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.

The licensed adjuvanted recombinant glycoprotein E (gE) subunit vaccine (HZ/su) is highly effective against herpes zoster (HZ). This randomised, active-controlled, non-inferiority trial (ChiCTR2300079076) compared the immunogenicity and safety of a novel gE-Fc fusion protein vaccine candidate (LZ901) with HZ/su in 300 healthy adults aged ≥50 years without prior HZ vaccination in Wuxi, China. Participants received either two doses of LZ901 (30-day interval; n = 151) or HZ/su (60-day interval; n = 149). The primary outcomes was the proportion of participants with simultaneous positive responses to two or more cytokines (IFN-γ, IL-2, TNF-α, or CD40L) 30 days after the second dose (referred to as gE-specific CD4/CD8 T-cell responses). LZ901 demonstrated non-inferiority to HZ/su (margin > -10%) for both CD4 and CD8 T-cell responses. Significantly higher response rates were observed with LZ901 for CD4 + T-cell responses (83.0% [117/141] vs 58.1% [79/136]; p < 0.0001) and CD8 + T-cell responses (46.8% [66/141] vs 8.8% [12/136]; p < 0.0001). Adverse reactions were markedly lower with LZ901 (41.1% [62/151] vs 87.9% [131/149]; p < 0.0001), including grade 3 events (0.7% [1/151] vs 6.0% [9/149]). LZ901 induced superior cellular immunogenicity and exhibited a better safety profile than HZ/su in adults ≥50 years, supporting its potential as a promising HZ prevention candidate vaccine.