Washington/Mexico City - An international AIDS vaccine
consortium called Tuesday for the setting of smaller, interim goals
in the elusive search for a vaccine and urged bolder research that
could raise objections from regulators.
The International AIDS Vaccine Initiative (IAVI) released its
latest blueprint for progress at the International AIDS Conference in
Mexico City, where 25,000 scientists, politicians, physicians and
activists are meeting this week.
The 20-page document also proposes more focus on the little-
researched group of natural 'controllers' - the estimated 10 per cent
of the world population that manages to keep HIV under control even
if infected.
To accomplish these goals, IAVI called for a division of efforts
'into components that are more readily attainable than the ultimate
prize - a finished vaccine - or even the intermediate goal of proof
of benefit in humans.'
The IAVI statement is the latest fallout for the AIDS vaccine
research field after the failure of an unconventional vaccine type
that had spurred hope in the world AIDS community.
In September 2007, pharmaceuticals firm Merck & Co dropped its
testing of a vaccine that was designed to work through a cell-
mediated immunity rather than using traditional antibodies. Merck
cancelled the test after it was found that some test subjects had a
higher risk of becoming infected with HIV.
Concerned about the results, the top US government AIDS research
institute in July pulled the plug before starting to test a similar
model. The move prompted critics to say that the estimated 700
million dollars a year spent on vaccine research was wasted and
should be spent on treating people with AIDS.
In an interview ahead of the blueprint's release, Seth Berkley,
head of the New York-based IAVI, dismissed such comments as
'overreaction' - but welcomed the reduced pressure for results,
saying the failures had helped to 'dial down the expectations.'
That doesn't mean the field will take a step backward, Berkley
said.
Rather, it means a more aggressive focus on finding the elusive
'broadly neutralizing antibodies' that can protect against the wide
variety of HIV circulating in the world, and on figuring out how to
better induce the cell-mediated immunity that Merck and other
researchers were pursuing, IAVI said.
Since the discovery of HIV in the mid 1980s, researchers proceeded
with caution. The lethal virus destroys the body's immune system and
causes Acquired Immune Deficiency Syndrome (AIDS), which has claimed
25 million lives and infected another 33.2 million people.
'We started with the safest vaccines, which were little pieces of
the virus, completely non-replicating,' said Berkley, who noted such
vaccines proved safe but ineffective.
The next step was to take live attenuated virus and turn it into a
vaccine that only replicated the HIV content once. Those attempts
ended in failure, such as the 2003 dead-end for Vaxgen in Thailand.
The next step, the IAVI document says, is accelerating focus on
'live replicating, vector-based vaccines,' which it concedes will
'raise novel questions for regulatory agencies.'
Live attenuated - which means the virus has been thinned down -
vaccines have been the basis for immunizing against measles, polio
and yellow fever, among others, Berkley said.
'We want to now go into that area between live attenuated and
current vaccines, which have been non-replicating,' Berkley said.
This 'will much more closely approximate the way a normal virus would
present to the immunity system.'
'We expect the regulatory hurdles to be slightly higher after the
Merck experience,' he said. 'You can imagine regulatory agencies are
going to ask hard questions about that. What they liked about the
existing (AIDS vaccine) products was that they didn't replicate,
they're not there forever.'
The biggest hurdle in the pursuit of a vaccine is HIV's
astonishing ability to change and disguise itself from the body's
defences. With HIV, the presence of antibodies does not protect
against the disease - but some people have immune systems that
control their HIV infections for decades.
IAVI says the research field has not devoted enough money to their
study.
'They may have critical clues. What we want to do is collect lots
of these experiences and do really extensive studies of them,'
Berkley said.
The small-pox vaccine, for example, was developed in the late
1700s after scientists noted that milkmaids had beautiful, unpocked
skin. It turned out that their daily exposure to a related disease,
cowpox, had given them immunity to the much more lethal virus.
The IAVI blueprint delivered a small history lesson, noting in a
table that it took 105 years to develop typhoid fever vaccine, 92
years for meningitis, 47 years for polio and 42 for whooping cough.
Berkley was hopeful about breaking down research into more
manageable components. An Indian research company, Chembiotek, in
Calcutta, for example, was using its specialty in glyco-biology - the
biology of sugar - to explore how to create an antibody that would
target a sugar-coated HIV receptor.
'We said to them, where's the structure for this neutralizing
antibody? What kind of substance can you inject into people to make
the immunogen?' Berkley said.
USA
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