Dong Chen, Dai Xing, Meng Ji-hong
Department of Microbiology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2007 Feb;23(2):130-3.
To evaluate the immunogenicity of experimentally combined hepatitis A and hepatitis E (cHA+E) vaccine and analyze the interactions between the two antigenic components in vaccine.
Nine different dosage ratio of the cHA+E vaccine, A500 + E200, A500 + E100, A500 + E50, A250 + E200, A250 + E100, A250 + E50, A125 + E200, A125 + E100 and A125 + E50 (U+mg)/L, was prepared from an inactivated hepatitis A (HA) vaccine and a hepatitis E (HE) vaccine. 120 mice were immunized with the cHA+E vaccine, HA vaccine and HE vaccine alone in different doses, respectively. Mice were bled before immunization and 2, 4, 6, 8, 10, 12 and 14 weeks post immunization. Specific antibodies against hepatitis A and E viruses were detected by ELISA and neutralization assay.
After immunization with different dosages of cHA+E vaccine, all animals developed hepatitis A virus antibody (anti-HAV) and hepatitis E virus antibody (anti-HEV). Anti-HAV responses increased with the concentration of the HA vaccine component in the cHA+E vaccine. Anti-HAV neutralizing antibody titers reached 1:1 024 when mice were immunized with cHA+E vaccine prepared from higher dosage (500 U/mL) of the HA vaccine. The titers only reached 1:512 when lower dosages (250 and 125 U/mL) of HA vaccine were applied. However, different dosages (200, 100 and 50 mg/L) of the HE vaccine component in the cHA+E vaccine developed no effects on the production of anti-HAV neutralizing antibody. In addition, comparing with the single HE vaccine, the cHA+E vaccine induced higher level of anti-HEV response. The anti-HEV level increased with the concentration of HA vaccine component in the cHA+E vaccine. However, there was no obvious relationship between the anti-HEV levels and the different dosages (200, 100 and 50 mg/L) of the HE vaccine component in the cHA+E vaccine. Immune sera elicited by the cHA+E vaccine neutralized HEV infectivity when detected by an in vitro RT-nPCR-based HEV neutralization assay.
In cHA+E vaccine, the HA vaccine component can increase the immunogenicity of the HE vaccine component, and the HE vaccine component plays no adverse effects on the immunogenicity of the HA vaccine component.
评估实验性甲型肝炎和戊型肝炎联合疫苗（cHA+E）的免疫原性，并分析疫苗中两种抗原成分之间的相互作用。
用灭活甲型肝炎（HA）疫苗和戊型肝炎（HE）疫苗制备九种不同剂量配比的cHA+E疫苗，即A500 + E200、A500 + E100、A500 + E50、A250 + E200、A250 + E100、A250 + E50、A125 + E200、A125 + E100和A125 + E50（U+mg）/L。分别用不同剂量的cHA+E疫苗、HA疫苗和HE疫苗单独免疫120只小鼠。在免疫前以及免疫后2、4、6、8、10、12和14周采集小鼠血液。通过酶联免疫吸附测定（ELISA）和中和试验检测针对甲型肝炎病毒和戊型肝炎病毒的特异性抗体。
用不同剂量的cHA+E疫苗免疫后，所有动物均产生了甲型肝炎病毒抗体（抗-HAV）和戊型肝炎病毒抗体（抗-HEV）。抗-HAV反应随cHA+E疫苗中HA疫苗成分浓度的增加而增强。当用高剂量（500 U/mL）HA疫苗制备的cHA+E疫苗免疫小鼠时，抗-HAV中和抗体滴度达到1:1024。当使用低剂量（250和125 U/mL）HA疫苗时，滴度仅达到1:512。然而，cHA+E疫苗中不同剂量（200、100和50 mg/L）的HE疫苗成分对抗-HAV中和抗体的产生没有影响。此外，与单一HE疫苗相比，cHA+E疫苗诱导产生的抗-HEV反应水平更高。抗-HEV水平随cHA+E疫苗中HA疫苗成分浓度的增加而升高。然而，cHA+E疫苗中抗-HEV水平与不同剂量（200、100和50 mg/L）的HE疫苗成分之间没有明显关系。通过基于逆转录巢式聚合酶链反应（RT-nPCR）的体外戊型肝炎病毒中和试验检测发现，cHA+E疫苗诱导产生的免疫血清可中和戊型肝炎病毒感染性。
在cHA+E疫苗中，HA疫苗成分可增强HE疫苗成分的免疫原性，而HE疫苗成分对HA疫苗成分的免疫原性没有不良影响。
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