Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.
Cell
; 187(1): 79-94.e24, 2024 01 04.
Article
en En
| MEDLINE
| ID: mdl-38181743
ABSTRACT
The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound to HIV-1 Env demonstrated binding angles and heavy-chain interactions characteristic of all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccine study initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishing the key first step in the development of an effective HIV-1 vaccine.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
VIH-1
/
Vacunas contra el SIDA
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Año:
2024
Tipo del documento:
Article