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Broadly Reactive Human CD8 T Cells that Recognize an Epitope Conserved between VZV, HSV and EBV

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Human herpesviruses can cause a wide range of serious infections. They are extremely common and individuals remain latently infected lifelong, with reactivations often causing recurrent or severe disease. T-cells are important in controlling herpesvirus infections and preventing their reactivation, so vaccines that induce T-cells are likely to improve control. Here, we examined human T-cells against VZV that might allow focused vaccine development. We identified a dominant target against which the majority of subjects had mounted a CD8 T-cell response. We found that very similar targets also exist in three other important herpesviruses, HSV-1, HSV-2 and EBV. We showed that CD8 T-cells recognizing the VZV target could also recognize the others and we hypothesized that recurrent encounter with these viruses could boost this common response. In some individuals, immunization with a VZV vaccine did cause activation of these cells, but in most it did not. This reflects the variable efficacy of the currently available VZV vaccine. Our findings suggest that T-cell targets may be shared between herpesvirus species and may therefore contribute to a novel “pan-herpesvirus” vaccine. However, current VZV vaccines cannot reliably stimulate these T-cells and new strategies will be necessary to achieve this goal.

Vyšlo v časopise: Broadly Reactive Human CD8 T Cells that Recognize an Epitope Conserved between VZV, HSV and EBV. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004008
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004008

Souhrn

Human herpesviruses can cause a wide range of serious infections. They are extremely common and individuals remain latently infected lifelong, with reactivations often causing recurrent or severe disease. T-cells are important in controlling herpesvirus infections and preventing their reactivation, so vaccines that induce T-cells are likely to improve control. Here, we examined human T-cells against VZV that might allow focused vaccine development. We identified a dominant target against which the majority of subjects had mounted a CD8 T-cell response. We found that very similar targets also exist in three other important herpesviruses, HSV-1, HSV-2 and EBV. We showed that CD8 T-cells recognizing the VZV target could also recognize the others and we hypothesized that recurrent encounter with these viruses could boost this common response. In some individuals, immunization with a VZV vaccine did cause activation of these cells, but in most it did not. This reflects the variable efficacy of the currently available VZV vaccine. Our findings suggest that T-cell targets may be shared between herpesvirus species and may therefore contribute to a novel “pan-herpesvirus” vaccine. However, current VZV vaccines cannot reliably stimulate these T-cells and new strategies will be necessary to achieve this goal.

Zdroje

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