Safety and Immunogenicity of an AS01- adjuvanted Varicella-zoster Virus Subunit Candidate Vaccine Against Herpes Zoster in Adults ≥50 Years of Age

Background. An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses. Methods. This was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were ran-domized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline. Following each dose, solicited events were recorded for 7 days and unsolicited adverse events for 30 days. Serious adverse events were collected for 1 year. Cell-mediated and humoral immune re-sponses were assessed at baseline and following each dose. Results. No vaccine-related severe adverse events were reported. Solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom. Immune responses were significantly enhanced by AS01B and AS01E compared to un-adjuvanted gE and were significantly stronger for gE/AS01B than for gE/AS01E. Conclusions. AS01 improved the immunogenicity of gE while retaining acceptable safety and reactogenicity profiles. The enhancement of gE-specific cellular and humoral responses was adjuvant dose dependent