Induction of multispecific Th-1 type immune response against HCV in mice by protein immunization using CpG and Montanide ISA 720 as adjuvants.
Recent studies demonstrate that Th1-type immune responses against a broad spectrum of hepatitis C virus (HCV) gene products are crucial to the resolution of acute HCV infection. We investigated new vaccine approaches to augment the strength of HCV-specific Th1-type immune responses. ELISPOT assay revealed that single or multiple protein immunization using both CpG ODN and Montanide ISA 720 as adjuvants induced much stronger IFN-gamma-producing Th1 responses against core, NS3 and NS5b targets than did the formulation without these adjuvants. Protein vaccination using CpG ODN and Montanide ISA 720 as adjuvants also greatly enhanced humoral responses to HCV core, E1/E2 and NS3. When specific IgG isotypes were assayed, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants produced higher titers of IgG2a dominant antibodies than did protein immunization alone, indicating a more Th1-biased pathway. This increase in IgG2a is consistent with the induction of Th1 cells secreting IFN-gamma demonstrated by ELISPOT assay. In conclusion, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants greatly enhanced cellular (Th1 type) as well as humoral immune responses against HCV in Balb/c mice. The use of adjuvants appears critical to the induction of Th1 immune responses during HCV vaccination with recombinant proteins.
Qiu
Qi
Q
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C711, 9000 Rockville Pike, Bethesda, MD 20892-1184, USA.
Wang
Richard Yuan-Hu
RY
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C711, 9000 Rockville Pike, Bethesda, MD 20892-1184, USA.
Jiao
Xuanmao
X
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C711, 9000 Rockville Pike, Bethesda, MD 20892-1184, USA.
Jin
Bo
B
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C711, 9000 Rockville Pike, Bethesda, MD 20892-1184, USA.
Sugauchi
Fuminaka
F
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C711, 9000 Rockville Pike, Bethesda, MD 20892-1184, USA.
Grandinetti
Teresa
T
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C711, 9000 Rockville Pike, Bethesda, MD 20892-1184, USA.
Alter
Harvey J
HJ
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C711, 9000 Rockville Pike, Bethesda, MD 20892-1184, USA.
Shih
J Wai-Kuo
JW
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Building 10, Room 1C711, 9000 Rockville Pike, Bethesda, MD 20892-1184, USA. Electronic address: jwshih@xmu.edu.cn.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000032:analysis / Q000096:biosynthesis; D018936:Hepatitis C Antigens / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007155:Immunologic Factors / Q000032:analysis / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009829:Oleic Acids / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D000276:Adjuvants, Immunologic; D006508:Hepatitis Antibodies; D018936:Hepatitis C Antigens; D007155:Immunologic Factors; D007371:Interferon-gamma; D015847:Interleukin-4; D008353:Mannitol; D009829:Oleic Acids; D009838:Oligodeoxyribonucleotides; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C001681:mannide monooleate; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase