This post initially appeared on Science Blogs

I promise, this will be my last semen post for a while.

I've talked about allergy to semen.

I've talked about allergens in semen.

And I've talked about autoimmunity to semen.

All of these are problems, leading to discomfort or infertility. But what if those problems could be leveraged for our benefit?

[Source: These drawings were made by Antonie von Leeuwenhoek - the first man to view sperm cells under a microscope]

Using the immune system as a contraceptive is not a new idea. In 1899, Karl Landsteiner

and Elie Metchnikoff (both of whom would later win Nobel Prizes) independently demonstrated that injection of sperm into animals could produce an antibody response, and others later demonstrated that this could lead to infertility. The first study in humans was in 1929, and a patent for a "spermatoxic" vaccine was filed in 1937.

Since then, there have been a number of advances in the using the immune system to intentionally induce infertility. But you may be asking yourself, "Why bother?" After all, hormonal birth control is safe and highly effective. But there are a number of problems associated with hormonal birth control that could be addressed by a vaccine. And I'm not even talking about side effects:

An estimated 80 million women have unintended/unwanted pregnancies worldwide annually, and 45 million of these end in abortion. In the United States, each year, half of all pregnancies are unintended, which results in over 1 million elective abortions. In over half of these unintended pregnancies, the women were using some type of contraceptive.

Another major problem is access. In the developing world, where one might argue family planning is most needed, medical services are not always readily available. Since hormonal birth control requires consistant use, and access to a daily pill or monthly shot just won't cut it.

This calls for a better method of contraception that is acceptable, effective, and available both in the developed and developing nations. It should be non-steroidal, non-barrier, non-surgical, intercourse independent, and reversible. Contraceptive vaccines (CV) have been proposed as valuable alternatives that can fulfill most, if not all, of the properties of an ideal contraceptive. Because of their high target specificity, long-term action, low cost, and without any side-effect, the development of CV is indeed an advancement in the field of contraception. As the developed and most of the developing nations have an infrastructure for mass immunization, constructing vaccines for contraception is an exciting proposition.

There are several approaches to a contraceptive vaccine, all involving different targets. Some target certain hormones, which would prevent the production or development of sperm/eggs. However, as many of these hormones are required for non-reproductive processes, these vaccines can have unwanted side effects. As an example, a protein called GnRH triggers the release of other hormones necessary for the development of sperm and eggs, and can be effectively targeted by a vaccine. However, loss of these hormones also leads to impotence, and so is essentially off the table for human use (though it is currently being used as a non-surgical way to sterilize pets and feral animals).Another target of vaccines is HcG, which is expressed on fertilized embryos. The selectivity of this protein is its strength - since there are no targets except those associated with pregnancy, the side effects should be minimal. However, scientists have had trouble achieving an effective immune response against this protein**. Plus, it leaves the burden of birth control on women (since an immune response against an embryo wouldn't mean much in a man).By contrast, a vaccine against sperm could solve many of these problems; it could be effective in both men and women (blocking production in men or stopping fertilization in women). And the inheritant immunogenicity of sperm that I've mentioned earlier means that it shouldn't be hard to generate an effective immune response. Indeed, several groups are currently working on making this a reality. The main drawback of this approach that I see is lack of intentional reversibility. So far, in all of the human trials dating back to 1929, the effect of the vaccine was not permanent - antibody titers against the sperm waned over time, and fertility returned - but turning the immune system off should the patient want to have a baby is not controllable. In principal, it should be possible to target only the B-cells making anti-sperm antibodies for destruction, but until such a process is validated, this method will not be a tenable option for anyone that may want to get pregnant at a later time.In any case, it seems we're stuck with hormonal and barrier methods for now, but I think this is a great example of leveraging the power of the immune system in ways nature never intended.


*It should be noted here that in many parts of the developing world, anti-vaccineconspiracy theories, which postulate that polio vaccination campaigns are really a secret plot to sterilize the population, have taken root. Should and actual contraceptive vaccine campaign ever occur in the developing world, folks had better make damn sure the intentions are out in the open.**Since the date of the review that I'm reading, there have been some advances on this front, but still no effective vaccine in humans.

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