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Fusion of HCV nonstructural antigen to MHC class II-associated invariant chain enhances T-cell responses induced by vectored vaccines in nonhuman primates.

Abstract
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.
AuthorsStefania Capone, Mariarosaria Naddeo, Anna Morena D'Alise, Adele Abbate, Fabiana Grazioli, Annunziata Del Gaudio, Mariarosaria Del Sorbo, Maria Luisa Esposito, Virginia Ammendola, Gemma Perretta, Alessandra Taglioni, Stefano Colloca, Alfredo Nicosia, Riccardo Cortese, Antonella Folgori
JournalMolecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 22 Issue 5 Pg. 1039-47 (May 2014) ISSN: 1525-0024 [Electronic] United States
PMID24476798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Differentiation, B-Lymphocyte
  • Antigens, Viral
  • Histocompatibility Antigens Class II
  • Recombinant Fusion Proteins
  • Vaccines
  • invariant chain
  • Interferon-gamma
Topics
  • Adenoviridae (genetics, immunology)
  • Animals
  • Antigens, Differentiation, B-Lymphocyte (immunology, therapeutic use)
  • Antigens, Viral (genetics, immunology, therapeutic use)
  • CD8-Positive T-Lymphocytes (immunology)
  • Genes, MHC Class II (immunology)
  • Hepacivirus (immunology)
  • Hepatitis C (immunology, therapy)
  • Histocompatibility Antigens Class II (immunology, therapeutic use)
  • Humans
  • Interferon-gamma (immunology, metabolism)
  • Mice
  • Pan troglodytes
  • Recombinant Fusion Proteins (immunology, therapeutic use)
  • Vaccines (immunology)

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