Updated vaccine protects against SARS-CoV-2 variants including Omicron (B.1.1.529) and prevents transmission in hamsters

Current COVID-19 vaccines are based on prototypic spike sequences from ancestral 2019 SARS-CoV-2 strains. However, the ongoing pandemic is fueled by variants of concern (VOC) escaping vaccine-mediated protection. Here we demonstrate how immunization in hamsters using prototypic spike expressed from yellow fever 17D (YF17D) as vector blocks ancestral virus (B lineage) and VOC Alpha (B.1.7) yet fails to fully protect from Beta (B.1.351). However, the same YF17D vector vaccine candidate with an evolved antigen induced considerably improved neutralizing antibody responses against VOCs Beta, Gamma (P.1) and the recently predominant Omicron (B.1.1.529), while maintaining immunogenicity against ancestral virus and VOC Delta (B.1.617.2). Thus vaccinated animals resisted challenge by all VOCs, including vigorous high titre exposure to the most difficult to cover Beta, Delta and Omicron variants, eliminating detectable virus and markedly improving lung pathology. Finally, vaccinated hamsters did not transmit Delta variant to non-vaccinated cage mates. Overall, our data illustrate how current first-generation COVID-19 vaccines may need to be updated to maintain efficacy against emerging VOCs and their spread at community level.

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