Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model

Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model

^*Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health; ^†Laboratory of Hepatitis Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892; ^§Department of Microbiology, Yamaguchi University School of Medicine, Yamaguchi 755, Japan; and ^¶Department of Microbiology, University of Virginia, Charlottesville, VA 22908

Communicated by Maurice R. Hilleman, Merck & Co., Inc., West Point, PA (received for review August 31, 1999)

Abstract

DNA vaccines express antigens intracellularly and effectively induce cellular immune responses. Because only chimpanzees can be used to model human hepatitis C virus (HCV) infections, we developed a small-animal model using HLA-A2.1-transgenic mice to test induction of HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs) and protection against recombinant vaccinia expressing HCV-core. A plasmid encoding the HCV-core antigen induced CD8⁺ CTLs specific for three conserved endogenously expressed core peptides presented by human HLA-A2.1. When challenged, DNA-immunized mice showed a substantial (5–12 log₁₀) reduction in vaccinia virus titer compared with mock-immunized controls. This protection, lasting at least 14 mo, was shown to be mediated by CD8⁺ cells. Thus, a DNA vaccine expressing HCV-core is a potential candidate for a prophylactic vaccine for HLA-A2.1⁺ humans.

Footnotes

↵ ‡ Present address: 2nd Dept. of Internal Medicine, Yamagata University School of Medicine, Yamagata 990-2331, Japan.
↵ ‖ To whom reprint requests should be addressed at: Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, Building 10, Room 6B-12 (MSC#1578), National Institutes of Health, Bethesda, MD 20892-1578. E-mail: berzofsk{at}helix.nih.gov.
Abbreviations:

CTL,

cytotoxic T lymphocyte;

HA,

hemagglutinin;

HCV,

hepatitis C virus;

rVV,

recombinant vaccinia virus;

pfu,

plaque-forming unit