Evaluation of human cell mediated immune responses to VZV antigens (VAC7P.993)

Zostavax© is a safe and effective vaccine against Herpes Zoster. The precise immune correlate of protection and the corresponding VZV antigens responsible for protective immunity are not currently defined. A few key pieces of data suggest that cell mediated immune responses are more important than humoral responses in the immune control over viral re-activation from latent infection. Primarily, the majority of Herpes Zoster outbreaks occur in the aging population in which antibody titers against VZV are maintained but cell mediated immune responses wane. Additionally, individuals who are immunocompromised as a result of disease or drug treatment have difficulty controlling the virus. A group of ten viral proteins of Varicella were chosen for evaluating human cell mediated immune responses. Donor samples were recruited in the following cohorts: i; Herpes Zoster outbreak within the last 5 years, ii; Subjects age 35+ with no history of Shingles or Zostavax© vaccination, and iii subjects pre and post Zostavax© vaccination. Blood samples from these donors were stimulated with the set of VZV antigens and a panel of cytokine responses from the plasma was measured. Here we show a ranking of VZV viral protein immunogenicity from these cohorts, as well as the cytokine profiles for each. These studies will help to define the viral proteins involved in generating protective cell mediated immunity correlated with protection.