Oral and intranasal Ad5 SARS-CoV-2 vaccines decrease disease and viral transmission in a golden hamster model

Transmission-blocking strategies that slow the spread of SARS-CoV-2 and protect against COVID-19 are needed. We have developed a shelf-stable, orally-delivered Ad5-vectored SARS-CoV-2 vaccine candidate that expresses the spike protein. Here we demonstrated that oral and intranasal SARS-CoV-2 vaccination of this candidate protected against disease in index hamsters, and decreased aerosol transmission to unvaccinated, naïve hamsters. We confirmed that mucosally-vaccinated hamsters had robust antibody responses. We then induced a post-vaccination infection by inoculating vaccinated index hamsters with SARS-CoV-2. Oral and IN-vaccinated hamsters had decreased viral RNA and infectious virus in the nose and lungs and experienced less lung pathology compared to mock-vaccinated hamsters post challenge. Naive hamsters exposed in a unidirectional air flow chamber to mucosally-vaccinated, SARS-CoV-2-infected hamsters had lower nasal swab viral RNA and exhibited less clinical symptoms of disease than control animals. Our data demonstrate that oral immunization is a viable strategy to decrease SARS-CoV-2 disease and aerosol transmission. ### Competing Interest Statement S.N.T, S.J., N.P., E.G.D., C.I.M., and S.N.T. are employees of Vaxart, Inc., and/or have received stock options. H.I., P.J.K, E.G.B, and A.W. are employees of Lovelace Biomedical. EGD and SNT are named as inventors covering a SARS- CoV-2 (nCoV-19) vaccine. SNT is named as an inventor on patent covering the vaccine platform. S.N.L. reports no conflicts.