In Vivo And In Vitro Studies Of Hepatitis E Virus

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Abstract

We have passaged a strain of HEV from serum collected from wild rats in Los Angeles to Sprague-Dawley laboratory rats and have generated a virus stock with an infectious titer of three and a half logs.. We collaborated in a large serosurvey of US swine handlers and demonstrated that they had a slightly higher risk of infection than did normal blood donors. Two baculovirus-expressed recombinant capsid protein vaccines we developed were compared for efficacy in rhesus macaques and a GLP challenge study in macaques of the most effective one was completed. The US Army began phase II/III clinical trials of this vaccine candidate in Nepal this summer.We showed that protective antibody induced by vaccination of macaques lasted at least one year. We have constructed two cDNA clones of HEV which differ by a single nucleotide. Transcripts from one cDNA clone encoded a virus which infected, but was attenuated for chimpanzees but it did not infect rhesus monkeys. Transcripts of the second recombinant virus infected rhesus monkeys in addition to chimpanzees and caused acute hepatitis in both species. The single mutation differentiating the two viruses identified the location of a cis-reacting element. We have shown that a chimeric virus of genotype one and part of either a genotype 2 or genotype 3 virus is infectious.We have identified monoclonal antibodies which recognize an epitope on the HEV capsid protein but do not neutralize the virus.