b型流感嗜血杆菌结合疫苗稳定性研究

Stability study of haemophilus influenzae type b conjugate vaccine

目的:评价以白喉毒素无毒突变体CRM197蛋白为载体的b型流感嗜血杆菌(haemophilus influenzae type b,Hib)结合疫苗原液及成品在不同储存条件下主要质量指标的变化,为该疫苗保存条件及有效期制定提供依据。方法:将b型流感嗜血杆菌结合物原液分别于2~8℃放置3,6,12个月,20~25℃放置4,8周,37℃放置2,4,6周后,进行多糖含量、游离多糖含量、蛋白含量、糖/蛋白比值、游离蛋白百分比、pH值、细菌内毒素检查、分子量等主要质量指标检测,结合疫苗成品分别于2~8℃放置6,12,18,24,30,36个月,20~25℃放置6,12个月,37℃放置1,3,6,9个月后,进行多糖含量、游离多糖含量、蛋白含量、糖/蛋白比值、游离蛋白百分比、pH值、细菌内毒素检查、分子量主要质量指标的检测。结果:b型流感嗜血杆菌结合物原液2~8℃放置12个月,20~25℃放置8周,37℃放置6周后,各项质量指标均符合规定;疫苗成品2~8℃放置36个月,20~25℃放置12个月,37℃放置6个月后,各项质量指标均符合规定。结论:以白喉类毒素无毒突变体CRM197蛋白为载体的b型流感嗜血杆菌结合疫苗原液及成品具有良好的稳定性。

Objective:To evaluate the changes of main quality indexes of bulk and final product of haemophilus influenzae type b(Hib)conjugate vaccine using CRM197,an avirulent mutant of diphtheria toxin as carrier protein under various conditions for storage and provide a reference for the determination of condition for storage and validity period of the vaccine.Methods:The bulk of Hib conjugate was stored separately at 2~8℃for 3,6 and 12 months,at 20~25℃for 4 and 8 weeks,and at 37℃for 2,4 and 6 weeks,while the final product was stored at 2~8℃for 6,12,18,24,30 and 36 months,at 20~25℃for 6 and 12 months,and at 37℃for 1,3,6 and 9 months.Then the main quality indexes,such as polysaccharide content,free polysaccharide content,protein content,ratio of carbohydrate/protein,free protein content,pH value,endotoxin detection,and molecular weight,were determined.Results:All the quality indexes of bulk of Hib met the relevant requirements after storage at 2~8℃for 12 months,at 20~25℃for 8 weeks and at 37℃for 6 weeks.All the quality indexes of final product met the relevant requirements after storage at 2~8℃for 36 months,at 20~25℃for 12 months and at 35~37℃for 6 months.Conclusion:Both the bulk and final product of Hib conjugate vaccine using CRM197 as carrier showed high stability.