Effective SARS-CoV-2 vaccines are urgently needed. Although most vaccine strategies have focused on systemic immunization, here we compared the protective efficacy of 2 adjuvanted subunit vaccines with spike protein S1: an intramuscularly primed/boosted vaccine and an intramuscularly primed/intranasally boosted mucosal vaccine in rhesus macaques. The intramuscular-alum–only vaccine induced robust binding and neutralizing antibody and persistent cellular immunity systemically and mucosally, whereas intranasal boosting with nanoparticles, including IL-15 and TLR agonists, elicited weaker T cell and Ab responses but higher dimeric IgA and IFN-α. Nevertheless, following SARS-CoV-2 challenge, neither group showed detectable subgenomic RNA in upper or lower respiratory tracts versus naive controls, indicating full protection against viral replication. Although mucosal and systemic protective mechanisms may differ, results demonstrate both vaccines can protect against respiratory SARS-CoV-2 exposure. In summary, we have demonstrated that the mucosal vaccine was safe after multiple doses and cleared the input virus more efficiently in the nasal cavity and thus may act as a potent complementary reinforcing boost for conventional systemic vaccines to provide overall better protection.
【저자키워드】 COVID-19, Adaptive immunity, Vaccines, Innate immunity, 【초록키워드】 neutralizing antibody, SARS-CoV-2, Efficacy, Vaccine, nasal, virus, immunization, SARS-CoV-2 vaccine, Spike protein, RNA, T cell, Viral, cellular immunity, IgA, viral replication, response, Subunit vaccine, respiratory, Nasal cavity, intranasal, boost, Protective, binding, rhesus macaques, IL-15, mucosal, subunit vaccines, Lower respiratory tract, complementary, Safe, IFN-α, protective mechanisms, protective mechanism, TLR agonists, spike protein S1, multiple doses, naive controls, controls, robust, PROTECT, detectable, demonstrated, elicited, systemically, dimeric, intramuscularly, multiple dose, 【제목키워드】 Vaccine, protection, SARS-COV-2 infection, rhesus macaque, mucosal,