Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding

TLDR

Broadly neutralizing HIV antibodies can prevent infection when passively transferred, implying that vaccines inducing such antibodies could be protective, yet few naturally occurring examples have been characterized. The study aimed to determine whether naturally occurring broadly neutralizing HIV antibodies belong to a larger related group. To address this, the authors cloned 576 new HIV antibodies from four unrelated individuals. The authors found that each donor produced expanded clones of potent CD4‑binding‑site antibodies that mimic CD4, share a consensus 68‑amino‑acid IgH sequence arising independently from two related genes, and structurally conserve key contacts with the HIV spike as seen in comparison to VRC01.

Abstract

Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.