国产b型流感嗜血杆菌结合疫苗PRP_TT加强免疫效果评价

b型流感嗜血杆菌（Haemophilus influenzae type b，Hib）可引起严重的脑膜炎、肺炎、会厌炎、蜂窝组织炎及骨关节感染。世界卫生组织估计，每年Hib可引起约300万5岁以下儿童患病，其中38.6万患者死亡，30％～40％的Hib脑膜炎患者有神经系统后遗症［1］。Hib结合疫苗于1987年批准上市后，一些国家在短期内几乎消灭了这种疾病，但数年后，在大量人群中

基金项目：科技部疫苗生产关键技术研究开发（2008BA166B01）．作者单位：1中国药品生物制品检定所菌种室（北京100050）；

2兰州生物制品研究所第一研究室（兰州730046）．

通讯作者：谢贵林，E-mail：glxie＠lzsws．gs．bnet．cn 【临床观察】

国产b型流感嗜血杆菌结合疫苗PRP-TT加强免疫效果评价

李亚南1乔瑞洁2李红1刘佳2王浩2史晓玲2叶强1谢贵林2

【摘要】目的评价国产b型流感嗜血杆菌（Haemophilus influenzae type b，Hib）结合疫苗PRP-TT的加强免疫效果。方法分别用安儿宝和呵儿贝两种Hib结合疫苗，对在广西柳州市常住儿童进行3、4、5月龄3针免疫，1年后，进行第4剂加强免疫。分别于3针免疫1年后和加强免疫1个月后采血，分离血清，采用ELISA和体外杀菌实验（Serum bactericidal assay，SBA）分别检测免疫前后血清IgG抗体浓度和加强免疫后SBA抗体滴度。结果安儿宝和呵儿贝疫苗3针免疫1年后，血清IgG抗体几何平均数浓度（Geometric mean concentrations，GMCs）分别为3.17μg／ml和3.00μg／ml，二者差异无统计学意义（P＞0.05）；其中，IgG抗体浓度在1.00μg／ml以上的血清所占的比例分别为79％（62／78）和76％（115／152），二者差异无统计学意义（P＞0.05）。加强免疫后1个月，两种疫苗免疫血清中IgG抗体GMCs分别为71.33μg／ml和65.35μg／ml，二者差异无统计学意义（P＞0.05）；IgG抗体浓度均能100％达1.00μg／ml以上。两种疫苗加强免疫后的血清IgG抗体浓度与各自加强免疫前比较，差异均有统计学意义（P＜0.05）。加强免疫后，两种疫苗免疫血清的SBA抗体滴度分别为5263和4637，二者差异无统计学意义（P＞0.05）。两种疫苗免疫后血清IgG抗体浓度和SBA抗体滴度均具有相关性（r值分别为0.696和0.689，P＜0.05）。结论3针免疫1年后，两种疫苗免疫血清中IgG抗体仍保持较高的水平，第4剂加强免疫后，抗体水平迅速显著升高，100％达1.00μg／ml 以上，且具有有效的体外杀菌功能。

【关键词】嗜血菌，流感，b型；疫苗，结合；免疫接种，加强；免疫效果

【中国图书分类号】R378.4＋1R392-33【文献标识码】A【文章编号】1004-5503（2011）02-0213-04

Immune Effect of a Booster with Domestic Haemophilus influenzae Type b PRP-TT Conjugate Vaccine

LI Ya-nan△，QIAO Rui-jie，LI Hong，LIU Jia，WANG Hao，SHI Xiao-ling，YE Qiang，XIE Gui-lin（△National Institute for the Control of Pharmaceutical and Biological Products，Beijing100050，China）

【Abstract】Objective To evaluate the immune effect of a booster with domestic Haemophilus influenzae type b（Hib）PRP-TT conjugate vaccine．Methods The infants resided in Liuzhou City，Guangxi Zhuang Autonomous Region，China were inoculated with two kinds of PRP-TT conjugate vaccine（Anerbao and Heerbei）respectively，for3times at ages of3，4and5months，and boosted with the same kind of vaccine12months later．The serum samples were collected12month after the3rd dose and one month after the booster，and determined for IgG titers by ELISA and serum bactericidal assay（SBA）respectively．Results The geometric mean concentrations（GMCs）of serum IgG of infants12months after inoculation with3doses of Anerbao and Heerbei were3.17and 3.00μg／ml respectively，which showed no significant difference（P＞0.05）．The percentages of serum samples with antibody con－centration of more than1.00μg／ml were79％（62／78）and76％（115／152）respectively，which showed no significant difference （P＞0.05）．One month after the booster，the GMCs of serum IgG of infants inoculated with the two kinds of conjugate vaccines were 71.33and65.35μg／ml respectively，which showed no significant difference（P＞0.05），while the percentage of serum samples with antibody concentration of more than1.00μg／ml was100％．The serum IgG concentration after booster with each vaccine was signif－icantly higher than that before booster（P＜0.05）.The SBA titers of serum IgG after booster with Anerbao and Heerbei were5263 and4637respectively，which showed no significant difference（P＞0.05）．However，the serum IgG concentrations after inoculation with the two kinds of conjugate vaccines were related to the corresponding SBA titers（r＝0.696，0.689，P＜0.05）．Conclusion The serum IgG12months after inoculation with two kinds of PRP-TT conjugate vaccines for3times remained at high levels，and in－creased rapidly after a booster，all of which reached more than1.00μg／ml and showed effective bactericidal activities in vitro．【Key words】Haemophilus，influenzae，type b；Vaccine，conjugate；Immunization，booster；Immune effect