IFNλ4 Gene Variants Are Associated with CD8⁺ T Cell IL-2 Response After COVID-19 Vaccination: A Preliminary Study

Individual responses to SARS-CoV-2 vaccination vary due to viral mutations, demographic factors, and genetic background, with T-cell responses being less affected by viral variability. However, less is known about the effect of age, sex, and genetic background on the T-cell response in vaccinated subjects. In particular, the influence of interferon lambda (IFN-λ) genetic polymorphisms on vaccine-induced cellular immunity has been poorly explored. Here, we assessed intracellular production of IFNγ, TNFα, and IL-2 in CD4⁺ and CD8⁺ T cells stimulated with SARS-CoV-2 spike peptides from 50 vaccinated subjects genotyped for IFNL3 (rs12980275 and rs8099917) and IFNL4 (rs11322783TT and rs12979860) SNPs. We found that the IFNL4 rs11322783TT/TT genotype is associated with increased IL-2 production in CD8⁺ T cells, whereas the ΔG allele correlates with a reduced IL-2 response. No significant effects on CD4⁺ T-cell cytokine production or other cytokines were observed. These preliminary findings suggest that type III interferon gene variants might be involved in CD8⁺ T-cell responses post-vaccination, opening the possibility that evaluation of IFNL4 SNPs might be useful in designing strategies of personalized vaccination.