Resurfaced ZIKV EDIII nanoparticle immunogens elicit neutralizing and protective responses in vivo.
Cell Chem Biol
; 29(5): 811-823.e7, 2022 05 19.
Article
em En
| MEDLINE
| ID: mdl-35231399
ABSTRACT
Zika virus (ZIKV) is a flavivirus that can cause severe disease, but there are no approved treatments or vaccines. A complication for flavivirus vaccine development is the potential of immunogens to enhance infection via antibody-dependent enhancement (ADE), a process mediated by poorly neutralizing and cross-reactive antibodies. Thus, there is a great need to develop immunogens that minimize the potential to elicit enhancing antibodies. Here we utilized structure-based protein engineering to develop "resurfaced" (rs) ZIKV immunogens based on E glycoprotein domain III (ZDIIIs), in which epitopes bound by variably neutralizing antibodies were masked by combinatorial mutagenesis. We identified one resurfaced ZDIII immunogen (rsZDIII-2.39) that elicited a protective but immune-focused response. Compared to wild type ZDIII, immunization with resurfaced rsZDIII-2.39 protein nanoparticles produced fewer numbers of ZIKV EDIII antigen-reactive B cells and elicited serum that had a lower magnitude of induced ADE against dengue virus serotype 1 (DENV1) Our findings enhance our understanding of the structural and functional determinants of antibody protection against ZIKV.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Vírus da Dengue
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Nanopartículas
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Zika virus
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Infecção por Zika virus
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos