国产流感裂解疫苗上市后安全性和免疫原性研究

发布时间：2018-01-02 08:48

本文关键词：国产流感裂解疫苗上市后安全性和免疫原性研究　出处：《中国疾病预防控制中心》2009年硕士论文　论文类型：学位论文

【摘要】：目的：1)进一步考察国产流感裂解疫苗在不同地区不同年龄人群中应用的安全性,追踪上市后流感疫苗大规模应用的安全性；2)考察60岁以上老年人中接种流感疫苗的安全性和免疫效果。方法：2007年-2008年间,在全国以东部地区为主、由北至南,不同省份选择1至2个城市为代表,共15个省、地市疾病预防控制中心参加的不同年龄人群接种国产流感疫苗的安全性观察,采用开放式临床研究设计。2934名年龄为6月至90岁受试者分布于幼儿组、儿童组、成人组和老年人组；其中140名老年人观察安全性的同时进行免疫原性考察。疫苗成人剂型为0.5 ml/支,含甲]型、甲3型和乙型抗原各15μg,免疫程序为1针；儿童剂型为0.25 ml/支,含甲1型、甲3型和乙型抗原各7.5μg,免疫程序为0,28天。所有受试者实行自愿报名、知情同意、遵从入选和排除标准进行志愿者筛选。每名受试者接种疫苗后做30分钟即时反应观察后离开,随后接受24,48,72小时的定期随访观察,多中心安全性研究接种后第7天如受试者未主动报告任何不良事件,将结束随访观察。湖南省老年人安全性和免疫原性研究对不良事件监测至接种第21天,免前及免后第21天采血,进行血清HI抗体检测。对全部受试者病例报告表进行核查,建立临床研究数据库,数据库锁定后进行统计分析；审核统计分析报告,确保试验结果真实性和科学性。结果：本次研究15个中心入组的2934名受试者,年龄范围在6月龄至90岁,按照实际年龄分组,各年龄组人数为幼儿组599人、儿童组613人、未成年组485人、成人组553人及老年组684人。受试者男女比例0.97：1,以汉族为主,其他为回、蒙、满等七个少数民族。 15个中心研究共观察到不良反应197例,反应率为6.7%。其中,儿童剂型不良反应发生率为10.7%,成人剂型不良反应发生率为5.7%。不良反应以轻度为主,发生率为4.6%；其次为中度反应,发生率为1.9%；偶见重度不良反应,发生率为0.3%。按不同症状反应分类,局部反应发生率为2.0%,以接种部位疼痛最多,发生率为1.7%,其他症状包括瘙痒、红、肿等；全身反应发生率为5.2%,以发热反应最多,发生率为4.0%,其他症状包括恶心、头痛、呕吐、食欲不振等症状。总体来看,国产流感裂解疫苗在不同年龄人群中应用安全性良好,未见严重不良反应及新的、罕见的不良反应。其中本次多中心研究共有66例受试者有既往病史,如高血压、糖尿病、心血管病等,并伴有不同程度的长期用药情况。所有有既往病史受试者中,观察到疫苗接种后不良反应3例,发生率为4.5%(3/66),均为老年组受试者。本次研究未发现疫苗接种不良反应与既往病史的相关性。 130名老年受试者有成对有效血清进行免疫原性分析,免前三个型别HI抗体保护率为14.6%-42.3%,GMT为9.5-26.5,受试者抗体滴度低于保护水平；接种疫苗后第21天,三个型别的HI抗体阳转率在72.3%-95.4%之间,GMT增长倍数在8.0-41.1之间,保护率在90.0%-100.0%之间。三个型别的三项指标均超过季节流感疫苗的欧盟标准和美国FDA的评价标准。结论：本试验结果表明接种流感裂解疫苗后不同年龄组安全性良好,同时发现老年人流感抗体水平低,需要接种流感疫苗,老年人群接种流感疫苗后免疫原性良好,抗体水平的提高增加了个体对流感病毒的抵御能力,同时也达到建立人群免疫屏障的目的。
[Abstract]:Objective : 1 ) To investigate the safety of domestic influenza vaccine in different age groups and to track the safety of large - scale application of influenza vaccine after marketing ; and 2 ) to study the safety and immune effect of influenza vaccination in older persons over 60 years of age . Methods : From 2007 to 2008 , in the eastern part of the country , 1 to 2 cities were selected from the north to south and different provinces . The safety of domestic influenza vaccine was observed in 15 provinces and different provinces . Results : Of the 29 34 subjects enrolled in 15 centers , the age ranged from 6 months to 90 years . According to the actual age group , there were 599 children in each age group , 613 children in the children group , 485 in the minor group , 553 in the adult group and 684 in the elderly group . There were 197 cases of adverse reactions observed in 15 centers . The rate of adverse reactions was 6.7 % . The incidence of adverse reactions in children was 10.7 % . The incidence rate was 4 . 0 % . The incidence rate was 1 . 7 % . There were 3 cases of adverse reactions after vaccination . The incidence rate was 4.5 % ( 3 / 66 ) . All of the patients had previous medical history . The incidence rate was 4.5 % ( 3 / 66 ) . In 130 elderly subjects , the immunogenicity of effective serum was analyzed . The protective rate of HI antibody was 14.6 % - 42.3 % , GMT was 9.5 - 26.5 , and GMT was 9.5 - 26.5 . The positive rate of HI antibody was 72.3 % - 95.4 % , GMT was between 8.0 % and 100.0 % . All three types of three types were higher than those of seasonal influenza vaccine and US FDA . Conclusion : The results of this study show that the safety of influenza vaccine after vaccination is good , meanwhile , it is found that the level of influenza antibody in the elderly is low , influenza vaccine needs to be vaccinated , the immunogenicity of influenza vaccine after vaccination is good , the antibody level is increased , the individual ' s ability to resist influenza virus is increased , and the purpose of establishing the immune barrier of the population is also achieved .

【学位授予单位】：中国疾病预防控制中心
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392

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