Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.29.227082v1?rss=1 Authors: Voic, H., de Vries, R. D., Sidney, J., Rubiro, P., Moore, E., Phillips, E. J., Mallal, S., Schwan, B., Weiskopf, D., Grifoni, A., Sette, A. Abstract: Infections with varicella zoster virus (VZV), a member of the Herpesviridae family, are associated with a range of clinical manifestations. Primary infection with VZV causes chicken pox, and due to the virus capacity to remain latent in neurons, it can reactivate later in life causing herpes zoster (HZ), also known as shingles. Two different licensed vaccines are available to prevent HZ, either based on a live attenuated VZV strain (Zostavax) or on adjuvanted gE recombinant protein(Shingrix). While Zostavax efficacy wanes with age, Shingrix protection retains its efficacy in elderly subjects (80 years of age and beyond). In this context, studies to evaluate the potential role of T cell immunity as a correlate of protection and Shingrix efficacy are of interest. In this study, we characterized 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 non-structural 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 responding subjects. Copy rights belong to original authors. Visit the link for more info