皮内免疫部分剂量组分无细胞百白破-Sabin株脊髓灰质炎联合疫苗的免疫持久性  

Immune persistence following intradermal vaccination with fractional dose of diphtheria-tetanus-acellular component pertussis and Sabin-derived inactivated poliovirus vaccine

作　　者：李婧妍 蔡路奎[1,2] 马艳 温嘉纳[1,2] 胡文著 廖宏玮[1,2] 史荔 杨净思 LI Jingyan;CAI Lukui;MA Yan;WEN Jiana;HU Wenzhu;LIAO Hongwei;SHI Li;YANG Jingsi(Institute of Medical Biology,Chinese Academy of Medical Science and Peking Union Medical College,Kunming 650118,Yunnan Province,China)

机构地区：[1]中国医学科学院,北京协和医学院,医学生物学研究所,云南昆明650118 [2]昆明市新发突发高致病性病原体疫苗研发和产业化企业科技创新中心,云南昆明650118

出　　处：《中国生物制品学杂志》2023年第5期513-517,523,共6页Chinese Journal of Biologicals

基　　金：国家科技重大专项重大新药创制(2015ZX09101031);云南省重大科技专项计划(202002AA100009)。

摘　　要：目的评价皮内免疫(intradermal,ID)部分剂量组分无细胞百白破-Sabin株脊髓灰质炎联合疫苗(diphtheria-tetanus-acellular component pertussis and Sabin-derived inactivated poliovirus vaccine,DTacP-sIPV)的免疫持久性。方法将40只Wistar大鼠(雌雄各半)分别经ID部分剂量(DTacP-sIPV 1/5和1/10剂量,即1/5D和1/10D ID组)及肌肉注射(intramuscular,IM)全剂量DTacP-sIPV(全剂量IM组),同时设空白对照组(ID PBS)。于0、1、2月共免疫3次,末次免疫后12个月经尾静脉采血,分离血清。微量中和试验法检测抗脊髓灰质炎病毒中和抗体滴度,间接ELISA法检测大鼠血清中抗白喉毒素(diphtheria toxin,DT)、破伤风毒素(tetanus toxin,TT)、百日咳毒素(pertussis toxin,PT)、丝状血凝素(filamentous haemagglutinin,FHA)和百日咳黏附素(pertactin,PRN)的IgG抗体滴度,并计算抗体几何平均滴度(geometric mean titer,GMT)及抗体阳性率。末次免疫后12个月,经雾化吸入百日咳杆菌气雾进行攻击,攻击时间为30 min,于气雾攻击后2、5、14 d检测各组大鼠白细胞数及肺、气管、鼻部位的菌落克隆形成数(colony-forming unit,CFU)。结果与全剂量IM组比较,1/5D和1/10D ID组脊髓灰质炎病毒Ⅰ、Ⅱ、Ⅲ型中和抗体阳性率差异均无统计学意义(P均>0.05),空白对照组各型抗体阳性率均为0。1/5D、1/10D ID及全剂量IM组DT、TT、PT、FHA和PRN的IgG抗体阳性率均为100%,空白对照组IgG抗体阳性率均为0。与攻击后2 d比较,空白对照组大鼠经百日咳杆菌气雾攻击后5 d的白细胞数明显升高(F=3.48,P<0.05),随后开始下降;其他组均随时间的延长保持平稳(F=0.14~1.30,P>0.05)。气雾攻击后,空白对照组大鼠肺部细菌载量明显高于其他3组(F=19.00~206.00,P<0.05),攻击后14 d仍可检测到百日咳杆菌;除空白对照组外,其他3组大鼠肺部细菌载量均于攻击后5 d达峰值,14 d时基本清除,各时间点组间差异无统计学意义(F=1.14~1.25,P>0.05)。空白对照组各时�Objective To evaluate the immune persistence following intradermal(ID)vaccination with diphtheria-tetanusacellular component pertussis and Sabin-derived inactivated poliovirus vaccine(DTacP-sIPV).Methods 40 wistar rats were randomly assigned into four groups.Two test groups were injected intradermally with fractional-doses(1/5 and 1/10dose)of DTacP-sIPV(1/5D ID and 1/10D ID group);The positive control group was intramuscularly injected with full dose of DTacP-sIPV(full-dose IM group);The negative control group was injected with PBS intradermally.Wistar rats were immunized 3 times at 0,1 and 2 months and the blood samples were collected via tail vein 12 months after the last immunization and the serum samples were isolated.The titer of neutralizing antibody against poliovirus was detected by micro-neutralization test,and the titers of IgG antibodies against diphtheria toxin(DT),tetanus toxin(TT),pertussis toxin(PT),filamentous hemagglutinin(FHA)and pertactin(PRN)in rat serum were detected by indirect ELISA.The geometric mean titer(GMT)and positive rate of antibody were calculated.The rats were challenged with aerosolized B.pertussis for 30 min 12 months after the last immunization and determined for the white blood cell(WBC)count and colony-forming unit(CFU)in lung,trachea and nose at day 2,5 and 14 after challenge.Results Compared with the full-dose IM group,there was no significant difference in the positive rates of poliovirus typeⅠ,ⅡandⅢneutralizing antibodies between 1/5D ID and 1/10D ID groups(each P>0.05)and the positive rates of all types of antibodies in the control group were 0.The positive rates of IgG antibodies against DT,TT,PT,FHA and PRN in 1/5D ID,1/10D ID and full-dose IM groups were all 100%,and those in control group were all 0.Compared with 2 d after challenge,the WBC counts of rats in control group increased significantly 5 d after aerosol challenge with B.pertussis(F=3.48,P<0.05),and then began to decrease,while those in other groups remained stable with time(F=0.14~1.30,P>0.05).After a

关 键 词：组分无细胞百白破-Sabin株脊髓灰质炎联合疫苗 部分剂量 皮内免疫 免疫持久性 

分 类 号：R392-33[医药卫生—免疫学]