PRELIMINARY EVIDENCE THAT A TRPE-HEV FUSION PROTEIN PROTECTS CYNOMOLGUS MACAQUES AGAINST CHALLENGE WITH WILD-TYPE HEPATITIS-E VIRUS (HEV)

Immunization of two cynomolgus macaques (cynos) with trpE-C2 protein, a trpE-HEV fusion protein that represents the carboxyl two thirds of t he putative capsid protein, prevented development of biochemical evide nce of viral hepatitis in these primates after challenge by wild-type HEV from either-a Burmese or Mexican stool isolate. Neither of the imm unized animals showed any elevation of alanine aminotransferase activi ty after challenge with wild-type HEV in marked contrast with the unim munized (control) cynos. In the case of the Burmese HEV challenged cyn o, the protective effect was complete with the animal failing to demon strate any evidence of HEV infection. The immunized cyno challenged wi th Burmese HEV did not exhibit any HEV RNA in its stools or HEV antige n in its liver. The immunized cyno (#8902) challenged with Mexican vir us exhibited HEV RNA in its stools and HEV antigen in its liver; howev er, microscopic examination of liver biopsy specimens from this cyno f ailed to detect histopathologic evidence of viral hepatitis. All of th e animals (naive and immunized) developed anti-HEV IgM and IgG respons es after HEV challenge. Our preliminary studies indicate that the trpE -C2 protein is a promising candidate HEV vaccine. (C) 1993 Wiley-Liss, Inc.