Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.
Nature
; 570(7762): 468-473, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-31142836
ABSTRACT
Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
VIH-1
/
Vacunación
/
Células Clonales
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Vacunas contra el SIDA
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Macaca mulatta
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nature
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos