Comparison of Antibody- and Cell-Mediated Immune Responses After Intramuscular Hepatitis C Immunizations of BALB/c Mice

• DOI: 10.1089/vim.2005.18.637
• Publication Date: 2005-12-16T21:56:32Z
• Authors: M. Ghorbani; T. Nass; A. Azizi; C. Soare; S. Aucoin; A. Giulivi; D.E. Anderson; F. Diaz-Mitoma
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; T-Lymphocytes; Viral Core Proteins; Oleic Acids; Hepatitis C Antibodies; Hepatitis C; Injections, Intramuscular; 3. Good health; Epitopes; Interferon-gamma; Mice; 03 medical and health sciences; Adjuvants, Immunologic; Neutralization Tests; Immunoglobulin G; Models, Animal; Vaccines, DNA; Animals; Mannitol; Interleukin-5; Cell Proliferation

Current treatments for hepatitis C infection have limited efficacy, and there is no vaccine available. The goal of this study was to compare the immune response to several immunization combinations against hepatitis C virus (HCV). Six groups of mice were immunized at weeks 0, 4, and 8 with different combinations of a candidate HCV vaccine consisting of 100 microg recombinant HCV core/E1/E2 (rHCV) DNA plasmid and/or 25 microg rHCV polyprotein and 50 microL Montanide ISA- 51. Four weeks after the last injection, all groups of mice were sacrificed and blood samples and spleens were collected for measuring the levels of specific HCV antibodies (total IgG, IgG1, and IgG2a). Cell proliferation and intracellular interferon-gamma were also measured. Among the groups of immunized mice, only the mice immunized with rHCV DNA plasmid, rHCV polyprotein, and montanide (group D) and mice immunized with rHCV polyprotein and montanide (group F) demonstrated a significant increase in the total IgG titer after immunization. IgG1 was the predominant antibody detected in both groups D and F. No IgG2a was detected in any of the groups. Proliferation assays demonstrated that splenocytes from group D and group C (rHCV DNA primed/rHCV polyprotein boost) developed significant anti-HCV proliferative responses. The combination of an rHCV DNA plasmid, rHCV polyprotein, and montanide induced a high antibody titer with a predominance of IgG1 antibodies and recognized the major neutralization epitopes in HVR1. In contrast, group C did not show an increase in anti-HCV antibodies, but did show a proliferative response.