Immunogenicity of a five-microgram dose of hepatitis B vaccine.

The immunogenicity of a 5-micrograms dose of vaccine (H-B-Vax, MSD) was evaluated in 50 young adults (17-19 years). Results were compared to our previous studies using similarly prepared vaccines using 20 micrograms and 10 micrograms per dose with the same trial protocol in a comparable population. Seroconversion rates for the 5-micrograms doses of vaccine were 80% after the first dose and 98% after the second dose. The remaining participants did not develop anti-HBs in the course of the trial. These results are not significantly different from those observed in the 10-micrograms and 20-micrograms studies. The increase of anti-HBs titers was slower for the 5-micrograms group. High geometric mean titers were observed after booster vaccination, but lower for the 5 micrograms (3,591 mIU/ml) than for 10 micrograms (9,277 mIU/ml) and 20 micrograms (12,975 mIU/ml) doses. It is concluded that 5-micrograms dose of the vaccine is effectively immunogenic for young adults.

Comparison of safety and immunogenicity of ADW and AYW hepatitis B vaccines.

The safety and immunogenicity of adw and ayw hepatitis B vaccines were compared in a double-blind randomized trial in Green Air Force recruits. One hundred and ten out of 240 eligible nonimmune recruits were randomly selected and allocated to the two vaccine treatment groups. Two 20-micrograms doses 1 month apart and a third 20-micrograms booster dose, at 6 months, were given intramuscularly. Severe local or general side effects were not observed. The frequency of mild side effects (local discomfort or pain, fever less than 37.5 degrees C, and malaise) was slightly higher than the adw than with the ayw vaccine. Antibodies developed earlier and in higher titers in adw vaccines. However, after the booster dose all ayw and all but one adw vaccines developed anti-HBs in almost similar titers. It is concluded that both vaccines are equally safe and immunogenic after administration of two doses at a 1-month interval followed by a booster dose at 6 months.

The effect of intradermal administration of Corynebacterium parvum on the immune response to hepatitis Bs antigen.

The immunopotentiating effect of the intradermal administration of a course of four doses (0.25 ml) of a standard suspension of killed C. parvum (2 mg/ml) was studied in a group of 10 asymptomatic chronic hepatitis B surface antigen (HBsAg) carriers, as well as in 11 persons with antibodies to HBsAg (anti-HBs) and six without HBsAg or anti-HBs. HBsAg, anti-HBs, and leukocyte migration inhibition (LMI) studies were performed in pre- and post-inoculation blood samples. C. parvum produced a substantial increase of anti-HBs titre in persons with preexisting anti-HBs. However, anti-HBs responses were not induced in carriers. HBsAg was not eliminated and its titre remained practically unchanged in carriers. These results support the hypothesis that in carriers the specific defect in the immune response to HBsAg possibly exists at the B cell level.

Geographic correlation between mortality from primary hepatic carcinoma and prevalence of hepatitis B surface antigen in Greece.

Average annual age-adjusted mortality rates per 100,000 from primary hepatic carcinoma (PHC) among males for 1971-1973 in the urban and rural areas of the 9 geographical regions of Greece were estimated. Hepatitis-B surface antigen (HBsAg) prevalence by region and area was evaluated in a sample of 22,844 Greek Air Force recruits from all parts of the country. Mortality from PHC was found significantly higher in urban areas (28-30 vs. 18-81) whereas prevalence of HBsAg was higher in rural areas (5-3% vs. 3-90%). Nevertheless further statistical analysis showed that there is a strong correlation between HBsAg prevalence and mortality from PHC, which is higher in rural (r = + 0-88) than in urban (+ 0-57) areas. The latter findings indicate that hepatitis B infection and PHC may be causally related.

Seroepidemiological study of HBV infections in Athens, Greece.

A seroepidemiological survey of a sample-roughly representative by age and sex - of 2744 persons of the Greater Athens area revealed that hepatitis B virus (HBV) infections are highly endemic in Greece. Hepatitis B surface antigen (HBsAg) was detected in 72(2-6%) of them. The subtype was identified in 70 of the 72 carriers, and 69 were ay; the other was ad. Determinant w was present in all 61 that were capable of being typed further, and a23y(w) was twice as common as a11y(w). Antibody to HBsAg (anti-HBs) was found in 514 (18-7%) persons. The prevalence of the HBsAg rose rapidly with age, reaching peak values (5-3%) at 20-29 years, while anti-HBs reached its highest value (42-1%) in older age groups (50-59 years). The frequency of HBsAg was significantly higher in males (3-4%) than in females (1-5%). The percentage of infected persons who become chronic HBsAg carriers (12-3%) was found higher than in other developed populations. It was also found higher in children (25%) than in adults (5-5%) and in males (14-6%) than in females (8-1%). These data indicate that HBV infection in early life is a major risk factor in the development of HBsAg carriers and support the hypothesis that males are more likely to become HBsAg carriers than females.

Epidemiologic study of the modes of spread of viral hepatitis in Greece.

We studied the possible correlation of VH morbidity or HBsAg carrier rate with the prevalence of malaria and enteric among the 50 geographical regions of Greece. Malaria was considered as an index of mosquito density and enteric as an index of the local hygienic conditions. Morbidity data on the studied reportable diseases for the period 1954-73 and the HBsAg carrier rate (4-7%) among 17,991 recruits of the Greek Air Force, coming from all the geographical regions of Greece, were used. The statistical analysis of our data showed that VH morbidity (which is mainly hepatitis A) is significantly correlated with enteric morbidity, while HBsAg carrier rate with malaria. Our data support the significance of the role of mosquitoes in the spread of HB at least under the prevailing conditions in Greece.

Incidence and nature of cytoplasmic hepatitis B antigen in hepatocytes.

Hepatitis B antigen (HB Ag) in the hepatocytic cytoplasm is detected by immunofluorescence after reaction with fluoresceinated antiserum to HB Ag or by electron microscopy as numerous 20- to 30-nm. tubular and circular structures in dilated cisternae of excess endoplasmic reticulum. On light microscopy, these hepatocytes can be recognized because their cytoplasm has a ground-glass appearance and stains with Gomori's aldehyde fuchsin. Aldehyde fuchsin-positive ground-glass hepatocytes were detected in all 14 asymptomatic carriers of HB Ag and in 16 of 60 HB Ag-seropositive patients with chronic hepatitis, but not in HB Ag-seropositive acute viral hepatitis or in various other HB Ag-seronegative liver diseases. These cells are helpful in identifying on light microscopy HB Ag carriers and a portion of patients with HB Ag-positive chronic hepatitis. Nuclear HB Ag did not stain with aldehyde fuchsin. Nucleic acids were not detected in the ground-glass cytoplasm by special stains at the light or electron microscopic level. We suggest that the tubular and circular structures in the hepatocytic cytoplasm are coat material of the hepatitis B virus or virally coded host cell reaction product rather than the complete hepatitis B virus.

Electron microscopy and immunoelectronmicroscopy of cytoplasmic hepatitis B antigen in hepatocytes.

The localization of hepatitis B antigen (HB Ag) and the nature of the virus-like particles in hepatocytes of patients with HB antigenemia are controversial. In many reports, numerous virus-like particles have been demonstrated in hepatocytic nuclei; the few reported in the cytoplasm are insufficient in number to explain the intense cytoplasmic fluorescence after staining with fluoresceinated antibody to HB Ag (HB Ab). We found numerous tubular and circular structures, measuring 20 to 30 nm in diameter, in the cisternae of the excess smooth endoplasmic reticulum (ER) of varying numbers of hepatocytes in 13 of 16 HB Ag carriers and in 4 of 9 patients with HB Ag-positive chronic hepatitis corresponding to cytoplasmic HB Ag-specific fluorescence. Direct immunoelectronmicroscopy using peroxidase-labeled HB Ab revealed that the intracisternal bodies and the surrounding membranes contain HB antigenic determinants. These bodies are an ultrastructural correlate of cytoplasmic HB Ag. It is suggested that they are virally coded coat material rather than the mature hepatitis B virus or its core.