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CLINICAL TRIAL article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1444686

Safety, immunogenicity and immune-persistence of a lyophilized human rabies vaccine (Vero Cells) under Zagreb and Essen regimens: A randomized, open-label, controlled phase III clinical trial in healthy participants aged 10 -60 years in China

Provisionally accepted
Zhenzhen Liang Zhenzhen Liang 1Xu Chen Xu Chen 2*Bo Xing Bo Xing 1*Xiaosong Hu Xiaosong Hu 1*Miaomiao Liu Miaomiao Liu 3*Xinpei Zhang Xinpei Zhang 4*Yugang Shen Yugang Shen 5*Yan Wang Yan Wang 3*Yingping Chen Yingping Chen 1*Huakun Lv Huakun Lv 1*Yu Mao Yu Mao 3*
  • 1 Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, China
  • 2 Xiamen University, Xiamen, Fujian Province, China
  • 3 Liaoning Chengda Biotechnology Co., Ltd, Shenyang, China
  • 4 Shangyu Disease Prevention and Control Center, Shaoxing, China
  • 5 Shengzhou Center for Disease Control and Prevention, Shaoxing, China

The final, formatted version of the article will be published soon.

    Background: Rabies continues to be a significant global public health concern, particularly in the Asia region where it is associated with high mortality rate. The administration of effective vaccination is essential in preventing this potentially fatal viral infection. The objective of this study was to evaluate the immunogenicity and safety of two rabies vaccination schedules: the Zagreb (2-1-1) and Essen (1-1-1-1-1) regimens, in a cohort of healthy Chinese individuals aged 10-60 years. Methods: We conducted a randomized, open-label, controlled, non-inferiority phase 3 trial from July 2021 to November 2022, enrolling a total of 1200 participant.Participants were randomly assigned to receive either the Zagreb or Essen vaccination regimen. The primary outcomes were safety, immunogenicity, and immune persistence. Safety was monitored through adverse event reporting, while immunogenicity was determined by measuring rabies-virus-neutralizing antibody (RVNA) concentrations using the rapid fluorescent focus inhibition test (RFFIT). Immune persistence was evaluated at 3, 6, and 12 months post-vaccination. Results: The two vaccination regimens exhibited comparable safety records, with mild and transient adverse events predominantly occurring within 0-3 days post-vaccination. The Zagreb regimen demonstrated non-inferiority in terms of seroconversion rates and geometric mean concentrations (GMCs) of antibodies compared to the Essen regimen at both 14 days post-first vaccination and 14 days post-full vaccination. Additionally, both groups displayed a nearly 100% seropositivity rate at 3,6, and 12 months. No serious adverse events associated with vaccination were reported. Conclusion: The findings of this Phase 3 clinical trial providet compelling evidencethat the Zagreb regimen is a feasible alternative when compared to the Essen regimen for rabies vaccination, offering a more pragmatic and cost-efficient approach to rabies prevention and control.

    Keywords: lyophilized human rabies vaccine (Vero cells), Essen and Zagreb regimens, Immunogenicity, Safety, Non-inferiority (trials)

    Received: 06 Jun 2024; Accepted: 16 Oct 2024.

    Copyright: © 2024 Liang, Chen, Xing, Hu, Liu, Zhang, Shen, Wang, Chen, Lv and Mao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xu Chen, Xiamen University, Xiamen, 361005, Fujian Province, China
    Bo Xing, Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, China
    Xiaosong Hu, Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, China
    Miaomiao Liu, Liaoning Chengda Biotechnology Co., Ltd, Shenyang, China
    Xinpei Zhang, Shangyu Disease Prevention and Control Center, Shaoxing, China
    Yugang Shen, Shengzhou Center for Disease Control and Prevention, Shaoxing, China
    Yan Wang, Liaoning Chengda Biotechnology Co., Ltd, Shenyang, China
    Yingping Chen, Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, China
    Huakun Lv, Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, China
    Yu Mao, Liaoning Chengda Biotechnology Co., Ltd, Shenyang, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.