Immunogenicity and Safety of 2 Doses of an Investigational Herpes Zoster Subunit Vaccine Administered 2, 6 or 12 Months Apart in Adults 50 Years and Older: Results of a Phase III, Randomized, Open-label, Multicenter Trial

Background: Two doses of a candidate herpes zoster (HZ) subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01_B Adjuvant System) administered 2 months (mo) apart in adults ≥50 years of age demonstrated >90% efficacy in preventing HZ and had a clinically acceptable safety profile. Here we report immunogenicity and safety of 2 HZ/su doses administered at intervals longer than 2 mo.

Methods: In this phase III, open-label trial (NCT01751165) conducted in the United States and Estonia, 354 adults ≥50 years of age were randomized 1:1:1 to receive 2 doses of HZ/su at 0,2 mo, 0,6 mo, or 0,12 mo. Blood samples for anti-gE ELISA were collected at pre-vaccination and at 1 and 12 mo post-dose 2. Primary objective: to compare immune responses to HZ/su 1 mo post-dose 2, when given on 0,6 mo and 0,12 mo schedules to those following 0,2 mo administration. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-each dose, respectively. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were recorded from dose 1 to 12 mo post-dose 2.

Results: 346 subjects completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. The mean age at dose 1 was 64.5 (0,2 mo), 64.0 (0,6 mo) and 64.1 (0,12 mo) years. One mo post-dose 2, vaccine response rates were similar following the 0,6 mo and 0,12 mo schedules and the pre-defined criterion was met (Figure 1). Consecutively, non-inferiority compared to the immune responses of HZ/su given at 0,2 mo was assessed, but demonstrated only for the 0,6 mo schedule (Figure 2). HZ/su elicited robust anti-gE immune responses, which remained at least 11.6-fold the pre-vaccination levels at 12 mo post-dose 2 (Figure 1). Pain was the most commonly reported solicited AE (Figure 3). 26 subjects reported at least one SAE (0,2 mo n=5, of which 1 fatal; 0,6 mo n=9, none fatal; 0,12 mo n=12, 1 fatal); none assessed as related to the vaccination. No pIMDs were reported.

Conclusion: Non-inferiority of the 0,6 mo schedule (but not of the 0,12 mo) compared to the 0,2 mo schedule was demonstrated. With an acceptable safety profile, HZ/su elicited robust anti-gE immune responses that persisted for up to at least 12 mo post-dose 2, irrespective of schedule.

Funding: GlaxoSmithKline Biologicals SA