We identified a 685-nucleotide gene fragment that codes for the transmembrane and cytoplasmic domains of glycoprotein of the LEP strain rabies virus and carried out experiments designed to express a novel fusion protein on the cell surface. The cDNA encoding the membrane anchor sequence was fused in the correct reading frame to the 3' end of the cDNA encoding the beta subunit of human chorionic gonadotropin (beta(h)CG), a secretory glycoprotein that is used as an antigen for a contraceptive vaccine being developed in our laboratory. The fusion gene cassette was placed under the control of a vaccinia virus early promoter and cloned in a host-restricted fowlpox viral vector. The recombinants, when used to infect mammalian cells that do not allow the replication of fowlpox virus, expressed the N-terminal 135 amino acid residues of beta(h)CG anchored in the cell membrane by the 75-amino acid C-terminal sequence derived from rabies virus glycoprotein. This hybrid protein is correctly processed post-translationally and transported efficiently to the plasma membrane of non-permissive cells such that the anchored beta(h)CG molecule retains the correctly folded native antigenic epitope(s).

Vaccines for control of fertility are likely to have an important impact on family planning methods. They are designed to act by mobilization of an internal physiological process and do not require external medication on a continuous basis. A number of birth control vaccines are at different stages of development, the most advanced being a vaccine inducing antibodies against human chorionic gonadotrophin (hCG). This vaccine consists of a heterospecies dimer (HSD, beta hCG associated with alpha-subunit of ovine luteinizing hormone, beta hCG:alpha oLH) linked to tetanus toxoid (TT) or diphtheria toxoid (DT) as carriers. The vaccine has recently passed an important milestone; it has completed the first leg of phase II efficacy trials. Women of proven fertility leading active sexual life were protected from becoming pregnant at antibody titres > or = 50 ng of hCG bioneutralization capacity per ml. This vaccine has previously been demonstrated to be reversible in its effect. It is free from any notable side-effects on endocrine, cardiovascular and other body functions. Ovulation was not disturbed and menstrual regularity was maintained. A logistic disadvantage of the present vaccine is the requirement for multiple injections. This is expected to be overcome by encapsulation of the requisite doses of the vaccine in biodegradable microspheres, which could be given at a single contact point for sustained antibody titres lasting over a year. A live recombinant vaccine has also been made that elicits high anti-hCG titres in monkeys for nearly 2 years following primary immunization and a booster at 8-9 months.

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