肠道病毒71型灭活疫苗(Vero细胞)分别与乙肝、乙脑疫苗联合接种的免疫原性研究

Immunogenicity of combined immunizing of inactivated enterovirus 71 vaccine(Vero cells)and hepatitis B,live-attenuated Japanese encephalitis vaccines respectively

目的评价、探索肠道病毒71型(enterovirus 71,EV71)灭活疫苗与免疫规划疫苗中的重组乙型肝炎疫苗(hepatitis B vaccine,HepB)、乙型脑炎减毒活疫苗(live-attenuated Japanese encephalitis vaccine,LJEV)联合接种的效果及可行性,为EV71灭活疫苗与免疫规划疫苗联合接种提供科学依据。方法采用随机、对照、多中心的研究方法,通过分层区组随机化方法给符合标准的对象分配研究编号入组,评价各组6/8月龄婴儿EV71灭活疫苗第1剂与重组HepB第3剂、LJEV第1剂联合接种的免疫原性及可操作性。结果EV71灭活疫苗与重组HepB第3剂联合免疫组(HepB:3+EV71组)和重组HepB单独接种组(HepB:3组)的HBsAb浓度的中位数免疫前分别为575.19 mIU/mlh和592.97 mIU/ml,差异无统计学意义(P>0.05);免疫后两组中位数分别为2766.11 mIU/ml和2153.63 mIU/ml,差异无统计学意义(P>0.05);EV71灭活疫苗与LJEV联合免疫组(LJEV+EV71组)和LJEV单独接种组(LJEV组)乙脑中和抗体滴度几何均值免疫前分别为1∶5.00和1∶5.13,差异无统计学意义(P>0.05);免疫后两组乙脑中和抗体滴度几何均值分别为1∶11.55和1∶9.75,差异无统计学意义(P>0.05);HepB:3+EV71组HBsAb阳转率为48.08%,HepB:3组HBsAb阳转率为51.85%,两组差异无统计学意义(P>0.05);LJEV+EV71组乙脑抗体阳转率为67.92%,LJEV组乙脑抗体阳转率为59.26%,两组差异无统计学意义(P>0.05);所有试验组(联合接种组)和EV71灭活疫苗单独接种组(EV71组)免疫后EV71中和抗体均阳转,免疫前EV71组的EV71中和抗体滴度几何均值为1∶4.21,HepB:3+EV71组为1∶4.62,两者差异无统计学意义(P>0.05),LJEV+EV71组为1∶4.16,与EV71组差异无统计学意义(P>0.05);免疫后EV71组的EV71中和抗体滴度几何均值为1∶612.93,HepB:3+EV71组为1∶1169.45,LJEV+EV71组为1∶1156.49,均高于EV71组,差异有统计学意义(P<0.05)。结论EV71灭活疫苗单独接种及EV71灭活疫苗分别与重组HepB、LJEV联合接种,其免疫后EV71中和抗体阳转率均为100%;EV71灭活疫苗与重组HepB、LJEV联合接种不会降低EV71中和抗体产生水平,也不会影响HBsAb、乙脑抗体的产生。EV71灭活疫苗与重组HepB、LJEV联合接种能有效提高接种效率与接种的及时性。

Objective To evaluate and explore the effects and feasibility of combined immunizing of inactivated enterovirus 71(EV71)vaccine and recombinant hepatitis B(HepB)vaccine,live-attenuated Japanese encephalitis vaccine(LJEV)respectively so as to provide a scientific basis for combined vaccination with inactivated EV71 vaccine and vaccines covered by immunization program.Methods A randomized,controlled and multicenter study was conducted.Subjects who met the inclusion criteria were assigned study numbers by stratified block randomization,and then we evaluated the immunogenicity and operability of combined immunizing of the first dose of inactivated EV71 vaccine and the third dose of recombinant HepB vaccine(HepB:3),the first dose of LJEV respectively in infants aged 6/8 months in each group.Results The median concentration of HBsAb in the HepB:3+EV71 group and the HepB alone immunization group(HepB:3 group)before the immunization was 575.19 mIU/ml and 592.97 mIU/ml,respectively,and no statistically significant difference was found(P>0.05).The median concentration in the above-mentioned two groups after the immunization was 2,766.11 mIU/ml and 2,153.63 mIU/ml,respectively,showing no statistically significant difference(P>0.05).The geometric mean titers of pre-vaccination EV71 neutralizing antibody in the EV71+LJEV group and the LJEV single immunization group(LJEV group)were 1:5.00 and 1:5.13,respectively,and no statistically significant difference was found(P>0.05).The geometric mean titers of post-vaccination EV71 neutralizing antibody in the above-mentioned two groups were 1:11.55 and 1:9.75,and the difference was not statisticallysignificant(P>0.05).No statistically significant difference was found in the positive conversion rate of HBsAb between theHepB:3+EV71 group and the HepB:3 group(48.08%vs.51.85%,P>0.05).No statistically significant difference was observedin the positive conversion rate of antibody against JE virus between the LJEV+EV71 group and the LJEV group(67.92%vs.59.26%,P>0.05).The post-vaccination EV71 neutralizing antibody showed positive conversion in all the experimental groups(the combined vaccination groups)and the EV71 group.No statistically significant difference was found in the geometric mean titerof pre-vaccination EV71 neutralizing antibody between the EV71 group and the HepB:3+EV71 group(1:4.21 vs.1:4.62,P>0.05)as well as between the LJEV+EV71 group and the EV71 group(1:4.16 vs.1:4.21,P>0.05).The geometric mean titer ofpost-vaccination EV71 neutralizing antibody was higher in the HepB:3+EV71 group(1:1,169.45)and the LJEV+EV71 group(1:1,156.49)as compared with the EV71 group(1:612.93),with statistically significant differences(bothP<0.05).Conclusion The positive conversion rate of post-vaccination EV71 neutralizing antibody was 100%when inactivated EV71 vaccine was inoculated either alone or combined with recombinant HepB vaccine and LJEV respectively.Combined immunizationwith inactivated EV71 vaccine and recombinant HepB vaccine or LJEV will not lead to a decrease in EV71 neutralizing antibody aswell as the production of HBsAb and JE antibody,but will effectively improve the efficiency and timeliness of vaccination.