The Immunogenicity Of The DTaP-HepB-sIPV Combination Vaccine To Boost Immunization And Sequential Sequential Immunization With SIPV And BOPV (type I + Type III)

The CFDA approved the world's first applications for producing and registering Inactivated Poliovirus Vaccine made from Sabin Strains on January 14th,2015.This vaccine was developed by the IMBCAMS through the use of existing production strain live attenuated polio vaccine(Sabin strain),cultured and harvested in Vero cells bioreactor,combined inactivated vaccine production technology.The purpose of this paper is to study the cellular immune response after booster vaccination the DTaP-HepB-sIPV and compare safety and immunogenicity of Inactivated poliomyelitis vaccine made fromSabin strain(sIPV)with bivalent type ? +? oral poliomyelitis attenuated live vaccine(bOPV)in Different Formulations combined with Sequential Immunization.This paper is divided into two parts:Section 1:Compare the different experimental group of DTaP-HepB-sIPV vaccine in cellular immune response after booster vaccination based on the basic immunization research results and strengthen the immune humoral immunity study.We prepared four groups(A-D)of the experimental DTaP-HepB-sIPV vaccine and other six groups(E,F,G,H,Q1,Q2)as control group.We also prepared a reference vaccine group:GSK listed vaccine InfanrixTM-hexa(DTaP-HepB-wIPV).Each groups' Wistar rats were carried out booster immunization at the 16th month of full dose immunization after 3 doses of basic immunization.Blood samples were taken before immunization and 15,30 days after immunization.Then we used the Flow cytometric Beads Array to detected IFN-?,TNF,IL-5.IL-2,IL-4 in serum,and measured the levels of CD3+CD4+T cells,CD3+CD8+T cells,CD8+CD28+T cells,CD45RA+CD27+memory B cells on the 30th day after booster immunization.The result showed that the combined vaccine could induce the cell to express the cellular immune response rapidly in the aspect of cellular immunity,the level of cytokine in combination vaccine group peaked at 15 days after the booster immunization.There was no statistical significance in CD3+CD4+T cells,CD3+CD8+T cells,CD8+CD28+T cells,CD45RA+CD27+memory B cells' level between groups.Section 2:To compare the safety and immunogenicity of two different sequential schedules of sIPV followed by bOPV in different dosage forms(Drug Candy form/liquid dosage form).According to the dosage form and the sequential schedules,participants were randomly(1:1:1:1)by random number table to receive a 3 dose of either sIPV+2bOPV or 2sIPV+bOPV at 0?28?56 days of enrolled day.Blood samples were taken prior to Dose 1 and 28 days after Dose 3.Polio ??? and ?antibody titers were assessed by virus-neutralizing antibody assay with Sabin strains and the seroconversion(4-fold increase in titer)from pre-Dose 1 to28 days post-Dose 3 was calculated.The results showed that during the vaccination,the incidence of whole AEs in sIPV+2bOPV(DC),sIPV+2bOPV(liquid),2sIPV+bOPV(DC)and 2sIPV+bOPV(liquid)were 79%,76%,79.8%,74%(p=0.76).The incidence of SAEs in each group 6%,5%,6.06%,4%(p=0.9),and none was considered to be vaccination related.After 3 dose sequential schedule,sIPV+2bOPV(DC),sIPV+2bOPV(liquid),2sIPV+bOPV(DC),2sIPV+bOPV(liquid),the poliovirus neutralizing antibody GMT of type ? were 1:4539.68,1:6243.43,1:6819.53,1:7916.29 respectively;Type?was 1:12.98,1:10.54,1:63.75,1:84.21 respectively;Type ? was 1:1172.55,1:1416.03,1:2648.89,1:3250.75respectively.The seroconversion of type ? was 98.85%,100.0%,98.86%,98.91%respectively;type ?was 47.13%,56.63%,79.55%,79.35%respectively;type?was 100.0%,98.80%,100.0%,98.91%respectively.On the same sequential schedules,there was no significant difference between the dosage forms,all of them have good safety and immunogenicity.In the same dosage forms with different sequential schedules,2 dose sIPV had higher serum neutralizing antibody level than the 1 dose sIPV group,especially in the neutralizing antibody GMT of type ?,?after vaccination.