Mucosal SARS-CoV-2 Nanoparticle Vaccine Based on Mucosal Adjuvants and Its Immune Effectiveness by Intranasal Administration

SARS-CoV-2 is a respiratory virus that causes significant threats to human health. Mucosal immunity provides a first-line defense to prevent the infection of SARS-CoV-2 in the respiratory tract. Because most SARS-CoV-2 vaccines could not stimulate mucosal immunity in the respiratory tract, appropriate mucosal adjuvants or delivery systems are needed for mucosal vaccine development. Mannan, polyarginine, and 2',3'-cGAMP are three mucosal adjuvants that could stimulate mucosal immunity. In the present study, the three adjuvants were assembled with a receptor-binding domain (RBD) by electrostatic interaction to generate a nanoparticle vaccine (RBD-MP-cG). RBD-MP-cG elicited mucosal IgA and IgG response in bronchoalveolar lavage and nasal lavage by intranasal administration. It induced a robust RBD-specific antibody response, high levels of protective neutralizing antibody, and ACE2-blocking activity in the mouse sera. It stimulated the splenic secretion of high levels of Th1-, Th2-, and Th17-type cytokines. Thus, RBD-MP-cG elicited strong mucosal immunity and systematic immunity by intranasal administration. RBD-MP-cG was expected to act as a safe, effective, and easily produced mucosal nanoparticle vaccine to combat the infection of SARS-CoV-2.