The South African trial of an HIV vaccine is in a state of animated suspension. The clinical sites of Baragwanath Hospital and the Durban Medical Research Council (MRC) have been chosen and approval has been received from the Wits University ethics committee. All that the National Institute for Virology, which is co-ordinating the process, is waiting for now is the go-ahead from the Medicines Control Council, and it is hoped that the trials can begin towards the middle of the year.
“We are having to strike a balance between being enthusiastic and realistic,” says EftyhiaVardas, who heads the Baragwanath HIV vaccine unit. The trials will involve a very lengthy process, and it will be about seven years before the vaccine can be bought off the shelves.
The plan, says Vardas, is to test as many vaccines as possible all at the same time, so that they do not waste time in finding the right candidate.
For over a decade, the search for a vaccine has been confounded by the unusual response of the body’s immune system to the HIV virus. But as scientists have come to better understand the immunological response of the body and the erratic behaviour of the virus, there is now a good chance that they will find an effective vaccine.
The main problem has been that the virus does not recognise the immune system, and there are still areas of the virus that are cryptic.
Most of the international focus has been on the Vaxgen trial, which was conducted in the US and in Thailand, but the results are taking so long to analyse that in the meantime, newer candidate vaccines are coming through and they look like they will hold greater promise.
The newer candidate vaccines may be better because they benefit from the latest discoveries of the workings of the immune system and of the virus.
The clinical sites are ready to go on two vaccine candidates – firstly with a vaccine from the US National Institutes of Health called Alphavax, which is made in conjunction with South Africa, and soon after that with a Kenyan vaccine produced in conjunction with the International Aids Vaccine Initiative (IAVI).
The initial Phase I trials, which test safety and efficacy, have been done on the IAVI vaccine in Kenya, and the South African sites will be able to start with the intermediate Phase II trials which will involve vaccinating about 100 participants to assess their immune response. Phase II would take about two years, and the final stage III, where several thousand people are vaccinated, would take another five years.
Phase II trials are currently being conducted in Kenya by the British and Kenya Aids Vaccine Initiative and the International Aids Vaccine Initiative, based in Nairobi and Oxford.
Vardas stresses the point that the vaccine “can never, ever cause HIV”, because the person is vaccinated with an artificial virus that can’t ever replicate. It only causes the body to react – to manufacture antibodies and to trigger an immune response. This means that when it is exposed to the real HIV virus, the body can recognise it and knows how to respond and defend itself.
There are three phases in these trials. Phase I involves 20-60 healthy, uninfected volunteers at low risk of HIV infection, and tests for safety. Phase II involves 100-400 low and high-risk volunteers and tests for an immune response. After a successful Phase II trial, a Phase III trial takes place. This involves several thousand high-risk volunteers to assess if the vaccine prevents natural infection with HIV.
The way the vaccines work is that a vaccinated person who is exposed to HIV through sexual contact or in any other way will still become infected with HIV, but the vaccine will keep the virus replication at such a low level that the person will not develop Aids, will not become sick and will have too low a viral load to be able to pass on the infection to a sexual partner or, in the case of a pregnant woman, to the baby.
Scientists have not found a way of completely eradicating the virus. The ideal scenario would be to vaccinate everyone in the population. There is also the important aspect of using the vaccine as treatment for a person who is already infected with HIV, and the clinical sites are hoping to pursue this application later this year. In this case, the vaccine will control replication of the virus and so have a dampening effect on the disease.
The advantage of recent vaccine candidates is that they are complex and wide enough to react to different genetic types of the virus so that even when the virus changes its genetic make up, it will not be able to mutate fast enough to evade the combative force of the vaccine. “But with HIV we never know,” says Vardas.