THE HSD-HCG VACCINE PREVENTS PREGNANCY IN WOMEN - FEASIBILITY STUDY OF A REVERSIBLE SAFE CONTRACEPTIVE VACCINE

PROBLEM: To develop a vaccine for reversible control of fertility in w omen. MATERIALS AND PROTOCOLS: Purified beta subunit of hCG annealed t o purified alpha subunit of ovine LH linked chemically to tetanus toro id (TT) and diphtheria (DT); vaccine employed at 300 mu g gonadotropin equivalent per injection adsorbed on alhydrogel with 1 mg SPLPS added in the first injection; Phase I safety trials in 47 women with electi ve tubal ligation; Phase II efficacy studies in 148 prover fertile wom en (2 children), sexually active, desirous of family planning using IU D; IUD removed when anti-hCG titres exceed 50 ng/ml hCG bioneutralizat ion capacity; boosters given to maintain above threshold antibody leve ls; post coital tests conducted in 8 volunteers; sera of protected wom en analysed for immune-determinants recognized by competitive enzyme i mmunoassays employing a panel of monoclonal antibodies and by direct b inding to synthetic peptides; recombinant vaccines expressing beta hCG as a secreted product or as a fused protein anchored on membrane. RES ULTS: Immunization was well tolerated with no significant changes in e ndocrine, metabolic and hematological indices. Normal ovulatory cycles were maintained as indicated by menstrual regulation. The vaccine was highly effective in preventing pregnancy (1 pregnancy in 1224 cycles) at and above antibody titres of 50 ng/ml. Antibodies declined in cour se of time in absence of boosters, with conceptions occurring below 35 ng/ml titres indicating regain of fertility. Ability of antibodies to prevent pregnancy was confirmed by post coital tests. High avidity (1 0(10) M(-1)) and other characteristics of antibodies generated by the vaccine are described and compared with those induced by two other hCG vaccines having undergone Phase I trials. The antibody response of th e HSD vaccine in humans is characterized predominantly to an epitope r ecognized by the monoclonals 206 and P3W80. The antibodies had low or no reactivity with the carboxy terminal peptide and 38-57 region pepti de. Live recombinant vaccines expressing beta hCG as a membrane anchor ed peptide generated antibody response to hCG in all animals following a single injection. CONCLUSIONS: Reversible fertility control is feas ible with the HSD-hCG vaccine without impairment of ovulation or distu rbance of menstrual regularity. Suggestions have been made for further optimization of the vaccine, which include replacement of TT and DT b y a panel of T non B determinants communicating with the entire MHC sp ectrum and development of recombinant vaccine expressing beta hCG alon g with membrane anchored carrier.