预灌封注射器森林脑炎灭活疫苗的临床前安全性及免疫原性评价

Preclinical safety and immunogenicity evaluation of pre⁃sealed syringe inactivated tick⁃borne encephalitis vaccine

目的评价0.5 mL/支的预灌封注射器森林脑炎(tick-borne encephalitis,TBE)灭活疫苗的临床前安全性和免疫原性。方法采用兔肌内刺激性试验和豚鼠全身主动过敏反应试验评价新规格TBE灭活疫苗的安全性,并与原规格包装形式(1.0 mL/瓶,西林瓶)TBE灭活疫苗进行比对。将新规格及包材TBE灭活疫苗经腹腔免疫体质量10~12 g的昆明小鼠30只,免疫2次,间隔7 d,初次免疫后第14天攻毒(“森张”株TBEV),试验组以10^(-2)~10^(-6)稀释度病毒,对照组以10^(-6)~10^(-10)稀释度病毒经腹腔攻毒,持续观察21 d判定结果,通过Reed-Muech法计算效价来评价TBE灭活疫苗的免疫原性。结果兔肌内刺激性试验的所有动物均未见死亡或濒死情况,各组豚鼠全身主动过敏反应试验临床观察未见异常反应。3批原规格包装形式的TBE灭活疫苗的免疫原性(免疫保护指数)分别为1.0×10^(8)、1.3×10^(8)、1.0×10^(8);3批新规格包装形式的TBE灭活疫苗的免疫原性(免疫保护指数)分别为1.1×10^(8)、1.0×10^(8)、1.3×10^(8),符合《中国药典》三部(2020版)大于1.0×10^(5)的要求,新、旧规格疫苗免疫原性差异无统计学意义(F=0.063,P>0.05)。结论0.5 mL/支的预灌封注射器TBE灭活疫苗的临床前安全性和免疫原性良好。

Objective To evaluate the preclinical safety and immunogenicity of 0.5 mL/dose of inactivated tick⁃borne encephalitis(TBE)vaccine with pre⁃sealed syringe.Methods The safety of the new packaged TBE inactivated vaccine was evaluated by using rabbit muscle irritation test and guinea pig systemic active anaphylaxis test,and compared with that of the original package(1.0 mL/bottle,cillin bottle).Thirty Kunming mice with 10⁃12 g body mass were immunized i.p.with TBE inactivated vaccines of new package and original package twice at an interval of 7 d,respectively.At 14 d after the initial immunization,the experimental group was challenged with virus(TBEV of“Senzhang”strain)of 10^(-2)⁃10^(-6) dilu⁃tion,while the control group with the virus of 10^(-6)⁃10^(-10) dilution by intraperitoneal administration.The results were observed continuously for 21 d,and the immunogenicity of the TBE inactivated vaccines was evaluated by calculating the titer using Reed⁃Muech method.Results No death or dying condition was observed in all the groups of animals in the rabbit irritation test,and no abnormal reaction was observed in all groups in the guinea pig systemic active allergic reaction test.The immuno⁃genicity(immune protection index)of three batches of TBE inactivated vaccines with original package was 1.0×10^(8),1.3×10^(8),1.0×10^(8),and that of three batches of TBE inactivated vaccines with new specification were 1.1×10^(8),1.0×10^(8) and 1.3×10^(8),respectively,which met the requirements of greater than 1.0×10^(5) in Chinese Pharmacopoeia(VolumeⅢ,2020 edition),with no significant difference in immunogenicity between the vaccines of new and original specifications(F=0.063,P>0.05).Conclusion The 0.5 mL/dose of pre⁃sealed syringe TBE inactivated vaccine has good preclinical safety and immunogenicity.