Induction of Humoral and Cellular Immunity After SARS-CoV-2 JN.1 Vaccination in Individuals With and Without Prior Infection

The continuous evolution of SARS-CoV-2 raises concerns about immune escape from preexisting immunity. The monovalent JN.1adapted mRNA vaccine was developed to better match circulating variants, yet data on its ability to induce and broaden humoral and cellular immunity in individuals with or without prior infection remain limited. We recruited 37 immunocompetent adults before and two weeks after JN.1 vaccination to assess vaccine-induced immunity. Spike-specific CD4 and CD8 T cells were quantified following stimulation with spike-derived peptides from the parental strain, XBB.1.5, and JN.1, and their CTLA-4 expression and cytokine profiles were analyzed by flow cytometry. Spike-specific IgG and neutralizing activity against authentic parental, XBB.1.5, JN.1, and KP.3.1.1 isolates were also measured. JN.1 vaccination significantly increased spike-specific CD4+ and CD8+ T-cell frequencies with comparable cytokine profiles across variants and enhanced CTLA-4 expression. IgG levels and neutralizing titers rose markedly, with the strongest relative increases against Omicron lineage variants. Prior infection was associated with higher neutralizing titers but did not influence T-cell responses. Influenza vaccine co-administration had no adverse effect on JN.1 immunogenicity. These findings indicate that hybrid immunity enhances antibody-mediated protection, while robust, cross-reactive T-cell responses may contribute to sustained protection against severe disease irrespective of infection history.