新规格冻干甲型肝炎减毒活疫苗的免疫原性及安全性评价  

Immunogenicity and safety of freeze-dried live attenuated hepatitis A vaccine with a new specification

作　　者：徐艳玲 王艺博 侯丽娟 李勇 岳立广 夏青娟 申文晋[2] 张春云[2] 范明源 刘令九 邹勇 XU Yan-ling;WANG Yi-bo;HOU Li-juan;LI Yong;YUE Li-guang;XIA Qing-juan;SHEN Wen-jin;ZHANG Chun-yun;FAN Ming-yuan;LIU Ling-jiu;ZOU Yong(Changchun Institute of Biological Products Co.,Ltd.,Changchun 130012,Jilin Province,China;不详)

机构地区：[1]长春生物制品研究所有限责任公司,吉林长春130012 [2]天津药物研究院新药评价有限公司,天津300301

出　　处：《中国生物制品学杂志》2022年第6期654-658,共5页Chinese Journal of Biologicals

基　　金：吉林省科技发展计划项目(20190404001YY,201603007YY)。

摘　　要：目的评价新规格(复溶后0.5 mL/剂)冻干甲型肝炎减毒活疫苗(简称甲肝减毒活疫苗)的免疫原性和安全性。方法将3批甲肝减毒活疫苗试验疫苗(复溶后0.5 mL/剂)和市售甲肝减毒活疫苗(复溶后1.0 mL/剂)分别经腹腔免疫小鼠,免疫28 d后,经心脏采血,分离血清,检测血清中甲型肝炎病毒抗体滴度;将上述6批疫苗经大鼠皮下注射给药,观察给药28 d内大鼠体重变化,并于28 d时进行大体剖检;将上述6批疫苗经家兔皮下注射给药,观察家兔的体重变化;剖检后观察背部给药部位及其周围皮肤和肌肉的刺激反应,并进行组织病理学检查。结果免疫6批疫苗的小鼠血清抗体阳转率均为100%,两种疫苗间血清抗体平均滴度差异无统计学意义(P>0.05)。给药后28 d,各组大鼠未见死亡及异常反应,体重呈增长趋势;各主要脏器未见肉眼可见的病理改变。给药对各组家兔体重无影响,也未发现全身毒性反应;注射部位皮肤未见充血、红肿等刺激反应;给药部位皮肤、皮下及肌肉各层结构清晰,形态正常,间质均未见异常。结论新规格甲肝减毒活疫苗(复溶后0.5 mL/剂)具有良好的免疫原性和安全性。Objective To evaluate the immunogenicity and safety of freeze-dried live attenuated hepatitis A(HA)vaccine with a new specification of 0.5 mL per container after reconstitution.Methods Three batches of freeze-dried live attenuated HA vaccine(0.5 mL per container after reconstitution)were prepared,with which mice were immunized intraperitoneally using three batches of commercial freeze-dried live attenuated HA vaccine(1.0 mL per container after reconstitution)as control.Heart blood samples were collected 28 d after immunization,from which sera were separated and determined for antibody titer against HA virus.Rats were immunized s.c.with above-mentioned vaccines respectively,observed for change of bodyweight within 28 d,and subjected to gross anatomy 28 d after immunization.Rabbits were immunized s.c.with above-mentioned vaccines and observed for change of bodyweight,of which the skin and muscle tissues in and around the injection sites were collected by anatomy for stimulation test and histopathological examination.Results All the positive conversion rates of serum antibody of mice immunized with the six batches of vaccines were100%,while the mean antibody titers induced by the prepared and commercial vaccines showed no significant difference(P>0.05).No deaths or abnormal reactions were observed in rats of various groups 28 d after immunization,while the bodyweights showed increasing trends.No pathological changes were observed visually in various organs.No changes of bodyweights or systemically toxic reactions were observed in rabbits of various groups after immunization;no stimulation reactions such as hyperemia,redness and swelling were observed in the skins in injection site.Clear structures and normal forms were observed in skin,subcutaneous and muscle tissues in injection sites,and no abnormality in mesenchyme.Conclusion Freeze-dried live attenuated HA vaccine with a specification of 0.5 mL per container after reconstitution showed good immunogenicity and safety.

关 键 词：冻干甲型肝炎减毒活疫苗 规格 免疫原性 安全性 

分 类 号：R186.3[医药卫生—流行病学]