Between Vaccinia Virus and Monkeypox Virus Antigens

By Manuka A, Mehmeti I, Radaelli A et al.

Background/Objectives: Recent outbreaks of the mpox virus (MPVX) have highlighted the threat posed by the Orthopoxvirus (OPXV) genus, which includes variola, the causative agent of smallpox. Since routine Vaccinia virus (VACV) vaccination campaigns terminated, the majority of the global population currently lacks immunity against OPXVs. Methods: Using enzyme-linked immunosorbent assays (ELISAs), this study evaluated antibody titers against both VACV proteins and their MPVX orthologs across various age groups. Cross-reactivity was analyzed using 220 serum samples collected from Albanian individuals between November 2023 and January 2024, arranged into five age cohorts. We measured plasma antibody levels against whole VACV, as well as specific surface antigens: L1, B5, A33, and A27 for VACV, and M1, H3, A35, and A29 for MPXV. Results: The data reveal a long-term, gender-independent immunological memory targeting both whole-virus particles and individual viral proteins. Conclusions: Notably, the oldest cohort exhibited higher antibody titers against specific single viral proteins, whereas the younger vaccinated groups showed stronger activity against the whole virus. Additionally, antibodies raised via VACV vaccination recognize MPXV ortholog proteins equally well. This cross-reactivity highlights the broad protective potential of VACV immunization across the entire Orthopoxvirus genus.

doi.org/10.3390/vaccines14100889 Open access PubMed 42931418 Mechanisms