Different formulations of inactivated SARS-CoV-2 vaccine candidates in human compatible adjuvants: Potency studies in mice showed different platforms of immune responses
Abstract Several inactivated SARS-CoV-2 vaccines were approved for human use but are not highly potent. Here, different formulations of inactivated SARS-CoV-2 virus in Alum, Montanide 51VG and Montanide ISA720VG adjuvants were developed and then immune responses were assessed. SARS-CoV-2 virus was inactivated with formalin and formulated in the adjuvants. BALB/c mice were immunized subcutaneously with 4µg of experimental vaccines on days 0 and 14 and two weeks after the final immunization, IL-4 and IFN-γ cytokines, CTL activity and specific IgG titer and IgG1, IgG2a, IgG2a/IgG1 ratio and also anti-RBD IgG response were assessed. Immunization with SARS-CoV-2-Montanide ISA51VG showed a significant increase in IFN-γ cytokine versus SARS-CoV-2-Alum, SARS-CoV-2-Montanide ISA720VG and control groups (P<0.0033). Cytokine IL-4 response in SARS-CoV-2-Alum group showed a significant increase versus SARS-CoV-2-Montanide ISA51VG, SARS-CoV-2-Montanide ISA720VG and control groups (P<0.0206). In addition, SARS-CoV-2-Montanide ISA51VG vaccine induced the highest IFN-γ/IL-4 cytokine ratio versus other groups (P<0.0004). CTL activity in SARS-CoV-2- Montanide ISA51 VG and SARS-CoV-2-Montanide ISA720 VG groups showed a significant increase versus SARS-CoV-2-Alum and control groups (P<0.0075). Specific IgG titer in SARS-CoV-2- Montanide ISA51 VG and SARS-CoV-2-Montanide ISA720VG showed significant increase versus SARS-CoV-2-Alum and control groups (P<0.0143). Results of specific IgG1and IgG2a level in SARS-COV-2-Alum, SARS-COV-2-Montanide ISA51VG and SARS-COV-2-Montanide ISA720VG vaccine showed a significant increase versus the control group (P<0.0001) but SARS-COV-2-Montanide ISA51VG and SARS-COV-2-Montanide ISA 720VG groups showed highest IgG2a/IgG1 ratio and a significant increase versus SARS-COV-2-Alum group (P<0.0379). Results of anti-RBD IgG response showed that inactivated SARS-COV-2+Alum and SARS-COV-2-Montanide ISA 720VG vaccine groups demonstrated a significant increase versus SARS-COV-2-Montanide ISA51VG group. It seems that the type of vaccine formulation is a critical parameter that effect on immunologic patterns and vaccine potency. Here, results showed that human compatible oil-based adjuvants were more potent than Alum adjuvant in the induction of cellular and humoral immune responses versus SARS-CoV-2 virus.