Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus.
The induction of protective or therapeutic cellular immunity against hepatitis C virus (HCV) is a difficult goal. In a previous work we showed that immunization with a recombinant adenovirus encoding HCV-NS3 (RAdNS3) could partially protect mice from challenge with a vaccinia virus encoding HCV antigens. We sought to investigate whether systemic administration of an immunostimulatory monoclonal antibody directed against the lymphocyte surface molecule CD137 could enhance the immunity elicited by RAdNS3. It was found that treatment with anti-CD137 mAb after the administration of a suboptimal dose of RAdNS3 enhanced cytotoxic and T helper cell responses against HCV NS3. Importantly, the ability of RAdNS3 to induce protective immunity against challenge with a recombinant vaccinia virus expressing HCV proteins was markedly augmented. Thus, combination of immunostimulatory anti-CD137 mAb with recombinant adenoviruses expressing HCV proteins might be useful in strategies of immunization against HCV.
Arribillaga
Laura
L
Division of Hepatology and Gene Therapy, University Clinic, Faculty of Medicine, Center for Applied Medical Research (CIMA), University of Navarra, Pio XII 55, 31008 Pamplona, Spain.
Sarobe
Pablo
P
Arina
Ainhoa
A
Gorraiz
Marta
M
Borrás-Cuesta
Francisco
F
Ruiz
Juan
J
Prieto
Jesús
J
Chen
Lieping
L
Melero
Ignacio
I
Lasarte
Juan José
JJ
D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D017475:Receptors, Nerve Growth Factor / Q000008:administration & dosage / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load / Q000379:methods
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines