Washington - After major disappointments, AIDS research in
the United States is making a significant turn away from human
clinical trials and back to laboratory basics in the search for an
elusive vaccine, according to the top US AIDS scientist in an article
published online Thursday.
Dr Anthony S Fauci, director of the National Institute of Allergy
and Infectious Diseases (NIAID), and his colleagues announced the
turnabout in an article in the magazine Science, which released the
item a day before its print publication on Friday.
In an interview with Deutsche Presse Agentur dpa ahead of the
embargoed publication, Fauci said that his federally funded institute
- which distributes about 80 per cent of the money spent worldwide on
vaccine research - would 'rev up the burners' to tackle the decades-
old puzzle of how to create antibodies against the disease without
causing an actual infection.
That means less money will be spent on human trials of vaccines
that work in less conventional ways, and which buoyed hopes in the
past several years only to disappoint.
More use will be made of animals, not humans, in the research,
Fauci said.
'What the emphasis right now will be, is on improving the non-
human primate model,' Fauci said. 'What is the best animal model that
we can perfect? Why does the body not make good neutralizing
antibodies in natural infection?'
The shift in focus follows intense discussion within the HIV/AIDS
research community, and comes just a week after Fauci decided to
cancel a large human trial of the institute's own PAVE vaccine
similar to one privately produced and tested by Merck pharmaceuticals
that was dropped in September 2007.
The Merck vaccine was found ineffective, and in fact appeared to
have inadvertently increased the HIV infection rate, and trials were
dropped midway, prompting Fauci to cancel the PAVE tests before they
started.
'It isn't that we're going to completely stop and turn around 180
degrees, but we're going to torque or turn the knob on the system
much more toward asking and answering some of the fundamental basic
questions that we have not been able to answer up to now,' Fauci
said.
Worldwide, an estimated 33.2 million people are living with
HIV/AIDS and at least 25 million people have died from the disease
that is transmitted through sex or infected blood.
The disease, which erodes the body's immunity against infections
and is fatal for those who don't take life-prolonging drugs, hits
hardest young adults in prime earning and parenting years, and has
carved huge holes in communities across large parts of Africa and
Asia.
Improvements in drug therapy have extended life expectancy, and in
the absence of a vaccine, the current fight focusses on wider access
to drugs and higher awareness of preventive measures like condoms.
The biennial international AIDS conference is next month in Mexico
City. Fauci, who will attend, had some not-very-comforting words for
the community about 'bringing expectations down to realistic levels.'
'We have to understand how difficult the situation is and not
expect that ... tomorrow we're going to start a large vaccine trial
and we're going to get the answer in a couple of years,' he told dpa.
'It is extremely unlikely that that will happen.'.
The traditional approach to vaccines - using the live virus to
induce antibodies and thus true immunity without causing the illness
- has not worked with HIV because the virus has an astonishing
ability to change and disguise itself from the body's defences.
Instead, the focus of recent years has been on alternatives to the
more familiar approach to vaccines of inducing antibodies, in order
to at least get something onto the market.
The PAVE and the Merck vaccines attempted to cause a cellular
immune response that programmed the body's T-cells to search out and
kill virus-infected cells.
The goal was to reduce the HIV virus count in the body, slow down
the progression of the disease and reduce transmissability from an
infected person - without expecting to totally eliminate the virus.
Hope for the Merck and NIAD's PAVE vaccines rose two years ago as
they headed into advanced trials on humans. But tests showed the
vaccines didn't work, and in some cases increased the likelihood of
infection.
Like the dead end with the Vaxgen vaccine in Thailand in 2003, the
failure has dashed soaring expectations.
Fauci says his goal has not changed since he started HIV research
in the 1980s. He wants to crack the code and 'identify that part of
the virus that actually is capable of inducing a (broadly)
neutralizing antibody.'
Ten percent of the world population appears to have a natural
immunity, but scientists haven't figured out how it works.
Among the keys to the mystery are what scientists call the
'correlates of immunity.'
In normal virus infections, this refers to the antibodies
that can be tested for and would indicate immunity to, say,
influenza, rubella, polio or measles.
But with HIV, the presence of antibodies does not protect against
the disease. That's why the search is still on for a correlate that
will neutralize a broad variety of HIV varieties.
Fauci, who controls 500 to 600 million dollars of US public funds
of the estimated 700 million spent worldwide every year on vaccine
research and testing, was adamant about the return to basic research
and reduction in human testing.
'You're not going to see a lot of these very large (human) trials
until we understand a lot more about things like correlates of
immunity, which are a big black box right now,' he said. 'The
fundamental basic philosophical shift is to focus more on a discovery
approach as opposed to a developmental approach.'
As part of the renewed effort, Fauci's institute is spending more
money on basic HIV research in the hopes of luring younger scientists
who think 'outside the box' and are willing to pursue 'innovative,
high risk, high impact' work, according to the NIAID documents about
the new programmes.
'We'd like to bring into the fold and embrace new people, young
investigators ... who have no preconceived notion,' Fauci said.
USA
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