The quest for safe and effective birth control strategies has been a long-standing matter in society, with the earliest methods conceived in ancient times. Women in ancient Egypt had brewed their own potion, consisting of honey, dates, and acacia, which they believed would be toxic to sperm. The earliest “condom” was documented in 3000 BCE, where Pasiphae, the wife of King Minos of Crete, used a membrane derived from an animal bladder to protect her from the “scorpions and serpents” in her partner’s semen. Nowadays, with the world’s population exponentially growing and the increased desire for family planning, the importance of accessible contraceptive use becomes paramount. This is especially true for women, where highly effective methods of birth control with minimal side effects are lacking.
Millions of women, especially in developing countries, have an unmet need for contraception options; inadequate contraception use is an important contributor to unintended pregnancies and induced abortions. Unsafe abortions are still a major cause of maternal mortality and severe health complications worldwide, with 95% of deaths occurring in low- to lower-middle-income countries. For example, public hospitals in Ogun, Lagos, and the Federal Capital Territory, Nigeria, spend over 800,000 USD annually on treating abortion-related complications. In countries where the population is growing at an alarming rate, such as India, coercive government policies intended to control population growth particularly disadvantage the poor. In the past, these policies disproportionately relied on the sterilization of poor women, rather than providing them with modern family planning methods or targeting the root causes of unintended pregnancies, such as poverty, illiteracy, or gender inequality.
Lastly, due to cultural beliefs that stigmatize unintended pregnancies, the decision to perform an abortion, or not, can weigh heavily on an individual’s feeling of social acceptance. Whether resulting in childbirth or risky abortion, unintended pregnancies may act as a barrier to women pursuing education or professional careers, limiting opportunities for them to climb the social ladder. Therefore, improving access to safe, efficacious, low-cost, and acceptable birth control measures is not only a vital public health intervention, but is also important for promoting gender equality and diminishing poverty.
Current contraceptive methods, some of which are highly efficacious, still have much to improve upon with regard to accessibility, acceptability, and safety. For example, while hormonal methods work well to prevent pregnancy in women, many suffer from side effects like headaches, mood swings, and risk of blood clots. Non-hormonal intrauterine devices can be used as a long-term alternative, but insertion can cause pain, bleeding, or damage to the uterus, especially when healthcare facilities in low-income countries lack training to perform this procedure. For men, vasectomy and condoms are the main contraceptive methods used, as hormonal methods also have side effects and mixed efficacy. Meanwhile, vasectomy is an expensive surgical procedure, with potential post-surgical complications. Condoms for both men and women, although widely accessible and providing the added benefit of protecting against sexually transmitted diseases, have a relatively lower efficacy as contraceptives due to user-dependent errors. Finding a safe, convenient, effective, and reversible contraceptive method is a highly coveted goal to tackle this unmet clinical need.
Immunocontraceptive vaccines are a promising strategy to overcome some of the hurdles that current contraceptives face. Immunocontraception leverages an individual’s own immune system to provide protection against components of the reproductive and fertilization process, much like traditional vaccines protect against viruses or bacteria. Rather than training the immune system to recognize viral or bacterial proteins, these “vaccines” introduce a specific protein component from the reproductive process, which causes immune cells to recognize and neutralize that component before it has a chance to contribute to an unintended pregnancy.
Conceptually, immunocontraceptives can intervene at multiple points of the reproductive process, from targeting sex hormones and gametes (the ova and sperm) to structural components of the male and female reproductive tracts, and even to molecules in the brain that signal the production of sex hormones. While many of these vaccines show promise in laboratory animals, only a few candidates have entered clinical trials. One of these candidates targets human chorionic gonadotropin (hCG), a protein that is conveniently only produced by a developing embryo and so only appears in the bloodstream following fertilization. hCG is released by an embryo to stimulate the corpus luteum in the ovary, which itself produces key hormones that allow pregnancy to take place. If hCG is cleared by immune cells, the corpus luteum would degrade, and a normal menstrual cycle would occur. Since this takes place very early on, the pregnancy would likely go completely unnoticed. Vaccines targeting hCG are furthest along in development, having successfully completed Phase I and II clinical trials that test safety and efficacy. Other vaccine candidates have also entered early clinical trial stages; these candidates target hormones required to produce sperm and ova, offering contraceptive options for both males and females.
Unlike traditional vaccines, the aim of immunocontraception is to provide long-term, but not permanent, protection against unintended pregnancy. Since the intention is also to target a healthy, naturally occurring cell or hormone in the body, immune cells must be mobilized in such a way as to not harm their host, or they would run the risk of promoting autoinflammatory or autoimmune diseases. As with other vaccines, efficacy can also vary from person to person depending on immune status. Compared to ancient methods, such as the condom, immunocontraceptive development is still in its infancy; research still needs to be done on the safety of long-term usage, acceptability and integration of the approach across different cultural and socio-political groups, defining specific biological mechanisms, and, perhaps most importantly, ensuring that the contraceptive effect could be reversed when required.
While its impact on society has yet to be seen, the objective of immunocontraceptives is to provide an efficacious, low-cost, and accessible alternative to existing contraceptives, while also lacking the often-debilitating side effects of hormonal therapies. Immunocontraceptives would not require complex surgical procedures and, therefore, staff in low-income countries can easily administer treatment and provide a feasible alternative to coercive sterilization tactics employed by some governments to curb population growth. Ultimately, immunocontraception will increase the arsenal of family planning tools available to couples, while also protecting women from the health-related and social implications of unintended pregnancies.
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