A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine

Sun, Weina; McCroskery, Stephen; Liu, Wen-Chun; Leist, Sarah R.; Liu, Yonghong; Albrecht, Randy A.; Slamanig, Stefan; Oliva, Justine; Amanat, Fatima; Schaefer, Alexandra; Dinnon, Kenneth H.; Innis, Bruce L.; Garcia-Sastre, Adolfo; Krammer, Florian; Baric, Ralph S.; Palese, Peter

A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections or significantly attenuated SARS-CoV-2 induced disease. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.