A Nasal Subunit Vaccine Candidate Based on The Viral Antigens RBD and N Combined with C-Di-AMP as an Approach to Enhance Specific Immunity to SARS-Cov-2

Abstract

Nowadays, immunization through vaccines continues being a best strategy to control the COVID-19 disease and prevent mortality. Recently evidences highlight the need of vaccines for COVID-19 that provides broader protection against new SARS-CoV-2 isolates. In this work we evaluated in BALB/c mice, a nasal vaccine candidate based on recombinant proteins RBD and N from SARS-CoV-2 combining with c-di-AMP as adjuvant, as an approach to enhance specific immunity to SARS-CoV-2. Follow the intranasal administration of the bivalent vaccine candidate plus c-di-AMP, systemic and mucosal humoral immunity was elicited, in terms of IgG, IgA and neutralizing antibodies against two relevant variants of concern (Delta and Omicron BA1.2). N- and RBD-specific IgG subclasses induced by immunization showed a balanced Th1/Th2 pattern. In addition, an immune-modulator effect in the cell-mediated immunity was detected in mice immunized with the nasal vaccine formulation that included both recombinant antigens plus c-di-AMP. Results of this work propose the nasal formulation RBD + N + c-di-AMP as a promising option using gentle route for the COVID-19 immunization.