Unexpectedly higher levels of naturally occurring anti-Vaccinia neutralizing antibodies are observed among gay men compared to general population

The confirmed cases in the current outbreak of Monkeypox are predominantly identified in the networks of men who have sex with men (MSM). It is suggested that special behavioral characteristics might make the virus spread more easily in this population, but the biological factors affecting the spread of this outbreak have not been fully clarified. In this study, we measured the anti-Monkeypox and anti-Vaccinia antibodies in an MSM cohort (comprising 326 individuals) and a general population cohort (comprising 295 individuals) and compared the antibody responses between the two cohorts. Meanwhile, we also compared the antibody responses between individuals born before and in/after 1981, when the smallpox vaccination was ceased in China. Our data showed that binding antibodies against Monkeypox H3L, A29L, A35R proteins and Vaccinia whole-virus lysate could be detected in individuals born both before and in/after 1981, of which the anti-Vaccinia binding antibody levels were found to be significantly higher among the individuals born before 1981 in the general population cohort. Moreover, we unexpectedly found that the levels of binding antibody responses against Monkeypox proteins were significantly lower among individuals of the MSM cohort born in/after 1981, but the anti-Vaccinia neutralizing antibody levels were significantly higher among these individuals compared to those age-matched participants of the general population cohort. Additionally, we demonstrated that the positive and negative rates of anti-Monkeypox antibody responses were associated with the anti-Vaccinia antibody responses among individuals born before 1981 in the general population cohort, but no significant association was observed among individuals born in/after 1981 in both cohorts. Further studies are warranted to clarify the impact of the naturally occurring anti-Orthopoxvirus antibodies on the transmission of Monkeypox, especially among gay men who have not been vaccinated against smallpox.