MF-59 Adjuvant Alum in an Inactivated SARS-CoV-2 Vaccine Model: Focusing on Heterologous Antigen-Binding Response

Abstract

Background: Clarifying the role of an adjuvant in vaccine formulation on the induction of a higher cross-reactivity response is very important in the vaccine formulation. In this study, the inactivated Wuhan-Hu-1 strain of SARS-CoV-2 virus was formulated in MF-59 and Alum adjuvants and the immunogenicity of these vaccines in the induction of cellular and humoral immune responses was assessed. In addition, the cross-binding IgG response Alpha variant (B.1.1.7) "English variant" was assessed by ELISA.

Methods: Experimental BALB/c mice were immunized subcutaneously three times with MF-59- and Alum-based vaccines. Three weeks after the last immunization, lymphocyte proliferation of spleen cells was evaluated by BrdU method, and IL-4 and IFN-γ cytokines were assessed on the spleen cell culture supernatant by quantitative ELISA kits. In addition, specific total IgG and IgG1/IgG2a isotypes were assessed with an optimized indirect ELISA. Furthermore, the cross-binding IgG titer Alpha variant was assessed by ELISA.

Results: The results showed that immunization with MF-59-inactivated SARS-CoV-2 vaccine led to a significant increase in lymphocyte proliferation, IFN-γ-associated responses, specific total IgG, and IgG1, and IgG2a isotypes compared with Alum group. In addition, inactivated SARS-CoV-2-MF59 vaccine revealed a numerically higher (70.83%) increase in the cross-binding IgG titer the inactivated SARS-CoV-2-Alum group.

Conclusion: MF-59 could be used as a suitable adjuvant in SARS-CoV-2 vaccine development due to a better induction of IgG and IFN-γ responses than alum adjuvant and a higher induction of the cross-binding IgG response the Alpha variant. These findings showed that vaccine formulation is important in inducing cross-binding responses.