Genetic Analysis Reveals Differences in CD8⁺ T Cell Epitope Regions That May Impact Cross-Reactivity of...

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Mumps is re-emerging in vaccinated populations, suggesting reduced vaccine effectiveness.
• Waning immunity and antigenic differences between vaccine and circulating mumps virus (MuV) strains are potential causes.
• CD8+ T cells are crucial for viral immunity, but their epitope variability in MuV is understudied.

Purpose of the Study:

• To investigate sequence variability in CD8+ T cell epitope regions of MuV.
• To compare epitopes from the Jeryl-Lynn vaccine strain with those from circulating MuV strains.
• To assess the impact of sequence variability on human leukocyte antigen Class I (HLA-I) binding.

Main Methods:

• Compared sequences of 40 CD8+ T cell epitope candidates from the Jeryl-Lynn mumps vaccine strain with 462 genomes of circulating MuV strains.
• Identified and analyzed amino acid differences within these epitope regions.
• Predicted the impact of sequence variations on HLA-I binding affinity.

Main Results:

• Amino acid differences were detected in 78% (31/40) of the epitope candidates.
• Reduced predicted HLA-I binding was observed in 43% (17/40) of epitope candidates from circulating MuV strains compared to the vaccine strain.
• Significant sequence variability exists in critical T cell epitope regions of MuV.

Conclusions:

• Antigenic differences between mumps vaccine strains and circulating MuV strains are prevalent in CD8+ T cell epitopes.
• These variations may lead to reduced T cell recognition and impaired immunity in vaccinated individuals.
• Findings suggest a potential mechanism for reduced vaccine effectiveness against contemporary mumps outbreaks.