Immunogenicity and Safety of Two-dose Schedules With Different Intervals of an ORF7-deficient Live Vaccine Candidate for Varicella: A Randomized, Double-blind, Controlled, Phase 2b Trial

BACKGROUND: Current Oka strain varicella vaccines are generally safe but may cause latent neuronal infections leading to herpes zoster in some vaccinees. A novel v7D candidate vaccine has been developed to prevent varicella and reduce these risks. METHODS: This randomized, double-blind, controlled, phase 2b clinical trial was conducted in Jiangsu, China. Healthy children 1-12 years old with no history of varicella infection or vaccination were enrolled and randomly assigned to 0-3-/6-month schedule for low/medium dose. Phase 2a participants (3-12 years of age) previously receiving low-/medium-/high-dose v7D or licensed vOka received a second dose in phase 2b (0-15-month schedule) for exploratory analysis. The primary outcome was immunogenicity via varicella-zoster virus immunoglobulin (Ig)G seroconversion and geometric mean titers at 30 and 90 days post-second vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2300068380. RESULTS: In the per-protocol analysis, IgG antibody response reached 100% seroconversion by day 30 after the second vaccination. Antibody levels were comparable among different vaccine groups under the same schedule at day 30 post-second vaccination. The occurrence of adverse reactions was similar among the different vaccine groups within the same schedule. Most adverse reactions were mild or moderate and resolved shortly. None of the serious adverse events were related to the vaccine. CONCLUSIONS: The 2-dose regimens of v7D vaccine demonstrated robust immune responses and excellent safety profiles. These findings warrant further evaluation of the safety advantages and efficacy v7D vaccine in the future.