Exploring monkeypox virus antibody levels: insights from human immunological research

Monkeypox(mpox) is a zoonotic disease caused by the monkeypox virus (MPXV), which was previously endemic to West and Central Africa. However, it has recently appeared in several non-endemic countries beyond Africa. On July 23, 202 WHO declared mpox outbreak a public health emergency of international concern, a declaration reaffirmed on August 14, 2024. In this context, understanding the antibody levels of MPXV in the population has become crucial, especially given the historical cross-protection provided by smallpox vaccination. To provide a comprehensive overview of the current understanding of MPXV antibody levels and the protective efficacy of smallpox vaccination, we conducted a review of the existing literature. We reviewed relevant studies published in peer-reviewed journals from 1958 to 2025, focusing on those that reported research on MPXV antibodies and the effects of smallpox vaccination. Here, we review the research progress of MPXV and smallpox virus(VARV) in epidemiology, etiology, mutation and mechanism of virus infection, clinical characteristics and vaccine application. In addition, the differences in MPXV levels in different populations and the cross-protective effect of smallpox vaccine against mpox were also discussed. Our review indicates that MPXV antibody levels are closely related to the level of immunity in the population, particularly among individuals who have received smallpox vaccination. This narrative review aims to synthesize existing evidence on the role of smallpox vaccination in protecting against mpox and to offer evidence-based guidance for public health policy. We aim to establish a theoretical foundation and practical recommendations for future research and mpox prevention strategies.