Cell-mediated immune responses to ZOSTAVAX© are characterized by a boost in polyfunctional central memory T cells (VAC4P.1115)

Herpes Zoster (HZ) is a debilitating disease caused by reactivation of latent varicella-zoster virus (VZV). ZOSTAVAX is approved for the prevention of HZ and its complications in individuals 50 years and older in many countries around the world. The mechanistic immune correlates of protection and VZV antigens responsible for induction of protective CMI are not defined. To screen for dominant VZV antigens, whole blood from subjects pre-and-post ZOSTAVAX vaccination were assessed for production of IFN-ϒ, IL-2 and, TNF-α. VZV antigens eliciting high cytokine levels were used to stimulate PBMC and intracellular cytokine staining performed. We show that the VZV antigens that led to a boost in the frequency of polyfunctional CD4 + T cells (T CD4+ ) were IE63>IE62>gB>ORF9>gE. Polyfunctional T CD4+ produced higher levels of cytokines than monofunctional cells, and a boost in expression of cytokines was observed, post-ZOSTAVAX. Phenotypic characterization of polyfunctional T CD4+ demonstrated that they are T CM cells. Notably, we detected ORF9-specific CD8 + T cells in 52% of subjects tested, however whether these responses are cross-functional or VZV-specific needs to be determined. Overall, these studies outline the CMI that may correlate with ZOSTAVAX protection.