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Identification and characterization of CD4+ T cell epitopes after Shingrix vaccination

Voic, H., de Vries, R.D., Sidney, J., Rubiro, P., Moore, E., Phillips, E., Mallal, S., Schwan, B., Weiskopf, D., Sette, A., Grifoni, A. and Goodrum, F. (2020) Identification and characterization of CD4+ T cell epitopes after Shingrix vaccination. Journal of Virology, 94 (24).

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Infections with varicella-zoster virus (VZV) are associated with a range of clinical manifestations. Primary infection with VZV causes chicken pox. The virus remains latent in neurons, and it can reactivate later in life, causing herpes zoster (HZ). Two different vaccines have been developed to prevent HZ; one is based on a live attenuated VZV strain (Zostavax), and the other is based on adjuvanted gE recombinant protein (Shingrix). While Zostavax efficacy wanes with age, Shingrix protection retains its efficacy in elderly subjects (individuals 80 years of age and older). In this context, it is of much interest to understand if there is a role for T cell immunity in the differential clinical outcome and if there is a correlate of protection between T cell immunity and Shingrix efficacy. In this study, we characterized the Shingrix-specific ex vivo CD4 T cell responses in the context of natural exposure and HZ vaccination using pools of predicted epitopes. We show that T cell reactivity following natural infection and Zostavax vaccination dominantly targets nonstructural (NS) proteins, while Shingrix vaccination redirects dominant reactivity to target gE. We mapped the gE-specific responses following Shingrix vaccination to 89 different gE epitopes, 34 of which accounted for 80% of the response. Using antigen presentation assays and single HLA molecule-transfected lines, we experimentally determined HLA restrictions for 94 different donor/peptide combinations. Finally, we used our results as a training set to assess strategies to predict restrictions based on measured or predicted HLA binding and the corresponding HLA types of the responding subjects.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: American Society for Microbiology
Copyright: © 2020 American Society for Microbiology
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