# Broadly neutralizing antibody responses in a Chinese acute HIV-1 infection cohort of men who have sex with men

## TL;DR

This study shows that people infected with multiple HIV strains, especially later after initial infection, develop stronger neutralizing antibodies, which could help design better HIV vaccines.

## Contribution

The study identifies delayed sequential HIV-1 strain exposure as a novel factor enhancing broadly neutralizing antibody responses.

## Key findings

- Individuals with multiple HIV-1 infections had stronger bnAb responses than those with monoinfection.
- Superinfection occurring beyond one year after primary infection showed a higher odds ratio for enhanced bnAb responses.
- Delayed sequential antigen exposure may promote bnAb development and inform vaccine strategies.

## Abstract

Numerous broadly neutralizing antibodies (bnAbs) have been isolated from individuals with chronic HIV-1 infection, yet eliciting bnAbs through active immunization remains challenging. Investigating naturally infected patients whose plasma exhibits broadly neutralizing activity may reveal the factors driving bnAb development and inform vaccine design. We analyzed the clinical, immunological, and virological correlates of bnAb responses in a longitudinally followed, antiretroviral therapy (ART)-naïve, acute HIV-1 infection (AHI) cohort (n = 52) of men who have sex with men (MSM) in Shenyang, China. Neutralizing activity was assessed in participant plasma samples collected at the last available time point (LTP), prior to ART initiation, loss to follow-up, or the study data cutoff (median: 3.82 years, range: 3.14–4.82 years). To determine the occurrence and timing of HIV-1 multiple infection, we amplified and deep-sequenced the env C2–V4 and pol-RT regions (~450 bp) from plasma collected at baseline, one year, two years, and LTP. Individuals with multiple infection developed significantly stronger bnAb responses at LTP than those with monoinfection. Notably, acquisition of a second HIV-1 strain within or beyond one year after primary infection was associated with enhanced bnAb responses, with a higher odds ratio (OR) observed for superinfection occurring beyond one year. These findings indicate the potential role of immunogen diversity and immunization timing in bnAb induction, supporting vaccine strategies that mimic delayed sequential antigen delivery.

Understanding the processes that drive the development of broadly neutralizing antibodies (bnAbs) during natural HIV-1 infection is crucial for effective vaccine design. In this study, we investigated clinical, immunological, and virological factors associated with bnAb responses in a cohort of men who have sex with men (MSM) with acute HIV-1 infection (AHI) in Shenyang, China. We found that individuals with multiple infection exhibited stronger bnAb responses, regardless of whether the second strain was acquired within or beyond one year after primary infection, with a greater effect in the latter group. These findings suggest that delayed sequential exposure to diverse HIV-1 strains may promote bnAb development and inform future vaccine strategies.