Applying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 Feb 2024
12 Feb 2024
Historique:
received:
26
10
2022
accepted:
09
01
2024
medline:
13
2
2024
pubmed:
13
2
2024
entrez:
12
2
2024
Statut:
epublish
Résumé
Conserved epitopes shared between virus subtypes are often subdominant, making it difficult to induce broadly reactive antibodies by immunization. Here, we generate a plasmid DNA mix vaccine that encodes protein heterodimers with sixteen different influenza A virus hemagglutinins (HA) representing all HA subtypes except H1 (group 1) and H7 (group 2). Each single heterodimer expresses two different HA subtypes and is targeted to MHC class II on antigen presenting cells (APC). Female mice immunized with the plasmid mix produce antibodies not only against the 16 HA subtypes, but also against non-included H1 and H7. We demonstrate that individual antibody molecules cross-react between different HAs. Furthermore, the mix vaccine induces T cell responses to conserved HA epitopes. Immunized mice are partially protected against H1 viruses. The results show that application of valency-based immuno-selection to diversified antigens can be used to direct antibody responses towards conserved (subdominant) epitopes on viral antigens.
Identifiants
pubmed: 38346952
doi: 10.1038/s41467-024-44889-w
pii: 10.1038/s41467-024-44889-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
850Informations de copyright
© 2024. The Author(s).
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