脊髓灰质炎病毒受体转基因小鼠接种Ⅰ+Ⅲ型二价脊髓灰质炎减毒活疫苗后的排毒规律

Poliovirus shedding pattern after immunization with types Ⅰ+Ⅲ oral bivalent live attenuated poliovirus vaccine in poliovirus receptor transgenic mice

目的通过脊髓灰质炎(简称脊灰)病毒受体转基因小鼠动物模型,探讨接种Ⅰ+Ⅲ型二价脊髓灰质炎减毒活疫苗(bivalent oral poliovirus vaccine,bOPV)后的排毒规律。方法以灌胃方式给脊灰受体转基因小鼠接种3剂bOPV,间隔28 d。每剂bOPV接种后第1、3、5、7天采集当天小鼠粪便样本,实时定量PCR检测每剂bOPV接种后的排毒量,ELISA法检测脊灰特异的肠道黏膜免疫球蛋白A(immunoglobulin A,IgA)抗体水平,分析排毒与接种剂次、黏膜IgA水平的关系。将接种了bOPV后检测到排毒量高和排毒量低的两组小鼠分别与洁净小鼠共居,观察洁净小鼠接触后的排毒反应。结果随着接种bOPV剂次的增加,疫苗所引发的排毒量逐渐减少。第1剂bOPV接种后排毒量较高的个体在接种下一剂bOPV后的排毒量显著低于首剂排毒量低的个体(P<0.05)。第1剂bOPV接种后IgA呈阳性的个体在第1剂接种后的排毒量高于IgA呈阴性组,但第2剂接种后排毒量低于IgA呈阴性组。与高排毒组小鼠共居后,洁净小鼠发生排毒的机率显著高于与低排毒的小鼠共居的洁净小鼠(P<0.05),且Ⅲ型脊灰疫苗株比Ⅰ型引起洁净小鼠的排毒反应持续性更长。结论在脊灰消灭的最后阶段,预防脊灰流行的一个关键仍在于激发人群对抗脊灰病毒复制的黏膜免疫,减少排毒。增加bOPV接种剂次可减少后续个体接触脊灰病毒后的排毒概率。在b OPV接种后,需加强排毒检测和个人卫生管理,特别是首剂bOPV接种后。

Objective To investigate the viral shedding pattern in poliovirus receptor transgenic mice after immunization with types Ⅰ + Ⅲ oral bivalent poliovirus vaccine(bOPV). Methods The poliovirus receptor transgenic mice were inoculated with three doses of bOPV by gavage each at an interval of 28 d,of which the fecal samples were collected on days 1,3,5 and 7 after each dose and determined for viral shedding level by real-time fluorescent quantitative PCR.Poliovirus-specific IgA level in intestinal mucosa was determined by ELISA,and the relationships of viral shedding to the dose of inoculation and IgA level were analyzed. Mice with high and low viral shedding levels after inoculation with bOPV were cohabitated with clean mice respectively,and the viral shedding of clean mice was observed. Results The viral shedding level caused by the vaccine decreased gradually with the increasing dose. The mice with high viral shedding level after the first dose showed significantly lower shedding level after the second dose than those with low viral shedding level after the first dose(P < 0. 05). The mice positive for IgA after the first dose showed higher viral shedding level after the first dose,while showed lower viral shedding level after the second dose,than those negative for IgA. The probability of shedding virus in clean mice after cohabitation with high viral shedding mice was significantly higher than that with low viral shedding mice(P < 0. 05),and the viral shedding of clean mice caused by type Ⅲ poliovirus vaccine strain was more persistent than that by typeⅠ. Conclusion In the final stages of polio eradication,a key to prevent polio epidemic remains the stimulation of population mucosal immunity against poliovirus replication and the reduction of shedding.Increasing the doses of bOPV can reduce the probability of shedding after exposure to poliovirus. Viral shedding monitoring and personal hygiene should be strengthened after bOPV inoculation,especially after the first dose.