Adam Abdullahi

United Kingdom

Sero-genomic evidence for occult mpox exposure in healthy Nigerian adults

Adam Abdullahi1

1. Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of
Medicine, University of Cambridge, Cambridge, UK

Abstract

Background

BACKGROUND: The 2022 multi-country mpox outbreak, driven by Monkeypox virus (MPXV) Clade IIb, spread to over 100 countries, reigniting global public health concern. With smallpox vaccination halted after eradication, large unvaccinated populations remain, and the extent to which residual immunity influences present-day susceptibility is unclear.

Methods

To determine whether vaccination-derived immunity continues to shape infection risk and to assess the burden of asymptomatic transmission in a West African population, we combined serological and phylogenetic analyses. Using a six-plex Luminex assay, we quantified IgG binding to six MPXV antigens (A35R, A29L, B6R, H3L, M1R, and A27L) in 176 Nigerian adults – 75 healthcare workers sampled in 2021 and 101 community volunteers sampled in 2023. Magnitude-breadth (MB) scores were calculated as a composite measure of immune reactivity, and paired samples were analysed over a median of 9 months to identify serological boosting consistent with exposure.

Results

At baseline, 24/176 (13.6%) participants were MPXV-seropositive, predominantly among those born before 1980, consistent with legacy smallpox vaccination. MB scores were two-fold higher in the pre-1980 compared with post-1980 cohort. Among 153 participants with follow-up samples, 5 (3%) demonstrated ≥2-fold increases in MB scores and antibody boosting against ≥4 of 6 antigens, consistent with cryptic exposure. These individuals were all seronegative at baseline and largely male, with no reported clinical mpox illness. The strongest median boosting was observed for B6R (11-fold), followed by M1R (6.2-fold) and A35R (5.2-fold), though inter-individual variability was notable. Complementary phylogenetic analysis of 105 Nigerian MPXV genomes revealed sporadic local transmission amid frequent dead-end infections, consistent with limited but ongoing community-level spread.

Conclusions

Combined serological and genomic evidence indicates that residual smallpox-derived immunity continues to shape population-level susceptibility to mpox in Nigeria, while asymptomatic exposure contributes to under-ascertained transmission. These findings underscore the importance of multi-antigen serological surveillance to detect cryptic infections and inform targeted vaccination strategies in African settings.