Hope rises in Africa for Aids vaccine

Skim low over Lake Victoria on the approach to Entebbe and with a setting sun you catch a glint from the white buildings dotting the near shore. Clustered on a slope, they stand out from the hotels and yacht clubs as an oddly shaped jumble of bungalows, storehouses and offices.

Since 1936, the Uganda Virus Research Institute has occupied this prime piece of property, screened by trees from a potholed road while seeking ways to contain killer diseases such as malaria and yellow fever. Now, with the help of British and Kenyan scientists, it is seeking the ultimate prize: a vaccine for Aids.

It is a coincidence, but follow the shore south for a few dozen miles and you reach the fishing villages where the destructive force of what they called Slim disease was first revealed. Two decades later, those stricken fishermen and their families are multiplied into millions as the HIV virus ravages Africa.

Were an effective vaccine to be found by Lake Victoria it would be a tragedy with an almost Hollywood ending, the story concluding where it opened. Recently that possibility became real.

Researchers at Entebbe have started recruiting dozens of volunteers, the first of thousands, to test a DNA-MVA vaccine widely seen as the most promising of a global crop of trial vaccines. It is supported by the International Aids Vaccine Initiative (IAVI), a not-for-profit body.

Designed at Oxford University and the University of Nairobi to combat the A-strain of the HIV virus prevalent in east Africa, the vaccine is, in fact, two in combination, with both made from copies of a selection of HIV genes which are incapable of forming the fully functional virus.

In the first, the genes are stitched into a ring of DNA and in the second, they are administered in a modified virus (MVA) with no link to HIV and rendered harmless so that it does not itself cause disease.

The idea is to boost the immune system to produce cells that seek out and destroy others infected by HIV. It is a conscious bid to mimic the responses of a small group of commercial sex workers in Kenya, who have some immunity to HIV despite being regularly infected.

The odds of that approach working have now risen. Entebbe has found another group apparently resistant to the virus: just over two-dozen people near Lake Victoria have remained uninfected despite unprotected sex with infected partners, a phenomenon called "discordant couples".

Some of the resistant individuals had a lower measured immune response than infected partners but their immune systems attacked the virus more effectively, allowing them to stay HIV negative. The finding suggests that what matters is quality, not quantity, of immune response.

The identities of the discordant couples have not been disclosed but researchers say they are a mix of rural and urban, peasant and professional. The new research is expected to be published later this year following submission to a journal next month.

Anthony Kebba, one of the paper's seven authors, flew into Britain yesterday to give a series of briefings on the findings. "Many more studies need to be done but I think this will be a step to an effective vaccine," he said.

Pontiano Kaleebu, the principal researcher at Entebbe's vaccine project, said the couples were an intriguing twist. "Why do some people get protected? Why do some live longer than others? We need these answers. I think we will not fail. So yes, there is optimism here."

A vaccine was possible within a decade but it was unlikely to be 100% effective. "We're already debating what would be an acceptable level of effectiveness." Health authorities in the US have suggested that, given the urgency, 30% effectiveness would be acceptable.

Any doubts about the need for a vaccine can be dispelled by a dawn visit to the Kenyan shores of Lake Victoria. Fishermen returning with the night's catch are mobbed by women traders wanting fish for their stalls. In a sellers' market, some men demand and get sex as well as cash, said Christopher Ouma, of ActionAid.

Uganda's safe sex and abstinence initiatives have been hailed as models for Africa yet Kampala's clinics still fill up with dying patients. Last week, Fred Bogere, 34, at an advanced stage of full-blown Aids, could not speak, eat or hear, and kept passing out. Tears streamed down his cheeks as a doctor tried to ask him questions.

Safe sex campaigns and cheaper, more available treatment drugs are crucial, but the best way to avoid another generation of Freds, say many scientists, is a vaccine. After faltering for want of funds and political will in the 1990s global vaccine research, though still underfunded, was now "moving in the right direction", Dr Kaleebu said.

One reason for the renewed interest was that sub-types of the virus once confined to Africa were increasingly cropping up in the west, he said. "People are beginning to realise the world is one village."

The IAVI, which is based in New York, is lobbying drug companies and governments to ensure that, once ready, an Aids vaccine is swiftly available in Africa, unlike the polio vaccine which took decades to reach some countries. Building up expertise in places such as Entebbe should also accelerate vaccine distribution.

Another reason for the new research momentum, despite disappointment over a US trial last year which went to phase 3 (the testing of thousands of high-risk patients), is renewed optimism in finding one that will work. South Africa, China and Ivory Coast are expected to start trials and, just last week, the HIV Vaccine Trials Network launched a joint trial in Botswana and the US.

The highest hopes are pinned on the Nairobi-Oxford vaccine. Phase 2 trials, (which involve testing hundreds of volunteers) are under way in Britain and Kenya. Entebbe, which is just starting phase 1(testing for drug safety and preliminary responses in a small sample, say a few dozen low-risk patients), will give Ugandan volunteers different dosages.

An advantage of working so close to a virus hotspot was not having to transport blood samples, said Josephine Birungi, who heads Entebbe's laboratory: "When you understand the science and how fast the virus evolves, it becomes scary. We need all the advantages we can get."

Conspiracy theories that HIV was a western plot against Africa, and that vaccines were a plot to sterilise, impeded volunteers, said Fred Nakwagala, a trial physician, but 20 have signed up and Entebbe is confident of recruiting 30 more for phase 1, hundreds for phase 2 and thousands for phase 3.

In the ground-floor clinic one male volunteer in his early 20s who cannot be named, grimaced as the needle jabbed into his arm. Later he smiled. "Everyone here knows somebody who has died of Aids. This can't go on, that's why I'm here."

Sprawled by a road not far from the institute, a dozen lads who came to a seminar for potential volunteers were less sure: could scientists under orders from the west be trusted? Could you get the virus from the vaccination? What was a placebo and was it dangerous?

An ethical issue bedevilling trials is whether volunteers who become infected through their own behaviour should receive the life-extending drugs available in the west but denied to most Africans.

It is feared the cost would deter other trials but the IAVI, which funds much of Entebbe's work, has urged it to consider making that commitment, said Dr Nakwagala. "I think we would be the first in Africa, and it would the right thing," he added.