Markedly prolonged incubation period of hepatitis B in a chimpanzee passively immunized with a human monoclonal antibody to the a determinant of hepatitis B surface antigen.
The protective efficacy of a human monoclonal antibody directed against the a determinant of hepatitis B virus (HBV) surface antigen was studied in a chimpanzee. A single high dose of 5 mg/kg (body weight) of monoclonal antibody SDZ OST 577 was intravenously administered to a chimpanzee, followed by intravenous challenge with 10(3.5) chimpanzee infectious doses of a wild-type HBV, the MS-2 strain (ayw subtype). The passively acquired antibody to HBV surface antigen could be detected for 40 weeks. Serum HBV DNA tested by a "nested" polymerase chain reaction assay was negative through the 36th week after virus challenge but became positive by the 38th week. The chimpanzee subsequently developed acute hepatitis B approximately 1 year after challenge. The nucleotide sequence of the a determinant of the surface gene of the replicated virus was identical with that of the inoculated wild-type virus. Thus, a human monoclonal antibody directed against the a determinant of HBV surface antigen delayed but did not prevent experimental infection of HBV and hepatitis in the chimpanzee. Our results indicate an incomplete ability of this antibody to protect against HBV infection in vivo after a single infusion.
Ogata
N
N
Hepatitis Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Ostberg
L
L
Ehrlich
P H
PH
Wong
D C
DC
Miller
R H
RH
Purcell
R H
RH
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001483:Base Sequence; D004279:DNA, Viral / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D006509:Hepatitis B / Q000097:blood / Q000276:immunology* / Q000503:physiopathology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007116:Immunization, Passive; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D002679:Pan troglodytes; D016133:Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D009838:Oligodeoxyribonucleotides