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Oral vaccination protects against SARS-CoV-2 in a Syrian hamster challenge model. Vaccines that are shelf stable and easy to administer are crucial to improve vaccine access and reduce SARS-CoV-2 transmission around the world. Here we demonstrate that an oral, adenovirus-based vaccine candidate protects against SARS-CoV-2 in a Syrian hamster challenge model. Hamsters administered two doses of VXA-CoV2-1 showed a reduction in weight loss and lung pathology and had completely eliminated infectious virus 5 days post challenge. Oral immunization induced anti-spike IgG and neutralizing antibodies were induced upon oral immunization with the sera demonstrating neutralizing activity. Overall this data demonstrates the ability of oral vaccine candidate VXA-CoV2-1 to provide protection against SARS-CoV-2 disease.