An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models

Abstract Although vaccines are usually given intramuscularly, the intranasal delivery route may lead to better mucosal protection and limit the spread of respiratory virus while easing administration and improving vaccine acceptance. The challenge, however, is to achieve delivery across the selectiv...

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Main Authors: Aina Karen Anthi, Anette Kolderup, Eline Benno Vaage, Malin Bern, Sopisa Benjakul, Elias Tjärnhage, Fulgencio Ruso-Julve, Kjell-Rune Jensen, Heidrun Elisabeth Lode, Marina Vaysburd, Jeannette Nilsen, Marie Leangen Herigstad, Siri Aastedatter Sakya, Lisa Tietze, Diego Pilati, Mari Nyquist-Andersen, Mirjam Dürkoop, Torleif Tollefsrud Gjølberg, Linghang Peng, Stian Foss, Morten C. Moe, Benjamin E. Low, Michael V. Wiles, David Nemazee, Frode L. Jahnsen, John Torgils Vaage, Kenneth A. Howard, Inger Sandlie, Leo C. James, Gunnveig Grødeland, Fridtjof Lund-Johansen, Jan Terje Andersen
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59353-6
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author Aina Karen Anthi
Anette Kolderup
Eline Benno Vaage
Malin Bern
Sopisa Benjakul
Elias Tjärnhage
Fulgencio Ruso-Julve
Kjell-Rune Jensen
Heidrun Elisabeth Lode
Marina Vaysburd
Jeannette Nilsen
Marie Leangen Herigstad
Siri Aastedatter Sakya
Lisa Tietze
Diego Pilati
Mari Nyquist-Andersen
Mirjam Dürkoop
Torleif Tollefsrud Gjølberg
Linghang Peng
Stian Foss
Morten C. Moe
Benjamin E. Low
Michael V. Wiles
David Nemazee
Frode L. Jahnsen
John Torgils Vaage
Kenneth A. Howard
Inger Sandlie
Leo C. James
Gunnveig Grødeland
Fridtjof Lund-Johansen
Jan Terje Andersen
author_facet Aina Karen Anthi
Anette Kolderup
Eline Benno Vaage
Malin Bern
Sopisa Benjakul
Elias Tjärnhage
Fulgencio Ruso-Julve
Kjell-Rune Jensen
Heidrun Elisabeth Lode
Marina Vaysburd
Jeannette Nilsen
Marie Leangen Herigstad
Siri Aastedatter Sakya
Lisa Tietze
Diego Pilati
Mari Nyquist-Andersen
Mirjam Dürkoop
Torleif Tollefsrud Gjølberg
Linghang Peng
Stian Foss
Morten C. Moe
Benjamin E. Low
Michael V. Wiles
David Nemazee
Frode L. Jahnsen
John Torgils Vaage
Kenneth A. Howard
Inger Sandlie
Leo C. James
Gunnveig Grødeland
Fridtjof Lund-Johansen
Jan Terje Andersen
author_sort Aina Karen Anthi
collection DOAJ
description Abstract Although vaccines are usually given intramuscularly, the intranasal delivery route may lead to better mucosal protection and limit the spread of respiratory virus while easing administration and improving vaccine acceptance. The challenge, however, is to achieve delivery across the selective epithelial cell barrier. Here we report on a subunit vaccine platform, in which the antigen is genetically fused to albumin to facilitate FcRn-mediated transport across the mucosal barrier in the presence of adjuvant. Intranasal delivery in conventional and transgenic mouse models induces both systemic and mucosal antigen-specific antibody responses that protect against challenge with SARS-CoV-2 or influenza A. When benchmarked against an intramuscularly administered mRNA vaccine or an intranasally administered antigen fused to an alternative carrier of similar size, only the albumin-based intranasal vaccine yields robust mucosal IgA antibody responses. Our results thus suggest that this needle-free, albumin-based vaccine platform may be suited for vaccination against respiratory pathogens.
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record_format Article
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spelling doaj-art-e437d11e1d4647a9aee9aebc214d701f2025-08-20T03:52:19ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59353-6An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse modelsAina Karen Anthi0Anette Kolderup1Eline Benno Vaage2Malin Bern3Sopisa Benjakul4Elias Tjärnhage5Fulgencio Ruso-Julve6Kjell-Rune Jensen7Heidrun Elisabeth Lode8Marina Vaysburd9Jeannette Nilsen10Marie Leangen Herigstad11Siri Aastedatter Sakya12Lisa Tietze13Diego Pilati14Mari Nyquist-Andersen15Mirjam Dürkoop16Torleif Tollefsrud Gjølberg17Linghang Peng18Stian Foss19Morten C. Moe20Benjamin E. Low21Michael V. Wiles22David Nemazee23Frode L. Jahnsen24John Torgils Vaage25Kenneth A. Howard26Inger Sandlie27Leo C. James28Gunnveig Grødeland29Fridtjof Lund-Johansen30Jan Terje Andersen31Department of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletProtein and Nucleic Acid Chemistry Division, Medical Research Council, Laboratory of Molecular BiologyDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletInterdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus UniversityDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology and Microbiology, The Scripps Research InstituteDepartment of Immunology, Oslo University Hospital RikshospitaletCenter of Eye Research, Department of Ophthalmology, Oslo University Hospital Ullevål and University of OsloThe Jackson LaboratoryThe Jackson LaboratoryDepartment of Immunology and Microbiology, The Scripps Research InstituteInstitute of Clinical Medicine, University of OsloDepartment of Immunology, Oslo University Hospital RikshospitaletInterdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus UniversityDepartment of Biosciences, University of OsloProtein and Nucleic Acid Chemistry Division, Medical Research Council, Laboratory of Molecular BiologyDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletAbstract Although vaccines are usually given intramuscularly, the intranasal delivery route may lead to better mucosal protection and limit the spread of respiratory virus while easing administration and improving vaccine acceptance. The challenge, however, is to achieve delivery across the selective epithelial cell barrier. Here we report on a subunit vaccine platform, in which the antigen is genetically fused to albumin to facilitate FcRn-mediated transport across the mucosal barrier in the presence of adjuvant. Intranasal delivery in conventional and transgenic mouse models induces both systemic and mucosal antigen-specific antibody responses that protect against challenge with SARS-CoV-2 or influenza A. When benchmarked against an intramuscularly administered mRNA vaccine or an intranasally administered antigen fused to an alternative carrier of similar size, only the albumin-based intranasal vaccine yields robust mucosal IgA antibody responses. Our results thus suggest that this needle-free, albumin-based vaccine platform may be suited for vaccination against respiratory pathogens.https://doi.org/10.1038/s41467-025-59353-6
spellingShingle Aina Karen Anthi
Anette Kolderup
Eline Benno Vaage
Malin Bern
Sopisa Benjakul
Elias Tjärnhage
Fulgencio Ruso-Julve
Kjell-Rune Jensen
Heidrun Elisabeth Lode
Marina Vaysburd
Jeannette Nilsen
Marie Leangen Herigstad
Siri Aastedatter Sakya
Lisa Tietze
Diego Pilati
Mari Nyquist-Andersen
Mirjam Dürkoop
Torleif Tollefsrud Gjølberg
Linghang Peng
Stian Foss
Morten C. Moe
Benjamin E. Low
Michael V. Wiles
David Nemazee
Frode L. Jahnsen
John Torgils Vaage
Kenneth A. Howard
Inger Sandlie
Leo C. James
Gunnveig Grødeland
Fridtjof Lund-Johansen
Jan Terje Andersen
An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models
Nature Communications
title An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models
title_full An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models
title_fullStr An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models
title_full_unstemmed An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models
title_short An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models
title_sort intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models
url https://doi.org/10.1038/s41467-025-59353-6
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