Neutralization of different geographic strains of the hepatitis E virus with anti-hepatitis E virus-positive serum samples obtained from different sources.

A recently developed polymerase chain reaction (PCR)-based cell culture neutralization assay was used to investigate cross-neutralization of known hepatitis E virus (HEV) strains obtained from various HEV-endemic regions of the world with different anti-HEV-positive serum samples. Serum specimens obtained from cynomolgus macaques experimentally infected with strains from Burma, Mexico, or Pakistan cross-neutralized the infectivity of each strain as well as an isolate from Morocco. Serum samples obtained either from infected patients who reside in HEV-endemic regions of the world or from U.S. residents who became infected while traveling to such regions also neutralized all four strains. In contrast, antibodies obtained from rabbits immunized with full-length Burma strain ORF2 protein neutralized only the Burma and Pakistan strains, not the Mexico or Morocco strains. In addition, antibodies obtained from guinea pigs immunized with an N-terminal truncated Burma strain ORF2 protein neutralized each strain except the Morocco strain. These data strongly suggest that antibodies elicited during an HEV infection demonstrate broad HEV neutralizing activity, whereas antibodies elicited after immunization with recombinant Burma ORF2 protein demonstrate a more limited ability to neutralize various HEV strains obtained from different regions of the world endemic for the disease.