A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses.
Science
; 366(6470)2019 12 06.
Article
en En
| MEDLINE
| ID: mdl-31672916
ABSTRACT
Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Anticuerpos Anti-VIH
/
Vacunas contra el SIDA
/
Evolución Molecular Dirigida
/
Productos del Gen env del Virus de la Inmunodeficiencia Humana
/
Inmunogenicidad Vacunal
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Anticuerpos ampliamente neutralizantes
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos