b型流行性感冒嗜血杆菌结合疫苗(磷酸多核糖基核糖醇-白喉毒素突变体197)在13～59月龄儿童中的安全性和免疫原性研究

Study on Safety and Immunogenicity of Haemophilus Influenzae Type b Conjugate Vaccine (Polyribosylribitol Phosphate -Cross Reacting Material 197) among the Children Aged 13-59 Months

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13～59月龄儿童中使用的安全性和免疫原性。方法选择728名13～59月龄儿童,按1:1的比例随机分配到试验组(365人)和对照组(363人),分别肌内注射接种1剂PRP-CRM197或Hib[PRP-T(Tetanus Toxoid,TT;破伤风类毒素)],观察接种后7d内的局部和全身反应,收集接种后30d内的不良事件和用药情况。在接种疫苗前和接种疫苗后30d采集静脉血,用酶联免疫吸附试验检测抗-PRP抗体(Antibody to PRP,Anti-PRP)。结果分别有99%和100%接种PRP-CRM197和PRP-T的受试者,达到了短期[≥0.15微克/毫升(g/ml)]和长期(≥1.0g/ml)血清保护性Anti-PRP水平。两种疫苗的安全性相似。结论 Hib(PRP-CRM197)的耐受性良好,免疫原性不劣于Hib(PRP-T),为99%的受试者提供了血清保护性Anti-PRP。Hib(PRP-CRM197)可在13～59月龄儿童中进行免疫。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 and immunogenicity of a Haemophilus in fluenzae type b （Hib） conjugated vaccine （polyribosylribitol phosphate-cross reacting material 197, PRP-CRM197） among the toddlers and young children froml3 months to 59 months. Methods 728 children from 13 to 59 months which were divided into two groups randomly, The trial group （N=365）were administered one dose of the PRP-CRM197 by intramuscular injection, the control group （N=363）were administered one dose of the PRP-T （tetanus toxoid）. Both the local and systemic adverse reactions were observed during the first 7 days after vaccination. The Adverse Events Following Immunization （AEFIs） and any medicine used were reported within 30 days after vaccination. Blood samples were collected before vaccination and 30 days after the vaccination. Levels of antibody to PRP （Anti-PRP） were measured by enzyme- linked immunosorbant assay（ElISA）. Results 99% and 100% of subjects receiving PRP-CRM197 and PRP-T achieved Short term（ ≥ 0.15μg/ml） and long-term（ ≥ 1.0μg/ml） seroprotective Anti-PRP levels respectively, were Both formulations had similar safety profiles. Conclusion One dose of PRP-CRM197 has good tolerance and the immunogenicity which is similar to one dose of PRP-T, which provide seroprotective antibody titres against Hib infection to 99% subjects. PRP-CRM197 is suitable for routine immunization against Haemophilus Influenzae Type b disease for children among the age of 13-59 months. Clinical Trial Registration State Food and Drug Administration Approval Number： 2008L03160.