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

Josien Lanfermeijer,Jelle De Wit,Patricia Kaaijk,Debbie Van Baarle,Cécile A C M Van Els,Marieke M Nühn,José A M Borghans,Martien C M Poelen,Maarten E Emmelot

doi:10.3390/vaccines9121431

Abstract

Waning of the mumps virus (MuV)-specific humoral response after vaccination has been suggested as a cause for recent mumps outbreaks in vaccinated young adults, although it cannot explain all cases. Moreover, CD8+ T cells may play an important role in the response against MuV; however, little is known about the characteristics and dynamics of the MuV-specific CD8+ T-cell response after MuV infection. Here, we had the opportunity to follow the CD8+ T-cell response to three recently identified HLA-A2*02:01-restricted MuV-specific epitopes from 1.5 to 36 months post-MuV infection in five previously vaccinated and three unvaccinated individuals. The infection-induced CD8+ T-cell response was dominated by T cells specific for the ALDQTDIRV and LLDSSTTRV epitopes, while the response to the GLMEGQIVSV epitope was subdominant. MuV-specific CD8+ T-cell frequencies in the blood declined between 1.5 and 9 months after infection. This decline was not explained by changes in the expression of inhibitory receptors or homing markers. Despite the ongoing changes in the frequencies and phenotype of MuV-specific CD8+ T cells, TCRβ analyses revealed a stable MuV-specific T-cell repertoire over time. These insights in the maintenance of the cellular response against mumps may provide hallmarks for optimizing vaccination strategies towards a long-term cellular memory response.

Highlights

Mumps is a viral infectious disease typically characterized by bilateral or unilateral swelling of the parotid glands
There was no significant difference in severity of symptoms related to mumps virus (MuV) infection between vaccinated and unvaccinated individuals (Table 1)
We investigated the frequency, phenotype, and T-cell receptor (TCR) repertoire of the MuV-specific CD8+ T-cell response in the memory phase from 1.5 to 36 months after the onset of natural MuV infection in previously vaccinated and unvaccinated adults

Summary

Introduction

Mumps is a viral infectious disease typically characterized by bilateral or unilateral swelling of the parotid glands. Many countries vaccinate their population against mumps, usually as a combination vaccine together with measles and rubella vaccine components (MMR vaccine) [2,3]. This has led to a dramatic decrease in the incidence of mumps virus (MuV) infection [2]. In the last decades, mumps outbreaks have been reported in various countries, despite high vaccination coverage [4,5]. In the Netherlands, several mumps outbreaks occurred between 2009 and 2013, mainly among young adults, most of which did receive their two childhood MMR vaccinations [6]

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Results

Conclusion