Immunogenicity and safety of a Recombinant gE-Fc Fusion Protein Subunit Vaccine for Herpes Zoster in Adults ≥50 Years of Age: a randomised, active-controlled, non-inferiority trial

Background The licensed adjuvanted recombinant glycoprotein E (gE) subunit vaccine (HZ/su) is highly efficient against herpes zoster (HZ). We compared the immunogenicity and safety of a novel gE-Fc fusion protein subunit vaccine candidate (LZ901) with HZ/su. Methods This was a randomised, active-controlled, non-inferiority trial conducted in Wuxi, China, involving healthy adults aged 50 years and older who had not previously received a HZ vaccine. Eligible participants were randomly assigned (1:1) to receive two doses of LZ901 (30-day interval) or HZ/su (60-day interval). This study was partially blinded, with all participants and investigators without access to the vaccines were masked till 30 days post-first dose, while the laboratory testing personnel remained blinded for the entire trial. Primary outcomes were the proportions of participants with CD4²⁺/CD8²⁺ T-cell responses (defined as co-expression of ≥2 activation markers: IFN-γ, IL-2, TNF-α, or CD40L) 30 days post-second dose. Non-inferiority of LZ901 to HZ/su was determined when the differences of proportions between LZ901 and HZ/su > -10% non-inferiority margin. This study is registered with chictr.org, ChiCTR2300079076. Findings Between December 25 and 29, 2023, we screened 357 individuals for eligibility. Of them, 300 were eligible and randomly allocated to receive either LZ901 vaccine (n=151) or HZ/su vaccine (n=149). LZ901 met non-inferiority criteria for both CD42⁺ and CD82⁺ T-cell responses compared to HZ/su. Participants receiving LZ901 demonstrated higher proportions of responders with at least two positive cytokines CD4²⁺ T-cell (96.5% [136/141] vs 79.4% [108/136]; p<0.0001) and the CD8²⁺ T-cell (69.5% [98/141] vs 22.8% [31/136]; p<0.0001) than participants receiving HZ/su did. Adverse reactions were significantly less frequently reported by LZ901 recipients (41.1% [62/151] vs 87.9% [131/149]; p<0.0001) than those reported by HZ/su recipients, as well as grade 3 adverse reactions (0.7% [1/151] vs 6.0% [9/149]). Interpretation LZ901 induced superior immunogenicity in terms of cellular immune responses than HZ/su did in adults ≥50 years, with a better safety profile. Our findings supported LZ901 as a promising candidate vaccine for HZ prevention. Funding National Key Research and Development Program of China, Medical Research Program of Jiangsu Health Commission and Beijing Luzhu Biotechnology Co., Ltd.