Research

Keywords: virus, protective immunity, inflammasome, hepatitis C virus, HIV, Hepatitis B virus, T cell, vaccine, immunotherapy

Our laboratory investigates the host immune response to chronic human viral infections, particularly HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). HBV and HCV infect nearly 400 million people worldwide and HIV infects about 37 million. We examine the role of the immune response in clearance of HBV and HCV upon exposure to these viruses by studying innate and adaptive responses from the earliest phases of infection through years following infection in longitudinal, prospective cohorts of people at risk of infection. This allows a comparison of the innate, humoral, and cellular immune responses to infection with clearance versus persistence of hepatitis viruses. We have demonstrated that spontaneous control of HCV does not uniformly generate sterilizing immunity, but reinfection is associated with a reduction in the magnitude and duration of viremia (compared with the initial infection), broadened cellular immune responses, and generation of cross-reactive humoral responses. These findings are consistent with development of adaptive immunity that is not sterilizing but protects against chronic disease. To identify mechanisms of protective immunity against HCV infection and improve prophylactic HCV vaccine design, we are determining the cellular and humoral responses associated with repeated HCV control. A significant barrier to the development of an HCV vaccine is that HCV is a highly diverse virus. Our laboratory has also developed and evaluated methods of HCV vaccine design that may overcome this diversity and stimulate an effective immune response. Dr. Cox leads HCV vaccine clinical trials and the lab studies immune responses to prophylactic HCV vaccines in human trials.

We have demonstrated that the development of HCV-specific T cell clones is arrested during the first year of HCV infection and that molecular phenotypes associated with this loss of functional activity vary based on whether lymphocytes recognize epitopes that do or do not undergo substitution. In order to better understand this, our laboratory studies regulation of molecules that control T cell function in the setting of chronic antigenic stimulation.

Our lab is also interested in activation of an innate sensing system, the inflammasome, which induces antiviral cytokines as well as inflammation. We have defined the mechanism through which both HIV and HCV activate the inflammasome and novel mechanisms through which inflammasome activation is suppressed. We are interested in global regulators of inflammasome function.

Publications and Interests: https://jhu.pure.elsevier.com/en/persons/andrea-cox