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目的评价b型流行性感冒嗜血杆菌结合疫苗(Haemophilus Influenzae Typeb Conjugate Vaccine,Hib)[磷酸多核糖基核糖醇-白喉毒素突变体197(Polyribosylribitol Phosphate-Cross Reacting Material197,PRP-CRM197)]在中国儿童使用的安全性、免疫原性和加强免疫后的抗体应答。方法研究分三个阶段:第一阶段为I期安全性研究,先入组20名16～20月龄的幼儿,接种1剂Hib PRP-CRM197;15d后入组20名2～4月龄的婴儿,按间隔1个月的程序接种3剂Hib PRP-CRM197。每剂接种后收集30d内的安全性数据。第二个阶段为Ⅲ期基础免疫,入组916名2～4月龄受试者,随机分配到试验组(611人)和对照组(305人),分别接种3剂Hib PRP-CRM197或Hib PRP-T(Tetanus Toxoid,TT;破伤风类毒素)对照疫苗,每剂间隔1个月。第三个阶段为Ⅲ期加强免疫,对基础免疫完成3剂疫苗接种的受试者,于1周岁后加强免疫1剂。在Ⅲ期临床研究中,收集安全性和免疫原性的数据。抗-PRP抗体测定采用酶联免疫吸附试验。结果Ⅰ期安全性研究发现,Hib PRP-CRM197在两个年龄组(婴儿和幼儿)都有良好的耐受性。基础免疫和加强免疫的Ⅲ期临床研究表明,Hib PRP-CRM197的安全性和HibPRP-T相似。在完成基础免疫后1个月,实验组和对照组的所有受试者均达到了短期血清保护性抗-PRP抗体水平[≥0.15微克/毫升(g/ml)],且分别有99%和97%的受试者达到了长期血清保护性抗-PRP抗体水平(≥1.0g/ml)。在完成加强免疫后,所有受试者均达到了短期和长期的血清保护性抗体水平。与HibPRP-T组相比,接种HibPRP-CRM197始终产生更高的抗体几何平均浓度。结论 Hib PRP-CRM197疫苗在基础免疫和加强免疫后,都显示了良好的耐受性和快速的抗-PRP抗体应答。Hib PRP-CRM197的免疫原性不劣于HibPRP-T,且安全性也相似。Hib PRP-CRM197可用于中国儿童抗Hib感染的常规免疫接种。临床试验注册国家食品药品监督管理局《药物临床批件》2008L03160。
Objective To evaluate the safety of Haemophilus Influenzae Typeb Conjugate Vaccine (Hib) [Polyribosylribitol Phosphate-Cross Reacting Material 197 (PRP-CRM197)] in Chinese children The safety of use, the immunogenicity and the boosting of antibody responses after immunization. Methods The study was divided into three phases: The first phase was a phase I safety study. Twenty children aged 16-20 months were enrolled in the study. One dose of Hib PRP-CRM197 was inoculated. After 15 days, 20 babies aged 2-4 months Three doses of Hib PRP-CRM197 were inoculated one month apart. Safety data were collected within 30 days after each dose. The second phase was stage III basic immunization. A total of 916 subjects aged 2 to 4 months were enrolled and randomly assigned to test group (611) and control group (305). Three doses of Hib PRP-CRM197 or Hib PRP-T (Tetanus Toxoid, TT; tetanus toxoid) control vaccine, each dose interval of 1 month. The third phase was phase III booster immunization. Subjects who completed three doses of vaccination on the basis of immunization were boosted one dose after the age of one. In phase III clinical studies, data on safety and immunogenicity were collected. Anti-PRP antibody assay using enzyme-linked immunosorbent assay. Results The phase I safety study found that Hib PRP-CRM197 was well tolerated in both age groups (infants and young children). Phase III clinical trials of basal and booster immunizations showed that the safety of Hib PRP-CRM197 was similar to that of HibPRP-T. One month after completion of the basal immunization, all subjects in the experimental group and the control group achieved short-term serum protective anti-PRP antibody levels [≥0.15 μg / ml], with 99% and Ninety-seven percent of subjects achieved long-term serum protective anti-PRP antibody levels (> 1.0 g / ml). After completion of booster immunization, all subjects achieved short and long term serum protective antibody levels. Inoculation of HibPRP-CRM197 consistently yielded higher antibody geometric mean concentrations than the HibPRP-T group. Conclusion The Hib PRP-CRM197 vaccine showed good tolerability and rapid anti-PRP antibody response after both basal and booster immunizations. The immunogenicity of Hib PRP-CRM197 is not inferior to that of HibPRP-T and the safety is similar. Hib PRP-CRM197 can be used for routine immunization against Hib infection in Chinese children. Clinical Trial Registration State Food and Drug Administration “Drug Clinical Approval” 2008L03160.