Evaluation Of The Immunization Effectiveness Of BOPV Booster Immunization And IPV Revaccination With Different IPV-OPV Sequential Immunization Schedule

Objective To evaluate the immunization effectiveness of booster immunization with one does of bOPV at 48 months of age after different polio immune schedules(especially after the use of sIPV)in order to provide a basis for the continuous optimization of polio sequential immunization schedule.Methods On the basis of a previously completed phase Ⅲ clinical trials,for subjects who have completed basic immunization and have paired neutralizing antibody results before and after basic immunization,blood was collected at 24,36,48 months of age to determine polio-specific neutralizing specific antibody,and then 1 dose of bOPV was vaccinated for booster immunization at 48 months of age,and venous blood was collected 28 days after booster immunization for neutralizing antibody detection.According to the ethical requirements and trial design,if any type of polio virus neutralizing antibody is found to be negative(neutralizing antibody titer<1:8)at the age of 24 months or 36 months or 48 months,it is necessary to promptly respond to the subject.Subjects were re-vaccinated with IPV,and this part of the subjects will be used as a reference for bOPV booster immunization in the analysis of results.Results There were 1200 subjects participated in the original phase Ⅲ clinical trial.Because of moving away,not meeting the inclusion criteria,and re-vaccinated with IPV et al.439 subjects participated the booster immunization clinical trial finally.After 439 subjects were vaccinated a dose of bOPV for booster immunization at the age of 48 months,except for the positive rates of PV1,PV2,and PV3 specific antibody of the wIPV-bOPV-bOPV(-bOPV)group were 100%,98.3%,and 100%,respectively.The positive rates of PV1,PV2,and PV3 specific antibody in the other groups were all 100%.There was no significant difference in the positive rates of PV1,PV2,and PV3 specific antibody among the groups(P=1;P=0.177273;P=1).The results of antibody level analysis showed that after booster immunization,there was no significant difference in the GMT of PV1 and PV3 specific antibody among the groups(P=0.0525;P=0.2431)and one does of bOPV as booster had a slight increase in PV2 specific antibody levels,but there was a significant difference between the groups(P<0.0001).For PV2 specific antibody levels,the sIPV-sIPV-tOPV(-bOPV)and wIPV-wIPV-tOPV(-bOPV)groups were much higher than the other four groups vaccinated with bOPV during the basal immunization phase,sIPV-bOPV-bOPV(-bOPV)and wIPV-bOPV-bOPV(-bOPV)groups were the lowest.Regardless of whether using wIPV or sIPV,a sequential immunization schedule with 2 IPV+1 bOPV for basic immunization required fewer people to vaccinate with IPV than 1 IPV+2 bOPV sequential immunization schedule.Re-vaccination with IPV in>10%subjects of wIPV-bOPV-bOPV group and sIPV-bOPV-bOPV group at 24 months of age.Re-vaccination with IPV in>30%of 1 IPV+2 bOPV subjects at 36 months of age and the proportion of re-vaccination with IPV at 36 months of age in the wIPV-wIPV-bOPV group was close to 10%,in the sIPV-sIPV-bOPV group was more than 10%.While after re-vaccination with IPV,the positive rates of PV1,PV2,and PV3 special antibody were almost 100%,and the three types of polio antibody GMT all reach high levels.Conclusion Through basic immunization,immune persistence observation,and booster immunization research,if the strategy of 1IPV+2bOPV is adopted in the basic immunization stage(especially after the use of sIPV),will result in insufficient persistence of neutralizing antibodies to PV2,with nearly(wIPV)or more than(sIPV)30%of children being antibody negative at 36 months of age and the 2IPV+1bOPV group will also have close to(wIPV)or more than(sIPV)10%of children who are antibody negative without intervention.Booster immunization with bOPV is not sufficient to induce high levels of PV2-specific neutralizing antibodies.Therefore,in accordance with the immunization program developed principle that "no less than 90%of the age-group population should have a neutralizing antibody positive for poliovirus types Ⅰ,Ⅱ and Ⅲ",it is recommended that children receiving the 1IPV+3bOPV immunization schedule after the switch in our polio immunization strategy should be given a booster dose of IPV if they have not yet completed the fourth dose,or a re-vaccinated dose of IPV if they have already completed four doses of the vaccine,to ensure that children have continuous protective efficacy against PV2.Booster immunization is recommended at 36 months of age.The sequential immunization schedule of 2IPV+1bOPV+1IPV can not only maintain high antibody levels to PV1 and PV3,but also increase immunity to PV2,and also has early intestinal mucosal immunity,with relatively good safety.The high-risk countries or regions where it occurred or imported polio virus may be the best sequential immunization schedule that can effectively prevent and control the occurrence of WPV,VAPP,and VDPV.