Four Chimpanzee Monoclonal Antibodies that Neutralize Hepatitis A Virus

This invention claims antibodies and/or fragments thereof specific for hepatitis A virus (HAV) and the use of the antibodies in the diagnosis, prevention, and treatment of hepatitis A. Hepatitis A is the most common type of hepatitis reported in the United States, which reports an estimated 134,000 cases annually, and infects at least 1.4 million people worldwide each year. HAV is a positive sense RNA virus that is transmitted via the fecal-oral route, mainly through contaminated water supplies and food sources. HAV is thought to replicate in the oropharynx and epithelial lining of the intestines, where it initiates a transient viremia and subsequently infects the liver. Humoral immunity has been shown to provide an effective defense against Hepatitis A. Prior to the availability of the current inactivated virus vaccines, pooled human immune globulin preparations were routinely used to protect individuals traveling to areas of the world where HAV is endemic. Chimpanzees are susceptible to infection with HAV and can produce antibodies that neutralize the virus. Chimpanzee immunoglobulins are virtually identical to those of humans; thus, they have the same potential as human antibodies for clinical applications. The inventors have shown that the four chimpanzee monoclonal antibodies described in the patent application neutralized HAV strains HM-175, AGM-27, and the HM-175 VP3-070 mutant. Since only a single serotype of HAV has been identified, these antibodies are predicted to neutralize most, if not all, isolates of HAV.