Elderly Individuals Exhibit Elevated Levels of Anti‐Monkeypox Virus Antibodies Compared to Adults, Youth, and Children

ABSTRACT The variola virus, the causative agent of smallpox, has claimed more human lives than all other infectious diseases combined. Consequently, any epidemiological event involving related viruses (orthopoxviruses) triggers significant concern, as was the case with the pandemic rise of monkeypox virus (MPXV), the causative agent of monkeypox in 2022−2023. Smallpox vaccines, based on vaccinia virus antigens, are expected to provide cross‐protection against MPXV. Studying the general seroprevalence of orthopoxviruses in populations worldwide is crucial for estimating susceptibility, risks, and the need for vaccination campaigns. In this study, we aimed to evaluate the seroprevalence of antibodies capable of recognizing MPXV in a Brazilian population and assess the potential for cross‐protection from previous smallpox vaccinations. We analyzed demographic data, vaccination records, and serum levels of anti‐MPXV IgG measured by enzyme‐linked immunosorbent assay (ELISA) in 319 volunteers from Barreiras, Bahia, Brazil. Our main findings show that the numbers of volunteers with serum samples recognizing MPXV in ELISA, as well as their serum levels of anti‐MPXV IgG, did not differ significantly according to gender or address type. However, both male and female elderly volunteers exhibited significantly higher concentrations of anti‐MPXV IgG than adults, youth, and children. These results suggest that the elderly may benefit from a cross‐reactive immune response due to previous smallpox vaccinations, whereas adults, youth, and children appear susceptible to MPXV. Further investigations involving other populations are necessary to assess the necessity of vaccinating potentially vulnerable groups.