An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models
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.
Authors
- Michael V. Wiles (ORCID: https://orcid.org/0000-0002-3620-8386)
- Inger Sandlie
- Jan Terje Andersen (ORCID: https://orcid.org/0000-0003-1710-1628)
- Fridtjof Lund‐Johansen (ORCID: https://orcid.org/0000-0002-2445-1258)
- Aina Karen Anthi (ORCID: https://orcid.org/0000-0002-1725-4571)
- Diego Pilati (ORCID: https://orcid.org/0009-0004-0651-9329)
- Kirk D.C. Jensen (ORCID: https://orcid.org/0000-0003-0707-964X)
- Jeannette Nilsen (ORCID: https://orcid.org/0000-0001-7892-0892)
- Lisa Tietze (ORCID: https://orcid.org/0000-0002-9179-2116)
- John Torgils Vaage (ORCID: https://orcid.org/0000-0003-0988-5768)
- Heidrun Elisabeth Lode (ORCID: https://orcid.org/0000-0002-1158-4879)
- Gunnveig Grødeland
- Fulgencio Ruso‐Julve (ORCID: https://orcid.org/0000-0001-6500-6807)
- Sopisa Benjakul (ORCID: https://orcid.org/0000-0003-3708-8125)
- Kenneth A. Howard (ORCID: https://orcid.org/0000-0002-9407-278X)
- Mari Nyquist-Andersen (ORCID: https://orcid.org/0000-0002-5248-6722)
- Frode L. Jahnsen (ORCID: https://orcid.org/0000-0003-3843-7171)
- Marina Vaysburd (ORCID: https://orcid.org/0000-0001-7236-678X)
- Eline Benno Vaage
- Anette Kolderup (ORCID: https://orcid.org/0000-0003-4019-8069)
- Leo C. James (ORCID: https://orcid.org/0000-0003-2131-0334)
- Morten C. Moe (ORCID: https://orcid.org/0000-0002-0615-804X)
- Benjamin E. Low (ORCID: https://orcid.org/0000-0003-0350-4602)
- Elias Tjärnhage (ORCID: https://orcid.org/0000-0002-2744-3472)
- Linghang Peng (ORCID: https://orcid.org/0000-0002-3600-2134)
- Stian Foss (ORCID: https://orcid.org/0000-0001-6527-051X)
- Siri Aastedatter Sakya (ORCID: https://orcid.org/0000-0002-5893-6771)
- Marie Leangen Herigstad
- Malin Bern (ORCID: https://orcid.org/0000-0002-6373-3776)
- Torleif Tollefsrud Gjølberg (ORCID: https://orcid.org/0000-0002-1719-7677)
- David Nemazee (ORCID: https://orcid.org/0000-0002-4769-6311)
- Mirjam Dürkoop
Institutions
- Scripps Research Institute (US)
- Oslo University Hospital (NO)
- MRC Laboratory of Molecular Biology (GB)
- University of Oslo (NO)
- Aarhus University (DK)
- Jackson Laboratory (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1038/s41467-025-59353-6
- Citations
- 10
- Primary Topic
- Respiratory viral infections research
- Type
- article
- Field-Weighted Citation Impact
- 13.54
Funders
- Wellcome Trust
- Coalition for Epidemic Preparedness Innovations
- Norges Forskningsråd
- Stockholms Universitet
- National Institutes of Health
- Harvard Digestive Diseases Center, Harvard University
- Medical Research Council
- Helse Sør-Øst RHF
- National Institute of Allergy and Infectious Diseases