RECOMBINANT FERTILIZATION ANTIGEN-1 CAUSES A CONTRACEPTIVE EFFECT IN ACTIVELY IMMUNIZED MICE

Recombinant (r) fertilization antigen (FA)-1 was investigated for its immunocontraceptive effect using the mouse as a model. Active immuniza tion with the murine rFA-1 antigen raised high antibody titers in all the immunized mice (n = 16 in two trials); these titers were long last ing and reached preimmunization levels by the 255th day. There was a s ignificant (p < 0.0001) effect (64% reduction in trial I and 70% reduc tion in trial II) in fertility of immunized animals compared to PBS-co ntrol animals (n = 22 in two trials). The effect on fertility was reve rsible. When the antibody titers declined to control levels, all the a nimals conceived and delivered healthy babies without a significant (p > 0.05) effect on the litter size compared to that of controls. There was a significant (p = 0.025) correlation (r = 0.76) between the redu ction in fertility and the circulating rFA-1 antibody titers. Anti-rFA -1 antibodies from immunized mice, and not the immunoglobulins from th e PBS-control mice, significantly (p < 0.001) blocked murine sperm bin ding to zona pellucida and in vitro fertilization of murine oocytes. I n a Western blot procedure, the anti-rFA-1 antibodies specifically rec ognized the protein band of similar to 47 kDa (dimeric form of cognate FA-1 antigen) only in the protein extract of testes and not in the ex tracts of somatic tissues tested, namely kidney, liver, intestine, spl een, muscle, heart, lung, brain, and ovary. In conclusion, our data in dicate that active immunization with rFA-1 antigen induces a strong an d sperm/testis-specific antibody response that causes a reversible inh ibition of fertility by affecting sperm-zona binding and the fertiliza tion process. These findings suggest that rFA-1 antigen is an exciting candidate for the development of a contraceptive vaccine.