Immunocontraception Postgraduate Research Training in Reproductive Health Faculty of Medicine, University of Yaounde Pierre Marie Tebeu (M.D) [email protected] 1 Specific objectives z Definition z Identify who will be able to use immunocontraception z Justify the development of immunocontraception z Identify the advantages of immunocontraception z Identify the disadvantages of immunocontraception z The target of immunocontraceptive agents z The mechanism of action of immunocontraceptive agents z Identify the actual limits of immunocontraception 2 What is Immunocontraception? z Immunity = Body defense mechanisms z Contraception = Protection against unplanned pregnancy z Immunocontraception = The use of body defense mechanisms to provide protection against an unplanned pregnancy 3 Distinguish anti-disease vaccine # Immunocontraception z Anti-disease vaccine. z Immunocontraception z Protection against disease z Protection for pregnancy z Target is foreign pathogen z Target is self cells/hormon z Immunity often boosted by z Vaccine induced immunity exposure to pathogens z Immunity is not boosted z Long acting vaccine by re-exposure to antigen induced immunity z Long acting vaccine induced immunity Why the Immunocontraception? (1)-Unplanned pregnancies z New pregnancies/year: 210 millions (Aitken 2002). z 38% are unplanned. z 22% are aborted 5 Why the Immunocontraception? (2)-population overgrowth z By year 2000: 6 billions z By year 2004: 6.4 billions z By year 2050: 10 billions z 97% worid growth is in developing countries z This overgrowth will worsen the impact of many social, ecologic , economic and medical trends 6 Why the Immunocontraception?(3) z To provide an additional long acting option to family planning users z Recourse to the self immune system, easily use 7 Why the Immunocontraception? (4)-To diminish whilelife animals z As wildlife habitat continues to diminish and animals adapt to living near us, we have a practical and perhaps a moral obligation to find new management solutions Why the Immunocontraception? (5)-A mean to control wildlife population Examples of biocontrol approach z Interfering with fertilisation z Preventing development of embryo z Preventing the development of the reproductive system z Interfering with lactation Target of immunocontraceptive agents z GnRH z FSH z Steroids z Gametes z hCG 11 Common mechanism of action z Induction to the body the production of antibodies against it's own reproductive proteins z This would block the action of the reproductive proteins or destroy them Various stages of clinical testing (1)-Phase I study z Safety of the preparation in human z About 50 subjects allocated sequentially to increase the dose. z Lasting 1-2 years Various stages of clinical testing (2)-Phase II study z The efficacy of selected dose z About 100-200 subjects allocated z Lasting 2-3years Various stages of clinical testing (3)-Phase III study z The safety and efficacy z About 1000 subjects randomized in groups z Lasting 4-6years GnRH immunocontraception z Immunological castration ( Preclinical trials) z Prolong anovulation in postpartum women (Clinical trials ongoing) z Hormonal suppression in man with prostatic cancer (Clinical trial) 16 FSH immunocontraceptives z Immunogenesis + effect on spermatogenesis (Phase I clinical trial) z Results: .Some reduction in sperm number and motility .No significant effect on semen parameters .Preparation was weakly immunogenic 17 Steroid immunocontraceptives z Only preclinical trials are conducted z No clinical trial conducted to date 18 Gamete immunocontraceptives (sponsor-agent) z Only preclinical trials are conducted z Sponsor: HSUS (Human Society of the United States) z Agent: Zona pellucida proteins (PZP) 19 Gamete immunocontraceptives (Mechanism of action) z Action of PZP:Spay-VacR:form of immunovaccine z After injection of pig PZP to the animal, that animal body produces antibodies to it. These antibodies attach to female ZP protein, then prevent sperm from attaching z No clinical trial conducted to date 20 hCG immunocontraceptives studies z Many preclinical trials completed z Many phase I, II clinical trials completed z Phase III clinical trials are ongoing 21 hCG immunocontraceptives sponsors z National Institute of Immunology, Delhi, India. z Population Council, New York, USA. z Word Health Organization, Geneva, Switzerland. 22 hCG immunocontraceptives sponsor and specific agent used: 1-National Institute of Immunology India z Agent: Heterospecies dimer of Beta-hCG .alpha-oLH, .tetanus toxoid, .dipthteria toxoid, .LPS, .alum z Many phase I, II clinical trials completed z Phase III clinical trials are ongoing 23 hCG immunocontraceptives sponsor and specific agent used: 2-Population Council, New York, USA z Agent: -beta hCG -tetanus toxoid, -alum. z Many pnase I, clinical trials completed 24 hCG immunocontraceptives sponsor and specific agent used: 3-World Health Organization, Geneva, Switzerland z Agent: .hCG specific peptides, .diptheria toxoid, .muramyl dipeptide, .slow-release copolymer matrix, .water-in-oil emulsion vehicle z Many phase I, clinical preparation 25 Specific needs for Immunocontraception z Clarification of mechanisms of action z Reversal of contraceptive effect on demand z Assessment of long term safety z Assess the acceptability z Clarify the social, economic and political issue 26 Conclusion z Immunocontraception is a long term family planning option for tomorrow z But we need to keep its development in mind 27.