Applying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 12. Feb., Seite 850 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hinke, Daniëla Maria [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Viral |
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| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 15.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-44889-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368370836 |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Hemagglutinins |2 NLM | |
| 650 | 7 | |a Influenza Vaccines |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
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| 650 | 7 | |a Hemagglutinin Glycoproteins, Influenza Virus |2 NLM | |
| 700 | 1 | |a Anderson, Ane Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Katta, Kirankumar |e verfasserin |4 aut | |
| 700 | 1 | |a Laursen, Marlene Fyrstenberg |e verfasserin |4 aut | |
| 700 | 1 | |a Tesfaye, Demo Yemane |e verfasserin |4 aut | |
| 700 | 1 | |a Werninghaus, Ina Charlotta |e verfasserin |4 aut | |
| 700 | 1 | |a Angeletti, Davide |e verfasserin |4 aut | |
| 700 | 1 | |a Grødeland, Gunnveig |e verfasserin |4 aut | |
| 700 | 1 | |a Bogen, Bjarne |e verfasserin |4 aut | |
| 700 | 1 | |a Braathen, Ranveig |e verfasserin |4 aut | |
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