Isolation and structure of broad SIV-neutralizing antibodies reveal a proximal helical MPER epitope recognized by a rhesus multi-donor class

TL;DR

Scientists found antibodies in SIV-infected monkeys that target a key region of the virus, similar to antibodies from a human HIV vaccine trial.

Contribution

Identification of a reproducible class of SIV broadly neutralizing antibodies targeting a helical MPER epitope.

Findings

Four SIV MPER-directed antibody lineages were isolated from two infected macaques.

The antibodies bind a helical epitope at the N-terminal region of the MPER.

This SIV antibody class overlaps with human vaccine-elicited HIV-1 antibodies in target region.

Abstract

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.

The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (nAbs) and vaccine development. Gorman et al. describe four SIV MPER-directed antibody lineages, from two rhesus macaques, that share immunogenetics and bind the MPER in a similar manner, thereby comprising a reproducible class of SIV bnAbs.

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