Induction of potent and long-lasting CD4 and CD8 T-cell responses against hepatitis C virus by immunization with viral antigens plus poly(I:C) and anti-CD40.
Development of vaccination strategies against hepatitis C virus (HCV) is of paramount importance. With this aim, we tested the ability of dendritic cell-activating reagents polyinosinic-polycytidylic acid (poly(I:C)) and anti-CD40, as adjuvants to induce T-cell responses against HCV. Immunization of mice with these adjuvants induced dendritic cell maturation in vivo. Also, joint administration of poly(I:C) and anti-CD40 plus HCV antigens had a synergistic effect on the induction of anti-HCV T-cell responses. CD4 responses displayed a Th1 cytokine profile, and CD8 responses could be induced by immunization with a minimal CD8 epitope. Addition of a low amount of NS3 protein (as a source of Th epitopes) to the immunization mixture enhanced CD8 responses, whereas immunization with higher doses of NS3 induced both CD4 and CD8 responses. Surprisingly, immunization with NS3 protein but not with CD8 epitopes was able to induce CD8 responses and able to recognize cells expressing HCV antigens endogenously. Moreover, immunization with these adjuvants activated NK cells, which in turn helped to induce Th1 responses. Finally, this combined immunization protocol afforded long-lasting T-cell responses, suggesting that this strategy may prove to be useful in vaccination and/or treatment of HCV infection.
Zabaleta
Aintzane
A
University of Navarra, Center for Applied Medical Research (CIMA), Division of Hepatology and Gene Therapy, 31008 Pamplona, Spain.
Arribillaga
Laura
L
Llopiz
Diana
D
Dotor
Javier
J
Lasarte
Juan J
JJ
Prieto
Jesús
J
Borrás-Cuesta
Francisco
F
Esteban
Juan I
JI
Quer
Josep
J
Vayreda
Francesc
F
Sarobe
Pablo
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology*; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology; D004357:Drug Synergism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology*; D013997:Time Factors; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000956:Antigens, Viral; D019013:CD40 Antigens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D011070:Poly I-C; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases