AIDS vaccine research 'blinkered'

Global efforts to develop a vaccine to prevent HIV infection and AIDS have intensified over the past few years, yet they continue to fall short of what is likely to be needed to achieve success, reports Phil Taylor.

This is the verdict of a report that has been presented at the ongoing International AIDS Conference in Bangkok, Thailand, by the International AIDS Vaccine Initiative, a non-profit organisation, funded by governments and other organisations.

And one of the major obstacles to progress is that the vaccine research community is mired in narrow concept regarding vaccine design, focusing on candidates that stimulate cell-mediated immunity. But with no large-scale trial results due on this approach until 2007, there is no way of knowing whether it is a valid one.

Currently, more than 30 vaccine candidates are being tested in small-scale clinical trials, but nearly all are based on the cell-mediated immunity hypothesis and are similar to each other.

"Too many scientists are working on the same idea," noted Wayne Koff,the IAVI's senior vice president and chief of vaccine research, and the lead author of Scientific Blueprint 2004. "The vaccine field must advance new and different candidates into trials," he said.

The report claims that strong alternative hypotheses have been neglected, including that a broadly neutralising antibody immune response could underpin an effective vaccine. None of the candidates in trials elicits this response, according to the IAVI.

In addition, a second neglected hypothesis is that it may be possible to develop an effective vaccine based on mucosal immunity - the stimulation of localised immune reactions in cells lining the genitalia - given that HIV is most often transmitted sexually.

A third avenue that deserves more attention is exploring why live-attenuated AIDS vaccine candidates have shown protection in monkeys that outperforms other vaccines. Although live vaccine can clearly not be used in humans for fear of inadvertently causing an HIV infection, the IAVI maintains that researchers should devote more time to working out the mechanism by which live, attenuated vaccines work

"With this insight, they may be able to design candidates that achieve the same effect safely," said the IAVI.

Meanwhile, global efforts toward a vaccine are inadequate despite scientificconsensus that a vaccine is possible, and growing international awareness that a vaccine is essential.

"The world is inching toward a vaccine, when we should be makingstrides," said Seth Berkley, president and chief executive of the IAVI."The single biggest obstacle is that vaccine development is not a topscientific, political and economic priority," he added.

The IAVI's Blueprint calls for a doubling of current spending to develop an AIDS vaccine, which at $650 million annually represents less than 1 per cent of what the world spends on health product R&D. Among its recommendations are incentives for greater private sector investment, in the same mould as the US's Project Bioshield, which gives tax credits to companies that develop vaccines against bioterror agents.

Additional money would help expand capacity to conduct vaccine trials in developing countries, where most new HIV infections occur and different subtypes of the virus are circulating. A number of developing countries have sites to conduct small-scale trials, but only Thailand has capacity for large-scale studies, the report notes.

According to the United Nations, more people became infected with HIV last year than in any other year - 14,000 every day, and 5 million in total.