DEVELOPMENT AND CHARACTERIZATION OF EFFECTIVE HEPATITIS C VIRUS-NEUTRALIZING ANTIBODIES FOR VACCINE DESIGN

Hepatitis C virus (HCV) is a major public health problem worldwide. There are 200 million people that are chronically infected with the virus and at risk for developing life-threatening liver disease. Critical gap in understanding HCV immunity has hindered the design of effective anti-HCV vaccines and immunotherapeutics. We hypothesize that subjects, who successfully cleared the viral infection, may possess higher levels of HCV-specific B-cell immunity, compared to those with chronic infections. We aim to study the nature of successful immune response against HCV and develop effective HCV-neutralizing antibodies.

Sera and B cells were collected from chronically infected (CI) patients and patients who achieved spontaneous clearance (SC). We have observed high titer of HCV-specific antibodies in the sera of CI patients compared to low levels of antibodies in the sera of SC`s. In contrast to the low level of binding, high levels of HCV neutralization was observed with these sera. Next, we constructed two antibody libraries using antibody engineering technology: one from the CI patients and the second from the SC`s. These libraries were screen for the selection of HCV binding antibodies by repetitive rounds of panning. A panel of antibodies from the two libraries was isolated and validated for their ability to bind and neutralize HCV.

This study suggests that the nature of successful anti-HCV B-cell immune response may be unique not only in its quick onset and quantity but also in its quality. The isolation of unique antibodies may open new avenues to effective immunoglobulin-based therapies that could prove helpful in preventing or treating HCV-related liver disease and would benefit vaccine development efforts.