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Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.

Abstract
Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world.
AuthorsCarmen Elena Gómez, Beatriz Perdiguero, Victoria Jiménez, Abdelali Filali-Mouhim, Khader Ghneim, Elias K Haddad, Esther D Quakkelaar, Esther D Quakkerlaar, Julie Delaloye, Alexandre Harari, Thierry Roger, Thomas Duhen, Thomas Dunhen, Rafick P Sékaly, Cornelis J M Melief, Thierry Calandra, Federica Sallusto, Antonio Lanzavecchia, Ralf Wagner, Giuseppe Pantaleo, Mariano Esteban
JournalPloS one (PLoS One) Vol. 7 Issue 4 Pg. e35485 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID22536391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • AIDS Vaccines
  • Antibodies, Viral
  • Antigens, Viral
  • Cytokines
  • HIV Envelope Protein gp120
  • Recombinant Proteins
  • Vaccines, Synthetic
  • gag Gene Products, Human Immunodeficiency Virus
  • gp120 protein, Human immunodeficiency virus 1
Topics
  • AIDS Vaccines (immunology)
  • Animals
  • Antibodies, Viral (blood)
  • Antigen Presentation
  • Antigens, Viral (biosynthesis)
  • Cell Proliferation
  • Cells, Cultured
  • Cross-Priming
  • Cytokines (metabolism)
  • Dendritic Cells (immunology, metabolism, virology)
  • Gene Expression
  • Gene Expression Profiling
  • HIV Envelope Protein gp120 (immunology)
  • HIV Infections (immunology, prevention & control)
  • HIV-1 (immunology)
  • Humans
  • Immunity, Active (genetics)
  • Immunity, Innate (genetics)
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins (biosynthesis)
  • Signal Transduction (genetics)
  • Systems Analysis
  • T-Lymphocytes (immunology, physiology, virology)
  • Vaccination
  • Vaccines, Synthetic (genetics, immunology)
  • Vaccinia virus (genetics, immunology)
  • gag Gene Products, Human Immunodeficiency Virus (biosynthesis)

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