# Comparative humoral profiles in mpox cases, survivors, and vaccinated individuals reveal correlates of protection against MPXV

## TL;DR

The study identifies key antibodies and factors that protect against mpox, offering insights into immune responses in infected and vaccinated individuals.

## Contribution

The paper identifies specific MPXV antigens and demographic factors that correlate with protective humoral immunity.

## Key findings

- MPXV antigens A29, E8, M1, A35, and B6 are key targets of neutralizing antibodies.
- Passive transfer of MPXV-immune plasma reduces viral replication in vivo.
- Age influences antibody levels in VACV-vaccinated individuals, but not gender.

## Abstract

Mpox is regarded as the most important orthopoxvirus infection since the eradication of smallpox, yet the determinants of protective antibody responses remain poorly defined. Here, we investigate factors shaping humoral protection against MPXV and observe a moderate correlation between orthopoxvirus antibody levels and age among vaccinia virus (VACV)-vaccinated individuals. No correlation is found between orthopoxvirus-binding antibodies and gender. Pre-existing humoral immunity does not impair the induction of MPXV-specific antibody responses in mpox cases. Despite a high seropositivity rate for neutralizing antibodies in both mpox cases and vaccinated individuals, the overall titers remain modest. Quantitative analyses identify MPXV antigens A29, E8, and M1 on intracellular mature virion (IMV), together with A35 and B6 on extracellular enveloped virion (EEV), as the principal targets of neutralizing antibodies elicited during both MPXV infection and vaccination. Passive transfer of plasma from mpox patients and convalescents significantly reduces viral replication in vivo. These findings provide critical insights into the correlates of protection against MPXV.

•Comprehensive profiling defines humoral correlates of protection to MPXV•Serology shows age-related differences in binding and neutralizing titers post-VACV•Antibody depletion reveals IMV and EEV neutralization hierarchies•Passive transfer of MPXV-immune plasma suppresses viral replication in vivo

Comprehensive profiling defines humoral correlates of protection to MPXV

Serology shows age-related differences in binding and neutralizing titers post-VACV

Antibody depletion reveals IMV and EEV neutralization hierarchies

Passive transfer of MPXV-immune plasma suppresses viral replication in vivo

Wang et al. compare humoral profiles in mpox patients, convalescents, and vaccinated individuals, identifying dominant MPXV-neutralizing targets and defining antigenic and demographic correlates of orthopoxvirus immunity. Infection- and vaccination-induced antibodies confer in vivo protection, revealing determinants of effective humoral defense against MPXV.