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

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Waning mumps virus (MuV) humoral immunity is implicated in recent outbreaks among vaccinated adults.
• The role and dynamics of CD8+ T cells in MuV response remain poorly understood.
• Understanding cellular immunity is crucial for evaluating vaccine effectiveness and designing improved strategies.

Purpose of the Study:

• To characterize the dynamics of MuV-specific CD8+ T-cell responses following MuV infection.
• To investigate the long-term maintenance of cellular memory against MuV.
• To identify potential targets for optimizing future mumps vaccination strategies.

Main Methods:

• Longitudinal follow-up of CD8+ T-cell responses to specific MuV epitopes in vaccinated and unvaccinated individuals post-infection.
• Analysis of T-cell receptor beta (TCRβ) repertoire and expression of inhibitory receptors and homing markers.
• Quantification of MuV-specific CD8+ T-cell frequencies over 36 months.

Main Results:

• The CD8+ T-cell response was primarily directed against the ALDQTDIRV and LLDSSTTRV epitopes.
• MuV-specific CD8+ T-cell frequencies decreased significantly between 1.5 and 9 months post-infection.
• Despite frequency changes, the TCRβ repertoire remained stable, indicating persistent cellular memory.

Conclusions:

• The cellular immune response to MuV involves a stable T-cell repertoire despite fluctuating T-cell numbers.
• Insights into CD8+ T-cell dynamics post-MuV infection can inform the development of vaccines eliciting durable cellular memory.
• Further research into cellular memory mechanisms is warranted for long-term protection against mumps.