Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
A vaccine against cervical cancer hit Page 1 of major newspapers and got top billing in network television newscasts last week. In a large-scale controlled clinical trial, the vaccine scored 100 percent efficacy in preventing the malignancy.
Cervical cancer ranks second as a cause of cancer-related mortality in women. More than 450,000 cases are diagnosed each year worldwide, resulting in nearly a quarter-million deaths. The sexually transmitted malignancy is spread by a potent carcinogenic variant of the human papillomavirus type 16.
A paper in the current New England Journal of Medicine (NEJM), reporting the unprecedented success of the cervical cancer vaccine, carries the neutral title: "A controlled trial of a human papillomavirus type 16 vaccine." Its principal investigator is Laura Koutsky, professor of epidemiology at the University of Washington's School of Public Health and Community Medicine in Seattle.
Using microbial or cellular expression systems, Merck Research Laboratories, of West Point, Pa., which funded the research, synthesized empty viral capsids, termed "virus-like particles," as antigenic targets for the immune defense mechanisms of vaccinees. Then, in their 16-center double-blind study, between October 1998 and November 1999, Koutsky and her co-authors enrolled at random 2,392 young women, 16 to 23 years of age, all of whom reported having had no more than five male sex partners during their lifetime. Of the total number of participants, 1,194 received three intramuscular injections of the virus-like-particle vaccine, given at day 0, month 2 and month 6. The other 1,398, controls, got placebo dummy injections.
The women were followed for a median of 17.4 months after completing the vaccination regimen. The incidence of persistent human papillomavirus (HPV-16) infection was 3.8 per 100 women-years at risk in the placebo group and zero per 100 in the vaccine contingent. That is, 100 percent efficacy. All 41 cases of HPV-16 infection, including nine cases of HPV-16-related cervical neoplasia, occurred among the placebo recipients.
The NEJM paper pointed out, "The scientific advance in 1991 that led to the successful HPV-16 prophylactic vaccine trial was the creation of papillomavirus-like particles in the laboratory. Virus-like particles are devoid of DNA and are therefore noninfectious. However, they mimic the natural structure of the virion and generate a potent immune response." It added: "The vaccine not only prevents the disease from developing, but also prevents its causative agent from residing in the genital tract where it can infect new sexual partners."
The paper concluded that "immunizing HPV-16-negative women may eventually reduce the incidence of cervical cancer." Koutsky observed, "More studies involving a larger group of women need to be done, but we are very excited thus far about the life-saving potential of vaccines to prevent cervical cancer."
Quest For Alzheimer Vaccine Runs Into Cerebral Hemorrhage In Weakened Blood Vessel Walls
Immunizing aged mice against a certain peptide helps clear their brains of damaging amyloid plaques, a hallmark of Alzheimer's disease (AD). However, Swiss scientists at the University of Basel report that the treatment aimed at AD vaccines also increases cerebral hemorrhaging.
Their paper in Science dated Nov. 15, 2002, bears the title: "Cerebral hemorrhage after passive anti-Ab immunotherapy." The authors studied passive immunization of APP (amyloid precursor protein) transgenic mice, a model that exhibits the age-related development of amyloid plaques and neurodegeneration as well as cerebral amyloid angiopathy, similar to that observed in the aging human AD brain.
Besides reduction of harmful amyloid, the immunization also induces increased microhemorrhages associated with amyloid-laden vessels. The authors suggest that this study provides important pointers for researchers seeking promising immunotherapies for the disease. At least 80 percent of people with AD, they note, have some related weakening of blood vessels in the brain, which in severe cases would make them poor candidates for this immunotherapy. They recommend that any future studies include mice with weakened blood vessels to ensure that the antibodies offer only the plaque-destroying benefits without the vessel-bursting danger.
As a potential mechanism, they propose that antibody binding to amyloid in the vessel wall triggers a local inflammatory reaction, which might be sufficient to destabilize the already weakened wall. "Although difficult to diagnose premortem," their paper concludes, "our results also suggest that the success of amyloid-beta immunotherapy may be improved by screening AD patients for the presence and severity of cerebral amyloid angiopathy before such therapies are undertaken."
Seven Or More Cups Of Java A Day Keep Insulin Needle Away, Reports Dutch Population Study
Can 17,111 Dutch men and women be wrong?
A survey of this adult population sample, aged 30 to 60, found that individuals who drank seven or more cups of coffee a day were 50 percent less likely to incur Type II diabetes mellitus than two-cup-a-day-or-fewer drinkers, who were at higher risk of diabetes. This counterintuitive finding is reported in The Lancet dated Nov. 9, 2002, under the title: "Coffee consumption and risk of type 2 diabetes mellitus." It takes account of confounding factors such as smoking, alcohol consumption and body mass.
"Higher coffee consumption," the paper reported, "was associated with male sex, a low educational level, a higher body-mass index, cigarette smoking, alcohol use, less leisure time physical activity, and a generally less favorable diet." It also made the point that "caffeine reduces sensitivity to insulin, which manages the metabolism of glucose."
The authors are at Vrije University in Amsterdam, the Netherlands, department of nutrition and health. Its senior author observed that "in view of the widespread use of coffee and the large health burden of Type II diabetes, our finding of an inverse association between coffee consumption and the risk of Type II diabetes could have important public health implications."