Boris Heger

THE scientific study of AIDS has dropped out of the headlines over the past year or two. The disease is still a mass killer, but the drugs used to combat it have become cheaper, and the mechanisms for getting them to the infected, most of whom live in poor countries (predominantly African ones), have got better. As to prevention, circumcision—though by no means a complete answer—has been shown to reduce a man's risk of becoming infected with HIV, the virus that causes the disease, and thus helps slow down the rate of transmission. The drugs, too, seem to do that, by reducing the number of viruses in an individual's body.

That is all good news. But it brings the field no nearer to what is really needed—a vaccine that will stop people getting infected in the first place. The last big vaccine trial, known as STEP, ended in failure in 2007. It may even have promoted susceptibility to the virus it was trying to curb. AIDS-vaccine researchers seemed to be running out of both ideas and hope. But a paper published in this week's Science shows that neither of those things is true. There are still original ideas around. And there is also a revival of hope.

The paper in question has been published by a team led by Laura Walker of the Scripps Research Institute, in San Diego, and Sanjay Phogat of the International AIDS Vaccine Initiative (IAVI), in New York. It confirms that there is a weakness in HIV's armour, and unveils weapons that might be able to exploit it.

The weapons in question are called broadly neutralising antibodies (known as bNAbs in the trade). These are antibodies that deactivate a wide range of HIV strains—which is particularly important for an effective vaccine, because HIV is so variable. Until now, though, those bNAbs which have been identified have not been broad enough. They have been effective only against strains circulating outside Africa. Moreover, no new bNAb has been found for more than a decade.

Taking the strain

The two new ones reported by Dr Walker and Dr Phogat are the first fruits of a project called Protocol G, one of several multi-centre investigations into various aspects of AIDS that IAVI is helping to organise. This particular project is looking specifically for bNAbs in volunteers from seven African countries (Côte d'Ivoire, Kenya, Nigeria, Rwanda, South Africa, Uganda and Zambia) and from America, Australia, Britain and Thailand.

The antibodies in question were found by screening blood serum from 1,800 volunteers from these countries. The researchers have zeroed in on antibodies that react with part of the virus called its spike. This consists of two sugar-protein molecules known as gp120 and gp41 that react with a protein called CD4, which is found on the surface of certain cells of the immune system. The reaction grants the virus entry to the cell. That is why HIV infects immune-system cells, rather than other sorts.

With the aid of two biotechnology firms, Monogram Biosciences of South San Francisco and Theraclone Sciences of Seattle, Dr Walker, Dr Phogat and their colleagues tested all their serum samples for anti-HIV activity, picked the top 10%, extracted all the antibodies from each of these samples, tracked down the cells that made each antibody, found the relevant genes, snipped them out, cloned them into other, faster-reproducing cells, made usable samples of pure antibody from each of these clones, and tested the results to see if they could stop HIV from docking with cells that have CD4 on their surfaces. Two such antibodies (both from the same donor and dubbed PG9 and PG16) could.

The next stage is to find out exactly which bits of the spike PG9 and PG16 lock onto. This knowledge is needed to design a chemical that looks enough like the relevant spike element to prompt the immune system to make antibodies that will neutralise it. That chemical might, just, be the basis of a vaccine. And if it is not, everyone involved hopes that Protocol G will soon throw up more bNAbs, and that they will help refine the search for HIV's weak spot. For unless it turns out to have one, the search for a vaccine could go on for ever.