Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 04, 2021
- Source ID
- 10.1371/journal.ppat.1009624
Entities
People
- Amanda Eaton
- Barton Haynes
- Bette Korber
- Celia C LaBranche
- David C. Montefiori
- Esther M. Lee
- Fangping Cai
- Georgia D. Tomaras
- Giovanna E. Hernandez
- Julia A Jones
- Kevin O Saunders
- Kevin Wiehe
- Kshitij Wagh
- Laura L Sutherland
- M Anthony Moody
- M Gordon Joyce
- Mattia Bonsignori
- Michael S Seaman
- Misook Choe
- Natalia de Val
- Neelakshi Gohain
- Nelson R Wu
- Richard M Scearce
- Sampa Santra
- Weimin Wu
- Wei‐Hung Chen
- Xiaoying Shen
Organizations
- Defense Health Agency
- National Institute of Allergy and Infectious Diseases
- Office of Basic Energy Sciences
- United States Department of Energy