# Immune profiling of mpox survivors reveals divergent durability of antibody and T cell responses

## TL;DR

This study shows that mpox survivors have strong long-term T cell immunity, but antibody levels decline over time.

## Contribution

The study provides new insights into the durability of MPXV-specific antibody and T cell responses over 18 months.

## Key findings

- Neutralizing antibodies decline from 328 at 12 months to 180 at 18 months post-infection.
- MPXV-specific CD4⁺ and Tfh cell responses remain robust and polyfunctional for up to 18 months.
- CD8⁺ T cells maintain sustained cytokine production, indicating durable cellular immunity.

## Abstract

Despite the global spread of mpox virus (MPXV), the durability and breadth of infection-induced immunity remain incompletely defined. Here, we comprehensively characterize MPXV-specific antibody and T cell responses up to 18 months after natural infection in male individuals. Neutralizing antibodies exhibit typical acute viral kinetics, with titers peaking early and declining over time, from a mean of 328 at 12 months to 180 at 18 months post-infection. Neutralization analyses against MPXV clade Ib, clade IIb and VACV WR strains demonstrate pronounced cross-neutralization among orthopoxviruses, but with lineage-specific reductions in neutralization, indicating incomplete cross-reactivity across different lineages. In parallel, MPXV-specific CD4⁺ and Tfh cell responses remain robust and polyfunctional throughout follow-up, and CD8⁺ T cells maintain sustained responses characterized by cytokine production, together supporting durable cellular immunity. These findings offer critical insights into the durability and breadth of post-infection immunity, with implications for reinfection risk and orthopoxvirus vaccine strategies.

Despite the global spread of the mpox virus, the long-term durability and breadth of infection-induced immunity are not fully understood. Here, the authors analyze MPXV-specific immune responses up to 18 months post-infection, revealing robust cellular immunity and cross-neutralization among orthopoxviruses, which inform reinfection risks and vaccine development strategies.