A simulated, randomized study on the safety and immunogenicity of three consecutive commercial-scale batches of the CTN-1V strain human rabies vaccine to verify the inter-batch consistency. Issue 6 (30th November 2022)

• Record Type: Journal Article
• Authors: Zhou, Lei; Liu, Jingjing; Li, Jia; Liu, Xuecheng; Zhang, Jingwu; Nie, Fei; Chen, Jianmin; Chai, Jing; Lv, Jinchao; Wang, Minghui; Yu, Jiajie; Wu, Wenjie; Li, Yuhua; Zhang, Yuhui
• Is Part Of: Human vaccines & immunotherapeutics. Volume 18:Issue 6(2022)
• Publication Date: 2022-11-30
• Subjects: Human rabies vaccine -- CTN-1V strain -- safety -- immunogenicity -- inter-batch consistency -- equivalency testing; Vaccines -- Periodicals; 615.372
• DOI: 10.1080/21645515.2022.2138049
• Languages: English
• ISSNs: 2164-5515

Abstract

ABSTRACT: In this study, we sought to evaluate the inter-batch consistency and safety of the CTN-1 V human rabies vaccine (Vero cells). A total of 594 healthy participants aged 10–60 years were enrolled from Mianzhu, Sichuan Province, and randomized into three batch groups to receive vaccination via the Essen Regimen, that is, a single dose on days 0, 3, 7, 14, and 28 in the deltoid muscle of the upper arm. The serum antibody geometric mean concentration (GMC) and positive conversion rate of each group were determined using a rapid fluorescence focus inhibition test (RFFIT) before the first-dose immunization, 14 d after the first-dose immunization, and 14 d and 12 mo after full immunization. Adverse events (AEs) 30 min and 30 d after immunization were observed in each group. There were 322 cases of AEs during the observation period, with an overall incidence of 54.4%. The incidences of AEs in groups A, B, and C were 57.4%, 51.5%, and 54.3%, respectively. There were no significant differences among the groups (P > .05). Moreover, there were no significant differences (P > .05) in the serum GMC or antibody-positive conversion rate between any two groups at any time point. The bilateral 95% confidence interval of the GMC ratio between any two groups 14 d after the first-dose immunization was within the range of 0.67–1.50. This study shows that the CTN-1 V human rabies vaccine (Vero cells) has reliable safety and stable immunogenicity between batches. Plain Language Summary: This was a randomized, double-blind, equivalent clinical study on the inter-batch consistency of rabies vaccine. The rabies virus CTN strain adopted for the vaccine was isolated by China National Institute for Food and Drug Control. It has a gene sequence homology of 82.0%–93.0% with the representative strains of street virus isolated in China (i.e., CQ92, HN06, and J strains), higher than that of other vaccine strains (aG, PM, and PV strains). A total of 594 participants were enrolled in this study, and were randomized into three batch groups. Blood samples were collected from participants in each group before vaccination, at 14 days after the first dose of vaccination, and at 14 d and 12 mo after the fifth dose of vaccination, in order to detect antibody levels and observe adverse reactions. There was no significant difference in serum antibody levels and adverse reactions between any two of the three groups, indicating that different vaccine batches manufactured at the commercial scale can maintain stable immunogenicity and safety profiles.