Fig. 1: Bivalent mRNA vaccine M1.2 elicit potent and broad nAbs.
A Schematic representation of spike protein mutations in Omicron subvariants. Top panel shows locations of mutated amino acids compared to Wuhan-Hu-1 spike, dark purple indicating presence of mutation and light purple indicating absence of mutation. NTD denotes N-terminal ___domain of spike, and RBD denotes receptor binding ___domain of spike. Lower panel shows the number of different amino acids of the pair-wise compared Wuhan-Hu-1 and Omicron subvariant spikes. B Immunogenicity and challenge experiment schedule. Six- to eight-week-old female C57BL/6 mice (n = 10) were immunized twice i.m. with 10 µg mRNA vaccines or control formulation buffer and challenged with Omicron BA.1 three weeks post 2nd vaccination. C nAbs of mice sera. Sera from mice in B were collected at 1 week post 2nd vaccination (week 4). For each group, every 2–3 mice sera were pooled (4 pools per group) to be used in nAb pseudovirus assay. Columns and error bars indicate geometric mean±95% confidence interval of the nAb ID50 (n = 4). Each dot represents an individual pool. The numbers above columns indicate geometric mean values of the nAb ID50. LLOQ of the nAb assay is 80, and when serum nAb ID50 values were below LLOQ, half of the LLOQ values (40) were assigned to the sera. D Immunogenicity experiment schedule. Six- to eight-week-old female C57BL/6 mice (n = 10 except n = 8 for Formulation buffer control group) were immunized twice i.m. with 10 µg mRNA vaccines or control Formulation buffer. Sera and spleens were collected 3 weeks post 2nd vaccination. E nAbs of mice sera. Sera from mice in D were collected at 3 weeks post 2nd vaccination (week 6). Individual mouse sera were used in nAb pseudovirus assay. Columns and error bars indicate geometric mean±95% confidence interval of the nAb ID50 (n = 10 except n = 8 for Formulation buffer control group). Each dot represents an individual mouse. The numbers above columns indicate geometric mean values of the nAb ID50. LLOQ of the nAb assay is 80 except 40 for XBB.1.5 pseudovirus. When serum nAb ID50 values were below LLOQ, half of the LLOQ values (40 except 20 for XBB.1.5 pseudovirus) were assigned to the sera. Two-way ANOVA followed by Tukey’s multiple comparison was used for statistical analysis. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.
