Gorman Jason, Du Renguang, Lai Yen-Ting, Ahmadi Mohammed S, King Hannah A D, Song Kaimei, Manalang Kimberly, Gonelli Christopher A, Schramm Chaim A, Cheng Cheng, Nguyen Richard, Ambrozak David, Druz Aliaksandr, Shen Chen-Hsiang, Yang Yongping, Douek Daniel C, Kwong Peter D, Roederer Mario, Mason Rosemarie D
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Rep. 2025 Jan 28;44(1):115163. doi: 10.1016/j.celrep.2024.115163. Epub 2025 Jan 9.
The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques. The nAbs displayed low potency but up to 90% breadth on a 20-strain SIV panel. Crystal structures of representative nAbs in complex with SIV MPER peptides revealed the SIV antibodies to bind a helical epitope at the N-terminal (proximal) region of the MPER, defining a reproducible multi-donor class encompassing all four lineages. HIV-1 comparison showed that this class of SIV MPER-directed antibodies targets a helical region overlapping that targeted by human vaccine-elicited ones. Thus, a prevalent and reproducible class of SIV bnAbs recognizes an epitope similar to that recently observed in an HIV-1-vaccine trial.
HIV-1包膜的膜近端外部区域（MPER）是广泛中和抗体（bnAbs）的作用靶点，最近一项人体临床试验报告了疫苗引发的针对MPER的抗体。在本研究中，我们试图在感染猿猴免疫缺陷病毒（SIV）的恒河猴中鉴定针对MPER的中和抗体。我们从两只感染SIV的猕猴中分离出四个谱系的针对SIV MPER的中和抗体。这些中和抗体效力较低，但在一个包含20种毒株的SIV组中具有高达90%的广度。代表性中和抗体与SIV MPER肽复合物的晶体结构显示，这些SIV抗体结合MPER N端（近端）区域的一个螺旋表位，定义了一个可重复的多供体类别，涵盖所有四个谱系。与HIV-1的比较表明，这类针对SIV MPER的抗体靶向的螺旋区域与人类疫苗引发的抗体所靶向的区域重叠。因此，一类普遍且可重复的SIV bnAbs识别的表位类似于最近在一项HIV-1疫苗试验中观察到的表位。
