Failure to detect infectious hepatitis B virus using high dose safety test for hepatitis B vaccine.
One hundred milliliters of an inactivated hepatitis B vaccine (20 microgram/ml) were inoculated intravenously into two colony-born infant chimpanzees. Immediately thereafter each received hepatitis B virus from a documented infectious inoculum intravenously at a separate site. Neither chimpanzee developed elevation of aminotransferase levels, hepatitis B surface antigen (HBsAg), or antibody to hepatitis B core antigen during six months of evaluation, the duration of the currently recommended safety test. Both chimpanzees developed antibody to HBsAg beginning 8 and 9 weeks, respectively, after inoculation. The administration of a large intravenous quantity of vaccine antigen thus appeared capable of masking or preventing infection by simultaneously administered hepatitis B virus. This study suggests that a chimpanzee safety test for hepatitis B vaccine should not employ large quantities of vaccine antigen, since such a safety test may fail to detect small amounts of residual infectious hepatitis B virus.
D000818:Animals; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000032:analysis; D006515:Hepatitis B virus / Q000276:immunology*; D007275:Injections, Intravenous; D002679:Pan troglodytes; D012449:Safety; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D006510:Hepatitis B Antibodies; D014613:Vaccines, Attenuated; D014765:Viral Vaccines