HCV core protein immunization with Montanide/CpG elicits strong Th1/Th2 and long-lived CTL responses.
An efficient vaccine against Hepatitis C virus (HCV) infection requires induction of strong humoral and cellular responses against viral proteins. We evaluated the immunogenicity of HCV core protein (HCVcp), a prime vaccine candidate, formulated in various human compatible adjuvants. An Escherichia coli-expressed HCVcp, purified in native conditions was used for murine immunization in separate groups of: free HCVcp (Ag), Ag+C/IFA (Freunds), Ag+CpG, Ag+M720 (Montanide ISA 720), Ag+F127 (Pluronic acid) and cocktails of Ag+F127+CpG and Ag+M720+CpG. Mice immunized with M720(+CpG) developed the highest HCVcp-specific titers of total IgG, IgG1, 2a, 2b, and that of IFN-gamma and IL-4 cytokines compared to all other groups. HCVcp-specific-CTLs against relevant MHC class I peptides were detected only for Ag+M720+CpG, Ag+M720, and Ag+CpG groups and could be blocked by antimouse-CD8 antibodies. While CTLs were stable, only F127 formulated groups demonstrated detectable IgG antibodies one year post-immunization. Hence, HCVcp formulated in M720 (with a synergistic effect by inclusion of CpG) could induce balanced and strong Th1/Th2 responses with long-lived CD4(-)CD8(+) CTLs.
Roohvand
Farzin
F
Hepatitis and AIDS Department, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran. rfarzin@pasteur.ac.ir
Aghasadeghi
Mohammad-Reza
MR
Sadat
Seyed Mehdi
SM
Budkowska
Agata
A
Khabiri
Ali-Reza
AR
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D018899:CpG Islands; D004926:Escherichia coli / Q000235:genetics; D018936:Hepatitis C Antigens / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009829:Oleic Acids / Q000008:administration & dosage / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D014758:Viral Core Proteins / Q000097:blood / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; D018936:Hepatitis C Antigens; D007074:Immunoglobulin G; D009829:Oleic Acids; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D015847:Interleukin-4; C001681:mannide monooleate; D008353:Mannitol; D007371:Interferon-gamma