纵向分析揭示了一名 HIV-1 感染者中三种靶向 MPER 的中和抗体谱系的早期发展。

Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.

机构信息

U.S. Military HIV Research Program, WRAIR, Silver Spring, MD, USA; Henry Jackson Foundation, Bethesda, MD, USA.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

出版信息

Immunity. 2019 Mar 19;50(3):677-691.e13. doi: 10.1016/j.immuni.2019.02.008. Epub 2019 Mar 12.

DOI:10.1016/j.immuni.2019.02.008

PMID:30876875

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6555550/

Abstract

Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.

摘要

基于谱系的疫苗设计是一种很有吸引力的方法，可以诱导针对 HIV-1 的广泛中和抗体（bNAb）。然而，迄今为止研究的大多数 bNAb 谱系都具有异常重组和/或发育的特征。从前瞻性 RV217 队列中的一个个体中，我们鉴定了针对 HIV-1 包膜的膜近端外部区域（MPER）的三种 bNAb 谱系。抗体 RV217-VRC42.01、-VRC43.01 和 -VRC46.01 分别采用不同的识别模式，中和了 208 株病毒的 96%、62%和 30%。这三种谱系的体细胞超突变和正常抗体环长度都较低，并且都是由创始病毒 MPER 启动的。最广泛的谱系 VRC42 与已知的 bNAb 4E10 相似。基于创始者 MPER 的多聚体免疫原激活了携带 VRC42 未突变的共同祖先的 B 细胞，早期 VRC42 中间体的适度成熟赋予了中和广度。这些特征表明 VRC42 可能是基于谱系的疫苗设计的一个有前途的模板。