Immune Monitoring Reveals Fusion Peptide Priming to Imprint Cross-Clade HIV-Neutralizing Responses with a Characteristic Early B Cell Signature.
Cell Rep
; 32(5): 107981, 2020 08 04.
Article
em En
| MEDLINE
| ID: mdl-32755575
ABSTRACT
The HIV fusion peptide (FP) is a promising vaccine target. FP-directed monoclonal antibodies from vaccinated macaques have been identified that neutralize up to â¼60% of HIV strains; these vaccinations, however, have involved â¼1 year with an extended neutralization-eclipse phase without measurable serum neutralization. Here, in 32 macaques, we test seven vaccination regimens, each comprising multiple immunizations of FP-carrier conjugates and HIV envelope (Env) trimers. Comparisons of vaccine regimens reveal FP-carrier conjugates to imprint cross-clade neutralizing responses and a cocktail of FP conjugate and Env trimer to elicit the earliest broad responses. We identify a signature, appearing as early as week 6 and involving the frequency of B cells recognizing both FP and Env trimer, predictive of vaccine-elicited breadth â¼1 year later. Immune monitoring of B cells in response to vaccination can thus enable vaccine insights even in the absence of serum neutralization, here identifying FP imprinting, cocktail approach, and early signature as means to improve FP-directed vaccine responses.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Proteínas Recombinantes de Fusão
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Linfócitos B
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Anticorpos Anti-HIV
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Monitorização Imunológica
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Anticorpos Neutralizantes
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article