Structural and epitope characterization of HIV-1 V1V2 highly effective neutralizing antibodies based on AlphaFold 3
10.3760/cma.j.cn112866-20250405-00077
- VernacularTitle:基于AlphaFold 3的HIV-1 V1V2高效中和抗体结构及表位特征
- Author:
Junjie ZHANG
1
;
Qianying WANG
1
;
Ying LIU
1
;
Shuhui WANG
1
;
Li REN
1
;
Shuo WANG
1
;
Yutao SHI
1
;
Yuhua RUAN
1
;
Xiaojing LIU
1
;
Xinran DU
1
;
Yanling HAO
1
;
Dan LI
1
Author Information
1. 传染病溯源预警与智能决策全国重点实验室 中国疾病预防控制中心性病艾滋病预防控制中心，北京 102206
- Publication Type:Journal Article
- Keywords:
Human immunodeficiency virus（HIV）;
Chronically infected individuals;
Neutralizing antibody;
AlphaFold 3;
Epitope
- From:
Chinese Journal of Experimental and Clinical Virology
2025;39(5):548-555
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.
