Hepatitis C virus (HCV) chronically infects 2-3% of the global population, predisposing the patients to chronic liver diseases and liver cancer. A broadly effective vaccine will be a cost- effective mean to solve this global problem. However, HCV is genetically varied and vaccines designed based on a single viral strain will not be effectively against genetically diverse circulating viruses. To overcome this scientific challenge, the vaccine candidates must target conserved regions on the virus. The goal of this application is to determine the molecular structure of virus neutralizing epitopes to aid the rational design o immunogens, that will focus antibody responses to the conserved epitopes in vaccination. This "epitope vaccine" approach include: (1) Determination of crystal structures of HCV antibody epitopes in complex with the corresponding broadly neutralizing antibodies;(2) Design and synthesis of immunogens as biomimetics of the known epitope structures;(3) Testing of the novel immunogens in a small animal model of HCV infection to identify lead vaccine candidates. If successful, this proposal can result in novel HCV vaccine candidates for clinical trials, and also significantly advance the HCV and vaccine fields.
Hepatitis C virus (HCV) is a leading cause of liver cirrhosis and cancer. A broadly effective vaccine will be vital for the eradication of this silent epidemic The goal of this project is to develop and evaluate vaccine candidates that target genetically conserved regions of the virus.
|McBride, Ryan; Head, Steven R; Ordoukhanian, Phillip et al. (2016) Low-Cost Peptide Microarrays for Mapping Continuous Antibody Epitopes. Methods Mol Biol 1352:67-83|
|Prentoe, Jannick; VelÃ¡zquez-Moctezuma, Rodrigo; Foung, Steven K H et al. (2016) Hypervariable region 1 shielding of hepatitis C virus is a main contributor to genotypic differences in neutralization sensitivity. Hepatology 64:1881-1892|
|Kong, Leopold; Lee, David E; Kadam, Rameshwar U et al. (2016) Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen. Proc Natl Acad Sci U S A :|
|Winer, Benjamin Y; Ploss, Alexander (2015) Determinants of hepatitis B and delta virus host tropism. Curr Opin Virol 13:109-16|
|Law, Mansun (2015) Editorial overview: Preventive and therapeutic vaccines (B cell epitope vaccine). Curr Opin Virol 11:viii-x|
|Scull, Margaret A; Shi, Chao; de Jong, Ype P et al. (2015) Hepatitis C virus infects rhesus macaque hepatocytes and simianized mice. Hepatology 62:57-67|
|Douam, Florian; Gaska, Jenna M; Winer, Benjamin Y et al. (2015) Genetic Dissection of the Host Tropism of Human-Tropic Pathogens. Annu Rev Genet 49:21-45|
|Gaska, Jenna M; Ploss, Alexander (2015) Study of viral pathogenesis in humanized mice. Curr Opin Virol 11:14-20|
|Douam, Florian; Ploss, Alexander (2015) Proteomic approaches to analyzing hepatitis C virus biology. Proteomics 15:2051-65|
|Kong, Leopold; Kadam, Rameshwar U; Giang, Erick et al. (2015) Structure of Hepatitis C Virus Envelope Glycoprotein E1 Antigenic Site 314-324 in Complex with Antibody IGH526. J Mol Biol 427:2617-28|
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