Renewed Hope

Despite questions, AIDS vaccine trial in Thailand spreads optimism

The long search for an AIDS vaccine has produced countless false starts and repeated failed trials, casting once bright hopes into shadows of disenchantment. The now familiar swings appeared in high relief last fall, with news of the most re¬cent, phase III trial in Thailand. Initial fanfare for a protective outcome gave way to disappointment after reanalysis showed that the protection could be attributed only to chance. But rather than dashing all hopes for an AIDS vaccine, the trial has heart¬ened some researchers, who see new clues in the battle against the fatal illness.

Costing $105 million and enrolling more than 16,000 sub¬jects, the Thai clinical trial was the largest AIDS vaccine test to date. It began in 2003, and early results released last September showed a slim but statistically sound benefit from the vaccine (a series of inoculations with drugs known as ALVAC-HIV and AIDSVAX B/E). But in October the full report, with various sta¬tistical analyses, was released in a Paris meeting to greater skep¬ticism. Specifically, 74 people who had received the placebo be¬came infected with HIV in the trial period, compared with the 51 people who became infected after receiving the vaccine, which makes for a protective effect of 31.2 percent. By including, how¬ever, the seven people who turned out to have had HIV at the start of the trial (two in the placebo group and five in the vaccine group), the effectiveness drops to 26.4 percent.

“There are still a huge number of uncertainties surrounding this trial,” says Dennis Burton, an immunologist at the Scripps Re¬search Institute in La Jolla, Calif. The subjects were in low- and moderate-risk groups, such as heterosexuals in monogamous relationships, rather than higher-risk groups such as intravenous drug users. “The numbers involved are small,” he adds, noting that sta¬tistically the protective effects could be the result of mere chance.

Still, many researchers are convinced that the trial has provid¬ed plenty of data to run with. “This contributes more evidence that an AIDS vaccine may be possible,” says Jerome Kim of the Walter Reed Army Institute of Research and co-author of the Thai trial study (which appeared in the New England Journal of Medicine in October). “We’ve taken a very small step,” Kim says. “It’s not a home run, but it opens the door to future work.” Vac¬cine proponents also point to the lessons learned from the failed Merck STEP trial. That vaccine test, halted in 2007, got only as far as phase II, but even so it did not leave researchers back at square one. It suggested, he notes, how some HIV strains could be blocked from infecting cells and offered data that could help in the interpretation of the Thai results. And a new analysis of the STEP trial, published last November in Proceedings of the National Academy of Sciences USA, provides a warning that the very vectors (adenoviruses, which are also employed in other vac¬cine development work) used to distribute the inactive HIV strains can actually make the immune system more vulnerable to infection by recruiting susceptible T cells to mucous membranes, where they are more likely to be infected during sexual activity.

Finding a vaccine has become an increasingly urgent under¬taking. Despite advances in therapies, HIV/AIDS is still incur¬able. Some 7,000 people worldwide contract HIV every day, and in the U.S. about 66,000 new cases are reported every year. Pre¬venting people from getting the virus would save millions of lives as well as greatly reduce health care costs associated with treat¬ment. A vaccine is “really the only optimal method of control for this dreadful pandemic,” says Raphael Dolin of the Beth Israel Deaconess Medical Center in Boston, who also wrote an edito¬rial accompanying the October paper.

Vaccines work by priming the immune system to recognize the target pathogen and attack it when detected. To fend off HIV, researchers introduced one vaccine (ALVAC) to induce a T cell response—thereby alerting the immune system—and another (AIDSVAX) later to spur an antibody response. In a previous phase III trial in intravenous drug users, AIDSVAX did not work. ALVAC, made by Sanofi Pasteur, had not been tested alone.
Using these two drugs together raised eyebrows in the vaccine community. Burton, along with 21 other researchers, co-au¬thored a 2004 paper in Science criticizing the choice to proceed to phase III with two vaccines that had never demonstrated any effectiveness alone. The trial collaborators, however, based their decision on previous research that a combined approach can boost helper T cell response better than a single vaccine.

Despite his earlier doubts, Burton has been inspired by the tri¬al results. “I feel more optimistic than I have in some time,” he says. Researchers are embarking on a host of new experiments to put the Thai findings to work. Volunteers from the trial will now be examined for immune responses—particularly neutral¬izing antibodies as well as cellular immunity in T cells—and some will get subsequent booster shots to see if protection can be sus¬tained. In the lab, researchers will try to re-create the Thai results in monkeys to validate a new animal model using multiple low doses. Other recent research has shown that the number of anti¬bodies needed to provide protection is lower than previously be-lieved, possibly making a vaccine easier to create.

Indeed, entirely new and promising candidates are now in an¬imal trials, including those by the U.S. military to address sub¬types A, C and E (rather than the Thai subtype B). Other orga¬nizations—including the International AIDS Vaccine Initiative (IAVI), the Karolinska Institute and the Swiss nonprofit Euro¬Vacc—and manufacturers also have other vaccines in the works. “The science is really moving,” says Seth Berkley, an epidemiol¬ogist at Columbia University’s Mailman School of Public Health and also president and founder of IAVI. All those confronting the epidemic hope that the momentum leads to a payoff sooner rath¬er than later.

Via: Radiology Technician

Source of Information : Scientific American January 2010

A surgical cure for diabetes?

The gastric bypass was originally developed as a treatment for obesity, but doctors have been amazed at how quickly it benefits people with type 2 diabetes sometimes within a matter of days or even hours. Some surgeons and learned societies have stopped calling the procedure obesity surgery and instead speak of metabolic surgery - referring to the fact that it can treat metabolic conditions such as diabetes. The radical idea now is that diabetes could be treated more routinely with this type of surgery. The key question is how overweight people have to be in order to qualify. At the moment the procedure is normally offered only to those with a body mass index of 35 or more (between 18.5 and 25 is considered normal), on the grounds that only at that weight will the clinical improvement outweigh the risks of surgery. But some doctors are lowering the BM I cut-off to 30 for people with diabetes. Some in South America have raised eyebrows by operating on diabetics with a BMI as low as 25. 'The excel lent results early after surgery before significant weight loss has led us to extend the surgical approach to people in whom significant weight loss is not required;' says Bruno Geloneze, an endocrinologist at the State University of (ampinas in Brazil. In May his team published a study of 12 diabetics whose BMI was between 25 and 30 - in other words, they were not obese, merely overweight. All experienced improvements in their symptoms after a bypass, and without unexpected complications. But only larger randomised trials will reveal if the benefits outweigh the risks. Francesco Rubino, a metabolic surgeon at (ornell University-New York Presbyterian Hospital, doesn't think surgery should automatically be offered to everyone with type 2 diabetes, but he agrees that using a cut-off for BMI is too crude a measure. "It should be based on more comprehensive considerations than BMI alone," he says.

Swine Ebola

A new reservoir for the infamous Ebola virus BY BRENDAN BORRELL

Don’t worry, it can’t hurt you— yet. Scientists have identified Reston ebolavirus— a member of the deadly Ebola group of hemorrhagic fever viruses—in domestic swine from the Philippines. Ebola is infamous for being highly contagious and causing death rates as high as 90 percent in some human outbreaks. This particular strain, first identified in monkeys in 1989 in a research laboratory in Reston, Va., is the only one of the family that is harmless to humans.

The outbreak in swine was discovered in July 2008 in the Philippines during an investigation of so-called blue ear disease in pigs, a respiratory condition that causes their ears to turn blue from lack of oxygen. Investigators there sent tissue and blood samples to Michael McIntosh of the U.S. Department of Agriculture at the Plum Island Animal Disease Center in Greenport, N.Y. McIntosh was surprised to find that the tissue samples also contained the Reston strain, which had not been previously identified in swine. His team also confirmed pig-to-human Ebola transmission, identifying six pig handlers whose blood tested positive for antibodies to the virus. The individuals showed no symptoms, indicating that this strain is as harmless to humans now as it was in 1989. Authorities in Manila had announced preliminary findings in January, and McIntosh’s details appear in the July 10 Science.

McIntosh says there are still a lot of unknowns, including how the virus was transmitted to the pigs and whether they show any symptoms independent of blue ear disease. He worries that the virus’s passage through pigs could enable it to mutate into something more dangerous. The research also raises the possibility that pigs could become infected with lethal Ebola strains. “What is the level of risk? We really don’t know,” he says. “The fact that it shows up in domestic pigs raises that risk.”


Source of Information : Scientific American September 2009