Immune Reconstitution and Antigenic Exposure History Shape Virus-Specific Humoral Immunity in People with HIV
- 1Wuhan University State Key Laboratory of Virology
Abstract
CD4+ T-cell recovery is widely used to assess immune reconstitution in people with HIV, but its relationship to virus-specific humoral immunity across pathogens remains unclear. We characterized neutralizing activity against SARS-CoV-2, HIV-1, and influenza viruses in ART-treated, virologically suppressed individuals spanning distinct CD4+ T-cell levels. BA.5 was the dominant SARS-CoV-2 neutralization target across CD4 strata, whereas D614G neutralization increased with greater immune reconstitution. This gradient was largely absent for the antigenically divergent NB.1.8.1 and XFG variants. HIV-1 neutralization was inversely associated with CD4+ T-cell count, while influenza showed strain-dependent patterns. Neutralization-to-protection bridging preserved a CD4-associated gradient for D614G but not for highly immune-evasive variants. These findings show that immune reconstitution does not translate uniformly into antiviral humoral function. Instead, antibody profiles reflect host immune status, prior antigenic exposure, and viral antigenic evolution, supporting pathogen-specific functional assessment alongside conventional immune monitoring.
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BibTeX
@misc{han2026immune,
title = {{Immune Reconstitution and Antigenic Exposure History Shape Virus-Specific Humoral Immunity in People with HIV}},
author = {J. Han and S. Zhang and C. Liu and S. Zou and L. Shi and T. Li and C. Xu and C. Chen and K. Liang and Q. Wang and L. Liu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.26.754322},
url = {https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Immune Reconstitution and Antigenic Exposure History Shape Virus-Specific Humoral Immunity in People with HIV
AU - J. Han
AU - S. Zhang
AU - C. Liu
AU - S. Zou
AU - L. Shi
AU - T. Li
AU - C. Xu
AU - C. Chen
AU - K. Liang
AU - Q. Wang
AU - L. Liu
PY - 2026
DA - 2026/09/26
PB - bioRxiv
DO - 10.64898/2026.09.26.754322
UR - https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1
AB - CD4+ T-cell recovery is widely used to assess immune reconstitution in people with HIV, but its relationship to virus-specific humoral immunity across pathogens remains unclear. We characterized neutralizing activity against SARS-CoV-2, HIV-1, and influenza viruses in ART-treated, virologically suppressed individuals spanning distinct CD4+ T-cell levels. BA.5 was the dominant SARS-CoV-2 neutralization target across CD4 strata, whereas D614G neutralization increased with greater immune reconstitution. This gradient was largely absent for the antigenically divergent NB.1.8.1 and XFG variants. HIV-1 neutralization was inversely associated with CD4+ T-cell count, while influenza showed strain-dependent patterns. Neutralization-to-protection bridging preserved a CD4-associated gradient for D614G but not for highly immune-evasive variants. These findings show that immune reconstitution does not translate uniformly into antiviral humoral function. Instead, antibody profiles reflect host immune status, prior antigenic exposure, and viral antigenic evolution, supporting pathogen-specific functional assessment alongside conventional immune monitoring.
ER -