An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

Hassan, A. O.; Shrihari, S.; Gorman, M. J.; Ying, B.; Yuan, D.; Raju, S.; Chen, R. E.; Dmitriev, I. P.; Kashentseva, E.; Adams, L. J.; Shi, P.-Y.; Fremont, D. H.; Curiel, D. T.; Alter, G.; Diamond, M. S.

doi:10.1101/2021.05.08.443267

bioRxiv · 10.1101/2021.05.08.443267

An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

Hassan, A. O.·Shrihari, S.·Gorman, M. J.·Ying, B.·Yuan, D.·Raju, S.·Chen, R. E.·Dmitriev, I. P.·Kashentseva, E.·Adams, L. J.·Shi, P.-Y.·Fremont, D. H.·Curiel, D. T.·Alter, G.·Diamond, M. S.

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Abstract

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy and the end of the COVID-19 pandemic. We recently reported the protective activity of a single-dose intranasally-administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose-response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351 and B.1.1.28 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.

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Hassan, A. O., Shrihari, S., Gorman, M. J., Ying, B., Yuan, D., Raju, S., Chen, R. E., Dmitriev, I. P., Kashentseva, E., Adams, L. J., Shi, P.-Y., Fremont, D. H., Curiel, D. T., Alter, G., Diamond, M. S.. 2021-05-09. An intranasal vaccine durably protects against SARS-CoV-2 variants in mice. https://doi.org/10.1101/2021.05.08.443267

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