Intranasal Administration of Bivalent RBD Nanoparticles Elicits Strong Systemic Responses That Effectively Block Distal Dissemination of COVID‐19

The intranasal vaccine against coronavirus disease 2019 (COVID-19) has gained more attention because of its ability to induce both mucosal and systemic immune responses. We have recently developed a c-GAMP-adjuvanted bivalent receptor-binding domain (RBD) vaccine, derived from the ancestral strain and the Omicron variant. We demonstrated here that intranasal administration of this vaccine candidate triggers not only the respiratory but also the systemic immune response against SARS-CoV-2. The immunized mice elicited the broadly neutralizing antibodies against the ancestral strain (Wuhan-1) and variants of concern (Delta, Omicron BA.1, and Omicron BA.5). This route of vaccination also induced potent systemic T cell responses with strong cytotoxic activity against both the Wuhan-1 and Omicron BA.1 strains. Additionally, intranasally immunized mice significantly suppressed SARS-CoV-2 RNA levels in circulation and spleens, indicating effective containment of the virus beyond the respiratory tract. These findings suggest that the intranasal bivalent RBD vaccine holds promise for combating SARS-CoV-2 infections.