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

ABSTRACT

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, CuMVTT -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: CuMVTT-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) of mutated SARS-CoV-2 RBDs. Conclusion: Our data demonstrate that intranasal administration of CuMVTT-RBD induces a protective systemic and local specific antibody response against SARS-CoV-2 and its VOCs.