Fig. 4: Monovalent and bivalent adapted JN.1 vaccines induce nAbs against JN.1, KP.2 and KP.3 lineages and specific T cell responses in the spleen and lung.

BALB/c mice were immunized at day 0 and day 14 via i.m. with: ARVAC JN.1 (n = 6), ARVAC XBB.1.5 (n = 6), ARVAC Gamma/BA.4/5 (n = 6), ARVAC Gamma/JN.1 (n = 6) and Spikevax XBB.1.5 mRNA vaccine. a Neutralizing antibody titers against KP.3.1.1, KP.2.3, JN.1, XBB.1.5, Omicron BA.5, Gamma and Ancestral SARS-CoV-2 were evaluated at 42 dpp. Neutralization titer was defined as the serum dilution that reduces 50% the cytopathic effect (NT50). Bars are GMT ± SD. *p < 0.05, ***p < 0.001. Kruskal–Wallis test. b Radar charts were drawn based on the GMTs of nAb in serum 42 dpp against live viruses. c Splenocytes from immunized mice were obtained a month after last immunization and stimulated with medium or JN.1 RBD-peptides pool plus recombinant JN.1 RBD for 18 h and then brefeldin A was added for 5 h. Afterward, cells were harvested and stained with anti-CD4 and anti-CD8 specific Abs, fixed, permeabilized, and stained intracellularly with anti-IFN-γ and anti-TNF-α. Results are presented as percentage of IFN-γ or TNF-α-producing CD4⁺ or CD8⁺ T lymphocytes^. Bars are means ± SEM. Each dot is an individual mouse. *p < 0.05, **p < 0.01, ***p < 0.001 vs. placebo. Kruskal–Wallis. d Splenocytes from immunized mice were stimulated with medium or recombinant JN.1 RBD for 3 d and then IL-5 was measured in the supernatant by ELISA. Results are presented as concentration of IL-5 in pg/ml. Bars are means ± SEM. Each dot is an individual mouse. *p < 0.05, ***p < 0.001 vs. placebo. Kruskal–Wallis. e Lung cells obtained from immunized mice were stimulated with medium or recombinant JN.1 RBD for 3 days and then IFN-γ, TNF-α and IL-5 were measured in the supernatant by ELISA. Results are presented as cytokine concentration in pg/ml. Bars are means ± SEM. Each dot is an individual mouse. *p < 0.05, **p < 0.01 vs. placebo. Kruskal–Wallis.