Injecting hope

KEN DANIELS reports on the vaccine trials that promise a future for millions of people.

Hope of turning the tide in the war against HIV/ AIDS remains distant, but some recent advances in the battle against the disease have brought the development of a safe and effective vaccine against HIV - the virus that causes AIDS - into the realms of possibility.

While scientists warn that the process still has a long course to run, the development of vaccines that are undergoing human trials has given new hope that the epidemic's rampant progression can ultimately be checked.

There is widespread agreement that, despite the success of prevention programmes in countries such as Uganda, the development of a safe preventative vaccine is seen as the best long-term hope of bringing the epidemic under control.

Two test vaccines are already in early human safety (phase I) trials in South Africa. Another four products, including two wholly developed by South African researchers at the University of Cape Town, could go into phase I trials shortly.

Dr Tim Tucker is the former director of the South African AIDS Vaccine Initiative (SAAVI) at the Medical Research Council in Cape Town. SAAVI is a multidisciplinary consortium involving over 220 people and coordinates AIDS vaccine research in South Africa.

Dr Tim Tucker

'What is happening in South Africa should be a model for the world. Local scientists are working in collaboration with international partners to streamline the process of discovering a preventive AIDS vaccine,' says Dr Tucker.

The urgent need for a safe and effective AIDS vaccine is undeniable, and while progress toward achieving this goal has been frustratingly slow, new advances indicate that a solution may eventually be found.

Professor Anna-Lise Williamson, associate professor in the National Health Laboratory Services' and University of Cape Town's Institute of Infectious and Molecular Medicine and head of a team researching the development of an anti-HIV vaccine, is confident that a vaccine is a possibility.

But it will take time.

Prof Anna-Lise Williamson

Prof Williamson said an AIDS vaccine could be effective in stopping the spread of the disease in the same way that vaccines for polio and smallpox had saved millions of lives in the past. She warns, however, that it could take more than ten years before a safe and effective vaccine is available for use in the developing world.

Among the obstacles to the speedy development of the vaccine are the complex nature of the HIV virus and the lengthy process needed to perform clinical trials. Williamson said the development of vaccines was always a complicated procedure but HIV was particularly difficult, because it had a high mutation rate.

The virus has the ability to create multiple variations of itself; eventually producing a swarm of viruses with which the body cannot cope. The virus is also able to escape the body's immune system by integrating with DNA and hiding in the human genome.

This has made the virus very difficult to treat. However, research had shown that, after the initial infection period, the virus goes into a phase of low viral load that lasts for a number of years.

At this stage, it may be possible to use a vaccine to keep the virus at bay and prevent it from multiplying and moving on to the devastating final stage of HIV infection: full-blown AIDS.

Of course, the perfect vaccine would protect people from becoming infected in the first place (this is called sterilising immunity). But this might be very difficult to achieve.

"First generation vaccines are unlikely to completely protect against HIV infection, but should either protect people from developing AIDS or at least extend the time it takes to deveop AIDS," says Prof Williamson.

The two phase I trials which started late in 2003 at two sites in South Africa are safety trials which aim to ensure that the two test vaccines do not produce significant side-effects in human volunteers.

Both test vaccines were extensively tested in laboratory and animal studies before the human trials commenced.

The trials were reviewed and approved by the US Food and Drug Administration (FDA), the South African Medicines Control Council (MCC) and a number of ethics committees in South Africa and the USA.

In phase II, a larger group of volunteers will participate, and the use of the vaccine in relation to the dosage required - and how it should be administered - will be tested.

Once that has been completed, the phase III stage will tests the efficacy of each vaccine in a large group of volunteers (in the thousands).

It is only after phase III is completed that researchers will know whether either of the vaccines work and can be licenced for use.

Williamson said the trials were time consuming and had to follow strictly controlled procedures to ensure that they were accurate. She dismissed the prospect of an overnight breakthrough because of the practicalities of conducting trials.

'The process must run its course. There is no way that it can be short-circuited before it has been properly completed,' she said.

Williamson said a further hurdle in the development of the vaccine was reluctance on the part of pharmaceutical companies to become involved.

She said pharmaceutical companies usually developed drugs for people who are already ill or in a highrisk category. An HIV/ AIDS vaccine would ultimately be used on healthy adults and children.

Dr Tucker from SAAVI also warned that the testing procedure for any vaccine or medication is no quick-fix operation, agreeing with Williamson that it will be at least ten years before the vaccine is available.

'All new medications and vaccines have to go through all three phases of testing,' he said.

According to SAAVI, the development of a vaccine is the strongest hope for bringing the disease under control. In theory, HIV transmission is preventable, but in practice, without the development of an effective vaccine, HIV will continue to infect millions throughout the world.

With two different test vaccines already being tested and others set to follow, South Africa - which has one of the highest HIV infection rates in the world, with an estimated 11% of the population infected - is now a key centre in the global effort to discover a vaccine.