title: Rabbit as a novel animal model for hepatitis E virus infection and vaccine evaluation.
abstract: BACKGROUND
  The identification of hepatitis E virus (HEV) from rabbits motivated us to assess the possibility of using rabbits as a non-human primate animal model for HEV infection and vaccine evaluation.
  
  
  RESULTS
  First, 75 rabbits were inoculated with seven strains of genotypes 1, 3, 4, and rabbit HEV, to determine the appropriate strain, administrative route and viral dosage. Second, 15 rabbits were randomly divided into three groups and vaccinated with 0 µg (placebo), 10 µg and 20 µg of HEV candidate vaccine, HEV p179, respectively. After three doses of the vaccination, the rabbits were challenged with 3.3×10(5) genome equivalents of genotype 4 HEV strain H4-NJ703. The strain of genotype 1 HEV was not found to be infectious for rabbits. However, approximately 80% of the animals were infected by two rabbit HEV strains. All rabbits inoculated with a genotype 3 strain were seroconverted but did not show viremia or fecal viral shedding. Although two genotype 4 strains, H4-NJ153 and H4-NJ112, only resulted in part of rabbits infected, another strain of genotype 4, H4-NJ703, had an infection rate of 100% (five out of five) when administrated intravenously. However, only two out of fifteen rabbits showed virus excretion and seroconversion when inoculated orally with H4-NJ703 of three different dosages. In the vaccine evaluation study, rabbits vaccinated with 20 µg of the HEV p179 produced anti-HEV with titers of 1∶10(4)-1∶10(5) and were completely protected from infection. Rabbits vaccinated with 10 µg produced anti-HEV with titers of 1∶10(3)-1∶10(4) and were protected from hepatitis, but two out of the five rabbits showed virus shedding.
  
  
  CONCLUSIONS
  Rabbits may be served as an alternative to the non-human primate models for HEV infection and vaccine evaluation when certain virus strains, appropriate viral dosages, and the intravenous route of inoculation are selected.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Cheng
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Dai
authors.forename: Chengbo
authors.initials: C
authors.lastname: Shi
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wen
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Shenwei
authors.initials: S
authors.lastname: Zhan
authors.forename: Jihong
authors.initials: J
authors.lastname: Meng
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D016678:Genome; D016679:Genome, Viral; D005838:Genotype; D016751:Hepatitis E / Q000503:physiopathology / Q000821:virology*; D016752:Hepatitis E virus / Q000378:metabolism*; D023421:Models, Animal; D010919:Placebos; D012367:RNA, Viral / Q000235:genetics; D011817:Rabbits; D017201:Virus Shedding / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; D010919:Placebos; D012367:RNA, Viral; D000410:Alanine Transaminase