HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.
Science
; 351(6280): 1458-63, 2016 Mar 25.
Article
em En
| MEDLINE
| ID: mdl-27013733
ABSTRACT
Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naïve B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naïve B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Anti-HIV
/
HIV-1
/
Vacinas contra a AIDS
/
Epitopos de Linfócito B
/
Células Precursoras de Linfócitos B
/
Anticorpos Neutralizantes
/
Células Germinativas
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Anticorpos Monoclonais
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article