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

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

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。

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 ＆lt;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 ＆gt; 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.