HIV-1 Neutralizing Antibodies Elicited in Humans by a Prefusion-stabilized Envelope Trimer Form a Reproducible Class Targeting Fusion Peptide

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2023 Jul 12

PMID 37436899

Authors

Shuishu Wang

Flavio Matassoli

Baoshan Zhang

Tracy Liu

Chen-Hsiang Shen

Tatsiana Bylund

Timothy Johnston

Amy R Henry

I-Ting Teng

Prabhanshu Tripathi

Jordan E Becker

Anita Changela

Ridhi Chaudhary

Cheng Cheng

Martin Gaudinski

Jason Gorman

Darcy R Harris

Myungjin Lee

Nicholas C Morano

Laura Novik

Sijy ODell

Adam S Olia

Danealle K Parchment

Reda Rawi

Jesmine Roberts-Torres

Tyler Stephens

Yaroslav Tsybovsky

Danyi Wang

David J Van Wazer

Tongqing Zhou

Nicole A Doria-Rose

Richard A Koup

Lawrence Shapiro

Daniel C Douek

Adrian B McDermott

Peter D Kwong

Affiliations

Soon will be listed here.

Abstract

Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability.

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