Abstract

The goals of this study are to evaluate the role of humoral and cellular (CTL) effector mechanisms in natural and induced immunity to HCV, and to achieve broadly cross reactive prophylactic immunization. Immune responses will be determined during the development of self-limited or chronic infections in HCV inoculated chimpanzees to evaluate correlates of immunity. The experiments will also evaluate a variety of HCV genomic constructs in plasmids and canary pox vectors, and E1E2 proteins, for induction of humoral and cellular immune responses in chimpanzees. Lymphokine genes (GM-CSF, IL-2 or IL-12) will be used together with HCV viral genes, to assess their efficacy in enhancement of immune responses. The humoral, CD4 T-helper and CTL responses will be analyzed quantitatively and qualitatively. The immunogenicity of HCV genes presented as fusion proteins with ubiquitin and secreting and non-secreting HCV gene-containing plasmids will be compared.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI047349-01
Application #
2907063
Study Section
Special Emphasis Panel (ZDK1-GRB-5 (M1))
Program Officer
Johnson, Leslye D
Project Start
1999-09-30
Project End
2004-08-31
Budget Start
1999-09-30
Budget End
2000-08-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
New York Blood Center
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Youn, Jin-Won; Hu, Yu-Wen; Tricoche, Nancy et al. (2008) Evidence for protection against chronic hepatitis C virus infection in chimpanzees by immunization with replicating recombinant vaccinia virus. J Virol 82:10896-905
Yao, Zhi Qiang; Shata, Mohamed Tarek; Tricoche, Nancy et al. (2006) gC1qR expression in chimpanzees with resolved and chronic infection: potential role of HCV core/gC1qR-mediated T cell suppression in the outcome of HCV infection. Virology 346:324-37
Shata, Mohamed Tarek M; Pfahler, Wolfram; Brotman, Betsy et al. (2006) Attempted therapeutic immunization in a chimpanzee chronic HBV carrier with a high viral load. J Med Primatol 35:165-71
Farid, A; Al-Sherbiny, M; Osman, A et al. (2005) Schistosoma infection inhibits cellular immune responses to core HCV peptides. Parasite Immunol 27:189-96
Al-Sherbiny, Maged; Osman, Ahmed; Mohamed, Nahla et al. (2005) Exposure to hepatitis C virus induces cellular immune responses without detectable viremia or seroconversion. Am J Trop Med Hyg 73:44-9
Prince, Alfred M; Brotman, Betsy; Lee, Dong-Hun et al. (2005) Protection against chronic hepatitis C virus infection after rechallenge with homologous, but not heterologous, genotypes in a chimpanzee model. J Infect Dis 192:1701-9
Prince, A M; Pawlotsky, J-M; Soulier, A et al. (2004) Hepatitis C virus replication kinetics in chimpanzees with self-limited and chronic infections. J Viral Hepat 11:236-42
Shata, Mohamed Tarek; Shan, Mei Mei; Tricoche, Nancy et al. (2003) Optimization of recombinant vaccinia-based ELISPOT assay. J Immunol Methods 283:281-9
Shata, Mohamed Tarek; Tricoche, Nancy; Perkus, Marion et al. (2003) Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees. Virology 314:601-16
Prince, Alfred M; Brotman, Betsy; Lee, Dong-Hun et al. (2002) Lack of evidence for HIV type 1-related SIVcpz infection in captive and wild chimpanzees (Pan troglodytes verus) in West Africa. AIDS Res Hum Retroviruses 18:657-60

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