Immunogenicity of mixture of SARS-CoV-2 mRNA vaccine and recombinant protein vaccine in mice
Objective To evaluate the immunogenicity of the mixture of lipid nanoparticle-encapsulated mRNA vaccine(mRNA-LNP)and aluminum adjuvanted protein subunit vaccine(PS-Alum)against SARS-CoV-2 in mice,and then to provide experimental data for the heterologous immunization strategy of different technology platforms.Methods Immune responses of mRNA-LNP and PS-Alum vaccines were compared in female BALB/c mice immunized with mRNA-LNP vaccine or PS-Alum vaccine alone,or in combination.The heterologous immunization strategies were bilateral immunization(bilateral)and mixed immunization(mix).In the bilateral group,the mice were immunized with mRNA-LNP vaccine in one side of the tibialis anterior muscle and with an equal volume of PS-Alum vaccine in the other.In the mix group,the mRNA-LNP and PS-Alum vaccines were mixed in equal volumes and administered separately to both sides of the tibialis anterior muscles of the mice.Antibody responses were detected after the primary and booster immunizations,and compared with those induced by mRNA-LNP alone to evaluate the immunogenic effect of the mixed vaccine.Additionally,the mRNA-LNP and PS-Alum vaccines were mixed in equal volumes and stored at 4 ℃ for 0,48 h,as well as 7,14,and 35 d,respectively,before immunizing female BALB/c mice.The antibody response and cellular immune response were then measured to prelimi-narily assess the stability of the mixed vaccine.Results The geometric mean titer(GMT)of RBD specific serum binding IgG of mice in the mix group was higher than that in the mRNA and bilateral groups 14 d after both the primary immunization and booster immunization(14 d:P＜0.000 1 and 0.243 9,respectively;35 d:each P＜0.000 1).When the mixed vaccine was stored at 4 ℃ in vitro for 0,48 h,and 7,14,and 35 d before immunizing the mice,the GMT of serum binding IgG slightly increased 48 h after the primary immunization compared to 0 h(P=0.017 7).As the storage time extended,the GMT of binding antibodies remained stable.After the booster immunization,compared to 0 h,the vaccine-induced binding antibody,pseudovirus neutralizing antibody,and T-cell response did not decrease with the extension of the storage time(P=0.421 1-0.999 9).Conclusion Compared with homologous mRNA vaccine,the mixture of mRNA-LNP vaccine and PS-Alum vaccine could enhance the vaccine immunogenicity effectively,and the immunogenicity of the vaccine mixture remained stable after storage at 4℃ for 35 d in vitro.
mRNA vaccineRecombinant protein vaccineHeterologous immunizationImmunization strategySARS-CoV-2
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