Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.

Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.

A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nA...

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Main Authors: Fangping Cai, Wei-Hung Chen, Weimin Wu, Julia A Jones, Misook Choe, Neelakshi Gohain, Xiaoying Shen, Celia LaBranche, Amanda Eaton, Laura Sutherland, Esther M Lee, Giovanna E Hernandez, Nelson R Wu, Richard Scearce, Michael S Seaman, M Anthony Moody, Sampa Santra, Kevin Wiehe, Georgia D Tomaras, Kshitij Wagh, Bette Korber, Mattia Bonsignori, David C Montefiori, Barton F Haynes, Natalia de Val, M Gordon Joyce, Kevin O Saunders
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-06-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009624&type=printable
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Summary:A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.
ISSN:1553-7366
1553-7374

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