A novel multi-antigenic parapoxvirus-based vaccine demonstrates efficacy in protecting hamsters and non-human primates against SARS-CoV-2 challenge

Abstract The next generation of COVID-19 vaccines needs to broaden the antigenic repertoire to improve breadth of immune response and efficacy against emerging variants of concern. This study describes a new parapoxvirus-based vector (ORFV) as a platform to design a multi-antigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Two vaccine candidates were engineered, one expressing spike protein alone (ORFV-S) and the other co-expressing the more conserved nucleocapsid protein (ORFV-S/N). Both vaccines elicited comparable levels of spike-specific antibodies and virus neutralization in mice. In a SARS-CoV-2 challenge model in hamsters, the multi-antigenic ORFV-S/N vaccine conferred protection in the upper and lower respiratory tract, while the ORFV-S-vaccinated animals showed protection restricted to the lungs. Similarly, in a non-human primates challenge model, vaccination with the ORFV-S/N vaccine resulted in rapid onset and long-term protection against SARS-CoV-2 infection. These results demonstrate the potential of ORFV as a platform for prophylactic vaccination and support ongoing first-in-man studies with the multi-antigenic ORFV vaccine.