Polypeptide micelles with relative molecular weights of 25,000 (p25) and 30,000 (gp30) daltons were prepared from native 22-nm hepatitis B surface antigen (HBsAg) particles. This p25/gp30 complex was alum-adsorbed, and three dosage levels (20 micrograms, 4 micrograms, and 0.8 micrograms) were administered at 0, 1, and 6 months to 51 human volunteers. Local and systemic reactions were clinically insignificant, and all vaccinees seroconverted, regardless of dose. As anticipated, antibody responses diminished as the dosage was reduced. Seroconversion rates and geometric mean antibody levels for the 20 micrograms dosage group were significantly better than those observed with a commercial vaccine and were comparable to those achieved after immunization with 40 micrograms of the intact 22-nm particles used to prepare the polypeptides. By 2 weeks, an anti-HBs response was elicited in 80% of the group receiving 20 micrograms of the polypeptide vaccine. This rapid response to immunization may be particularly beneficial for postexposure prophylaxis where the early development of immunity is advantageous.
Three groups of Copenhagen municipality male employees-77 sewer workers, 81 gardeners, and 79 clerks-matched for age and duration of employment, were studied for clinical and serological evidence of infection with viral hepatitis types A and B and pathogenic leptospires. "Antibody against hepatitis A virus" (anti-HAV) was found significantly more often among sewer workers (80.5%), than among gardeners (60.5%) or clerks (48.1%). The anti-HAV prevalence rates correlated with age rather than duration of employment. Of all the 11 cases of jaundice reported, only 3 cases (sewer workers) occurred while employed for the city. One case of the 11 resulted from leptospirosis. Anti-HAV was detected in the other 10 subjects and was assumed to be of etiological importance. Hepatitis B serological markers were similar in each group. It is concluded that exposure to metropolitan sewage provides a limited risk of enteric infections, such as hepatitis A, while the hepatitis B virus apparently is not successfully transmitted by this route.
The morphological forms of hepatitis B antigen (HBsAg) present in an HBsAg-positive plasma (15–25 nm spheres, filaments 20–22 nm in diameter and 80–300 nm in length, and 42 nm Dane particles) were isolated and characterized biophysically. The HBsAg in this plasma was fractionated into five distinct populations, containing predominately 15–19 nm spheres, 20–22 nm spheres, 20 × 300 nm filaments, a mixture containing 23–25 nm spheres and rare filaments, and 42 nm Dane particles, respectively. These populations were labeled with 125I and electrofocused in a pH ampholyte gradient. Each population had a distinct isoelectric pH with values ranging from 3.65 to 4.70. Sodium dodecyl sulfate polyacrylamide gel electrophoretic analysis of each of the above labeled populations revealed the presence of 7, 10, 9, 5, and 9 polypeptides, respectively. The population containing predominately 23–25 nm spheres failed to react with antibody specific for HBsAg and probably was composed of inner cores of the Dane particles.
The purification is described of liver-derived hepatitis B core antigen (HBe Ag) from human hepatocytes demonstrating only intranuclear particles by electron microscopy. The purified preparation contained 5 × 10u particles per ml. The particles were mono-dispersed and relatively free of background material. DNA-dependent polymerase activity was present and had greater activity than an equal number of cores derived from Dane particles isolated from plasma. Specificity of the polymerase reaction was confirmed by precipitation of the activity with specific anti-HBc antiserum. A proportion of the liver-derived core particles was nonreactive for DNA polymerase activity. The polymerase-positive population of particles had a larger size than the polymerase-negative population of liver-derived cores as evidenced by gel filtration in Sepharose 4B.
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