A single cycle influenza virus coated in H7 hemagglutinin provides heterotypic protection and neutralising antibody responses to both glycoproteins
Abstract A non-replicating form of pseudotyped influenza virus, inactivated by suppression of the hemagglutinin signal sequence (S-FLU), can act as a broadly protective vaccine. S-FLU can infect for a single round only, and induces heterotypic protection predominantly through activation of cross-reactive T cells in the lung. Unlike the licensed live attenuated virus, it cannot reassort a pandemic HA into seasonal influenza. Here we present data on four new forms of S-FLU coated with the H7 hemagglutinins from A/Anhui/1/2013 and A/Shanghai/1/2013, H7N9 viruses that emerged recently in China, and A/Netherlands/219/2003 and A/New York/107/2003. We show that vaccination in the lung induced a strong local CD8 T cell response and protected against heterosubtypic X31 (H3N2) virus and highly virulent PR8 (H1N1), but not influenza B virus. Lung vaccination also induced a strong neutralising antibody response to the encoded neuraminidase. If given at higher dose in the periphery, H7 S-FLU induced a specific neutralising antibody response to H7 hemagglutinin coating the particle. Polyvalent vaccination with mixed H7 S-FLU induced a broadly neutralising antibody response to all four H7 strains. S-FLU is a versatile vaccine candidate that could be rapidly mobilized ahead of a new pandemic threat..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 29. Aug. Zur Gesamtaufnahme - year:2023 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Powell, Timothy J [VerfasserIn] |
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Links: |
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Themen: |
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doi: |
10.1101/224550 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI000205931 |
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520 | |a Abstract A non-replicating form of pseudotyped influenza virus, inactivated by suppression of the hemagglutinin signal sequence (S-FLU), can act as a broadly protective vaccine. S-FLU can infect for a single round only, and induces heterotypic protection predominantly through activation of cross-reactive T cells in the lung. Unlike the licensed live attenuated virus, it cannot reassort a pandemic HA into seasonal influenza. Here we present data on four new forms of S-FLU coated with the H7 hemagglutinins from A/Anhui/1/2013 and A/Shanghai/1/2013, H7N9 viruses that emerged recently in China, and A/Netherlands/219/2003 and A/New York/107/2003. We show that vaccination in the lung induced a strong local CD8 T cell response and protected against heterosubtypic X31 (H3N2) virus and highly virulent PR8 (H1N1), but not influenza B virus. Lung vaccination also induced a strong neutralising antibody response to the encoded neuraminidase. If given at higher dose in the periphery, H7 S-FLU induced a specific neutralising antibody response to H7 hemagglutinin coating the particle. Polyvalent vaccination with mixed H7 S-FLU induced a broadly neutralising antibody response to all four H7 strains. S-FLU is a versatile vaccine candidate that could be rapidly mobilized ahead of a new pandemic threat. | ||
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