The efficacy, immunogenicity and safety of a recombinant tetrameric gE-Fc fusion protein vaccine for herpes zoster in adults 40 years of age or older：a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Abstract A recombinant gE-Fc fusion protein adjuvanted with aluminum hydroxide, LZ901, has elicited favorable cellular immunogenicity in adults, non-inferiority to HZ/su (GSK) in previous study. Here we conducted a randomized, placebo-controlled, phase 3 trial across 14 sites of four provinces in China, to evaluate the efficacy and safety of LZ901 in adults ≥40 years. Participants (1:1) received two intramuscular doses of LZ901 or placebo 30 days apart. The primary objective was to assess the efficacy of LZ901during the first 12 months after vaccination, in reducing the risk of herpes zoster. 26018 participants (13010 in LZ901 group, 13008 in placebo group) were evaluated. Over median 332 days follow-up, herpes zoster was confirmed in 15 LZ901 recipients and in 178 placebo recipients (1.3 versus 15.8 per 1000 person-years) in the pre-protocol cohort. Overall vaccine efficacy against herpes zoster was 91.6% (95% confidence interval [CI], 86.3 to 95.3; p<0.001). Efficacy against in participants between 40 and 69 years of age was 93.9% (95% CI, 89.1 to 97.0; p<0.001), while that in participants who were older than 70 years was 66.9% (95% CI, 14.6 to 89.2; p=0.016). Post-herpetic neuralgia (PHN) was identified in one of 15 cases in LZ901 group and in 24 of 178 cases in placebo group, resulting a vaccine efficacy of 95.9% (95% CI, 63.9 to 99.93; p<0.001) against PHN. LZ901 group had more injection-site and systemic reactions within 7 days than the placebo group, but the occurrences of grade 3 reactions were low and similar in both groups (0.4% versus 0.3%). No serious adverse events or safety concerns associated with LZ901 were noted. LZ901 significantly reduced the risk of herpes zoster in adults who were 40 years of age or older in 12 months, with a favorable safety profile. This study has already completed the trial registration at Chinese Clinical Trial Registry, ChiCTR (ChiCTR2300076253).