One week from today, on Sept. 7, statesmen and scientists from allover the world will gather in Cairo to confront the planet's twin crisesof poverty and birthrate. Contraception figures high on the agenda ofthis week-long International Conference on Population andDevelopment.India, with a 1990 population of 850 million, is projected to reach 899million by next year, second only to China's 1995 estimated 1.184billion. India's population is proliferating at a million new mouths amonth to feed. India, too, pursues one of the world's most advancedresearch efforts devoted to developing effective, humane methods ofbirth control.The internationally acknowledged leader of this research movement isG. P. "Pran" Talwar, who head's the National Institute of Immunologyin New Delhi. Talwar leads a team of a dozen Indian investigators whoreport in yesterday's (Aug. 30) Proceedings of the National Academyof Sciences (PNAS) on "A vaccine that prevents pregnancy inwomen."Their still-experimental immunization construct, developed since the1970s, raises circulating antibodies that block a hormone essential forgetting pregnancy started. That hormone is human chorionicgonadotropin (hCG). It maintains proper levels of estrogen andprogesterone in early pregnancy, thus maintaining the placenta, whichrelays life from mother to fetus.As of August 1, 1993, with 1,224 menstrual cycles recorded in 148women who had received three primary injections plus booster shots,only one participant had become pregnant. Moreover, the vaccineproved to be reversible: when boosters were discontinued, andantibody levels declined, women regained their fertility, and conceived."This study," Talwar concluded, "presents evidence of the feasibility ofa vaccine for control of human fertility."His group's initial anti-pregnancy formulation consisted of the hCGalone as antigen; it proved weak, because women have a built-inimmunotolerance to the hormone. To beef up the vaccine'simmunogenicity, the team combined it with a subunit of ovineluteinizing hormone, which initiates pregnancy in sheep by inducingprogesterone.This laboratory-made heterospecies dimeric hormone recognizesreceptors on target tissues, so it generated a stronger immune responsethan hCG alone. Then to maximize this response, the team attached itsdual-species hormone to either tetanus or diphtheria toxoid carriers, foralternate vaccination.Volunteers Raised High-Avidity Antibodies to hCGBasic immunization in this latest version of the vaccine consisted ofthree basic injections, six weeks apart, followed by boosters every threemonths.As a result, 80 percent of the volunteers who took part in the large-scale contraceptive trial reported in PNAS raised high-avidityantibodies to hCG, above the titer of 50 nanograms per milliliter. Thiswas the critical cutoff level of efficacy; below 35 ng/mk, contraceptivecapacity fell off.Talwar's birth-control vaccine received its earliest clinical confirmationin Phase I trials with 16 women in Finland, Sweden, Salvador andChile, sponsored by the New York-based Population Council'sinternational contraceptive research committee. Besides inducing anti-hCG antibodies in all subjects, it found no abnormalities of ovulationor menstruation, and no symptoms of autoimmune disease, or othersignificant side effects."Nevertheless," the PNAS paper cautions, "the potential for tissuecross-reactivity needs to be considered as vaccine developmentproceeds." Also, the three-month period during which antibody titersbuild to protective levels "must be covered by a compatible companion[contraceptive] approach." n

-- David N. Leff Science Editor

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