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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cai, F; Chen, W-H; Wu, W; Jones, JA; Choe, M; Gohain, N; Shen, X; LaBranche, C; Eaton, A; Sutherland, L; Lee, EM; Hernandez, GE; Wu, NR; Scearce, R; Seaman, MS; Moody, MA; Santra, S; Wiehe, K; Tomaras, GD; Wagh, K; Korber, B; Bonsignori, M; Montefiori, DC; Haynes, BF; de Val, N; Joyce, MG; Saunders, KO

Published Date

  • June 2021

Published In

Volume / Issue

  • 17 / 6

Start / End Page

  • e1009624 -

PubMed ID

  • 34086838

Pubmed Central ID

  • PMC8216552

Electronic International Standard Serial Number (EISSN)

  • 1553-7374

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1009624

Language

  • eng

Conference Location

  • United States