Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.
PLoS Pathog
; 17(6): e1009624, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-34086838
ABSTRACT
A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Anti-HIV
/
Vacinas contra a AIDS
/
Produtos do Gene env do Vírus da Imunodeficiência Humana
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Anticorpos Neutralizantes
Limite:
Animals
/
Humans
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos