Genetic Analysis Reveals Differences in CD8+ T Cell Epitope Regions That May Impact Cross-Reactivity of Vaccine-Induced T Cells against Wild-Type Mumps Viruses

Abstract

Nowadays, mumps is re-emerging in highly vaccinated populations. Waning of vaccine-induced immunity plays a role, but antigenic differences between vaccine and mumps outbreak strains could also contribute to reduced vaccine effectiveness. CD8+ T cells play a critical role in immunity to viruses. However, limited data are available about sequence variability in CD8+ T cell epitope regions of mumps virus (MuV) proteins. Recently, the first set of naturally presented human leukocyte antigen Class I (HLA-I) epitopes of MuV was identified by us. In the present study, sequences of 40 CD8+ T cell epitope candidates, including previously and newly identified, obtained from Jeryl–Lynn mumps vaccine strains were compared with genomes from 462 circulating MuV strains. In 31 epitope candidates (78%) amino acid differences were detected, and in 17 (43%) of the epitope candidates the corresponding sequences in wild-type strains had reduced predicted HLA-I-binding compared to the vaccine strains. These findings suggest that vaccinated persons may have reduced T cell immunity to circulating mumps viruses due to antigenic differences.

Longitudinal Characterization of the Mumps-Specific HLA-A2 Restricted T-Cell Response after Mumps Virus Infection

“…CD8 + T cells are known to play an important role in the clearance of viruses and in disease outcome, and generally recognize the more conserved parts of a virus. Despite some mismatch epitopes between the vaccine and circulating MuV strains [15], many CD8 + epitopes are conserved, and may therefore play an important role in the prevention of vaccine failure, despite antigen mismatch. However, current insights into the MuV-specific cellular response are limited.…”

Antibody Levels at 3-Years Follow-Up of a Third Dose of Measles-Mumps-Rubella Vaccine in Young Adults

“…An MMR vaccine booster dose, as intervention to control a mumps outbreak, should be given in the early phase of an outbreak to persons at risk for mumps, such as young adults that have been vaccinated for longer time ago. Apart from an additional MMR dose, the development of a new polyvalent mumps vaccine combining diverse genotypes including circulating outbreak strains have been suggested to provide a solution for better and long-term protection against mumps [29][30][31].…”

Exploring the Mumps Virus Glycoproteins: A Review

“…This was determined by the production of virus escape mutants, which were then tested for antibody recognition via ELISA using antibodies that had been shown to bind specific regions of the HN protein [40,47,49]. Five T-cell recognition regions have been predicted (74-82, 88-96, 157-165, 326-334, 503-513) of which amino acid variations in four of the regions (74-82, 157-165, 326-334, 503-513) have been shown to reduce HLA binding for genotype G [50]. When the predicted mumps epitopes on the HN protein are mapped, they are predicted to fall near αhelices in the HN head domain.…”

“…In particular, the L336S SNV is predicted to strengthen the HN protein as it allows for the formation of added hydrogen bonds with amino acids [55]. Amino acid variations of JL5 compared to other mumps genotypes showed mutations at positions: K74M, R76K, E77A, A80T, A158A/F, H161R, V334I/L, T511A and T513A/I, resulting in reduce HLA binding which could affect T-cell Immunogenicity [50].…”