Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model

T cell responses directed against highly conserved viral proteins contribute to the clearance of the influenza virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses in mice and ferrets. We examined the protective efficacy of mucosal delivery of...

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Main Authors: Anna Schmidt, Basudev Paudyal, Sonia Villanueva-Hernández, Adam Mcnee, Eleni Vatzia, Brigid Veronica Carr, Selma Schmidt, Amy Mccarron, Veronica Martini, Silke Schroedel, Christian Thirion, Ryan Waters, Francisco J. Salguero, Wilhelm Gerner, Matthias Tenbusch, Elma Tchilian
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1181716/full
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author Anna Schmidt
Basudev Paudyal
Sonia Villanueva-Hernández
Adam Mcnee
Eleni Vatzia
Brigid Veronica Carr
Selma Schmidt
Amy Mccarron
Veronica Martini
Silke Schroedel
Christian Thirion
Ryan Waters
Francisco J. Salguero
Wilhelm Gerner
Matthias Tenbusch
Matthias Tenbusch
Elma Tchilian
author_facet Anna Schmidt
Basudev Paudyal
Sonia Villanueva-Hernández
Adam Mcnee
Eleni Vatzia
Brigid Veronica Carr
Selma Schmidt
Amy Mccarron
Veronica Martini
Silke Schroedel
Christian Thirion
Ryan Waters
Francisco J. Salguero
Wilhelm Gerner
Matthias Tenbusch
Matthias Tenbusch
Elma Tchilian
author_sort Anna Schmidt
collection DOAJ
description T cell responses directed against highly conserved viral proteins contribute to the clearance of the influenza virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses in mice and ferrets. We examined the protective efficacy of mucosal delivery of adenoviral vectors expressing hemagglutinin (HA) and nucleoprotein (NP) from the H1N1 virus against heterologous H3N2 challenge in pigs. We also evaluated the effect of mucosal co-delivery of IL-1β, which significantly increased antibody and T cell responses in inbred Babraham pigs. Another group of outbred pigs was first exposed to pH1N1 as an alternative means of inducing heterosubtypic immunity and were subsequently challenged with H3N2. Although both prior infection and adenoviral vector immunization induced strong T-cell responses against the conserved NP protein, none of the treatment groups demonstrated increased protection against the heterologous H3N2 challenge. Ad-HA/NP+Ad-IL-1β immunization increased lung pathology, although viral load was unchanged. These data indicate that heterotypic immunity may be difficult to achieve in pigs and the immunological mechanisms may differ from those in small animal models. Caution should be applied in extrapolating from a single model to humans.
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spelling doaj.art-7a124e0b2d554bd1b327bae9c7f98cfe2023-04-20T05:58:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11817161181716Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza modelAnna Schmidt0Basudev Paudyal1Sonia Villanueva-Hernández2Adam Mcnee3Eleni Vatzia4Brigid Veronica Carr5Selma Schmidt6Amy Mccarron7Veronica Martini8Silke Schroedel9Christian Thirion10Ryan Waters11Francisco J. Salguero12Wilhelm Gerner13Matthias Tenbusch14Matthias Tenbusch15Elma Tchilian16Virologisches Institut-Klinische und Molekulare Virologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, GermanyHost Responses, The Pirbright Institute, Pirbright, United KingdomHost Responses, The Pirbright Institute, Pirbright, United KingdomHost Responses, The Pirbright Institute, Pirbright, United KingdomHost Responses, The Pirbright Institute, Pirbright, United KingdomHost Responses, The Pirbright Institute, Pirbright, United KingdomHost Responses, The Pirbright Institute, Pirbright, United KingdomHost Responses, The Pirbright Institute, Pirbright, United KingdomInstitute for Research in Biomedicine, Bellinzona, SwitzerlandSIRION Biotech GmbH, Martinsried, GermanySIRION Biotech GmbH, Martinsried, GermanyHost Responses, The Pirbright Institute, Pirbright, United KingdomUnited Kingdom Health Security Agency, UKHSA-Porton Down, Salisbury, United KingdomHost Responses, The Pirbright Institute, Pirbright, United KingdomVirologisches Institut-Klinische und Molekulare Virologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, GermanyMedical Immunology Campus Erlangen (MICE), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, GermanyHost Responses, The Pirbright Institute, Pirbright, United KingdomT cell responses directed against highly conserved viral proteins contribute to the clearance of the influenza virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses in mice and ferrets. We examined the protective efficacy of mucosal delivery of adenoviral vectors expressing hemagglutinin (HA) and nucleoprotein (NP) from the H1N1 virus against heterologous H3N2 challenge in pigs. We also evaluated the effect of mucosal co-delivery of IL-1β, which significantly increased antibody and T cell responses in inbred Babraham pigs. Another group of outbred pigs was first exposed to pH1N1 as an alternative means of inducing heterosubtypic immunity and were subsequently challenged with H3N2. Although both prior infection and adenoviral vector immunization induced strong T-cell responses against the conserved NP protein, none of the treatment groups demonstrated increased protection against the heterologous H3N2 challenge. Ad-HA/NP+Ad-IL-1β immunization increased lung pathology, although viral load was unchanged. These data indicate that heterotypic immunity may be difficult to achieve in pigs and the immunological mechanisms may differ from those in small animal models. Caution should be applied in extrapolating from a single model to humans.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1181716/fullinfluenza viruspigmucosal immunityIL-1βheterotypic protectionporcine B cells
spellingShingle Anna Schmidt
Basudev Paudyal
Sonia Villanueva-Hernández
Adam Mcnee
Eleni Vatzia
Brigid Veronica Carr
Selma Schmidt
Amy Mccarron
Veronica Martini
Silke Schroedel
Christian Thirion
Ryan Waters
Francisco J. Salguero
Wilhelm Gerner
Matthias Tenbusch
Matthias Tenbusch
Elma Tchilian
Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model
Frontiers in Immunology
influenza virus
pig
mucosal immunity
IL-1β
heterotypic protection
porcine B cells
title Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model
title_full Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model
title_fullStr Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model
title_full_unstemmed Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model
title_short Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model
title_sort effect of mucosal adjuvant il 1β on heterotypic immunity in a pig influenza model
topic influenza virus
pig
mucosal immunity
IL-1β
heterotypic protection
porcine B cells
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1181716/full
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