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Applying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins.
Hinke, Daniëla Maria; Anderson, Ane Marie; Katta, Kirankumar; Laursen, Marlene Fyrstenberg; Tesfaye, Demo Yemane; Werninghaus, Ina Charlotta; Angeletti, Davide; Grødeland, Gunnveig; Bogen, Bjarne; Braathen, Ranveig.
Afiliación
  • Hinke DM; K.G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, Oslo, Norway.
  • Anderson AM; Institute of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Katta K; K.G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, Oslo, Norway.
  • Laursen MF; Institute of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Tesfaye DY; Institute of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Werninghaus IC; Institute of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Angeletti D; Institute of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Grødeland G; Institute of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Bogen B; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Braathen R; K.G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, Oslo, Norway.
Nat Commun ; 15(1): 850, 2024 Feb 12.
Article en En | MEDLINE | ID: mdl-38346952
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas contra la Influenza / Infecciones por Orthomyxoviridae / Gripe Humana Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas contra la Influenza / Infecciones por Orthomyxoviridae / Gripe Humana Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Reino Unido