Sabin株和野毒株脊髓灰质炎灭活疫苗在恒河猴体内不同免疫方案的比较

目的评价Sabin株脊髓灰质炎灭活疫苗(Sabin strain inactivated poliovirus vaccine,sIPV)和野毒株脊髓灰质炎灭活疫苗(Wild strain inactivated poliovirus vaccine,wIPV)在恒河猴体内不同免疫方案的免疫原性。方法将25只恒河猴随机分为5组:sIPV组(免疫3剂sIPV)、sIPV/口服脊髓灰质炎减毒活疫苗(oral attenuated poliovirus vaccine,OPV)组(免疫2剂sIPV后,再免疫2剂OPV)、wIPV组(免疫3剂wIPV)、wIPV/OPV组(免疫2剂wIPV后,再免疫2剂OPV)和对照组(免疫3次稀释液M199),每组5只。OPV口服接种,IPV和M199经上臂三角肌处肌肉注射,2剂间免疫间隔时间为1个月。首次免疫前和每剂免疫后1个月采血,分离血清,采用微量中和试验法测定血清中抗脊髓灰质炎病毒Ⅰ、Ⅱ、Ⅲ型中和抗体效价。结果除对照组外的4个试验组全程免疫结束后,恒河猴血清中均可检出较高水平的中和抗体,且所有恒河猴血清中Ⅰ、Ⅱ、Ⅲ型中和抗体全部阳转。Ⅰ型和Ⅲ型抗体免疫应答中,接种sIPV的2个试验组中和抗体水平高于接种wIPV的2个试验组(P<0.05);Ⅱ型免疫应答中,接种wIPV的2个试验组中和抗体水平高于接种sIPV的2个试验组(P<0.05)。采用wIPV/OPV序贯免疫,Ⅰ、Ⅱ、Ⅲ型抗体免疫应答均可获得与单独接种wIPV同样的效果;而采用sIPV/OPV序贯免疫,Ⅰ型抗体免疫应答效果低于单独接种sIPV,Ⅱ型抗体水平差异无统计学意义(P>0.05),Ⅲ型抗体第4剂免疫后水平也有所上升。结论 sIPV和wIPV在恒河猴体内均可诱导良好的免疫应答,初步证实了IPV/OPV序贯免疫的可行性,为今后免疫策略的制定提供了一定的实验依据。

Comparative study on different immune schemes of inactivated poliovirus vaccines prepared with Sabin and wild strains in rhesus monkeys

Objective To evaluate the immunogenicity of different immune schemes of inactivated poliovirus vaccine prepared with Sabin strain(sIPV) and wild strain(wIPV) in rhesus monkeys.Methods Twenty-five rhesus monkeys were divided into five groups randomly,five for each.The monkeys in sIPV group were immunized with 3 doses of sIPV,while those in sIPV/OPV group with 2 doses of sIPV and 2 dose of OPV,those in wIPV group with 3 doses of wIPV,those in wIPF/OPV group with 2 doses of wIPV and 2 doses of OPV,and those in control group with 3 doses of M199 as diluent.OPV was given by oral route,while IPV and M199 by i.m.injection in deltoid of upper arm.The time interval between 2 doses was one month.Serum samples were collection before the first dose and one month after each dose re spectively,and determined for neutralizing antibody titers against poliovirus types Ⅰ,Ⅱ and Ⅲ by micro-neutralization test.Results High neutralizing antibody titers were detected in the monkeys except those in control group.All the posi tive conversion rates of antibodies against poliovirus types Ⅰ,Ⅱ and Ⅲ in sera of monkeys in four test groups were 100%.The neutralizing antibody levels against poliovirus types Ⅰand Ⅲ in sIPV and sIPV/OPV groups were significantly higher,while that against type Ⅱ was significantly lower,than those in wIPV and wIPV/OPV groups(each P <0.05).The immune response levels against poliovirus typesⅠ,Ⅱ and Ⅲ in wIPF/OPV group were comparable to those in wIPV group.However,compared with those in sIPV group,the immune response level against poliovirus type Ⅰ in sIPV/OPV group decreased significantly,and that against type Ⅱ showed no significant difference(P > 0.05),while that against type Ⅲ increased after the forth dose was given.Conclusion Both sIPV and wIPV induced effective immune responses in rhesus monkeys,which preliminarily proved the feasibility of IPV/OPV sequential immune scheme and provided a certain experimental basis for further development of immune strategy.