Immune Reconstitution and Antigenic Exposure History Shape Virus-Specific Humoral Immunity in People with HIV
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: SUMMARY 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.
Institutions: Wuhan University, State Key Laboratory of Virology, Zhongnan Hospital of Wuhan University, Chinese Academy of Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Jinyintan Hospital, Wuhan Institute of Virology, Huazhong University of Science and Technology, Xinjiang Institute of Materia Medica, Xinjiang University
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Award: G6261861418
OpenAlex ID: W7214925930