Current COVID-19 vaccines, based on ancestral SARS-CoV-2 strains, are challenged by emerging variants. This study demonstrates that a yellow fever 17D (YF17D) vectored vaccine with a prototypic spike protein effectively protects against ancestral and Alpha variants but not Beta. However, an updated YF17D vaccine with an evolved antigen significantly improved neutralizing antibody responses against Beta, Gamma, and Omicron variants, while maintaining immunogenicity against ancestral and Delta variants. Vaccinated hamsters resisted challenge by all VOCs, showed undetectable virus levels, and improved lung pathology. Importantly, vaccinated hamsters did not transmit the Delta variant. This highlights the need for updated vaccines to maintain efficacy against emerging variants.

Sapna Sharma, Thomas Vercruysse, Lorena Sanchez-Felipe, Winnie Kerstens, Madina Rasulova, Lindsey Bervoets, Carolien De Keyzer, Rana Abdelnabi, Caroline S. Foo, Viktor Lemmens, Dominique Van Looveren, Piet Maes, Guy Baele, Birgit Weynand, Philippe Lemey, Johan Neyts, Hendrik Jan Thibaut, Kai Dallmeier