Extended Data Fig. 6: Three-component vaccine elicits cross-neutralizing responses and enhances immunity as a heterologous booster following mRNA vaccination.
a, The radar chart was generated using the Log10 GMT data presented in main Fig. 1g and Fig. 4d to compare the tropism of the sera neutralizing antibody response induced by the two-component and three-component vaccines. The numbers represent the fold difference of GMTs between the neutralizing antibodies induced by the three-component vaccine and those induced by the two-component vaccine. b, Sera Neutralizing antibodies induced by the three-component vaccines containing RBDXBB.1.5-HR and RBDBA.5-HR with different antigenic ratios. BALB/c mice were intranasally immunized three times with the three-component vaccine composed of RBDXBB.1.5-HR and RBDBA.5-HR at antigenic ratios of 3:1, 1:1, and 1:3, respectively. Sera were collected to determine the neutralizing antibody levels and compared with titers of neutralizing antibodies induced by the three-component vaccine with antigenic ratios of 3:1 (n = 6 mice per group). c-e, The percentage of TRM cells in lung tissues (c), Tfh (d) cells, and RBD-specific GC B cells (e) in mLNs after four doses of mRNA vaccine or 3 doses of mRNA followed by twice intranasal delivery of three-component vaccine (n = 6 mice per group). f-k, BALB/c mice were intramuscularly immunized with four doses of encapsulated liposome (LPX)/Spike-mRNA, or immunized with three doses of mRNA followed by once intranasal delivery of three-component vaccine (3×mRNA+1×Three-component vaccine) (n = 6 mice per group). The sera anti-RBD IgG (g), BALF anti-RBD IgG (h), BALF IgA antibody (i), BALF TRM cells (j), and Spike-specific T cells in lung tissue (k) were detected. Schematic illustration in f was created in BioRender. Wang, Y. (2025) https://BioRender.com/tp7lcm5. Data are presented as geometric mean values with SD in b, g-i, and as mean with SEM in c-e, and j-k. P values were calculated by two-tailed Unpaired Student’s t-tests in d-e and g-i, and by two-way ANOVA analysis followed by Sidak’s multiple comparisons test in c and j-k. ns, not significant.
