Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models

Park, J.-G.; Oladunni, F. S.; Rohaim, M. A.; Whittingham-Dowd, J.; Tollitt, J.; Assas, B. M.; Alhazmi, W.; Almilaibary, A.; Iqbal, M.; Chang, P.; Escalona, R.; Shivanna, V.; Torrelles, J. B.; Worthington, J. J.; Jackson-Jones, L. H.; Martinez-Sobrido, L.; Munir, M.

doi:10.1101/2021.01.08.425974

bioRxiv · 10.1101/2021.01.08.425974

Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models

Park, J.-G.·Oladunni, F. S.·Rohaim, M. A.·Whittingham-Dowd, J.·Tollitt, J.·Assas, B. M.·Alhazmi, W.·Almilaibary, A.·Iqbal, M.·Chang, P.·Escalona, R.·Shivanna, V.·Torrelles, J. B.·Worthington, J. J.·Jackson-Jones, L. H.·Martinez-Sobrido, L.·Munir, M.

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Abstract

The global deployment of an effective and safe vaccine is currently a public health priority to curtail the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a Newcastle disease virus (NDV)-based intranasal vectored-vaccine in mice and hamsters for its immunogenicity, safety and protective efficacy in challenge studies with SARS-CoV-2. The recombinant (r)NDV-S vaccine expressing spike (S) protein of SARS-CoV-2 administrated via intranasal route in mice induced high levels of SARS-CoV-2-specific neutralizing immunoglobulin A (IgA) and IgG2a antibodies and T cell-mediated immunity. Hamsters vaccinated with two doses of vaccine showed complete protection from clinical disease including lung infection, inflammation, and pathological lesions after SARS-CoV-2 challenge. Importantly, a single or double dose of intranasal rNDV-S vaccine completely blocked SARS-CoV-2 shedding in nasal turbinate and lungs within 4 days of vaccine administration in hamsters. Taken together, intranasal administration of rNDV-S has the potential to control infection at the site of inoculation, which should prevent both the clinical disease and transmission to halt the spread of the COVID-19 pandemic.

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Park, J.-G., Oladunni, F. S., Rohaim, M. A., Whittingham-Dowd, J., Tollitt, J., Assas, B. M., Alhazmi, W., Almilaibary, A., Iqbal, M., Chang, P., Escalona, R., Shivanna, V., Torrelles, J. B., Worthington, J. J., Jackson-Jones, L. H., Martinez-Sobrido, L., Munir, M.. 2021-01-11. Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models. https://doi.org/10.1101/2021.01.08.425974

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