International AIDS Vaccine Initiative Neutralizing Antibody Center, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10004, USA.
UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda; Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala-Uganda.
Immunity. 2019 Jul 16;51(1):141-154.e6. doi: 10.1016/j.immuni.2019.06.004.
The VH1-2 restricted VRC01-class of antibodies targeting the HIV envelope CD4 binding site are a major focus of HIV vaccine strategies. However, a detailed analysis of VRC01-class antibody development has been limited by the rare nature of these responses during natural infection and the lack of longitudinal sampling of such responses. To inform vaccine strategies, we mapped the development of a VRC01-class antibody lineage (PCIN63) in the subtype C infected IAVI Protocol C neutralizer PC063. PCIN63 monoclonal antibodies had the hallmark VRC01-class features and demonstrated neutralization breadth similar to the prototype VRC01 antibody, but were 2- to 3-fold less mutated. Maturation occurred rapidly within ∼24 months of emergence of the lineage and somatic hypermutations accumulated at key contact residues. This longitudinal study of broadly neutralizing VRC01-class antibody lineage reveals early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.
针对 HIV 包膜 CD4 结合位点的 VH1-2 受限 VRC01 类抗体是 HIV 疫苗策略的主要关注点。然而，由于在自然感染过程中这些反应的罕见性以及缺乏对这些反应的纵向采样，对 VRC01 类抗体的发展进行详细分析受到了限制。为了为疫苗策略提供信息，我们对感染亚型 C 的 IAVI 协议 C 中和 PC063 中的 VRC01 类抗体谱系（PCIN63）的发展进行了映射。PCIN63 单克隆抗体具有标志性的 VRC01 类特征，并表现出与原型 VRC01 抗体相似的中和广度，但突变率低 2-3 倍。成熟在谱系出现后的大约 24 个月内迅速发生，体细胞超突变积累在关键接触残基上。对广泛中和的 VRC01 类抗体谱系的这项纵向研究揭示了在亲和力成熟过程中早期与 N276-聚糖结合，这可能对疫苗设计具有重要意义。
