Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody.

Journal Article (Journal Article)

Human immunodeficiency virus type 1 (HIV-1) vaccination of cows has elicited broadly neutralizing antibodies (bNAbs). In this study, monoclonal antibodies (mAbs) are isolated from a clade A (KNH1144 and BG505) vaccinated cow using a heterologous clade B antigen (AD8). CD4 binding site (CD4bs) bNAb (MEL-1872) is more potent than a majority of CD4bs bNAbs isolated so far. MEL-1872 mAb with CDRH3 of 57 amino acids shows more potency (geometric mean half-maximal inhibitory concentration [IC50]: 0.009 μg/mL; breadth: 66%) than VRC01 against clade B viruses (29-fold) and than CHO1-31 against tested clade A viruses (21-fold). It also shows more breadth and potency than NC-Cow1, the only other reported anti-HIV-1 bovine bNAb, which has 60% breadth with geometric mean IC50 of 0.090 μg/mL in this study. Using successive different stable-structured SOSIP trimers in bovines can elicit bNAbs focusing on epitopes ubiquitous across subtypes. Furthermore, the cross-clade selection strategy also results in ultra-potent bNAbs.

Full Text

Duke Authors

Cited Authors

  • Heydarchi, B; Fong, DS; Gao, H; Salazar-Quiroz, NA; Edwards, JM; Gonelli, CA; Grimley, S; Aktepe, TE; Mackenzie, C; Wales, WJ; van Gils, MJ; Cupo, A; Rouiller, I; Gooley, PR; Moore, JP; Sanders, RW; Montefiori, D; Sethi, A; Purcell, DFJ

Published Date

  • May 17, 2022

Published In

Volume / Issue

  • 3 / 5

Start / End Page

  • 100635 -

PubMed ID

  • 35584627

Pubmed Central ID

  • PMC9133467

Electronic International Standard Serial Number (EISSN)

  • 2666-3791

Digital Object Identifier (DOI)

  • 10.1016/j.xcrm.2022.100635

Language

  • eng

Conference Location

  • United States