Fusion of HCV nonstructural antigen to MHC class II-associated invariant chain enhances T-cell responses induced by vectored vaccines in nonhuman primates.
Despite viral vectors being potent inducers of antigen-specific T cells, strategies to further improve their immunogenicity are actively pursued. Of the numerous approaches investigated, fusion of the encoded antigen to major histocompatibility complex class II-associated invariant chain (Ii) has been reported to enhance CD8(+) T-cell responses. We have previously shown that adenovirus vaccine encoding nonstructural (NS) hepatitis C virus (HCV) proteins induces potent T-cell responses in humans. However, even higher T-cell responses might be required to achieve efficacy against different HCV genotypes or therapeutic effect in chronically infected HCV patients. In this study, we assessed fusion of the HCV NS antigen to murine and human Ii expressed by the chimpanzee adenovirus vector ChAd3 or recombinant modified vaccinia Ankara in mice and nonhuman primates (NHPs). A dramatic increase was observed in outbred mice in which vaccination with ChAd3 expressing the fusion antigen resulted in a 10-fold increase in interferon-γ(+) CD8(+) T cells. In NHPs, CD8(+) T-cell responses were enhanced and accelerated with vectors encoding the Ii-fused antigen. These data show for the first time that the enhancement induced by vector vaccines encoding li-fused antigen was not species specific and can be translated from mice to NHPs, opening the way for testing in humans.
Okairos, Rome, Italy.
Stefania
S
Capone
Okairos, Rome, Italy.
Mariarosaria
M
Naddeo
Okairos, Rome, Italy.
Anna Morena
AM
D'Alise
Okairos, Rome, Italy.
Adele
A
Abbate
Okairos, Rome, Italy.
Fabiana
F
Grazioli
Okairos, Rome, Italy.
Annunziata
A
Del Gaudio
Okairos, Rome, Italy.
Mariarosaria
M
Del Sorbo
Okairos, Rome, Italy.
Maria Luisa
ML
Esposito
Okairos, Rome, Italy.
Virginia
V
Ammendola
Cellular Biology and Neurobiology Institute (IBCN) National Research Council of Italy, Rome, Italy.
Gemma
G
Perretta
Cellular Biology and Neurobiology Institute (IBCN) National Research Council of Italy, Rome, Italy.
Alessandra
A
Taglioni
Okairos, Rome, Italy.
Stefano
S
Colloca
1] Okairos, Rome, Italy [2] CEINGE, Naples, Italy [3] Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
Alfredo
A
Nicosia
1] Okairos, Rome, Italy [2] Okairos AG, c/o OBC Suisse AG, Basel, Switzerland.
Riccardo
R
Cortese
Okairos, Rome, Italy.
Antonella
A
Folgori
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000627:therapeutic use; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005802:Genes, MHC Class II / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000628:therapy*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D002679:Pan troglodytes; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000627:therapeutic use; D014612:Vaccines / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D000956:Antigens, Viral; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C045084:invariant chain; D007371:Interferon-gamma