Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers.
Science
; 363(6427): 649-654, 2019 02 08.
Article
em En
| MEDLINE
| ID: mdl-30573546
ABSTRACT
In vaccine design, antigens are often arrayed in a multivalent nanoparticle form, but in vivo mechanisms underlying the enhanced immunity elicited by such vaccines remain poorly understood. We compared the fates of two different heavily glycosylated HIV antigens, a gp120-derived mini-protein and a large, stabilized envelope trimer, in protein nanoparticle or "free" forms after primary immunization. Unlike monomeric antigens, nanoparticles were rapidly shuttled to the follicular dendritic cell (FDC) network and then concentrated in germinal centers in a complement-, mannose-binding lectin (MBL)-, and immunogen glycan-dependent manner. Loss of FDC localization in MBL-deficient mice or via immunogen deglycosylation significantly affected antibody responses. These findings identify an innate immune-mediated recognition pathway promoting antibody responses to particulate antigens, with broad implications for humoral immunity and vaccine design.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polissacarídeos
/
Proteína gp120 do Envelope de HIV
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Infecções por HIV
/
Vacinas contra a AIDS
/
Centro Germinativo
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Imunidade Inata
/
Formação de Anticorpos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos