乙脑风疹联合减毒活疫苗病毒间的相容性

目的研究乙脑风疹联合减毒活疫苗中乙脑病毒和风疹病毒的相容性。方法将乙脑病毒SA14-14-2疫苗株制备的乙脑减毒活疫苗原液与风疹病毒RA27/3疫苗株制备的风疹减毒活疫苗原液按体积比1∶1比例混合,加入保护剂,冻干制成乙脑风疹联合减毒活疫苗。采用BHK21细胞蚀斑法测定联合疫苗中的乙脑病毒滴度,细胞病变法检测风疹病毒滴度;通过鉴别试验、热稳定性试验、乙脑疫苗免疫原性试验、安全性试验、异常毒性试验、无菌试验以及基因稳定性分析观察联合疫苗病毒间的相容性。结果联合疫苗的乙脑和风疹病毒滴度与单价疫苗的病毒滴度变化在检测误差的允许范围内;联合疫苗于37℃放置7 d,与放置前相比,风疹病毒和乙脑病毒的滴度值下降分别小于1.0 LgCCID50/ml和1.0 LgPFU/ml,符合《中国药典》三部(2010版)要求;联合疫苗中的风疹疫苗对乙脑疫苗的免疫原性无明显的干扰效应;鉴别试验、安全性试验、异常毒性试验、无菌试验结果均符合《中国药典》三部(2010版)要求;联合疫苗在BHK21细胞上传代5次后,乙脑和风疹病毒基因序列均未发生变化。结论乙脑风疹联合减毒活疫苗中的乙脑和风疹病毒具有较好的相容性,本实验为乙脑风疹联合疫苗的进一步研制奠定了基础。

Compatibility between viruses in live attenuated Japanese encephalitis and rubella combined vaccine

Objective To investigate the compatibility between viruses in live attenuated Japanese encephalitis(JE)and rubella combined vaccine.Methods The bulk of live attenuated JE vaccine prepared with SA14-14-2 strain was mixed with the bulk of live attenuated rubella vaccine prepared with RA27/3 strain at a volume ratio of 1 ∶ 1,then added with stabilizer and lyophilized to prepare live attenuated JE and rubella combined vaccine.The JE virus titer in the prepared combined vaccine was determined by BHK21 cell plaque assay,while rubella virus titer by CPE method.The compatibility between viruses was evaluated by identity test,heat stability test,immunogenicity test on JE vaccine,safety test,abnormal toxicity test,sterility test and genetic stability test.Results The differences between either JE or rubella virus titers in combined and monovalent vaccines were within the permitted range.The JE and rubella virus titers in combined vaccine after storage at 37 ℃ for 7 d decreased by less than 1.0 LgCCID50/ml and 1.0 LgPFU/ml,respectively which met the requirements in Chinese Pharmacopoeia(Volume Ⅲ,2010 edition).The rubella component in combined vaccine showed no significant interference to the immunogenicity of JE vaccine.The results of identity test,safety test,abnormal toxicity test and sterility tests met the requirements in Chinese Pharmacopoeia(Volume Ⅲ,2010 edition).The gene sequences of JE and rubella viruses in the combined vaccine showed no significant change after subculture in BHK21 cells for five passages.Conclusion The JE and rubella viruses in live attenuated JE and rubella combined vaccine showed good compatibility,which laid a foundation of further study on the combined vaccine.