Lang J, Cetre J C, Picot N, Lanta M, Briantais P, Vital S, Le Mener V, Lutsch C, Rotivel Y
Pasteur Mérieux Connaught, Lyon, France.
Biologicals. 1998 Dec;26(4):299-308. doi: 10.1006/biol.1998.0156.
Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (Verorab; Pasteur Mérieux Connaught). The immunogenicity and safety of primary immunization, followed by a booster at one year, with CPRV was compared to that of the purified Vero cell vaccine (PVRV) in a randomized, double-blind study carried out at four veterinary schools in France. A total of 330 healthy, male and female, first-year veterinary students, aged at least 18 years and who required pre-exposure rabies prophylaxis, were enrolled in this study. Included subjects were randomly assigned either CPRV (n = 163) or PVRV (n = 167) to be given as a primary immunization series of three intramuscular injections (D0, D7, D28), followed by a booster after 1 year (D365). Blood samples for serological analysis were taken at D0 (before first injection), D28, D42, D180, D365 (before booster) and D379. All subjects developed a strong immune response to the primary series, and at D42, all subjects had seroconverted for rabies neutralizing antibody (serum titre > or = 0.5 IU/ml). The rabies virus-neutralizing antibody GMT value at D42 in the CPRV group (23.0 IU/ml) was non-inferior to that in the PVRV group (29.6 IU/ml), according to a one-sided non-inferiority test. While antibody titres tended to decrease over the period of follow-up, at D365 (before booster), 97.5% subjects in the CPRV group and 98.8% of subjects in the PVRV group remained seroconverted. After booster, although the rabies antibody GMT value in the CPRV group was lower than that in the PVRV group, all subjects in both groups were seroconverted, and the difference is probably not clinically important. The incidence of local and systemic reactions tended to decrease with each dose during the primary immunization series, followed by a slight increase after booster (significant time-effect in an exploratory logistic regression analysis). Although mild or moderate local reactions tended to be more frequent after injection with CPRV compared to PVRV, systemic reactions were reported less often (significant group-effects in exploratory logistic regression analyses). One serious adverse event possibly related to vaccine occurred during this study (severe asthenia after the third dose of PVRV). This comparative study in healthy young adults demonstrates that the new chromatographically purified rabies vaccine is as immunogenic as PVRV, and seems to be associated with fewer systemic reactions.
色谱纯化程序的最新进展使得通过进一步纯化目前由Vero细胞培养制备的狂犬病疫苗（Verorab；巴斯德梅里埃康诺特公司生产）来开发一种新的色谱纯化狂犬病疫苗（CPRV）成为可能。在法国四所兽医学院进行的一项随机、双盲研究中，将CPRV进行初次免疫（随后在一年后进行加强免疫）的免疫原性和安全性与纯化的Vero细胞疫苗（PVRV）进行了比较。共有330名健康的一年级男女兽医学生，年龄至少18岁且需要进行暴露前狂犬病预防，参与了本研究。纳入的受试者被随机分配接受CPRV（n = 163）或PVRV（n = 167），作为三次肌肉注射的初次免疫系列（D0、D7、D28），随后在1年后（D365）进行加强免疫。在D0（首次注射前）、D28、D42、D180、D365（加强免疫前）和D379采集血样进行血清学分析。所有受试者对初次免疫系列均产生了强烈的免疫反应，在D42时，所有受试者的狂犬病中和抗体均已血清转化（血清滴度≥0.5 IU/ml）。根据单侧非劣效性试验，CPRV组在D42时的狂犬病病毒中和抗体GMT值（23.0 IU/ml）不劣于PVRV组（29.6 IU/ml）。虽然抗体滴度在随访期间有下降趋势，但在D365（加强免疫前），CPRV组97.5%的受试者和PVRV组98.8%的受试者仍保持血清转化。加强免疫后，尽管CPRV组的狂犬病抗体GMT值低于PVRV组，但两组所有受试者均发生了血清转化，且这种差异可能在临床上并不重要。在初次免疫系列期间，局部和全身反应的发生率随每次剂量的增加而趋于下降，加强免疫后略有增加（探索性逻辑回归分析中有显著的时间效应）。尽管与PVRV相比，注射CPRV后轻度或中度局部反应往往更频繁，但全身反应的报告较少（探索性逻辑回归分析中有显著的组效应）。在本研究期间发生了1例可能与疫苗相关的严重不良事件（第三剂PVRV后出现严重乏力）。这项针对健康年轻成年人的比较研究表明，新的色谱纯化狂犬病疫苗与PVRV具有相同的免疫原性，且似乎全身反应较少。
