Plant-produced RBD and cocktail-based vaccine candidates are highly effective against SARS-CoV-2, independently of its emerging variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel and highly pathogenic coronavirus that caused an outbreak in Wuhan City, China, in 2019 and then spread rapidly throughout the world. Although several coronavirus disease 2019 (COVID-19) vaccines are currently available for mass immunization, they are less effective against emerging SARS-CoV-2 variants, especially the Omicron (B.1.1.529). Recently, we successfully produced receptor-binding domain (RBD) variants of the spike (S) protein of SARS-CoV-2 and an antigen cocktail in Nicotiana benthamiana, which are highly produced in plants and elicited high-titer antibodies with potent neutralizing activity against SARS-CoV-2. In this study, based on neutralization ability, we demonstrate that plant-produced RBD and cocktail-based vaccine candidates are highly effective against SARS-CoV-2, independently of its emerging variants. These data demonstrate that plant-produced RBD and cocktail-based proteins are the most promising vaccine candidates and may protect against Delta and Omicron-mediated COVID-19. This is the first report describing vaccines against SARS-CoV-2, which demonstrate significant activities against Delta and Omicron variants.