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Clinical and Vaccine Immunology, February 2009, p. 163-171, Vol. 16, No. 2
1071-412X/09/$08.00+0     doi:10.1128/CVI.00287-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Generation of Immune Responses against Hepatitis C Virus by Dendritic Cells Containing NS5 Protein-Coated Microparticles {triangledown}

Stephan Gehring,1,3 Stephen H. Gregory,2 Philip Wintermeyer,1 Costica Aloman,4 and Jack R. Wands1*

The Liver Research Center,1 Laboratory of Infectious Diseases, Department of Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903,2 Kinderklinik der Johannes Gutenberg-Universität, 55101 Mainz, Germany,3 Mount Sinai School of Medicine, New York, New York 100294

Received 8 August 2008/ Returned for modification 8 October 2008/ Accepted 8 December 2008

Dendritic cells (DCs) internalize and process antigens as well as activate cellular immune responses. The aim of this study was to determine the capacity of DCs that contain antigen-coated magnetic beads to induce immunity against the nonstructural hepatitis C virus (HCV) antigen 5 (NS5). Splenocytes derived from Fms-like tyrosine kinase receptor 3 (Flt3) ligand-pretreated BALB/c mice were incubated with magnetic beads coated with HCV NS5, lipopolysaccharide (LPS), and/or anti-CD40; purified; and used for immunization. Cellular immunity was measured using cytotoxic T-lymphocyte (CTL) and T-cell proliferation assays, intracellular cytokine staining, and a syngeneic tumor challenge using NS5-expressing SP2/0 myeloma cells in vivo. Splenocytes isolated from animals vaccinated with DCs containing beads coated with NS5, LPS, and anti-CD40 secreted elevated levels of interleukin-2 (IL-2) and gamma interferon in the presence of NS5. The numbers of CD4+, IL-2-producing cells were increased >5-fold in the group immunized with DCs containing beads coated with NS5, LPS, and anti-CD40, paralleled by an enhanced splenocyte proliferative response. Immunization promoted antigen-specific CTL activity threefold compared to the level for control mice and significantly reduced the growth of NS5-expressing tumor cells in vivo. Thus, strategies that employ NS5-coated beads induce cellular immune responses in mice, which correlate well with the natural immune responses that occur in individuals who resolve HCV.

* Corresponding author. Mailing address: The Liver Research Center, 55 Claverick St., 4th Floor, Providence, RI 02903. Phone: (401) 444-2795. Fax: (401) 444-2939. E-mail: Jack_Wands_MD{at}Brown.edu

{triangledown} Published ahead of print on 17 December 2008.

Clinical and Vaccine Immunology, February 2009, p. 163-171, Vol. 16, No. 2
1071-412X/09/$08.00+0     doi:10.1128/CVI.00287-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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