| Enterovirus71(EV71),which is a major pathogen of hand-foot and mouth disease (HFMD) often infects infants and children. The clinical symptom caused by EV71is usually characterized by HFMD, aseptic meningitis, acute flaccid paralysis, brainstem encephalitis and accompanied by other severe neurological manifestation, such as pulmonary edema and cardiopulmonary dysfunction. HFMD was taken into type C infectious diseases since2008as the whole country has began to be epidemic of EV71in recent years, and it is an urgent public health issue that how to prevent from EV71infection.Vaccine inoculation is the most effective method for control and prevention. Human inactivated vaccine successfully developed by Institute of Medical Biology, Chinese Academy of Medicine Science using EV71FY-23K-B strain as virus seed is undergoing Phase III Clinical Trials Program after Phase I and Ⅱ Clinical Trials Program indcating safety and immunogenicity of the vaccine. The cross protection of the vaccine against different genotypic enterovirus71is related to its preventive effect. In order to further investigation of the cross-protection of this vaccine against other EV71strains, we conducted neutralization test in response to20EV71strains including K9, SI, R20-9J-3, S19, He49, BrCr and so on, and8non-EV71enterovirus, such as polio Ⅰ/Ⅱ/Ⅲ. Cox A16、 ECHO2/6. The results indicated that the vaccine exerts wide antigenicity for type A strains and subtype C4strains, among which4U of neutralizing antibody in the serum show the significant protection efficacy, while2U serum only have35%neutralization efficacy, whereas the serum of this vaccine show weak or no cross protection for non-EV71enterovirus in our study.The combined vaccine is a hopeful development of vaccines. To primarily evaluate the feasibility of inactivated combined vaccine of EV71and Hepatitis A virus (HAV),combined vaccine was prepared by formulation of inactivated HAV (EU/ml) and inactivated EV71vaccines (EU/ml) at the following dosage ratios:640/320.640/160.640/80.160/1280.160/640.320/640.640/640.ICR mice were immunized according to the above dosage ratio groups and the counterpart monovalent ones were made as control groups. The specific humoral and cellular immune response were determined28d after primary immunization and7d after booster immunization. The results demonstrated that protective HAV antibody was induced in the sera of mice in all the groups28d after primary immunization. The antibody of160/640(EV71/HAV) group is the highest and the80EU/ml monovalent group is the lowest. The titers of antibody of all the groups increased by12.2times on average after booster, and the highest one was the160/640group.And there is no statistic significance among the groups160/640,320/640and640/640(P>0.05).The positive rates of neutralizing antibody against EV71in the sera of mice in all the groups reached100%28d after primary immunization, and the average GMT is14.7.While the neutralizing antibody titers were dose-dependent, and640/640group reached the highest titer (P<0.05).The percentage of CD8+cells in spleens of mice in all the groups were significantly higher than those of CD4+cells (P<0.001)28d after primary immunization (P<0.001), while the result reversed7d after booster immunization. Either HAV or EV71polypeptide stimulated weak positive response of splenoecytes28d after primary immunization. And7d after booster immunization, IL-4secreted by splenoecytes was significantly higher than those of IFN-y (P<0.05).In conclusion, combined immunization of HAV and EV71vaccines at certain dosages can induce high humoral immune response and relatively low cellular immune response. It is regarded that group640/640(EV71/HAV) is the ideal dose ratio according to the result of humoral immune response. However, no interference or synergism was observed in the combined vaccine groups. |
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