Herpes zoster recurrence, and safety and immunogenicity of the recombinant zoster vaccine in adults aged ≥50 years with a history of herpes zoster: A phase 3, randomized controlled trial

Abstract

Objectives: To assess HZ recurrence (primary objective), safety and immunogenicity of the recombinant zoster vaccine (RZV) in adults with prior HZ.

Methods: This phase 3, observer-blind, multi-country study (NCT04091451) enrolled participants ≥50 years with one resolved HZ episode >6 months prior, randomized 1:1 to receive two RZV or placebo doses 2 months apart. Recurrent HZ cases were confirmed by an algorithm comprising varicella-zoster virus-PCR and HZ adjudication determination. The non-inferiority objective for HZ recurrence over ≥26 months was met if the upper limit of the 95% confidence interval (CI) of the HZ recurrence incidence rate ratio (IRR) in the RZV vs placebo groups was <5. Reactogenicity, broad safety, humoral and cell-mediated immunogenicity were also evaluated.

Results: Among 1426 participants receiving ≥1 dose of RZV (714)/placebo (712), eight HZ recurrence cases were confirmed, all in placebo recipients (IRR RVZ vs placebo: 0.00 [95%CI: 0.00-0.46]; non-inferiority objective met). No safety signals were identified. Two RZV doses elicited robust immune responses in this population.

Conclusion: In participants ≥50 years with prior HZ, RZV does not increase HZ recurrence risk. RZV was immunogenic, and safety results were consistent with the vaccine's known safety profile, providing evidence to support RZV use in this population.

Keywords: Adult; Herpes zoster; Herpes zoster vaccine; Humans; Immunity, Cellular; Immunity, Humoral; Immunogenicity, Vaccine; Incidence; Recurrence.