Another major difference is that traditional vaccines are also based on, and directed against, foreign antigens contained in the disease-causing micro-organism; in contrast, antifertility immunization is directed against isologous antigens from the egg, sperm, or certain reproductive hormones. Since isologous antigens may not be as immunogenic as foreign antigens, development of sustained immune responses to them may be difficult, owing in part to mechanisms of immunologic tolerance.

Finally, the ideal traditional vaccine confers long-term protective immunity, usually aided by boosting throughout the lifetime of the individual as a result of exposure to the natural antigen. Because it will be generally desirable for an immunocontraceptive to be reversible, the immunity induced should be of relatively short duration, that is, measured in months or a few years, and should not be boosted naturally by exposure to the target antigen; in other words, insemination should not boost a sperm-based immunocontraceptive.

The Pathway to Development of an Immunocontraceptive

The pathway for development of an immunocontraceptive follows a series of steps not unlike those followed in traditional vaccine development. These include: (1) fundamental discovery and characterization of appropriate immunogens derived from reproductive hormones and/or from the sperm, egg, egg investments, conceptus, or accessory reproductive organs; (2) development of methods for producing the immunogens to high standards of purity through (a) genetic engineering of genes encoding specific immunogens, (b) peptide syntheses, or (c) isolation of the antigen from natural sources; (3) production and purification of immunogens under good laboratory practices (GLP); (4) formulation of immunogen doses; (5) small animal and primate testing of immunogen formulations for immunogenicity, safety, and efficacy; (6) evaluation of mechanisms of immunogen action; (7) human trials for immunogenicity, safety, and efficacy, using formulations produced under good manufacturing practices (GMP); and (8) development of diagnostics to monitor infertility status in recipients of effective immunogens.

The first step—discovery and characterization of immunocontraceptive components—is perhaps the most complicated; it is also the stage at which many research projects currently stand. This step is subdivided into several milestones: (1) definition of events or processes in reproduction accessible to immune intervention; (2) identification of molecules (immunogens) whose elimination or neutralization will have an antifertility effect; (3) biochemical characterization of the structure of the immunogen(s); and (4) determination of whether the immunogen is unique to the reproductive event or tissue targeted and is absent in all other tissues.

In considering which molecules might be best for a contraceptive immuniza-



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