Sampath Gadey, Banzhoff Angelika, Deshpande Alaka, Malerczyk Claudius, Arora Ashwani Kumar, Vakil Hoshang, Preiss Scott
a Institute of Preventive Medicine, Anti-Rabies Clinic , Hyderabad , India.
b GSK Vaccines GmbH , Marburg , Germany.
Hum Vaccin Immunother. 2017 Jul 3;13(7):1531-1538. doi: 10.1080/21645515.2017.1307483. Epub 2017 Apr 13.
This phase IV, single blind study assessed the immunogenicity and safety of India-manufactured purified chick embryo cell rabies vaccine (PCECV), compared with a German-manufactured batch obtained by the same production process. A total of 340 participants enrolled at 2 study sites in India were randomized (1:1:1:1) in 4 groups to receive a 5-dose Essen regimen with either 1 of the 3 Indian batches (PCECV-I) or the German batch (PCECV-G), administered on Days (D) 0, 3, 7, 14 and 30. The lot-to-lot consistency of PCECV-I batches in terms of induced immune response at D14 was demonstrated. The immune response elicited by PCECV-I was shown to be non-inferior to that induced by PCECV-G, as the lower limit of the 95% confidence interval for the ratio (PCECV-I/PCECV-G) of rabies virus neutralising antibody (RVNA) geometric mean concentrations was higher than 0.5 at D14. At least 96% of participants developed adequate RVNA concentrations (≥ 0.5 IU/mL) by D14 and all achieved RVNA concentrations ≥ 0.5 IU/mL by D90. RVNA levels were comparable across all groups throughout the entire study. Solicited local and general symptoms had a similar incidence in all groups. Unsolicited adverse events (AEs) were reported by 11% of participants. Only 1 serious AE (leg fracture) was reported and was not related to vaccination. No deaths and no rabies cases were recorded during the 90 days of observation. The study showed that the 3 PCECV-I and the PCECV-G batches induced a similar immune response and had a comparable safety profile when administered according to a 5-dose schedule.
本IV期单盲研究评估了印度生产的纯化鸡胚细胞狂犬病疫苗(PCECV)的免疫原性和安全性,并与通过相同生产工艺获得的德国生产批次进行了比较。在印度的2个研究地点招募的340名参与者被随机(1:1:1:1)分为4组,接受5剂埃森方案,分别接种3个印度批次(PCECV-I)中的1个或德国批次(PCECV-G),于第0、3、7、14和30天给药。结果表明,PCECV-I批次在第14天时诱导的免疫反应具有批间一致性。PCECV-I引发的免疫反应被证明不劣于PCECV-G,因为在第14天时,狂犬病病毒中和抗体(RVNA)几何平均浓度之比(PCECV-I/PCECV-G)的95%置信区间下限高于0.5。到第14天时,至少96%的参与者产生了足够的RVNA浓度(≥0.5 IU/mL),到第90天时所有参与者的RVNA浓度均≥0.5 IU/mL。在整个研究过程中,所有组的RVNA水平相当。所有组中,主动报告的局部和全身症状发生率相似。11%的参与者报告了非主动不良事件(AE)。仅报告了1例严重AE(腿部骨折),且与疫苗接种无关。在90天的观察期内未记录到死亡和狂犬病病例。该研究表明,3个PCECV-I批次和PCECV-G批次按照5剂方案给药时,诱导的免疫反应相似,安全性相当。