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Ten
years into the search for an AIDS vaccine, hope mounts with each
new test. Though most scientists are cautious in their predictions,
an effective vaccine may be available in two to five years.
By
Patricia Grogg
HAVANA
- The discovery of a vaccine to prevent infection with HIV, a virus
that led to the deaths this year of three million people worldwide,
could be just around the corner, but the scientific community opts
for caution when it comes to predicting exactly when it will happen.
"We are still a long way from an effective vaccine against
HIV. Even the most advanced companies do not appear to have much
chance of success, at least in the immediate future," says
Carlos Duarte, head of the research team that is seeking to create
a vaccine in Cuba, the Latin American country with the longest history
in this effort - nearly a decade.
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Scientists
from numerous countries participating in an international
conference on AIDS earlier this year in the US city of Philadelphia
also took a prudent stance, stressing that the research is
a long, slow process.
Norman
Levin, with the Harvard Medical School, told the conference
that what realistically expected is to achieve a vaccine that
diminishes the disease. Later, a better vaccine that prevents
infection in some people, and so on, until scientists figure
out how to come up with a protective immunological response,
he said.
But
expectations rise with each new test, leading some to forecast
results within two to five years. "Even if this vaccine
does not prove effective, I know that this study is an important
step towards the discovery of a vaccine," commented one
of the volunteers involved in a clinical trial initiated in
Brazil in early November.
Coordinated
by the Pasteur Institute of France and the University of Pittsburgh
and the University of Rochester, of the United States, the
project in Brazil is testing a vaccine that is a combination
of the gp-120 protein, which is found in the surface of HIV,
and the Canarypox vector, which holds copies of the virus's
genes reproduced through genetic engineering techniques.
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One of the
most promising AIDS vaccines is based on the gp-120 protein,
by the US company VaxGen.
Credit: Photo Stock.
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The
Canarypox vector is produced by Aventis Pasteur in France, while
VaxGen, based in the US state of California, makes the gp-120. Both
involve the B subtype of the virus.
Scientists
identify the different classes of HIV with the letters A through
J, each one with its specific genetic characteristics. The subtype
A is found largely in sub-Saharan Africa, B in the Americas, Europe,
Japan and Australia, and C in South Africa and India.
The
experiment in Brazil, which is in Phase II (trials with volunteers),
is intended to study the patient's reaction and development of antibodies,
according to participants in the project.
Phase
III (test of effectiveness among larger populations) is slated for
the first months of 2003 in the United States, several Caribbean
countries (Haiti, Trinidad and Tobago, and possibly the Dominican
Republic) and Latin America (Argentina, Brazil, Honduras and probably
Peru).
But
before then, the test results will be known for a vaccine produced
by VaxGen through genetic engineering, based on the gp-120 protein
in two versions, corresponding to the HIV subtypes B and E.
The
tests to determine the effectiveness of that vaccine prototype began
in the United States in 1998 and are aimed at the B subtype, which
predominates in that country.
Tests
of a similar experimental vaccine, based on subtype E, began in
Thailand in March 1999.
The
results of US clinical trials will be known by late next year, and
those of the Thailand testing by the next year, says José
Esparza, coordinator of HIV vaccine initiatives at the World Health
Organisation (WHO) and at UNAIDS.
The
specialist commented that "it is very difficult to determine"
which vaccine is the most promising, but that the most advanced
vaccine is the one based on gp-120 (produced by VaxGen) to induce
the production of antibodies - though it remains to be seen if it
will work.
The
ideal vaccine for fighting HIV, says Esparza, would be capable of
inducing both humoral immunity (antibodies) as well as cellular
immunity (cytotoxic T-lymphocytes - CTL), which is why the vaccines
being tested are combinations of the two.
"The
best preventive vaccine should completely protect someone from HIV
infection, but that could be very difficult to achieve and may only
diminish the viral burden in the vaccinated persons who become infected,"
he said.
In
Esparza's opinion, such a vaccine, though "imperfect",
would be very valuable from the individual and public health perspective.
But he stressed that the important message is that a future antidote
against HIV is not going to be the "silver bullet" the
replaces other forms of prevention.
Once
an effective vaccine is discovered, said the UNAIDS expert, it would
be at least one year before world health authorities approve it.
Then the vaccine would have to be commercially produced in the necessary
quantities, which could mean further delays for its widespread application.
The
number of doses to be produced will depend on many factors, in Esparza's
opinion, including the vaccine's level of effectiveness in relation
to the various subtypes of the virus, the duration of the vaccine's
protective qualities and its costs, among others.
"A
vaccine will not immediately eradicate the HIV/AIDS epidemic, but
it will certainly contribute towards reducing the number of new
infections, particularly in developing countries," said Esparza.
"We
view the vaccine as another intervention that would form part of
a package of preventive measures against the disease," he added.
The
development process for vaccines begins with laboratory research,
followed by tests using animals, then come the clinical trials in
humans, which occur in three phases.
The
first phase determines, in general terms, whether the vaccine is
safe, the second is an in-depth study of the human immunological
response to the vaccine, and the third phase determines the vaccine's
overall effectiveness against the disease.
The
first Phase I tests of a candidate vaccine against HIV began in
1987 in the United States. To date, more than 30 experimental vaccines
have reached Phase I and II, mostly in the United States and Europe,
but also in countries of the developing South, such as China, Brazil,
Thailand and Cuba.
Cuba's
decade-long efforts to obtain a vaccine against HIV have prompted
some optimism in research chief Duarte that its therapeutic application
among AIDS patients will take place in the near future, but, like
most of his colleagues around the world, he prefers not to predict
exactly when.
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