Guangxi Center for Disease Prevention and Control (CDC), No. 18, JinZhou Road, Nanning, Guangxi Province, China.
Vaccine. 2013 Dec 5;31(50):5940-7. doi: 10.1016/j.vaccine.2013.10.043. Epub 2013 Oct 19.
BACKGROUND: As an evolution of its currently licensed rabies vaccine Verorab(®), Sanofi Pasteur has developed a next-generation, serum-free, highly purified Vero rabies vaccine (PVRV-NG). Through this Phase III clinical trial, we aimed to demonstrate the non-inferiority of PVRV-NG over Verorab when administered according to a post-exposure regimen and to assess its clinical safety. METHODS: A total of 816 healthy subjects aged ≥10 years were randomized according to a 2:1 ratio to receive PVRV-NG or Verorab. Half of the subjects were aged 10-17 years, the other half were aged ≥18 years. All subjects were to receive 5 injections on days 0, 3, 7, 14 and 28. Three blood samples were taken for rabies virus neutralizing antibodies (RVNA) assessment, at baseline, on day 14 and day 42. Solicited adverse reactions (between injections 1, 2 and 3, and within 7 days post-injections 4 and 5) and adverse events (up to 28 days after the last injection) were collected for clinical safety assessment; serious adverse events were reported up to 6-months after the last injection. RESULTS: The proportion of subjects with an RVNA titer ≥0.5 IU/mL after the third injection of PVRV-NG was non-inferior to the proportion of those who received Verorab. PVRV-NG was shown to be as immunogenic as Verorab in each age range in the per-protocol and full analysis sets. PVRV-NG induced a strong immune response in both age ranges, with high RVNA levels and increased geometric mean titers compared to baseline after each measured time point. PVRV-NG had a satisfactory safety profile after each injection, similar to Verorab with regards to the nature, frequency, duration and severity of adverse events. Two serious adverse events were reported, none was related to vaccination. CONCLUSIONS: This trial demonstrated the immunogenic non-inferiority of PVRV-NG over Verorab and showed that both vaccines have similar safety profiles. This trial is registered at ClinicalTrials.gov (NCT01339312). This manuscript is the first full report of the study. An abstract of the study results was previously presented at the Rabies in the Americas (RITA) conference in October 2012 in São Paulo, Brazil. FUNDING: Sanofi Pasteur.
背景：作为目前许可的狂犬病疫苗 Verorab（®）的一项发展，赛诺菲巴斯德公司开发了一种新一代、无血清、高度纯化的 Vero 狂犬病疫苗（PVRV-NG）。通过这项 III 期临床试验，我们旨在证明 PVRV-NG 在按照暴露后方案给药时与 Verorab 相比具有非劣效性，并评估其临床安全性。
方法：总共 816 名年龄≥10 岁的健康受试者按照 2:1 的比例随机分为 PVRV-NG 或 Verorab 组。一半受试者年龄为 10-17 岁，另一半受试者年龄≥18 岁。所有受试者均在第 0、3、7、14 和 28 天接受 5 次注射。在基线、第 14 天和第 42 天采集 3 份狂犬病病毒中和抗体（RVNA）评估样本。在第 1、2 和 3 次注射之间以及第 4 和 5 次注射后 7 天内收集（注射后）不良反应（不良事件），在最后一次注射后 28 天内收集不良事件（AE），直至最后一次注射后 6 个月报告严重不良事件。
结果：PVRV-NG 第三次注射后 RVNA 滴度≥0.5IU/mL 的受试者比例与接受 Verorab 的受试者比例相当。在符合方案集和全分析集的每个年龄组中，PVRV-NG 均显示出与 Verorab 相当的免疫原性。PVRV-NG 在两个年龄组中均诱导了强烈的免疫反应，与基线相比，每个测量时间点的 RVNA 水平均较高，几何平均滴度增加。每次注射后，PVRV-NG 的安全性良好，与 Verorab 相似，不良事件的性质、频率、持续时间和严重程度相似。报告了 2 例严重不良事件，均与疫苗接种无关。
结论：这项试验证明了 PVRV-NG 与 Verorab 相比具有免疫非劣效性，并表明两种疫苗具有相似的安全性。该试验在 ClinicalTrials.gov 注册（NCT01339312）。本报告是该研究的首次完整报告。该研究结果的摘要已于 2012 年 10 月在巴西圣保罗举行的美洲狂犬病（RITA）会议上提交。
资金：赛诺菲巴斯德。
Vaccines (Basel). 2023-3-29
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