Vaccination induces broadly neutralizing antibody precursors to HIV gp41.
Nat Immunol
; 25(6): 1073-1082, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38816615
ABSTRACT
A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Anti-HIV
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Proteína gp41 do Envelope de HIV
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Infecções por HIV
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HIV-1
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Vacinas contra a AIDS
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Anticorpos Neutralizantes
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Macaca mulatta
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article