title: [Immunogenicity of experimentally combined hepatitis A and hepatitis E vaccine at different dosage ratio].
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.forename: Xing
authors.initials: X
authors.lastname: Dai
authors.forename: Ji-hong
authors.initials: JH
authors.lastname: Meng
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D035922:Hepatitis A Antibodies / Q000276:immunology; D022362:Hepatitis A Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D030041:Hepatitis A virus / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000276:immunology; D016752:Hepatitis E virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D035922:Hepatitis A Antibodies; D022362:Hepatitis A Vaccines; D006508:Hepatitis Antibodies; D014761:Viral Hepatitis Vaccines