Bert L. Murphy

The Prevention of Hepatitis B with Vaccine: Report of the Centers for Disease Control Multi-Center Efficacy Trial Among Homosexual Men

A randomized, double-blind, vaccine/placebo trial of the Merck 20-micrograms hepatitis B virus (HBV) vaccine was done among 1402 homosexual men attending venereal disease clinics in five American cities. Vaccination was followed by only minimal side effects. Two doses of vaccine induced antibody in 80% of vaccine recipients. A booster dose 6 months after the first dose induced antibody in 85% of recipients and markedly increased the proportion of recipients who produced high antibody titers. The incidence of HBV events was markedly less in the vaccine recipients compared to that in the placebo recipients (p = 0.0004). Between month 3 and 15 after the first dose, 56 more significant HBV events (hepatitis, or hepatitis B surface antigen positive, or both) occurred in the placebo group while only 11 occurred in the vaccine group. Ten of the 11 HBV events in the vaccine recipients occurred in hypo- or nonresponders to the vaccine. This vaccine appears to be safe, immunogenic, and efficacious in preventing infection with hepatitis B virus.

e Antigen, Dane Particles, and Serum DNA Polymerase Activity in HBSAg Carriers

Sera of 103 carriers of hepatitis B surface antigen were assayed for e-antigen and anti-e. Twenty-four were e-antigen-positive, 31 anti-e-positive, and 48 had neither detectable (e-negative). Aminotransferases were elevated in 75% of the e-antigen-positive carriers compared with 25% of e-negative carriers (P less than 0.001) and 13% of anti-e-positive carriers (P less than 0.001). Serum DNA polymerase activity was significantly higher in the e-antigen-positive carriers than in carriers without e-antigen. Dane particles were shown in 10 of 12 carriers with e-antigen, compared with one of 12 e-negative carriers (P less than 0.0003) and none of 12 anti-e-positive carriers (P less than 0.00003). These results suggest that ongoing hepatitis B viral replication is more active in e-antigen-positive carriers than in carriers without e-antigen, a finding that may help explain the high prevalence of chronic active hepatitis described in these individuals.

Antiviral Effects of Virazole in Chronic Hepatitis B Surface Antigen-Seropositive Chimpanzees

Virazole (Ribavirin, ICN 1229), a broad-spectrum, antiviral chemotherapeutic agent was used to treat two adult chronically hepatitis B surface antigen (HBs Ag)-seropositive chimpanzees. No significant change in serum hepatitis B surface antigen was noted and no adverse reactions were observed. The role of viral replication in the chronic carrier state of hepatitis B is discussed.

Immunofluorescent Localization of Hepatitis B Antigens in Chimpanzee Tissues

Three chimpanzee chronic carriers of hepatitis B surface antigen (HBs Ag) were examined by immunofluorescent techniques to determine the localization of HBs Ag and hepatitis B core antigen (HBc Ag) in their tissues. All specimens were quick-frozen in liquid nitrogen and stored at -70degrees until sectioned. Frozen sections were prepared and stained for examination by fluorescent microscopy. For staining, anti-HBs and anti-HBc labeled with fluorescein isothiocyanate were used. HBs Ag was found in the liver of all three animals. In two animals which were necropsied, HBs Ag was detected in other tissues, e.g., lymph nodes, spleen, and kidney. Specificity of these tests was demonstrated by blocking with purified HBs Ag. Examination of various tissues revealed HBc Ag only in the liver. 32 samples of liver, from different sites from one chimpanzee, were examined and all were positive for both HBs Ag and HBc Ag. The finding of HBc Ag only in the liver further supports the assertion that the liver is the sole site of replication of hepatitis B virus in chronic carriers.