News (Updated September 26, 2010)

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Nonstick Coating Of A Protein Found In Semen Reduces HIV Infection

25 Sep 2010   

A non-stick coating for a substance found in semen dramatically lowers the rate of infection of immune cells by HIV a new study has found.

The new material is a potential ingredient for microbicides designed to reduce transmission of HIV, a team from the University of Rochester Medical Center and the University of California , San Diego reports in a forthcoming issue of the Journal of Biological Chemistry.

The coating clings to fibrous strings and mats of protein called SEVI - for semen-derived enhancer of viral infection - which was first discovered just three years ago. SEVI seems to attract the virus and deposit it onto the surface of T-cells, components of the immune system that are the primary target of HIV infection, and may play an important role in sexual transmission of HIV.

Like the fibrous strings that bind senile plaques associated with Alzheimer's disease, SEVI is a kind of protein superstructure called an amyloid.

Jerry Yang, associate professor of chemistry at UC San Diego and his research group developed non-stick coatings for amyloids as a potential treatment for Alzheimer's disease in 2006. Their idea was to minimize damage by preventing amyloid proteins from interacting with other molecules in the brain.

When this new amyloid, SEVI, was discovered in 2007, Yang was interested in testing whether the coating strategy might interfere with SEVI's role in promoting HIV infection.

Yang's group teamed up with a researchers led by Stephen Dewhurst, chair of the microbiology and immunology department at the University of Rochester Medical Center, who studies HIV.

"We tested one of our molecules out on SEVI and found it was able to stop SEVI-enhanced infection of HIV in cells," Yang said. "It works in semen too. Something in semen enhances viral infection - SEVI and maybe other things. This molecule stops that."

When the researchers added the molecule that forms non-stick coatings to a mix of SEVI, virus and cells, rates of infection dropped to levels observed when SEVI was absent. They saw a similar effect with semen as well, evidence that this potential microbicide supplement works to inhibit infection within a mixture of proteins and other molecules found in seminal fluid.

The coating molecule is a modified form of thioflavin-T, a dye that stains amyloid proteins. It fits in between the individual small proteins that cluster to form SEVI and blocks SEVI's interactions with both the virus and the target immune cells.

"Other people have tried to do the same thing by targeting the virus or the cells it infects. What we do is target the mediator between the virus and the cells," Yang said. "By neutralizing SEVI, we prevent at least one way for HIV to attach to the cells."

The new molecule has another advantage. Unlike many current microbicide candidates aimed at reducing HIV infection, this one doesn't cause inflammation in cervical cells.

"Recent studies have shown for the first time that a topical microbicide gel can protect women from HIV-1 infection. This is a huge step forward but not a perfect solution. We need to figure out ways to further improve protection - and our studies suggest one way of doing so," said Dewhurst, who is the corresponding author of the report. "It may be possible to produce a next-generation microbicide that includes both an antiviral agent, as has been used in the past, and an agent that targets SEVI. We're very excited about exploring this idea."

The National Institutes of Health and the National Science Foundation funded this work.

Additional co-authors include Joanna Olsen, Caitlin Brown, Todd Doran, Rajesh Srivastava, Changyong Feng and Bradley Nilsson of the University of Rochester, and Christina Capule and Mark Rubinshtein of the University of California, San Diego.

Source: University of California -- San Diego

 

TB conference to map out vaccine plan

21 Sep 2010

Source: SciDev.Net

Mićo Tatalović

[ TALLINN ] One of the largest international tuberculosis (TB) gatherings for a decade begins tomorrow to agree on a plan for the development of vaccines.

The 'Blueprint for TB Vaccines' will be put together at 'The Second Global Forum on TB Vaccines: A Framework for Introducing Improved TB Vaccines to the World Community', in Estonia this week (21-24 September).

"Vaccines are really the 'plan A' so far [as] tuberculosis control is concerned," Christopher Dye, director of Health Information in the Office of HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases at the WHO, Switzerland , told SciDev.Net.

A new vaccine could cut the number of new cases by 90 per cent within a period of three or four decades, he said.

Vaccination would also circumvent weak health systems that hinder efforts to diagnose and treat TB. Hundreds of millions of children could be vaccinated in a short time, he added.

The current TB vaccine, BCG (Bacillus Calmette-Guerin), is effective only in very young children and ceases to work once the child has grown up.

Michael Brennan, senior advisor for Global Affairs at Aeras Global TB Vaccine Foundation, said that there are three priorities for the TB field: to use information from clinical studies to make better vaccines; to keep the pipeline filled with innovative vaccines as more is learned from research, combining the findings with new, needle-free delivery devices; and to understand why vaccines work, by getting to the root of the immune responses that they trigger.

"If we knew what the key immune responses were to effective vaccines it would be easier to evaluate them," he said.

There are around ten vaccine candidates in various stages of clinical trials and about 50 more in development, according to Jelle Thole, director of the TuBerculosis Vaccine Initiative. Thole predicted that there should be a new TB vaccine available within the next five to ten years.

The WHO has set a medium-term goal of eliminating TB by 2050 - which means less than one case per million people, compared with around 1,000 cases per million at the moment.

Although the UN Millennium Development Goal targets for TB are on track, according to a UN report published in June, the disease remains the second largest killer after HIV/AIDS, killing nearly two million people and infecting almost ten million each year. The HIV/AIDS epidemic, and the rise of antibiotic resistance, are further hampering the fight.

"If you had a vaccine against TB it would work for drug-sensitive and drug-resistant TB, and [resistance] then becomes an irrelevant problem, and that is another major advantage of having a vaccine," said Dye.

 

Study to Test New Tuberculosis Vaccine in Infants by Aeras and Crucel

Sep 22, 2010  

Leiden, The Netherlands / Rockville, MD, USA (September 22, 2010) – Dutch biopharmaceutical company Crucell N.V. (Euronext, Nasdaq: CRXL; Swiss Exchange: CRX) and the Aeras Global TB Vaccine Foundation today announced the start of a Phase II clinical trial in infants of the jointly developed tuberculosis (TB) vaccine candidate, AERAS-402/Crucell Ad35.  

The main objective of the trial is to test the safety and efficacy of the TB vaccine candidate in infants previously vaccinated with the Bacille Calmette-Guérin (BCG) vaccine, which is currently the only vaccine licensed to help prevent TB. The first part of this clinical trial, which will be conducted in Kenya , will establish the optimal dosing regimen. The selected regimen will then be tested in the second part of the trial, which is planned to begin in 2011 in Kenya , Mozambique , South Africa and Uganda .  

The Phase II study of AERAS-402/Crucell Ad35 is being led in Kenya by a joint research project of the Kenya Medical Research Institute and the US Centers for Disease Control and Prevention, called the KEMRI/CDC Research and Public Health Collaboration. Participants from the Siaya District in Nyanza Province of Western Kenya will be enrolled.  

"Despite the availability of the BCG vaccine, two million men, women and children die from tuberculosis every year.  We urgently need a new TB vaccine to ensure long-term and effective TB protection," said Jim Connolly, President and CEO of the Aeras Global TB Vaccine Foundation. "This clinical trial represents an important step in our collaboration among a global network of researchers and the people of Kenya , who continue to be at high-risk for TB infection."

 In 2004, Aeras and Crucell began jointly developing this vaccine candidate using Crucell's AdVac® vaccine technology and PER.C6® manufacturing technology. 

 "I am extremely pleased at the pace in which our work to develop a next generation vaccine against TB is progressing. Our successful collaboration with Aeras, enabling the initiation of yet another Phase II study, is an important step towards our ambition of reducing the global burden of this fatal disease," said Jaap Goudsmit, Crucell's Chief Scientific Officer.

  Kenya is ranked 13th on a list of 22 high-burden TB countries, according to the World Health Organization.  In 2007, 24,000 Kenyans died from TB and there were 132,000 new cases. 

 "The communities in which we work are hard hit by both TB and HIV/AIDS, two leading courses of mortality," said Videlis Nduba , MD , MPH, Principal Investigator for the trial at KEMRI/CDC Research and Public Health Collaboration.  "We are pleased to apply our research expertise at this stage in the development of this vaccine-a vaccine which has undergone considerable early-stage safety testing." fAERAS-402/Crucell Ad35 has been tested in seven early-stage clinical trials including a phase I clinical trial in infants in South Africa .  A Phase II trial to test its safety and efficacy in adults living with HIV is ongoing in South Africa . To date, the candidate has been shown to have an acceptable safety profile in these populations.

   

Malaria comes courtesy of gorillas, DNA study shows

Photo

Sep 23 2010

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) - Malaria appears to have jumped to humans from gorillas, and the parasite may have spread globally from a single gorilla to a single human, researchers reported on Wednesday.

DNA from the droppings of nearly 3,000 apes -- gorillas, chimpanzees and bonobos -- shows the strain of malaria parasite most common in humans is virtually identical to one of many strains that infects gorillas.

It is far more distant than strains affecting chimps and their close cousins, the bonobos, Beatrice Hahn of the University of Alabama at Birmingham and colleagues reported.

Hahn and colleagues used ape droppings collected to study the origins of the AIDS virus for their study, published in the journal Nature.

"We had them all nicely organized, genetically characterized in our freezer," Hahn said in a telephone interview.

Hahn's team tested genetic material from the human immunodeficiency virus for their AIDS studies and took a similar approach for the latest work, looking for DNA from malaria parasites, including the Plasmodium falciparum parasite that causes most human cases.

"Wild apes, in particular the common chimps and the western gorillas, are naturally infected with at least eight or nine different Plasmodium species," Hahn said.

For years chimps were the chief suspects. But Hahn's data shows that gorillas, and only gorillas, are infected by a Plasmodium species virtually identical on the genetic level to the type that infects humans.

"Now, how many mosquitoes were biting however many humans or gorillas I do not know," Hahn said. "But the end result is, based on sequence analysis of 105 human Plasmodium parasites, it looks like there was a single transmission."

In other words, the parasite only had to infect one person or a small group of people before quickly taking hold and spreading to much of the world.

Malaria, which kills an estimated 800,000 people a year according to the World Health Organization, is spread when a mosquito feeds on an infected person and carries the parasite to another human. There is no cure and no vaccine, although drugs can control the infection and help prevent the spread.

The findings could eventually have implications for efforts to get rid of malaria, said Dr. Larry Slutsker, who heads the malaria program at the U.S. Centers for Disease Control and Prevention.

"If we were trying to eradicate, meaning we were trying to rid the planet of every last parasite and there was a reservoir in western gorillas, that would have implications for eradication. I don't think we are there, obviously," he said.

Gorillas, or the areas where they live, would likely have to be included in any such program so the parasite could not once again move into people.

Slutsker said the parasite may not necessarily have spread to people from apes via a mosquito. It can also be spread by direct blood transfer -- perhaps while a gorilla was being butchered for food. Many experts believe this is how HIV first spread to humans.

What the researchers cannot say is when this happened. HIV mutates -- evolves -- quickly and these changes can be used as what is known as a molecular clock to date changes. Malaria parasites change much more slowly, Edward Holmes of Pennsylvania State University wrote in a commentary on the Nature study.

Many human diseases come from animals, including influenza, plague and West Nile virus.

(Editing by Cynthia Osterman)


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