Robust cross-neutralizing antibody responses but variable cellular immunity following either Comirnaty and Spikevax...

The rapid evolution of SARS-CoV-2 continues to challenge vaccine effectiveness, particularly in elderly individuals at higher risk of severe disease. The World Health Organization has recommended the use of a monovalent JN.1 lineage vaccine antigen for updated COVID-19 vaccines since April 2024. It remains crucial to determine whether these JN.1-adapted vaccines induce cross-protective immunity against emerging variants, including KP.2, KP.3, XEC, XDV, LP.8.1, and NB.1.8.1.

A cohort of 62 participants (median age 63.5 years; 41 Comirnaty and 21 Spikevax recipients) was studied before and one month after JN.1 mRNA vaccination. Neutralizing antibody titres were assessed by surrogate virus neutralization test (sVNT) or plaque-reduction neutralization test (PRNT). T cell responses were analyzed by intracellular cytokine staining, and S2-specific antibody levels were quantified by ELISA.

Both JN.1 vaccines markedly enhanced neutralizing antibodies against wild-type, JN.1, and multiple sublineages. S2-targeting antibodies also increased significantly, indicating recognition of conserved spike regions. Approximately half of the participants showed induction of IFNγ⁺CD8⁺ or CD4⁺ T cells.

The monovalent JN.1 mRNA vaccines elicit broad cross-neutralizing and S2-directed humoral immunity in the elderly, though cellular responses remain heterogeneous. Continued monitoring and inclusion of conserved T cell epitopes in next-generation vaccine designs are warranted to sustain protection against future variants.