Wu Xiaohong, Li Jia, Zhou Lei, Chen Jianmin, Jin Zhongqiang, Meng Qingwei, Chai Jing, Gao Hongxia, Wang Yunpeng, Zhao Danhua, Wu Heng, Yu Jieran, Chen Nan, Wang Yanan, Lin Yuan, Huang Peifang, Li Yuhua, Zhang Yuhui
Arbovirus Vaccine Department, National Institutes for Food and Drug Control, Beijing 102629, China.
School of Chemical Engineering, Dalian University of Technology, Dalian 116023, China.
Vaccines (Basel). 2023 Aug 1;11(8):1311. doi: 10.3390/vaccines11081311.
In this paper, we aim to show that the immunogenicity of the lyophilized human rabies vaccine (Vero cells) (investigational vaccine) developed by Dalian Aleph Biomedical Co., Ltd. in healthy participants aged 10-60 years old is non-inferior to the lyophilized PVRV (positive control) manufactured by Liaoning Chengda Biotechnology Co., Ltd. (Shenyang, China), and that its safety is clinically acceptable.
A total of 2776 participants were enrolled in this study and divided into four groups: a five-dose test group, a five-dose control group, a four-dose test group, and a four-dose control group. The patients in the four-dose groups (Zagreb) were vaccinated on Days 0 (two doses), 7 (one dose), and 21 (one dose), and those in the five-dose groups (Essen) were vaccinated on Days 0, 3, 7, 14, and 28 (one dose each). The rabies-virus-neutralizing antibody assay with the RFFIT was used to assess the immunogenicity, and the adverse events (AEs) and serious adverse events (SAEs) were identified and collated.
The positive seroconversion rate was up to 100% on Days 14 and 35/42 after vaccination following any procedures in pre-immunization antibody-negative participants, and the positive seroconversion rate and geometric mean concentration (GMC) of the test groups (Zagreb and Essen vaccination procedures) was not inferior to that of the control groups. On Day 7 after vaccination, the immunogenicity of the Zagreb procedure with two doses of the vaccine on Day 0 was superior to the Essen procedure with one dose of vaccine, that is, the former had a higher seroconversion rate and RVNA titer. The non-inferiority criterion of immunogenicity was met for the whole population, the population aged 10-18 years and ≥18 years, and the pre-immunization antibody-positive population. The incidences of all AEs, solicited AEs, and unsolicited AEs in both groups were not statistically significant, and no vaccination-related SAEs were observed.
The investigated vaccine is safe, its immunogenicity is non-inferior to that of the control vaccine, and the efficacy of the Zagreb procedure is superior to that of the Essen procedure 7 days after the first dose.
在本文中，我们旨在证明大连艾美生物医学有限公司研发的冻干人用狂犬病疫苗（Vero细胞）（研究用疫苗）在10至60岁健康受试者中的免疫原性不劣于辽宁成大生物股份有限公司（中国沈阳）生产的冻干人用狂犬病疫苗（Vero细胞）（阳性对照），且其安全性在临床上是可接受的。
本研究共纳入2776名受试者，分为四组：五剂次试验组、五剂次对照组、四剂次试验组和四剂次对照组。四剂次组（萨格勒布方案）的受试者于第0天（两剂次）、第7天（一剂次）和第21天（一剂次）接种疫苗，五剂次组（埃森方案）的受试者于第0天、第3天、第7天、第14天和第28天（各一剂次）接种疫苗。采用快速荧光灶抑制试验（RFFIT）检测狂犬病病毒中和抗体来评估免疫原性，并识别和整理不良事件（AE）和严重不良事件（SAE）。
在免疫前抗体阴性的受试者中，无论采用何种接种程序，接种后第14天以及第35/42天的阳性血清转化率均高达100%，试验组（萨格勒布和埃森接种程序）的阳性血清转化率和几何平均浓度（GMC）不劣于对照组。接种后第7天，第0天接种两剂疫苗的萨格勒布程序的免疫原性优于接种一剂疫苗的埃森程序，即前者的血清转化率和狂犬病病毒中和抗体（RVNA）滴度更高。在总体人群、10至18岁人群、≥18岁人群以及免疫前抗体阳性人群中，免疫原性均符合非劣效标准。两组中所有AE、预期AE和非预期AE的发生率均无统计学差异，未观察到与疫苗接种相关的SAE。
所研究的疫苗是安全的，其免疫原性不劣于对照疫苗，且萨格勒布程序在首剂接种7天后的效果优于埃森程序。
