不同方法配制的DTaP-sIPV中sIPV的免疫原性研究

目的 对采用不同配制方式制备的,含不同剂量Sabin株脊髓灰质炎(脊灰)灭活疫苗(Sabin strain inactivated poliovirus vaccine,sIPV)的DTaP-sIPV联合疫苗中sIPV的免疫原性进行研究.方法 按照2种不同方式配制含高、低剂量sIPV的DTaP-sIPV联合疫苗.将70只大鼠按简单随机法分成7组,分别为F1H(DTaP-sIPV高剂量组,配制方式1)、F2H(DTaP-sIPV高剂量组,配制方式2)、sIPV-H(sIPV高剂量组)、F1L(DTaP-sIPV低剂量组,配制方式1)、F2L (DTaP-sIPV低剂量组,配制方式2)、sIPV-L(sIPV低剂量组)、赛诺菲巴斯德五联疫苗潘太欣对照组.每组10只大鼠,间隔3周双侧后腿肌内注射,0.5 ml/只,共免疫3针.于第0、3、6、9、13、17、21、25周眼眶采血、分离血清,采用微量细胞病变效应抑制法分别测定血清中抗I、Ⅱ、Ⅲ型脊灰病毒中和抗体滴度,并进行多样本均数方差分析.结果 每针免疫后,各组抗各型中和抗体滴度均持续上升,第9周均达到最高水平,第13周开始显著下降,至第25周仍维持在一定水平.3针免疫完成后3周,F2H组的抗Ⅰ型脊灰病毒中和抗体几何平均滴度显著高于潘太欣组(F=0.988,P=0.027);抗Ⅱ型中和抗体,F2H组显著高于F1H组,sIPV-H组显著高于F1H和潘太欣组(F=2.391,P值均＜0.05);抗Ⅲ型中和抗体,各组间差异均无统计学意义.3针基础免疫后各时间点F2H组抗各型中和抗体滴度均为最高,但除第9周其抗Ⅱ型中和抗体显著高于F1H组外,其他差异均无统计学意义.结论 DTaP-sIPV联合疫苗免疫大鼠后可以诱导产生抗各型脊灰病毒中和抗体,且其滴度和持续时间均优于或等同于潘太欣组.DTaP-sIPV诱导的中和抗体滴度不低于相应剂量的sIPV.虽然配制方式2可能更佳,但2种配制方式间sIPV的免疫原性差异无统计学意义.

Immunogenicity of Sabin strain inactivated poliovirus vaccine (sIPV) in different preparations of DTaP-sIPV

Objective To evaluate the immunogenicity and sustainability of different doses Sabin strain inactivated poliovirus vaccine (sIPV) in different preparations of DTaP-sIPV.Methods DTaP-sIPV with high or low dose sIPV was produced using 2 fomulations.Seventy rats were simply randomized into 7 groups (10 per group),which were F1 H (DTaP-sIPV high dose,formulation 1),F2H (DTaP-sIPV high dose,formulation 2),sIPV-H (sIPV high dose),F1L (DTaP-slPV low dose,formulation 1),F2L (DTaP-sIPV low dose,formulation 2),sIPV-L (sIPV low dose),and Sanofi Pasteur pentavalent vaccine PENTAXIM control group.Animals were immunized intramuscularly with 0.5 ml vaccine on hind limbs at 0,3,and 6 week.Blood was drawn from eyes at 0,3,6,9,13,17,21,and 25 week.The titers of neutralizing antibodies against 3 types of poliovirus (PV) were determined by microcytopathic effect inhibition assay.Results The neutralizing antibodies against PV1,PV2,and PV3 continuously increased after each immunization to reach peak at 9 week,then decreased significantly from 13 week but retained relatively high levels up to 25 week.Comparing the geometric mean titers (GMT) of neutralizing antibodies in 7 groups,3 weeks after 3 injections,anti-PV1 in F2H group was significantly higher than in PENTAXIM group (F =0.988,P =0.027);anti-PV2 in F2H group was higher than in F1H group,in sIPV-H group was higher than in F1H and PENTAXIM groups (F =2.391,all P ＜0.05);anti-PV3 showed no significant difference among all groups.The neutralizing antibodies against all 3 PV in F2H group after 3 immunizations were the highest at every point,but only anti-PV2 at 6 week reached statistical significance over F1H group.Conclusions DTaP-sIPV immunization can induce neutralizing antibodies against all 3 PV in rats.The immunogenicity and sustaining time are no less than PENTAXIM.The GMT in DTaP-sIPV is no less than sIPV at same dose.The 2 preparations have no statistically significant effect on the immunogenicity of sIPV in DTaP-sIPV,though formulation 2 may be more preferred.