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September 26, 2010)
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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
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:
21 Sep 2010
Source: SciDev.Net
Mićo Tatalović
[
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
"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,
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.
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
The Phase II study of
AERAS-402/Crucell Ad35 is being led in
"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
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
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
Many human diseases come
from animals, including influenza, plague and
(Editing by Cynthia
Osterman)