Figure 1.

Heterologous IM/IN prime-boost immunization induces robust S protein-specific IgG and enhances mucosal IgA production compared to homologous mRNA IM/IM prime-boost

(A) C57Bl/6 mice were given two immunizations 4-weeks apart. Mice were primed either IM with 0.4 μg of BNT162b2 mRNA or PBS, or IN with 15 μg full-length S protein with either NE or NE/IVT. Mice were then boosted IM with 0.4 μg of BNT162b2 mRNA or PBS, or IN with PBS or S protein in PBS, NE or NE/IVT as indicated. Serum antigen-specific total IgG titers against (B) WT S protein and (C) WT RBD as measured by ELISA 2 weeks after the prime immunization, and (D, E) 2 weeks after the boost immunization (wk6). (F–H) Subclass profiles for S-specific serum antibodies measured at wk6. BALF S-specific (I) IgA and (J) IgG measured at wk6. (n = 5/group; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗∗p < 0.0001 by Mann-Whitney U test shown only for select groups (full statistical analysis is shown in Table S1).