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

Author(s): Iris Valdes, Laura Lazo, Edith Suzarte, Karem Cobas, Yusleidi Pérez, Rocío Garateix, Enrique Noa, Rubén Amaya, Dionne Casillas, Elias Nelson, Yinet Cartaya, Monica Bequet, Julio C. Aguilar, Carlos A. Guzmán, Gerardo Guillen

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.