MnOx@HMSN(CDA + RBD) as a vaccine platform against SARS-CoV-2. (a) MnOx@HMSN(CDA) was incubated with RBD protein for 30 mins at RT, followed by centrifugation (8000 g, 5 min) and SDS-PAGE analysis of pellet and supernatant for RBD. (b) IVIS images of inguinal lymph nodes after 6 h or 24 h of SC administration with (1) PBS, (2) Cy7-CDN + RBD, or (3) MnOx@HMSN(Cy7-CDN + RBD). (c) Quantification of average fluorescence intensity in inguinal lymph nodes. (d) Vaccine study design with MnOx@HMSN(CDA + RBD). (e-f) IFN-γ ELISPOT assay of SARS-CoV-2 RBD protein-specific T-cell response using mouse PBMCs harvested on week 4. (g) Humoral RBD protein-specific IgG serum titer at various time points. (h) In vitro pseudo-typed virus neutralization assay using mouse sera harvested on week 6. The data show mean ± SEM with n = 4 in (c, h) and n = 5 in (f-g). Data were analyzed by one-way (c, f, h) or two-way (g) ANOVA with Tukey’s HSD multiple comparison post hoc test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P <0.0001.