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Broad Humoral Immunity Generated in Mice by a Formulation Composed by Two Antigens from Delta Variant of SARS-CoV-2

Yadira Lobaina, Rong Chen, Edith Suzarte, Panchao Ai, Vivian Huerta, Changyuan Tan, Liz Alvarez-Lajonchere, Yang Liling, Alexis Musacchio, Ricardo Silva, Gerardo Guillén, Jiang Zaixue, Ke Yang, Yasser Perera, Lisset Hermida

Study background: Due to the rapid development of new variants of SARS-CoV-2 virus, as well as the real threat of new Coronavirus zoonosis events, the development of a preventive vaccine with a broader scope of functionality is highly desirable. Previously, we reported the functionality of a nasal formulation based on the preparation of the nucleocapsid protein with the ODN-39M and combined with RBD, both antigens from Delta variant of SARS-CoV-2. This combination induces a cross reactive immunity in mucosal and systemic compartments until sarbecovirus level. In the present study, we explored the magnitude of the immunity generated in Balb/C mice by the same formulation, but adding alum as adjuvant, so as to enhance the humoral immunity against the two antigens.

Methods: Animals were immunized with three doses of the bivalent formulation, administered by subcutaneous route. The humoral immunity was tested by ELISA and by a surrogate of viral neutralization test. The cell mediated immunity was also explored.

Results: High levels of antibodies against both antigens (N and RBD) were obtained upon immunization. Additionally, the anti-RBD Abs with neutralizing capacity reacted against the three SARS-CoV-2 variants of RBD assayed, including omicron. At the same time, the Abs also recognized the nucleocapsid proteins from: SARSCoV- 1 and SARS-CoV-2 delta and omicron.

Conclusion: Taken together, these results make the bivalent formulation tested, an attractive component of a pan Corona vaccine able to broaden the scope of humoral immunity against both antigens. This will be particularly important in the reinforcement of immunity from previously vaccinated and/or infected populations.