流行性出血热地鼠肾细胞双价灭活疫苗的人体观察  

HUMAN TRIAL OF A BIVALENT INACTIVATED GOLDEN HAMSTER KIDNEY CELL (GHKC) VACCINE AGAINST EPIDEMIC HEMORRHAGIC FEVER (EHF )

作　　者：宋干[1] 黄永成[2] 杭长寿[1] 李淑兰[2] 刘为民[1] 傅增武 李德新[1] 郝富勇[2] 霍子威[1] 惠连[2] 张全福[1] 回良杰[2] 詹发先[3] 王伟[1] 石晓宏 郑晓丽 林静 王晓宏[1] 王琪[2] 

机构地区：[1]中国预防医学科学院病毒学研究所,北京100052 [2]卫生部长春生物制品研究所 [3]湖北省医学科学院病毒研究所

出　　处：《病毒学报》1993年第2期144-151,共8页Chinese Journal of Virology

基　　金：国家科委重点科技项目(K89-01-36)

摘　　要：为了研制一种对两型流行性出血热(EHF)均有良好预防效果的灭活疫苗,采用地鼠肾细胞(GHKC)传代适应滴度高(≥8.5logTCID50/ml)的两型EHF病毒株(家鼠型L99株及野鼠型JR株)试制出GHKC双价灭活疫苗(90-1批液体苗和90-2批冻干苗),经卫生部批准,进行了约200人的人体免疫观察。疫苗用福尔马林灭话,加AI(OH)_3佐剂。共免疫242人,其中206人免疫前血清抗体反应阴性。全部接种者除极少数有轻、中度反应,余均无不良反应。两批疫苗接种后,IFA抗体阳转率分别为95.9％及89.2％,ELISA抗体分别为93.5％及91.8％。抽样检查中和抗体反应(每批疫苗30人),用酶斑减少中和试验(EFRNT)检查,两批疫苗对L99株病毒中和抗体阳转率均为100％;对JR株抗体阳转率分别为88.2％及66.7％。每个接种者免前及第一针疫苗接种后56,180,360天血清同时用ELISA法检查抗体,并抽样(每批疫苗30例)检查中和抗体,发现两种抗体的阳性率有逐渐降低的动态变化。两批疫苗三种免疫程序(0,7,28天,0,28,42天及0,28天)接种者的免疫反应基本相似,仅0,28天接种者的抗体水平稍低。对68例接种者于免疫后1年用同一疫苗(90-2批)加强免疫一次,其ELISA及中和抗体均显著升高。试用淋巴细胞转化试验检查20人按种后细胞免疫反应。An inactivated GHKC vaccine against EHF has been developing since 1984, and a preliminary human trial of a monovalent GHKC vaccine(with thc rat, virus L99 strain ) had been made and reported elsewhere. In or-der to get a vaccine effective for EHF caused either by Hantaan-type or by Seoul-type viruses, a bivalent GHKC vaccine ( lot 90-1 fluid vaccine and lot 90-2 lyophilized vaccine ) was prepared with GHKC adapted Han-taan virus, JR strain and Seoul virus, L99 strain, and a trial was made in more than 200 human volunteers after the approval of the Ministry of Public Health, P.R. China. The vaccine was produced by inactivation with formalin, and aluminum hydroxide was added as adjuvant. A total of 242 humans were immunized, 206 of them were seronegative in their pre-immunization sera ard served as the objectives of clinical observation. Very few of them had shown mild or moderate side effects, the others were all free from untoward reaction. After immunization with these 2 lots of vaccines, the seroconversion rates of IFA antibody of the total seronegative ( pre-immunization ) vaccinees on 56 days after the first ino-culation were 95.9% and 89.2% ( for lot 90-1 and lot 90-2 respectively ) , and those of ELISA antibody were 93.5% and 91.8%. The seroconversion rates of neutralizing antibody ( by EFRNT ) in the sampled sera of vaccinees ( of 30 vaccinees in each lot of vaccine) were 100% to challenge with L99 virus in vaccinees immunized with both lots of vaccine, with GMT of 237.6 and 155.2 respectively, and 88.2% and 66.7% to challenge with JR virus, with GMT of 24.9 and 6.7. Sera of the vaccinees were obtained 56, 180 and 360 days respectively after the first dose of the vaccine, and NT antibody was detected in sera of sampled vaccinees (of 30 vaccinees in each lot of vaccine ) . A decreasing dynamic change was observed in the positive r鈚es of the NT antibodies to both types of challenge virus. The immune resp onses of vaccinees immunized with 3 different immuni zation schedules with each of the 2 lots of vaccin

关 键 词：流行性出血热 地鼠 肾细胞 疫苗 

分 类 号：R392－33[医药卫生—免疫学]