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

TitleBroad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody.
Publication TypeJournal Article
Year of Publication2022
AuthorsHeydarchi 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
JournalCell Rep Med
Volume3
Issue5
Pagination100635
Date Published2022 May 17
ISSN2666-3791
KeywordsAnimals, Antibodies, Monoclonal, Antibodies, Neutralizing, Binding Sites, Broadly Neutralizing Antibodies, Cattle, CD4 Antigens, env Gene Products, Human Immunodeficiency Virus, Female, HIV Antibodies, HIV Infections, HIV-1, Vaccines
Abstract

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.

DOI10.1016/j.xcrm.2022.100635
Alternate JournalCell Rep Med
PubMed ID35584627
PubMed Central IDPMC9133467
Grant ListP01 AI110657 / AI / NIAID NIH HHS / United States

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