BROAD NEUTRALISING ANTIBODIES FORMED IN LABORATORY WITH CHANGE IN PROTEIN OF HIV VIRUS TO PRODUCE A HIV VACCINE

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a crucial step towards developing a successful HIV vaccine, researchers have been able, for the first time, to stimulate immune cells that can produce broadly neutralizing antibodies: a feat that has eluded vaccine researchers for decades. The exciting results are published in this month's issue of the Journal of Experimental Medicine.
It is widely accepted that a successful vaccine against HIV/AIDS would have to elicit antibodies to prevent infection from a wide spectrum of HIV strains. So far, no candidate vaccine for HIV has been able to produce such antibodies.
Leonidas Stamatatos, Andrew McGuire and their team of researchers at Seattle BioMed, in collaboration with colleagues at The Rockefeller University, the Scripps Research Institute and CalTech, wanted to understand why that was the case. A major goal of an HIV vaccine is to stimulate B cells to create antibodies that can effectively block HIV from entering a human host cell. The first generation of antibodies -- called "germline antibodies" -- are partially embedded in a B cell's membrane. If a germline antibody binds to a protein (called an "envelope protein") on the surface of HIV, even weakly, then the B cell is activated and begins producing antibodies not only on the surface of B cells, but also in the bloodstream. Activated B cells evolve to produce antibodies with even higher binding affinity to HIV, eventually resulting in a "mature" antibody. Some mature antibodies can bind to envelope proteins of many different HIV strains and prevent them from infecting cells. For this reason, these antibodies are called "broadly neutralizing antibodies." These are the antibodies a vaccine needs to elicit.
They discovered that several sugar molecules, called glycans, which HIV adds to its envelope protein to evade the immune system, were blocking the germline antibody from binding to and activating B cells.After engineering an HIV envelope protein that lacks specific glycans, McGuire and Stamatatos ran their binding tests again. This time, the germline antibodies were able to bind the modified HIV protein. They also verified that the modified HIV protein was capable of starting the process of antibody maturation in B cells, kicking off an immune response that could eventually result in broadly neutralizing antibodies.