If there is a Holy Grail in modern medical science, it is the pursuit of a vaccine for a disease that is devastating swathes of the developing world and that has no cure. An Aids vaccine is the one real chance to stop the epidemic, but the hunt has become bogged down by infighting and thwarted by the extraordinary potential of this lethal virus to out-trick the best scientific efforts.
In 1997 Bill Clinton, as president, committed the United States to developing a vaccine within 10 years. ”If the 21st century is to be the century of biology, let us make an Aids vaccine its first great triumph,” he said. At the half-way mark, the prospects for an effective vaccine by 2007 look slim, even though the lobbying, the campaigning and the funding have all moved up several gears.
Big commercial pharmaceutical companies like Merck and GlaxoSmithKline are now in the picture as well as the dedicated academics in their university labs.
The International Aids Vaccine Initiative (IAVI), headed by the dynamic New Yorker Seth Berkley, has successfully lobbied for more funds from governments and Bill Gates and is pushing hard for trials of anything that looks promising.
For all that, only one potential vaccine is in phase III trials — the final stages of testing. Aidsvax, made by American company VaxGen, is being given to a large population of Thai intravenous drug users at high risk of contracting the HIV virus that leads to Aids. Next year we should find out whether Aidsvax saved substantial numbers from infection.
Last week at the 14th International Aids Conference in Barcelona, VaxGen declared it would have a vaccine ready within five years. But the excitement is muted. Don Francis, the US government scientist turned chief executive of the private company he had to launch to get the trials carried out, is about the only person still saying his vaccine could be as much as 80% effective. Most people think that if it has protected any of the Thai injecting-drug users who took part in the three-year trials, it won’t be more than a third.
There are as many different views on what an acceptable vaccine will look like as there are players in the field. There are commercial companies such as Merck and sharp-suited US businessmen in the Aids vaccine business these days, aware that the potential market for a vaccine is enormous and that wealthy donor countries are prepared to pick up the tab.
There are big name immunologists, such as Jonas Salk, father of the polio vaccine, who threw himself into HIV research in the years before his death in 1995. Yet, by some accounts, one of the best hopes for saving Africa, if not the world, from the modern plague comes from the laboratories of a British academic.
Professor Andrew McMichael is a shy, sandy-haired man, wearing an unobtrusive, loose, camel-coloured v-neck pullover over his shirt and a permanent, embarrassed smile. He works in a big glass building tucked behind the maternity wing of Oxford’s John Radcliffe Hospital. It is comparatively new but has the early signs of academic shabbiness.
This is the Weatherall Institute of Molecular Medicine, part of Oxford University, where bright young scientists and students stride through the functional corridors with the cheerfulness of those who are certain they will save the world.
McMichael is rather more circumspect. ”I think it will work if we get everything right,” he says slowly, but then adds in all the caveats. ”By that I mean we go through phase II trials and make sure it stimulates a big enough and broad enough immune response that is long lasting. And then that it matches the viruses in the populations we are going to vaccinate.”
Finding a vaccine that will protect against HIV is difficult beyond the imaginings of the earliest researchers, because the virus infiltrates and destroys the very immune system that should protect the body against it. It also mutates with extraordinary rapidity and frequency.
Vaccines for other diseases have successfully been manufactured by using a killed or weakened form of the virus itself, which stimulates the immune system to produce antibodies ready to see off the real thing. But fears of accidentally infecting healthy people with HIV and the possibility that the weakened virus might mutate into a lethal strain have deterred most scientists from this approach.
So they have tried selected bits of the virus. The AidsVax vaccine is based on a protein that lives on the surface of the HIV virus and is responsible for locking on to receptors of white blood cells in the immune system.
McMichael and his team have taken an entirely different route, inspired by the discovery of prostitutes in Kenya who remained HIV-negative in spite of frequent sex with infected men. The Kenyan women were remarkable not for their antibodies but for the high levels of what are known as killer T-cells — those white blood cells that divide and attack other cells that have been invaded by a virus. The Oxford vaccine, now in trials there, in London and in Nairobi, uses DNA to trigger a strong killer cell response. The results in mice have been good. Now the vaccine is being tested in healthy people with no likelihood of exposure to HIV. In two to three years, it could face the crunch test in people at risk. ”It will be about five to six years before we know if it works,” says McMichael.
Some feel the need is too desperate for the usual scientific caution. Not McMichael, though, who has firm if politely understated views on what he feels he must achieve and what to him is not acceptable. ”I think I’m going to be a bit more stringent than some people in what we have to get right,” he says. ”You might get a vaccine that works in half the people and doesn’t exactly match the strains — and some people might put that into trials. There are pressures to go on and get into these trials, but if you are not too careful somebody — and I don’t think it would be us — might go in a bit too early.”
Some think it might be acceptable to go for ”partial prevention” by making a vaccine that does not stop HIV infection but blocks the development of Aids. ”I wouldn’t be happy with that,” he says. It can take 10 years for someone who is infected to become ill and such a vaccine might just delay the process further. It would be a long time before you would realise you were wrong, he says.
McMichael’s team is no longer alone in working on their type of vaccine. Merck, the pharmaceutical giant, is pursuing a similar approach. If the Oxford/Nairobi partnership succeeds in getting good results in the final trials, ”we will be in uncharted territory”, the professor says. ”We’re complete amateurs. We’re going to be taken over by the professionals. Merck has got more than 100 people working on it. We have got maybe 20.”
It might work. It might not. The best brains in virology and immunology are largely punting theories and backing hopes. ”We still don’t know yet what to do,” says John Moore, a professor of microbiology and immunology at Weill Medical College, part of Cornell University in New York. ”We have ideas but anybody who says, ‘I know what to do’ is bullshitting or misunderstanding the problem.
”It’s not a tomorrow afternoon type of solution. It’s difficult. This is probably one of the hardest medical problems that any of us will ever encounter in our careers.” Most other viruses are simple organisms beside HIV — even flu, which has always been tricky because it has a capacity to mutate into a new form that can trigger a massive and lethal outbreak in humans. ”The kind of variation that causes influenza pandemics happens every day with HIV,” says Moore.
His own exasperation with the slow progress made to date spilled over in an article he wrote in Nature magazine earlier this year. He lashed out at the rivalry between the two leading institutions involved in Aids research in the US — the National Institutes of Health and the Department of Defence.
Between them they have hundreds of millions of dollars to spend on the hunt for a vaccine, but they were wasting time and a massive amount of money by duplicating research. The interests of the dying were left behind in the race to be first.
”It has seemed as if each agency has felt compelled to ‘shadow’ the other, to insure against the embarrassing outcome of a working vaccine candidate emerging that was sponsored by the other agency,” he wrote.
The arrival of the IAVI, he said, as a third body looking to score the ultimate goal, had made things worse. ”Whatever is said in public, the rivalry between the [National Institutes of Health], the [Department of Defence] and the IAVI is an open secret among scientists working on HIV1 vaccine development,” he wrote.
Maybe somebody took note. Things have changed since January, when the article appeared. The Department of Defence’s vaccine programme has been taken over by the National Institutes of Health. Both had been planning phase III trials of a vaccine made of the canarypox virus (harmless to man) combined with the protein gp120.
The institute’s trial on 11 000 volunteers in the US, the Caribbean and South America has been scrapped, while the defence department’s plans for a similar trial in Thailand go on.
The great quest is less a forward charge than a stumbling, lurching, two steps forward and one step back. But it’s the best everyone can do in the face of a virus that is wreaking more destruction on mankind than any act of war or terrorism and is, as yet, smarter than science.