Intranasal administration of a VLP‐based vaccine induces neutralizing antibodies against SARS‐CoV‐2 and variants of concern

BACKGROUND: The highly contagious SARS‐CoV‐2 is mainly transmitted by respiratory droplets and aerosols. Consequently, people are required to wear masks and maintain a social distance to avoid spreading of the virus. Despite the success of the commercially available vaccines, the virus is still uncontained globally. Given the tropism of SARS‐CoV‐2, a mucosal immune reaction would help to reduce viral shedding and transmission locally. Only seven out of hundreds of ongoing clinical trials are testing the intranasal delivery of a vaccine against COVID‐19. METHODS: In the current study, we evaluated the immunogenicity of a traditional vaccine platform based on virus‐like particles (VLPs) displaying RBD of SARS‐CoV‐2 for intranasal administration in a murine model. The candidate vaccine platform, CuMV(TT)‐RBD, has been optimized to incorporate a universal T helper cell epitope derived from tetanus‐toxin and is self‐adjuvanted with TLR7/8 ligands. RESULTS: CuMV(TT)‐RBD vaccine elicited a strong systemic RBD‐ and spike‐IgG and IgA antibodies of high avidity. Local immune response was assessed, and our results demonstrate a strong mucosal antibody and plasma cell production in lung tissue. Furthermore, the induced systemic antibodies could efficiently recognize and neutralize different variants of concern (VOCs). CONCLUSION: Our data demonstrate that intranasal administration of CuMV(TT)‐RBD induces a protective systemic and local specific antibody response against SARS‐CoV‐2 and its VOCs.