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A critical camouflage mechanism that allows HIV to hide from the body’s defences and foil immunisations has been rebuilt in the laboratory in research that could transform the prospects for an effective Aids vaccine, The Times has learnt.
The advance by British scientists should allow them to turn one of the virus’s great strengths into its Achilles’ heel, promising a first vaccine that offers strong protection against HIV.
If offers a way of overcoming HIV’s remarkable capacity to shapeshift so that it becomes unrecognisable to the human immune system, which has so far thwarted efforts to create a workable vaccine.
By making synthetic versions of the virus’s “camouflage jacket” and injecting them into patients, scientists believe that it should be possible to teach the immune system to recognise and neutralise HIV. Candidate vaccines based on the new approach are already being evaluated in animal studies and the first human trials could potentially begin in two years. The research, led by Ben Davis, Professor of Organic Chemistry at the University of Oxford, is the latest in a series of recent milestones in the search for an Aids vaccine.
Last month the world’s largest trial of a candidate vaccine, in Thailand, suggested that an agent called RV144 could reduce the chances of HIV infection by almost a third. Though the results were only just statistically significant and the effect was small, they have offered the best indication yet that it might be possible to immunise people against the virus.
Further hope has been raised by another study published last month, which identified two new antibodies that neutralise a broad range of HIV strains. This has provided important clues to the design of vaccines that are more effective than RV144.
Professor Davis’s research, which has been supported with almost $1 million (£600,000) from the International Aids Vaccine Initiative (IAVI), now offers another method of creating better vaccines against HIV. It is an example of the new field of “synthetic biology”, in which scientists seek to rebuild natural molecules with subtle modifications that make them medically useful.
HIV binds to T-cells of the human immune system to infect them using a surface molecule called glycoprotein 120 (GP-120). While most elements of GP-120 mutate rapidly to escape the immune system, one feature called the “silent face” always remains the same, making it a prime target for antibodies that could be raised by a vaccine.
This silent face, however, is generally invisible to the human immune system because it is coated with sugars that are difficult for antibodies to recognise and grab. “The virus uses this trick to decorate itself with what is effectively camouflage,” Professor Davis told The Times. “It has a cloak of invisibility, as it were.”
Most people who become infected with HIV do not produce antibodies against the silent face, but one such antibody, 2G12, has been discovered in one unknown patient. “This tells us that nature can find a way of finding this apparently invisible target, which we might be able to exploit to make a vaccine,” Professor Davis said.
His team has manufactured synthetic versions of the sugars that camouflage HIV’s silent face, which have been slightly modified to make them easier for the immune system to recognise. In laboratory tests the 2G12 antibody binds to these artificial molecules, suggesting that they should prime the body to produce such antibodies when used in immunisations.
“We’ve done the whole thing with chemistry,” he said. “We’ve built constructs that look like the silent face, but which the body recognises as being unnatural. We hope it will create an immune response. We’re turning the virus’s shield into its Achilles’ heel. If we can build something that elicits antibodies towards the silent face, we could have a vaccine against HIV.”
About 30 slightly different synthetic versions of the silent face molecule are being tested in rabbits to determine whether they can promote the production of antibodies. The first results are expected in three to six months.
Any of the candidate vaccines that elicit antibodies are then likely to progress quickly to clinical trials. “IAVI would then move immediately towards filing with the FDA [the US Food and Drug Administration] for a human trial,” Professor Davis said. “As soon as one shows neutralising properties, we hope within two years we could see it in people.”
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