Four chimpanzee monoclonal antibodies that neutralize hepatitis A virus

Abstract

Chimpanzee immunoglobulins are virtually identical to human immunoglobulins and thus may have clinically useful applications. in a recent manuscript we described 4 chimpanzee monoclonal antibodies (MAbs) that neutralized hepatitis A virus (HAV) (1). The MAbs were isolated from a combinatorial cDNA library of chimpanzee gamma1/kappa antibody genes using bacteriophage displaying Fab fragments on their surfaces. Three of the MAbs recognized the same or overlapping epitopes on the HAV capsid, whereas the fourth recognized a different, nonoverlapping epitope on the capsid. All 4 MAbs neutralized the homologous HAV strain, HM-175, in a radioimmunofocus assay and 2 of the 4 MAbs. neutralized a heterologous simian HAV strain. AGM-27. From these data. we conclude that the MAbs must recognize at least 3 epitopes on the HAV capsid. Competition assays performed with neutralizing murine MAbs suggested that 3 of the chimpanzee MAbs recognized epitopes on the HAV capsid which have not been defined previously. it is hoped that these MAbs may be used directly in passive immunoprophylaxis to prevent hepatitis A in susceptible populations, e.g., travelers to legions where HAV is endemic or at risk individuals where epidemics are occurring.