Inter Press Service - December 6, 2001
Patricia Grogg*

"We are still a long way from an effective vaccine against HIV. Even the most advanced pharmaceutical companies do not appear to have much chance of success, at least in the immediate future," said Carlos Duarte, head of the research team in Cuba that is seeking a vaccine.

With nearly a decade of AIDS research under its belt, Cuba has the longest trajectory in this effort in Latin America.

Scientists from numerous countries participating in an international conference on AIDS treatments, held earlier this year in the U.S. city of Philadelphia, also took a prudent stance, stressing that research is a long, slow process.

Norman Levin, with the Harvard Medical School, told the conference that what realistically can be expected in the near future is a vaccine that diminishes the presence of the virus.

Later, a better vaccine that prevents infection in some people will be developed, and so on, until scientists figure out how to trigger a protective immune response in all humans, according to Levin.

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 one that is," 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 Pittsburgh and Rochester universities, 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.

The Aventis Pasteur corporation in France produces the Canarypox vector, while VaxGen, based in the U.S. 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 (clinical trials with volunteers), is intended to study each 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 Peru).

But before then, the scientific community will have the test results 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 clinical trials 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 U.S. clinical trials will be known by late next year, and those of the Thailand testing by the next year, says Jos 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 inoculation 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 form of immunisation 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 treatment is safe, the second is an in-depth study of the human immune response to the vaccine, and the third phase determines its 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.

* This article was produced with the support of the Pan-American Health Organisation (PAHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS).

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