A common idiotype was defined by a rabbit anti-idiotypic antiserum generated against human antibodies to hepatitis B surface antigen (anti-HBs). This idiotype was detected in anti-HBs from eight different individuals who had been previously infected with hepatitis B virus and is referred to as the CHBs idiotype. The CHBs idiotype was also identified in sera from rabbits, mice, guinea pigs, swine, goats and chimpanzees that had been immunized with hepatitis B surface antigen (HBsAg). Expression of the CHBs idiotype in sera from other species was associated with anti-HBs molecules. These results suggested that variable-region genes responsible for the CHBs idiotype have been conserved through long periods of evolution. It was noteworthy that the CHBs idiotype was not detected in the sera of a nonmammalian species, chickens, that had been successfully immunized with HBsAg.
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.
Anti-idiotype reagents that recognize a common idiotype associated with the combining site of antibodies to hepatitis B surface antigen (anti-HBs) were used to manipulate the immune response to hepatitis B surface antigen in BALB/c mice. The injection of antibodies to the idiotype before antigenic stimulation resulted in an increase in the number of cells secreting immunoglobulin M antibodies to hepatitis B surface antigen. Anti-HBs-secreting cells were also induced by administration of antibodies to the idiotype without subsequent antigen exposure. These findings indicate that the immune response to hepatitis B surface antigen in mice is regulated through an idiotype-anti-idiotype network.
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