Spermistatics’ may lead to new contraceptives

While research is still in the early stages, scientists at the University of Virginia Health System’s Center for Recombinant Gamete Contraceptive Vaccinogens in Charlottesville have identified a class of molecules that may lead to new forms of contraceptives.

The scientists coined the word "spermistatic" in a just-published paper to indicate a class of molecules whose principal mechanism of contraceptive action takes place by agglutinating and coating sperm, rather than simply by direct membrane lysis, as is the case with detergent-based spermicides, says John Herr, PhD, center director and professor of cell biology at the university.1

Spermicides act by direct killing ("-cidal" activity), whereas a spermistatic may act by preventing the progression of sperm through the female tract and by blocking fertilization, even though the sperm may not be "dead" in a metabolic sense, Herr explains.

If such molecules could be proven safe and effective for human use, products using this novel technology would give women another option in female-controlled methods.

Spermicides have several advantages over other methods: They are controlled by women, have no systemic side effects, are available without prescription, and can be used with little advance planning, says Elizabeth Raymond, MD, MPH, associate medical director of the biomedical affairs division at Family Health International in Research Triangle Park, NC. However, according to the 1995 National Survey of Family Growth,2 spermicides are used by a very small percentage (1.3%) of women at risk for unintended pregnancy.

The reason for the low usage is not known, says Raymond. One possibility is that women may understand that spermicides are not as effective at preventing pregnancy as other contraceptive methods, or perhaps they are simply not as aware of this class of methods, she observes.

"Introduction of a new spermicide might result in increased awareness about spermicides in general," says Raymond. "A new product would be especially desirable if it were more effective than existing products."

Focus on sperm

University of Virginia researchers have discovered a unique carbohydrate epitope, sperm agglutination antigen-1 (SAGA-1), on the sperm surface, says Herr. The SAGA-1 epitope was present on all surface domains of the head and flagellum of the sperm, scientists report.

An extensive study of the tissue distribution of the SAGA-1 antigen revealed its specificity to the epididymis and sperm surface and revealed its complete absence in the female reproductive tract, Herr notes. This indicates that an antibody to SAGA-1 would not cross-react with female tract tissues, he explains.

"These properties, coupled to the need for new strategies for intravaginal contraceptives, led us to test if a miniantibody could be genetically engineered that would be active against the sperm surface and used as a topical reagent," states Herr.

The scientists developed a recombinant anti-sperm antibody (RASA), which they are now refining to render it theoretically less immunogenic in humans.

"It is not clear if RASA, which is based upon a murine immunoglobulin structure, will be seen as a foreign antigen by some women," says Herr. "To reduce this possibility, the framework regions of human immunoglobulins are being substituted for the murine framework regions of the RASA molecule."

The researchers are looking at the other half of the contraceptive coin and examining their SAGA-1 findings to develop better treatments for immune-induced infertility.3

Delivery system eyed

By binding to the sperm surface, RASA monoclonal antibodies inhibit sperm penetration into cervical mucus, scientists theorize.

University of Virginia researchers are collaborating with Columbia, MD-based Novavax to examine the company’s trilamellar liposomes as carriers for the new technology. The liposomes can be formulated as a cream or foam, says Herr. Preliminary studies have shown that this preparation inhibits sperm penetration into cervical mucus and immobilizes sperm over a wide range of pH concentrations.

References

  1. Norton EJ, Diekman AB, Westbrook VA, et al. RASA, a recombinant single-chain variable fragment (scFv) antibody directed against the human sperm surface: Implications for novel contraceptives. Hum Reprod 2001; 16:1,854-1,860.
  2. Abma JC, Chandra A, Mosher WD, et al. Fertility, family planning, and women’s health: New data from the 1995 National Survey of Family Growth. National Center for Health Statistics. Vital Health Stat 23 1997 May; (19):1-114.
  3. University of Virginia. University of Virginia Researchers find key to infertility problem. Press release. Charlottesville, VA; Aug. 5, 1999. Accessed at web: hsc.virginia.edu/newstips/Archives99/infertility.html.