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PMID: 12477843 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

DNA immunization with hepatitis C virus (HCV) polycistronic genes or immunization by HCV DNA priming-recombinant canarypox virus boosting induces immune responses and protection from recombinant HCV-vaccinia virus infection in HLA-A2.1-transgenic mice.

Journal of virology ·Vol. 77 ·No. 1 ·2003-01-00 ·Pages 382-90

Pancholi P, Perkus M, Tricoche N, Liu Q, Prince AM

Abstract

We studied immune responses to hepatitis C virus (HCV) genes delivered as DNA encoding the entire HCV protein coding genome in two polycistronic plasmids encoding HCV capsid-E1-E2-NS2-NS3 and HCV NS3-NS4-NS5 in HLA-A2.1-transgenic mice. Immune responses to HCV DNA prime and recombinant canarypox virus boost were also studied with the above constructs. At 8 weeks after a canarypox virus boost, the DNA prime/canarypox virus boosting regimen induced potent cellular immune responses to HCV structural and nonstructural proteins on target cells expressing the HLA-A2.1 allele. High frequencies of gamma interferon-secreting cells, as detected by enzyme-linked immunospot assay, were obtained in response to several endogenously expressed HCV proteins. We also observed cytotoxic-T-lymphocyte reactivity in response to endogenously expressed HCV proteins in fresh spleen cells without in vitro expansion. Upon challenge with a recombinant vaccinia virus expressing HCV proteins at 2 months postimmunization, the HCV DNA prime/canarypox virus-immunized mice showed a complete reduction in vaccinia virus titers compared to HCV DNA prime/boost- and mock-immunized controls. Immune responses were still detectable 4 months after canarypox virus boost in immunized mice. Interestingly, at 10 months postimmunization (8 months after canarypox virus boost), the protection in HCV DNA prime/boost-immunized mice against recombinant HCV-vaccinia virus challenge was higher than that observed in HCV DNA prime/canarypox virus boost-immunized mice.

MeSH Terms
Animals CD8 Antigens/physiology Canarypox virus/genetics Cytokines/biosynthesis,genetics Genes HLA-A2 Antigen/physiology Hepacivirus/genetics,immunology Hepatitis C/prevention & control Immunization Immunologic Memory Interferon-gamma/biosynthesis Mice Mice, Inbred C57BL Mice, Transgenic T-Lymphocytes, Cytotoxic/immunology Tumor Cells, Cultured Vaccines, DNA/immunology Vaccines, Synthetic/immunology Viral Hepatitis Vaccines/immunology
Chemicals
CD8 Antigens Cytokines HLA-A2 Antigen Vaccines, DNA Vaccines, Synthetic Viral Hepatitis Vaccines Interferon-gamma
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pancholi Preeti
Laboratory of Virology, Lindsley F. Kimball Research Institute of the New York Blood Center, New York 10021, USA.
Perkus Marion
Tricoche Nancy
Liu Qingyan
Prince Alfred M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.77.1.382-390.2003
Published
2003-01-00
Pages
382-90
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC140575
Subset
IM
Grants
PHS HHS · A147349 · United States
External Links
PubMed source DOI: 10.1128/jvi.77.1.382-390.2003 PMC Full Text View journal details
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