---
title: "CD4+ Recovery and Exposure History Determine Virus-Specific Antibody Function in People with HIV"
id: "biorxiv-3-immune-reconstitution-and-antigenic-exposure-history-shape-virus-specific"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-3-immune-reconstitution-and-antigenic-exposure-history-shape-virus-specific"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1?rss=1"
published_at: "2026-09-30T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CD4+ Recovery and Exposure History Determine Virus-Specific Antibody Function in People with HIV
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-3-immune-reconstitution-and-antigenic-exposure-history-shape-virus-specific
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1?rss=1)
- **Published At:** 2026-09-30T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- This preprint evaluated how **CD4+ T-cell recovery** (immune reconstitution) and prior antigenic exposure influence virus-specific humoral responses in people with HIV who are on ART and virologically suppressed. - The authors measured neutralizing activity against SARS-CoV-2, **HIV-1**, and **influenza** across participants stratified by CD4+ T-cell levels. - For SARS-CoV-2, the BA.5 lineage was the dominant neutralization target across all CD4 strata, while neutralization of the ancestral **D614G** variant increased with greater immune reconstitution. - The CD4-associated gradient in neutralization seen for D614G was largely absent for antigenically divergent, immune-evasive SARS-CoV-2 variants NB.1.8.1 and XFG. - Neutralizing activity against **HIV-1** showed an inverse association with CD4+ T-cell count—higher HIV-1 neutralization in individuals with lower CD4 counts. - Influenza neutralization patterns depended on the viral strain; no uniform relationship with CD4 status was reported. - When neutralization measurements were translated into inferred protection (neutralization-to-protection bridging), the CD4-associated gradient persisted for D614G but not for highly immune-evasive SARS-CoV-2 variants. - The authors conclude that immune reconstitution (CD4 recovery) does not uniformly restore antiviral humoral function; instead, antibody profiles reflect a combination of host immune status, prior antigenic exposure, and viral antigenic evolution. - The study supports adding pathogen-specific functional serologic assessment to routine immune monitoring in people with HIV. - This work is a preprint and has not been peer reviewed; methodological details and full data were not reported in the abstract.
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Juan Han 1 Wuhan University State Key Laboratory of Virology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Juan%2BHan%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Han%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJuan%2BHan%2B) Shuyan Zhang 1 Wuhan University State Key Laboratory of Virology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Shuyan%2BZhang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Zhang%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AShuyan%2BZhang%2B) Chunhai Liu 1 Wuhan University State Key Laboratory of Virology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Chunhai%2BLiu%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Liu%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AChunhai%2BLiu%2B) Shi Zou 2 Zhongnan Hospital of Wuhan University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Shi%2BZou%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Zou%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AShi%2BZou%2B) Lanfang Shi 1 Wuhan University State Key Laboratory of Virology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Lanfang%2BShi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Shi%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALanfang%2BShi%2B) Tongtong Li 1 Wuhan University State Key Laboratory of Virology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Tongtong%2BLi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Li%20T&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ATongtong%2BLi%2B) Chenxia Xu 1 Wuhan University State Key Laboratory of Virology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Chenxia%2BXu%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Xu%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AChenxia%2BXu%2B) Chong Chen 1 Wuhan University State Key Laboratory of Virology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Chong%2BChen%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Chen%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AChong%2BChen%2B) Ke Liang 3 Wuhan Jinyintan Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ke%2BLiang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Liang%20K&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AKe%2BLiang%2B) Qian Wang 1 Wuhan University State Key Laboratory of Virology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Qian%2BWang%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Wang%20Q&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AQian%2BWang%2B) Lihong Liu 1 Wuhan University State Key Laboratory of Virology; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Lihong%2BLiu%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Liu%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALihong%2BLiu%2B) * For correspondence: llh3411@whu.edu.cn * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5828837/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5828837/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5828837/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5828837/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5828837/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## 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. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared National Natural Science Foundation of China, 92569102 Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China State Key Laboratory of Virology and Biosafety, Wuhan University, Wuhan, China 2026 National Science and Technology Major Program for New-Generation Artificial Intelligence, 2026ZD0127500, 2026ZD0127501, 2026ZD0127503 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY 4.0 International license](http://creativecommons.org/licenses/by/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/09/30/2026.09.26.754322.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.09.26.754322v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Immune Reconstitution and Antigenic Exposure History Shape Virus-Specific Humoral Immunity in People with HIV Juan Han, Shuyan Zhang, Chunhai Liu, Shi Zou, Lanfang Shi, Tongtong Li, Chenxia Xu, Chong Chen, Ke Liang, Qian Wang, Lihong Liu bioRxiv 2026.09.26.754322; doi: https://doi.org/10.64898/2026.09.26.754322 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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