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bioRxiv · 10.1101/2025.03.14.640671

Intranasal AAV Vaccination of SARS-CoV-2 Induce Strong and Sustained Neutralizing Antibodies in Mice

Ji, Y.·Di Pasquale, G.·Zheng, C.·Afione, S.·Esperanza, T.·Yin, H.·Burbelo, P. D.·Chiorini, J. A.
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Abstract

The COVID-19 pandemic continues to pose significant health challenges, despite existing vaccines. This study evaluates the immunogenicity of recombinant adeno-associated viruses (AAV) expressing SARS-CoV-2 spike proteins, administered intramuscularly and intranasally in mice. Both delivery methods of AAV5-spike, AAV5-spike stabilized trimer as well as AAV44.9-spike elicited robust serum anti-spike antibodies within 8-12 weeks, with high levels of anti-spike antibodies sustained for over a year. Comparison of mouse serum antibodies 16 weeks post intramuscular or intranasal AAV5 administration demonstrated similar SARS-CoV-2 spike binding neutralizing activity in vitro. Analysis of changes in cellular immunity by ELISpot at 12 weeks post-AAV spike transduction revealed interferon-{gamma} induction in response to peptide challenge. Despite a decline in AAV vector DNA at the injection site, the persistence of anti-spike antibodies demonstrated that AAV-vectors can elicit lasting immune responses, highlighting nasal AAV administration as a potential strategy to block respiratory virus infections.

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Ji, Y., Di Pasquale, G., Zheng, C., Afione, S., Esperanza, T., Yin, H., Burbelo, P. D., Chiorini, J. A.. 2025-03-14. Intranasal AAV Vaccination of SARS-CoV-2 Induce Strong and Sustained Neutralizing Antibodies in Mice. https://doi.org/10.1101/2025.03.14.640671

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