Posted by fenbilimleri Eylül 6, 2009
“It’s the discovery of the target that’s the key thing,” says Wayne Koff, senior vice president of research and development at the International AIDS Vaccine Initiative in New York, and a key member of the team reporting the breakthrough.
Vaccine developers have been beset by one failure after another. One explanation for the failures is that HIV rapidly mutates to escape detection by the immune system. As a result, many of the mutated strains are no longer recognised by antibodies.
But lab tests show the new antibodies bind to many more strains and variants of HIV than usual, potentially giving patients protection against any strains that infect them, or any new mutants that evolve in their own bodies.
They found that about 10 per cent of the donors made so-called “broadly-neutralising antibodies” (bNAbs) that recognise multiple strains of HIV. Eventually the researchers whittled these down to two extremely potent antibodies – both from the same African donor – that massively outperformed the others.
This variant is the way gp120 appears on the virus itself and on infected cells – and therefore the way it will appear to someone’s immune system. By contrast, most previous searches for potent antibodies have focused on whether they attach to a single unit of gp120, called a monomer.
Now, thanks to the antibodies, researchers have realised that the trimer is a viral weak spot because it’s indispensable to the virus. So unlike many other targets on the virus, it’s shared by many, if not all, strains of HIV.
The antibodies are only a starting point, however, and the race is on now to develop synthetic vaccines that have the same shape as the “weak spot”, or epitope, so people receiving vaccinations make antibodies that recognise it when the real virus comes along.
“The identity of this epitope is a major advance and will lead many groups to explore ways to produce new vaccines,” says Dan Barouch of the Beth Israel Deaconess Medical Center in Boston, Massachusetts, and leader of a recent study exploring why one of the leading vaccine candidates was a failure. “It shows exactly the site on HIV that broadly neutralising antibodies can target.”
Koff says follow-up studies are now under way at IAVI’s Neutralizing Antibody Center at Scripps – due to open officially on 24 September – to screen for more broadly neutralising antibodies, hopefully revealing yet more sites on the viral anatomy that are indispensable.