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Scripps Research Institute scientists find promising vaccine targets on hepatitis C virus
Date:4/3/2012

h and used it as "bait" for a panel of antibodies derived from the blood of a person with chronic HCV infection. The exhaustive panning technique involves exposing this bait protein to different anti-HCV antibodies in sequence, so that the known antibody-binding sites on the complex are progressively covered until only new ones are left.

In this way, Giang catalogued 73 new anti-HCV antibodies, which bind to five distinct "antigenic regions" on the E1-E2 complex. In standard cell culture tests of HCV-neutralizing ability, several of these antibodies showed an ability to neutralize infection by a wide range of HCV strains. One, AR4A, turned out to bind to an almost-unvarying spot on E1-E2 complex, close to the surface of the virus's outer coat of fat molecules. AR4A showed significant neutralizing ability against all 22 HCV strains in a test panelnot only in tests in Law's lab, but also in confirmatory tests at the University of Copenhagen.

The new antibody thus is more broadly protective than the previous top contender, AR3A, which Law described in his 2008 Nature Medicine paper. "This human antibody AR4A has the broadest HCV-neutralizing activity known to the field," Law said.

Collaborating researchers at Rockefeller University, who recently engineered a line of HCV-infectable mice, showed that AR4A antibodies protected these mice from two widely different HCV strains. A combination of half-doses of AR3A and AR4A antibodies worked less well.

The next step for Law and his colleagues is to start making and testing prototype vaccines based on the vulnerable HCV binding sites that have been revealed by these antibody studies. The researchers also plan to use the new antibodies to study the structure and function of HCV proteins such as the all-important E1-E2 complex.

Anti-HCV antibodies such as AR4A and AR3A could have some therapeutic use, too. Although they wouldn't be able to clear existing HCV infections and wou
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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