After AIDS vaccine setbacks, US makes U-turn (News Feature)

Washington - After major disappointments, AIDS research in the United States is making a significant turn away from human clinical trials and back to laboratory basics in the search for an elusive vaccine, according to the top US AIDS scientist in an article published online Thursday. Dr Anthony S Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), and his colleagues announced the turnabout in an article in the magazine Science, which released the item a day before its print publication on Friday. In an interview with Deutsche Presse Agentur dpa ahead of the embargoed publication, Fauci said that his federally funded institute - which distributes about 80 per cent of the money spent worldwide on vaccine research - would 'rev up the burners' to tackle the decades- old puzzle of how to create antibodies against the disease without causing an actual infection. That means less money will be spent on human trials of vaccines that work in less conventional ways, and which buoyed hopes in the past several years only to disappoint. More use will be made of animals, not humans, in the research, Fauci said. 'What the emphasis right now will be, is on improving the non- human primate model,' Fauci said. 'What is the best animal model that we can perfect? Why does the body not make good neutralizing antibodies in natural infection?' The shift in focus follows intense discussion within the HIV/AIDS research community, and comes just a week after Fauci decided to cancel a large human trial of the institute's own PAVE vaccine similar to one privately produced and tested by Merck pharmaceuticals that was dropped in September 2007. The vaccines were found ineffective, and in fact appeared to have inadvertently increased the HIV infection rate, and trials were dropped midway. 'It isn't that we're going to completely stop and turn around 180 degrees, but we're going to torque or turn the knob on the system much more toward asking and answering some of the fundamental basic questions that we have not been able to answer up to now,' Fauci said. Worldwide, an estimated 33.2 million people are living with HIV/AIDS and at least 25 million people have died from the disease that is transmitted through sex or infected blood. The disease, which erodes the body's immunity against infections and is fatal for those who don't take life-prolonging drugs, hits hardest young adults in prime earning and parenting years, and has carved huge holes in communities across large parts of Africa and Asia. Improvements in drug therapy have extended life expectancy, and in the absence of a vaccine, the current fight focusses on wider access to drugs and higher awareness of preventive measures like condoms. The biennial international AIDS conference is next month in Mexico City. Fauci, who will attend, had some not-very-comforting words for the community about 'bringing expectations down to realistic levels.' 'We have to understand how difficult the situation is and not expect that ... tomorrow we're going to start a large vaccine trial and we're going to get the answer in a couple of years,' he told dpa. 'It is extremely unlikely that that will happen.'. The traditional approach to vaccines - using the live virus to induce antibodies and thus true immunity without causing the illness - has not worked with HIV because the virus has an astonishing ability to change and disguise itself from the body's defences. Instead, the focus of recent years has been on alternatives to the more familiar approach to vaccines of inducing antibodies, in order to at least get something onto the market. The PAVE and the Merck vaccines attempted to cause a cellular immune response that programmed the body's T-cells to search out and kill virus-infected cells. The goal was to reduce the HIV virus count in the body, slow down the progression of the disease and reduce transmissability from an infected person - without expecting to totally eliminate the virus. Hope for the Merck and NIAD's PAVE vaccines rose two years ago as they headed into advanced trials on humans. But tests showed the vaccines didn't work, and in some cases increased the likelihood of infection. Like the dead end with the Vaxgen vaccine in Thailand in 2003, the failure has dashed soaring expectations. Fauci says his goal has not changed since he started HIV research in the 1980s. He wants to crack the code and 'identify that part of the virus that actually is capable of inducing a (broadly) neutralizing antibody.' Ten percent of the world population appears to have a natural immunity, but scientists haven't figured out how it works. Among the keys to the mystery are what scientists call the 'correlates of immunity.' In normal virus infections, this refers to the antibodies that can be tested for and would indicate immunity to, say, influenza, rubella, polio or measles. But with HIV, the presence of antibodies does not protect against the disease. That's why the search is still on for a correlate that will neutralize a broad variety of HIV varieties. Fauci, who controls 500 to 600 million dollars of US public funds of the estimated 700 million spent worldwide every year on vaccine research and testing, was adamant about the return to basic research and reduction in human testing. 'You're not going to see a lot of these very large (human) trials until we understand a lot more about things like correlates of immunity, which are a big black box right now,' he said. 'The fundamental basic philosophical shift is to focus more on a discovery approach as opposed to a developmental approach.' As part of the renewed effort, Fauci's institute is spending more money on basic HIV research in the hopes of luring younger scientists who think 'outside the box' and are willing to pursue 'innovative, high risk, high impact' work, according to the NIAID documents about the new programmes. 'We'd like to bring into the fold and embrace new people, young investigators ... who have no preconceived notion,' Fauci said.