News (Updated July 5, 2009)

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Canadian HIV vaccine ready for human tests

Wednesday, July 1, 2009

CBC News

Dozens of HIV vaccines have already been developed and tested in animal models but only a handful have been tested in humans, none successfully. (Canadian Press)

An HIV/AIDS vaccine developed in Canada has passed safety tests in animals and the researchers are awaiting approval to begin human trials in the U.S.

"It is a very important milestone for us," said Yong Kang, a professor of microbiology at the University of Western Ontario in London who has been working on the vaccine for 20 years.

Kang said he expects to get the go-ahead soon from the U.S. Food and Drug Administration to begin human toxicology tests and two phases of clinical trials in the United States .

If all three trials are successful, the vaccine should be available within the next decade, Kang told CBC News on the phone while attending a meeting in South Korea .

According to a 2008 United Nations report on the global AIDS epidemic, 33 million people were living with HIV in 2007. Two million people died of causes related to the disease that year.

Dozens of HIV vaccines have already been developed and tested in animal models, but few have been tested in humans, none successfully. A promising trial in 2007 by pharmaceutical giant Merck and Co. was shut down after those receiving the vaccine contracted HIV at a higher rate than those who received the placebo.

Kang has partnered with a Curacom, a South Korean holding company, that has agreed to open an office in London , Ont., to help fund research in Kang's lab and commercialize the vaccine.

A test vaccine is being manufactured in a lab in Maryland near Washington , D.C.

Lab tests showed the vaccine produced no adverse effects or safety risks during immunology tests on animals.

The toxicology tests are expected to include 40 to 50 HIV-positive volunteers in the U.S. , and will be designed to test whether the vaccine is toxic in humans.

 

Tuberculosis Vaccine Too Risky For HIV-Infected Infants

03 Jul 2009   

HIV-infected infants risk contracting a deadly form of tuberculosis from the bacille Calmette-Guerin (BCG) vaccine, instead of receiving protection against the disease, according to research published today in the international public health journal, the Bulletin of the World Health Organization.

While the BCG vaccine is given to approximately 75% of newborn babies worldwide, a South African study has found that its harm may outweigh the benefits for HIV-infected infants. The study recommends delaying vaccination until the infant's HIV status is known.

"There is an urgent need to assess the risk versus benefits of this vaccine in settings where both HIV infection and tuberculosis burdens are high," says co-author Professor Simon Schaaf, from the Desmond Tutu TB Centre at Stellenbosch University in South Africa .

The Bulletin of the World Health Organization is one of the world's leading public health journals. It is the flagship periodical of the World Health Organization, with a special focus on developing countries. Research papers are peer reviewed and are independent of WHO recommendations and guidelines.

 

HIV-related Death: Predicting Fatal Fungal Infections

ScienceDaily (July 4, 2009) — In a study published in The Journal of Infectious Diseases, researchers from Albert Einstein College of Medicine of Yeshiva University have identified cells in blood that predict which HIV-positive individuals are most likely to develop deadly fungal meningitis, a major cause of HIV-related death. This form of meningitis affects more than 900,000 HIV-infected people globally—most of them in sub-Saharan Africa and other areas of the world where antiretroviral therapy for HIV is not available.

 A major cause of fungal meningitis is Cryptococcus neoformans, a yeast-like fungus commonly found in soil and in bird droppings. Virtually everyone has been infected with Cryptococcus neoformans, but a healthy immune system keeps the infection from ever causing disease.

The risk of developing fungal meningitis from Cryptococcus neoformans rises dramatically when people have weakened immunity, due to HIV infection or other reasons including the use of immunosuppressive drugs after organ transplantation, or for treating autoimmune diseases or cancer. Knowing which patients are most likely to develop fungal meningitis would allow costly drugs for preventing fungal disease to be targeted to those most in need. (In the U.S. , the widespread use of antiretroviral therapy by HIV-infected people, and their preventive use of anti-fungal drugs, has dramatically reduced their rate of fungal meningitis from Cryptococcus neoformans to about 2%.)

In this study, Liise-anne Pirofski, M.D., describes a technique for predicting which HIV-infected patients are at greatest risk for developing fungal meningitis caused by Cryptococcus neoformans. Dr. Pirofski is chief in the division of infectious diseases at Einstein.

Dr. Pirofski and her colleagues counted the number of immune cells known as IgM memory B cells in the bloodstream of three groups of individuals: people infected with HIV who had a history of fungal meningitis caused by Cryptococcus neoformans; people infected with HIV but with no history of the disease; and those with no history of either HIV infection or the disease.

"We were astounded to find a profound difference in the level of these IgM memory B cells between the HIV-infected groups," said Dr. Pirofski. "The HIV-infected people with fungal meningitis caused by Cryptococcus neoformans had much lower levels of these cells."

The research team wanted to know if the lower levels of IgM memory B cells in certain HIV-infected individuals resulted from the fungal disease, or whether their reduced levels of these cells preceded their development of the disease.

To find out, Dr. Pirofski analyzed frozen blood samples taken from HIV-infected patients before they had developed fungal meningitis due to Cryptococcus neoformans. Years before these HIV-infected patients were diagnosed with meningitis, their blood had far fewer IgM memory B cells than HIV-infected patients who didn't come down with the disease. This suggests that some people are predisposed to develop fungal meningitis because they have low levels of IgM memory B cells that may be due to their genetic makeup.

These findings could be important for many other immunocompromised patients in addition to those infected with HIV. "We think that knowing whether transplant recipients or other patients taking immunosuppressive drugs have low numbers of IgM memory B cells could be useful in deciding which patients should receive antifungal drugs to prevent meningitis caused by Cryptococcus neoformans," says Dr. Pirofski.

Krishanthi Subramanian, Ph.D., who did her thesis work in Dr. Pirofski's laboratory, is the first author of the study.

 

Parkinson’s Drugs May Fight Drug Resilient Tuberculosis

Drugs used to care for Parkinson's disease might be a new way to halt the increase of drug-resistant forms of tuberculosis, U.S. researchers announced on Thursday.

They stated that both computer models and lab experiments found that the drugs tolcapone, or Tasmar, made by Valeant Pharmaceuticals, and entacapone, or Comtan, made by Novartis AG have the possibility to fight multiple-drug-resistant strains of TB.

Computer programs forecasted that the chemically comparable drugs should throw off the TB bacillus, and tests in labs using the drug Comtan established it, the researchers said.

1.8 million people die globally every year from tuberculosis and 2 billion people are infected, stated the World Health Organization.

Quite a few people unintentionally have dormant infections that can become active if their immune system becomes destabilized with other viruses, like HIV.

The WHO noted that of the 9 million new TB cases every year, 490,000 are multiple-drug resilient TB or MDR-TB and 40,000 are considerably drug resilient or XDR-TB.

"Given the continuing emergence of M. tuberculosis strains that are resistant to all existing, affordable drug treatments, the development of novel, effective and inexpensive drugs is an urgent priority," said Sarah Kinnings, a graduate student at the University of California , San Diego who led the study, to Reuters News.

Kinnings and his fellow researchers utilized computer models and conducted experiments to find established drugs that might treat resilient forms of TB.

They discovered that the active factor in both Comtan and Tasmar could also impede the multiple-drug defiant tuberculosis bacterium.

The drugs obstruct the brain chemical COMT, which prevents it from breaking down the Parkinson's drugs. Their molecular configuration also lets them impede a compound that TB bugs require to thicken their defensive cell wall.

Tasmar can harm the liver but Comtan does not and could be taken to battle TB, said Philip Bourne of the University of California , San Diego , who worked on the study.

"We have computational and experimental data to support this repositioning," Bourne said in a statement.

Internationally, drug-resistant tuberculosis has the highest rates ever seen, says the World Health Organization. They are specifically a threat in Russia and other former Soviet republics, India , China and South Africa .

The study is published in the Public Library of Science journal PLoS Computational Biology.

 


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