Fertility regulating and immunotherapeutic vaccines reaching human trials stage

Abstract

The progress and current status of vaccines which induce antibodies against human chorionic gonadotrophin (HCG) and luteinizing hormone-releasing hormone (LHRH) are reviewed. Three vaccines devised against HCG have undergone phase I clinical trials documenting their safety, and reversibility. One of these, the heterospecies dimer (HSD)-HCG vaccine has also completed phase II efficacy trials in sexually active women of proven fertility. Immunization with the vaccine prevents pregnancy, as long as the antibody titres remain > or =50 ng/ml HCG bioneutralization capacity. There is no disturbance of menstrual regularity and women continue to ovulate normally. The antibody response is predominantly against an epitope in the core part of beta-HCG. Fertility is regained at titres <35 ng. These observations have laid the scientific foundations of a birth control vaccine. Research suggests the feasibility of making a cost-effective recombinant vaccine. The carriers tetanus toxoid (TT) and diptheria toxoid (DT) can be advantageously replaced by peptide determinants recognizing T, not B cells. In addition to optional fertility control, HCG vaccines may have tumour growth inhibition potential in lung cancers which produce HCG. The vaccine against LHRH can be used in both males and females. As it is a structurally conserved molecule, the same vaccine is applicable to both animals and humans. Antibodies against LHRH block the generation of gametes and sex steroids, with the result that the vaccine can be used for fertility control (domestic pets, prolongation of lactation amenorrhoea); as well as for sex hormone-dependent cancers. Phase I/phase II clinical trials have been conducted with the LHRH vaccine in advanced metastazing carcinoma of prostate patients with encouraging results. Bioeffective monoclonal antibodies have been developed against both LHRH and HCG. These can be 'humanized' and produced cost-effectively in bacteria and plants, thus paving the way for passive use of such antibodies for immunotherapy of cancers and fertility control.