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

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.