HCV infection of humans induces a complex immune response characterized by induction of innate immunity followed by both cell mediated and humoral adaptive immune responses. In -20% of acute HCV Infections, the anti-HCV Immune response controls the infection. Analysis of both human and primate HCV infection indicates that clearance is associated with robust CD4 and CDS T cell responses specific for HCV epitopes. Although the generation of neutralizing humoral responses is also likely important in HCV infection, their ultimate role in clearance remains to be determined. Understanding the mechanisms of immune evasion that allow HCV to develop and maintain chronic infection in the majority of cases is critical to prophylactic and therapeutic vaccine development. HCV has a highly error-prone polymerase with a correspondingly high mutation rate, allowing HCV to rapidly escape developing immune responses. Therefore, complete understanding of the successful immune response to HCV with its mechanisms of evasion and escape from sterilizing immunity requires serial analysis of both HCV sequence and HCV-specific adaptive immune responses from the time of initial infection until outcome is determined. In addition to the technical complexity of specific quantitative analysis of epitope specific T cell and humoral responses, the study of HCV immunity is further complicated by the fact that acute infection is generally asymptomatic and therefore typically not detected. The vast majority of HCV infected patients are therefore diagnosed during their chronic phase, long after the critical immune responses to acute infection are generated. The Center includes a unique cohort of injection drug users followed on a monthly basis, thereby allowing high frequency detection of de novo acute HCV infection and longitudinal evaluation of infection outcome. Thus, the proposed research brings together unique patient resources with leaders in the study of HCV-specific T cell and humoral immune responses and HCV sequence evolution. The combination of cohort and sequence evolution and immunologic expertise make the proposed projects feasible, potentially increasing understanding of human chronic viral infections and enhancing development of immunotherapies.
Infection with hepatitis C virus (HCV) is the number one reason for people to need liver transplantation in the United States, but the early infection is hard to detect. We study people at high risk for HCV infection, and focus on the early immune responses to HCV. Understanding how the virus escapes immune responses that eliminate most viral infections could guide future efforts to detect, treat, and prevent HCV infection.
|Kinchen, Valerie J; Cox, Andrea L; Bailey, Justin R (2018) Can Broadly Neutralizing Monoclonal Antibodies Lead to a Hepatitis C Virus Vaccine? Trends Microbiol 26:854-864|
|Esmaeili, Aryan; Mirzazadeh, Ali; Morris, Meghan D et al. (2018) The Effect of Female Sex on Hepatitis C Incidence Among People Who Inject Drugs: Results From the International Multicohort InC3 Collaborative. Clin Infect Dis 66:20-28|
|Kinchen, Valerie J; Zahid, Muhammad N; Flyak, Andrew I et al. (2018) Broadly Neutralizing Antibody Mediated Clearance of Human Hepatitis C Virus Infection. Cell Host Microbe 24:717-730.e5|
|Kinchen, Valerie J; Bailey, Justin R (2018) Defining Breadth of Hepatitis C Virus Neutralization. Front Immunol 9:1703|
|Rose, Rebecca; Lamers, Susanna L; Massaccesi, Guido et al. (2018) Complex patterns of Hepatitis-C virus longitudinal clustering in a high-risk population. Infect Genet Evol 58:77-82|
|Ke, Ruian; Li, Hui; Wang, Shuyi et al. (2018) Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence. Proc Natl Acad Sci U S A 115:E7139-E7148|
|Bailey, Justin R; Barnes, Eleanor; Cox, Andrea L (2018) Approaches, Progress, and Challenges to Hepatitis C Vaccine Development. Gastroenterology :|
|Mankowski, Madeleine C; Kinchen, Valerie J; Wasilewski, Lisa N et al. (2018) Synergistic anti-HCV broadly neutralizing human monoclonal antibodies with independent mechanisms. Proc Natl Acad Sci U S A 115:E82-E91|
|Morris, Meghan D; Shiboski, Stephen; Bruneau, Julie et al. (2017) Geographic Differences in Temporal Incidence Trends of Hepatitis C Virus Infection Among People Who Inject Drugs: The InC3 Collaboration. Clin Infect Dis 64:860-869|
|Vergara, C; Thio, C; Latanich, R et al. (2017) Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections. Genes Immun 18:82-87|
Showing the most recent 10 out of 59 publications