Immunogenicity of intraperitoneal and intranasal liposome adjuvanted VLP vaccines against SARS-CoV-2 infection

Humans get SARS-CoV-2 infection through inhalation; thus, vaccine that induces protective immunity at the virus entry site is appropriate for early control of the infection. In this study, two anionic liposome-adjuvanted VLPs vaccines made of full-length S, M and E proteins SARS-CoV-2 were formulated. S1-S2 junction of S protein displayed on VLPs of one vaccine (L-SME-VLPs) contained furin cleavage site, while VLPs of another (L-S¢ME-VLPs) did not. Both vaccines were similarly/equally immunogenic in mice. Mice immunized parenterally with the vaccines had principally serum IgG3 neutralizing antibodies, while mice immunized intranasally produced predominantly specific Th1-antibody isotypes (IgG2a and/or IgG2b) in bronchoalveolar lavage samples. IgG3 isotype is known to be highly efficient in complement activation, opsonophagocytic activities, and antibody-dependent cell-mediated cytotoxicity, which causes virus clearance upon infection. Nevertheless, complement fixation and immune-complex formation may exacerbate tissue inflammation, cytokine storm, and lung immunopathology in the SARS-CoV-2-infecting host, which exacerbate the COVID-19 morbidity. Th1 antibodies are less efficient in complement fixation and phagocytic activity but exhibit stronger anti-viral effects than other antibody isotypes; thus, confer protection with minimal immunopathology upon new infection. The intranasal liposome-adjuvanted VLP vaccines should be tested further towards the clinical use as effective, safe, and better compliant vaccines against SARS-CoV-2.