The breadth of HIV-1 neutralizing antibodies depends on the conservation of key sites in their epitopes.
PLoS Comput Biol
; 15(6): e1007056, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-31170145
ABSTRACT
Developing HIV-1 vaccines that trigger broadly neutralizing antibodies (bnAbs) is a priority as bnAbs are considered key to elicitation of a protective immune response. To investigate whether the breadth of a neutralizing antibody (nAb) depended on the conservation of its epitope among circulating viruses, we examined AntibodyEnvelope (AbEnv) interactions and worldwide Env diversity. We found that sites corresponding to bnAb epitopes were as variable as other accessible, non-hypervariable Env sites (p = 0.50, Mann-Whitney U-test) with no significant relationship between epitope conservation and neutralization breadth (Spearman's ρ = -0.44, adjusted p = 0.079). However, when accounting for key sites in the AbEnv interaction, we showed that the broadest bnAbs targeted more conserved epitopes (Spearman's ρ = -0.70, adjusted p = 5.0e-5). Neutralization breadth did not stem from the overall conservation of Ab epitopes but depended instead on the conservation of key sites of the AbEnv interaction, revealing a mechanistic basis for neutralization breadth that could be exploited for vaccine design.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Anticuerpos Anti-VIH
/
Secuencia Conservada
/
Anticuerpos Neutralizantes
Idioma:
En
Revista:
PLoS Comput Biol
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos