Published on Monday, December 30, 2002 by the lndependent/UK
Moment of Truth Draws Near for Humanity's Best Hope to Date in the Battle Against AIDS
by Steve Connor
The gathering of information about the only AIDS vaccine to go through the final phase of a clinical trial is expected to finish within days so that the findings can be made public early in the new year.
Scientists are about to lock away the huge volume of data on some 5,400 volunteers who received in total about 35,000 injections over the past four years. The paperwork alone would stand higher than the Statue of Liberty.
Once the data has been locked away, scientists will be unable to interfere with it in any way, while a team of statisticians and health professionals comb through the information to reach a judgment on whether the vaccine has worked.
The volunteers are from North America, Puerto Rico and the Netherlands and form part of the only phase-three clinical trial of a potential prophylactic vaccine against HIV. The health of each participant has been monitored closely.
Some in the group were given the real vaccine, designed to protect against two strains of the subtype B form of HIV, most common in America and Europe. Others were given a harmless placebo injection.
No one in the double blind, placebo-controlled trial knows who is in which group until the code for the experiment is broken by the statisticians within the next week or so. The second part of the trial, involving some 2,500 participants in Thailand, will test a slightly modified version of the vaccine designed to combat the two HIV strains common in south-east Asia. These findings will be ready in the second half of 2003.
This is a critical time for AIDS research, which is about to mark 20 years since the discovery of HIV. In that time, huge advances have been made in understanding the virus but the vital step of producing a working vaccine has so far eluded some of the world's best scientists.
Vaxgen, a company in Brisbane, California, is orchestrating the phase-three trial of its HIV vaccines, which are based on triggering an effective immune reaction to the outer protein envelope of the virus in the hope that the body can block infection before it happens.
If Vaxgen can show that the infection rates among the vaccinated groups are anything between 45 per cent and 65 per cent lower than in the unvaccinated group, the company should be able to persuade the world that the trial has been a resounding success.
Don Francis, the president of Vaxgen, said that even a 30 per cent reduction in infection rates would be deemed an important step forward because some epidemiologists believe that such a partially effective vaccine could eventually curb the epidemic if it were used for mass vaccination.
But even if the Vaxgen trials prove a success, there still remains the question of whether the vaccine will be effective against the whole, broad range of HIV subtypes and strains in existence around the world.
Dr Francis said: "That's the biggest issue we'll be facing. We don't really understand the immunity to subtypes and that's the biggest risk to the trial."
The discovery of the human immunodeficiency virus in 1983 led to a blood test that saved thousands of lives. The discovery also offered hope for the quick development of a vaccine, but then scientists realized that the virus was extraordinarily varied, which made it difficult to design an effective vaccine.
It is estimated that 25 million people have died so far of AIDS and another 42 million are infected with the virus.
The early days of AIDS research were not helped by a dispute between two groups of scientists, one led by Luc Montagnier, of the Pasteur Institute in France, and the other by Robert Gallo, of the US National Cancer Institute in Washington. Although M. Montagnier's groups discovered HIV in 1983, it took a year for the discovery to be accepted, largely because Mr Gallo was chasing another virus. A legal wrangle over patents led finally to an agreement between the two groups to share credit, but it has not helped in terms of vaccine development.
The search for a vaccine has been one of the most important goals of AIDS research because it is seen as the only way of effectively controlling the global pandemic. But 20 years on, the optimism which ran high at the start has been gradually tempered with pragmatism. Ten years ago, a researcher at Harvard Medical School boasted that a vaccine for the monkey form, called SIV, had protected an animal against enough of that virus to kill 1,000 animals.
The Vaxgen vaccine was also tried on animals with good results, but protecting a chimpanzee or a monkey against HIV or the simian virus is not the same as protecting people against the human virus.
HIV is perhaps the most difficult virus to target with a vaccine. The virus's killer nature arises from the way that it eventually disables the immune system. But the key to its survival is the way that it initially outwits that system by evolving at an incredible speed. Its genetic structure mutates about a million times faster than that of humans. With influenza, it is the fastest-evolving lifeform on the planet. In the course of infecting one person it spawns hundreds or even thousands of slightly different strains. A person can be infected with one strain of HIV and die years later with a totally different population of its "quasispecies", each slightly different in its genetic alphabet to the next.
That makes it difficult to design anti-viral drugs, because one is trying to hit a moving target, biologically speaking. The aim of a vaccine is to give the body the clues about what the protein coat of the viral DNA looks like, so that it knows what to attack. When the chameleon-like coat of HIV keeps changing its identity it is hard to define the essence of what must be attacked. That thwarts the immune system and it has frustrated vaccine designers for decades.
Ultimately, is will be the US Food and Drug Administration (FDA) that will decide whether the Vaxgen trials have worked well enough to justify giving the product its official endorsement. Two weeks ago, the FDA awarded Vaxgen's vaccine a fast track designation to speed up the process of evaluation.
"Every day thousands of people become infected with HIV. Designation of the vaccines against the two subtype-B strains as fast track products recognizes the severity of the pandemic and the need for a vaccine to prevent new infections," DR Francis said.
Without an effective vaccine, there is little hope of containing the spread of HIV, which has already reached levels of 30 per cent among the general population of some African countries. It is also spreading fast in Asia and Eastern Europe. "The public needs to understand that AIDS is not under control," said Margaret Johnston, associate director of HIV/AIDS research at the US National Institute for Allergy and Infectious Diseases in Washington.
"HIV continues to spread unabated in many parts of the world. What we need is to stop that spread, and the best hope to do that is through a safe and effective preventive HIV vaccine," DR Johnston said.
2002 Independent Digital (UK) Ltd