Immunogenicity and Safety of a Live-Attenuated Varicella Vaccine in a Healthy Population Aged 13 Years and Older: A Randomized, Double-Blind, Controlled Study

Abstract

Objectives: Vaccines for prevention against varicella are important for adolescents and adults, who have an increased risk of severe varicella. This study aimed to evaluate the immunogenicity and safety of a two-dose immunization schedule of a live-attenuated varicella vaccine (VarV) manufactured by Sinovac (Dalian) in healthy adolescents and adults.

Methods: A randomized, double-blind, controlled clinical trial was conducted in healthy population aged ≥13 years old in China. Participants in block 1 were randomly assigned (1:1) to receive two doses of either the test vaccine or an active control vaccine, administered 4, 6 or 8 weeks apart. Participants in block 2 were randomly assigned (2:1) to receive two doses of test vaccine or placebo, administered 10 weeks apart. The primary immunogenicity endpoint was the seroconversion rates and GMTs of varicella zoster virus (VZV) antibodies measured by fluorescent-antibody-to-membrane-antigen (FAMA) 4 weeks post-immunization. The primary safety endpoint was the incidence of adverse reactions within 4 weeks after each dose.

Results: A total of 2398 participants were enrolled. The seroconversion rates of VZV antibodies were 79.55% in the test group and 76.41% in the active control group respectively 4 weeks after two doses of pooled schedule, with the difference of 3.14% (95%CI: -0.69%, 6.97%). The GMTs were 1:162.07 and 1:160.04 respectively, with the ratio of 1.013 (95%CI: 0.910, 1.127). Both the seroconversion rates and GMTs reached the prespecified non-inferiority criteria. Two-dose schedule with an interval of 10 weeks could also induce high immune responses, with a seroconversion rate of 83.22% and a GMT of 1:160.38 in the test group. Safety profiles were similar among the test group, active control group and placebo group.

Conclusion: VarV, manufactured by Sinovac (Dalian), demonstrated higher immune response and better flexibility in the immunization schedule among heathy population aged 13 years and older, without increased safety risk.

Note:
Funding declaration: The study was funded by Sinovac (Dalian) Vaccine Technology Co Ltd.

Conflict of Interests: Financial support was received from Sinovac (Dalian) Vaccine Technology Co Ltd. Hongxue Yuan and Chunfang Luan are employed by Sinovac (Dalian) Vaccine Technology Co Ltd. Yufei Song and Ningning Jia are employed by Sinovac Biotech Co Ltd. The other authors report no conflicts of interest relevant to this article.

Ethical Approval: The study was approved by the Ethics Committee of Henan Provincial Center for Disease Control and Prevention (2021-YM-013-05-1). Participants or parents provided written informed consent, and adolescents aged 13-17 years old provided written assent before enrollment.

Trial Registration: NCT05015686

Keywords: live-attenuated varicella vaccine, immunogenicity, safety, two-dose immunization schedule