HCV infects nearly 3% of the world population and is a leading cause of liver cirrhosis and cancer. A vaccine that can stop virus transmission will be a highly valuable tool for the public health system. However, HCV is antigenically variable and an effective vaccine must target conserved immune epitopes on the virus. An important goal in HCV vaccine is to develop antigens that will elicit broadly neutralizing antibodies (bNAbs). The proposed project aims to discover the epitopes targeted by bNAbs during vaccination and natural infection, and the evolutionary pathways of bnAbs. The knowledge learned from the human studies will be applied to studying the antibody responses in mice, guinea pigs and non-human primates immunized with candidate HCV vaccine antigens. The research will help uncover the pros and cons of each animal model as a preclinical model for efficacy study of future HCV vaccine candidates. This project will contribute to the knowledge and tools for the development of a broadly effective HCV vaccine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI123861-04
Application #
9670674
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Tzarum, Netanel; Wilson, Ian A; Law, Mansun (2018) The Neutralizing Face of Hepatitis C Virus E2 Envelope Glycoprotein. Front Immunol 9:1315
Aleman, Fernando; Tzarum, Netanel; Kong, Leopold et al. (2018) Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors. Proc Natl Acad Sci U S A 115:7569-7574
Velázquez-Moctezuma, Rodrigo; Galli, Andrea; Law, Mansun et al. (2018) Hepatitis C virus escape studies for human antibody AR3A reveals a high barrier to resistance and novel insights on viral antibody evasion mechanisms. J Virol :
Gopal, Radhika; Jackson, Kelli; Tzarum, Netanel et al. (2017) Probing the antigenicity of hepatitis C virus envelope glycoprotein complex by high-throughput mutagenesis. PLoS Pathog 13:e1006735
Velázquez-Moctezuma, Rodrigo; Law, Mansun; Bukh, Jens et al. (2017) Applying antibody-sensitive hypervariable region 1-deleted hepatitis C virus to the study of escape pathways of neutralizing human monoclonal antibody AR5A. PLoS Pathog 13:e1006214
Morris, Charles D; Azadnia, Parisa; de Val, Natalia et al. (2017) Differential Antibody Responses to Conserved HIV-1 Neutralizing Epitopes in the Context of Multivalent Scaffolds and Native-Like gp140 Trimers. MBio 8:
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 113:12768-12773