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IgG subclass distribution of antibodies against human chorionic gonadotropin (hCG) and diphtheria toxoid (DT) was determined in the sera of women recruited into Phase II clinical trials of a beta-hCG based immunocontraceptive vaccine. Serum samples from 30 different individuals were analyzed. Anti-hCG antibody response was predominantly of IgG1 subclass, with a mean titer of 537.94 +/- 560 antibody units (AU). The other 3 subclasses showed considerably lower mean levels (IgG2, 16.46 +/- 8.33; IgG3, 3.22 +/- 8.48; IgG4, 56.65 +/- 82.60 AU). A good correlation was observed between the anti-hCG IgG1 antibody titers (r = 0.57, P < 0.01) and the bioneutralization capacity of sera. However, bioneutralization capacity of the sera from subjects capable of inducing IgG4 response was not significantly different from subjects not showing IgG4 antibodies. Similarly, a dominant IgG1 response was observed against diphtheria toxoid (DT) which has been used as one of the carrier proteins in the vaccine.

The immunological determinants on hCG, to which an antibody response is generated in women by the contraceptive HSD vaccine, were mapped by using a panel of anti-hCG monoclonal antibodies. Two types of inhibition enzyme immunoassays (EIAs) were used to analyze 126 serum samples from 18 subjects immunized with the vaccine and protected from pregnancy. Monoclonal antibody (MAb) 357-2, which recognizes beta-hCG loop peptide 38-57, did not inhibit significantly the binding of immune sera to hCG. Moreover, none of the sera reacted with this loop peptide in a direct binding EIA, suggesting weak immunogenicity of this epitope. All sera competed with MAb 206 and a preponderance of antibodies was seen against this epitopic region on beta-hCG. The antibody titers against the MAb 206 epitope showed a good correlation with the bioneutralization capacity of the sera throughout the course of immunization. These studies indicate the presence of an immunodominant antigenic determinant on hCG as recognized by the human immune system.