Abstract
<title>Abstract</title> <p> <bold>Background</bold> Low uptake of HZ vaccination among adults aged 50 years or older in China underscores the critical need for accessible and well-tolerated vaccine options. We therefore evaluated the safety and immunogenicity of LZ901, a tetrameric glycoprotein E (gE)-Fc fusion recombinant zoster vaccine candidate, in adults aged 50–70 years. <bold>Methods</bold> We conducted a randomised, double-blind, placebo-controlled, phase 2 trial at a single centre in China between Apr 22, 2022, and Jun 07, 2024. Eligible participants were aged 50–70 years, had no history of HZ within the previous 10 years and no HZ vaccination. Participants were randomly assigned (1:1:1) to receive two intramuscular injections, 30 days apart, of LZ901 50 μg, LZ901 100 μg, or placebo containing aluminium hydroxide. Primary outcomes were safety and immunogenicity. Safety outcomes included the incidence of adverse events (AEs) within 6 months after full vaccination and serious adverse events (SAEs) throughout follow-up. Immunogenicity was evaluated by geometric mean concentrations of anti-glycoprotein E (anti-gE) antibodies and geometric mean titres of anti-varicella-zoster virus (anti-VZV) antibodies at prespecified timepoints up to 24 months after vaccination. Between-group geometric mean ratios (GMRs) were estimated using analysis of variance on log-transformed antibody values. The trial is registered with chictr.org.cn, ChiCTR2200058609. <bold>Results</bold> Among 450 participants, the mean (SD) age was 58.7 (5.6) years overall. In the safety set (50 μg, n=150; 100 μg, n=149; placebo, n=151), any AE during the 30 days post-full vaccination occurred in 39.33%, 38.93%, and 28.48%, respectively; most AEs were grade 1 or 2. Grade 3 vaccine-related AEs occurred in 2.0% of the 100 μg group. No SAEs were considered vaccine-related. For immunogenicity, anti-gE antibody responses peaked at 30 days after full vaccination (16.03, 24.19, and 1.21 IU/mL for the 50 μg, 100 μg, and placebo groups, respectively) while anti-VZV antibody responses peaked at 6 months after full vaccination (324.10, 381.79, and 93.20). Both antibody responses remained 2.18-5.28-fold above baseline through month 24, between-group GMRs supported consistently higher responses in the 100 μg group than in the 50 μg group. <bold>Conclusions</bold> LZ901 was safe and immunogenic in adults aged 50 years or older, supporting further evaluation of the 100 μg dose in phase 3 clinical trial. <bold>Trial registration</bold> ChiCTR.org.cn, ChiCTR2200058609. Registered on April 12, 2022. </p>