An intranasal albumin-based vaccine technology for induction of protective mucosal and systemic antibody immunity against respiratory virus

Vaccines save millions of lives every year, but there is still an urgent need for more efficient vaccines. Strategies to combat serious outbreaks of viral infections are particularly important. Such infections are initiated at mucosal surfaces, where there is a close association between polarized epithelial cells and immune effector cells. However, vaccines are usually given intramuscularly or subcutaneously, and often do not provide sufficient protection at the actual site of infection.

In the current paper, the laboratory of Professor Jan Terje Andersen and collaborators report on a novel vaccine technology platform, in which the subunit antigen is genetically fused to albumin. Albumin was chosen as a carrier as it is actively transported across the mucosal barrier by FcRn, a receptor found on mucosal epithelial cells. Upon intranasal delivery to several different mouse strains, the albumin-antigen fusion vaccines induced both systemic and mucosal antigen-specific antibody responses. The mice were found to be protected against challenge with SARS-CoV-2 and influenza A. Adjuvant was included and could also be site-specifically conjugated to the albumin carrier.

Importantly, when the new albumin-based vaccine strategy was benchmarked against an intramuscularly administered mRNA vaccine or an intranasally administered alternative where an antigen was fused to a carrier of similar size as albumin, only the albumin-based intranasal vaccine gave rise to robust mucosal IgA antibody responses.

The study thus suggests that this needle-free, albumin-based vaccine platform may be attractive for design of vaccines against multiple respiratory pathogens.

“There is a critical need for improved vaccines that target pathogens transmitted through the respiratory tract and may cause fatal infections. Thus, we are happy to report on a new versatile vaccine technology, where the antigen may be any identified protein subunit from an infectious agent. Our strategy is based in an in-depth understanding of the complex biology of FcRn, a receptor expressed on mucosal cells. Albumin is a ligand for FcRn, and we have engineered a human albumin variant with increased ability to engage the receptor to enhance active transport across mucosal barriers. Transport is followed by induction of antibody responses against the vaccine subunit. Importantly, we have explored the new vaccine platform in carefully designed pre-clinical in vivo systems, where we have taken into consideration important cross-species binding differences, which is critical in a translational perspective. We are very encouraged by the results that we hope will pave the way for vaccines that provide not only systemic immunity, but also protection at the actual site of infection”, says Jan Terje Andersen, the study’s senior author.

Funding

The study was financed through the Research Council of Norway, the South-Eastern Norway Regional Health Authority, the Coalition for Epidemic Preparedness and Innovation (CEPI) and Independent Research Fund Denmark.

Publication

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, Steve 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, and Jan Terje Andersen. "An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models," Nature Communications, online 1 May 2025, 10.1038/s41467-025-59353-6.