Impact of genotypic variability of measles virus T-cell epitopes on vaccine-induced T-cell immunity

After the COVID-19 pandemic, significant increases in measles cases were observed globally. Community-wide vaccination remains the most effective strategy for preventing measles. However, it is crucial to understand whether prevalent genotypes, when circulating in populations with suboptimal vaccination coverage, may undergo adaptive mutations that allow them to escape vaccine-induced immunity. In this study, a bioinformatics-guided approach was used to predict universal helper T-cell epitopes specific to the measles vaccine virus (vaccine-MeV) presented by multiple HLA-DR, -DP, and -DQ alleles to achieve population-wide coverage. By using MeV-specific T-cell lines, we identified 37 functional epitopes out of 83 predicted candidates, including 25 novel ones. Strikingly, 73% of these epitope regions were associated with sequence variations in wild-type viruses. More importantly, we demonstrated that mutations disrupted the ability of vaccine-induced CD4⁺ T cells to respond to circulating viruses. Consequently, mutations in epitope regions of circulating viruses may affect the effectiveness of vaccine-induced T-cell immunity.