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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.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (4), pp. e35485. Date of Electronic Publication: 2012 Apr 19. - Publication Year :
- 2012
-
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.
- Subjects :
- Animals
Antibodies, Viral blood
Antigen Presentation
Antigens, Viral biosynthesis
Cell Proliferation
Cells, Cultured
Cross-Priming
Cytokines metabolism
Dendritic Cells immunology
Dendritic Cells metabolism
Dendritic Cells virology
Gene Expression
Gene Expression Profiling
HIV Envelope Protein gp120 immunology
HIV Infections immunology
HIV Infections prevention & control
Humans
Immunity, Innate genetics
Mice
Mice, Inbred BALB C
Recombinant Proteins biosynthesis
Signal Transduction genetics
T-Lymphocytes immunology
T-Lymphocytes physiology
T-Lymphocytes virology
Vaccination
Vaccines, Synthetic genetics
Vaccines, Synthetic immunology
Vaccinia virus genetics
gag Gene Products, Human Immunodeficiency Virus biosynthesis
AIDS Vaccines immunology
HIV-1 immunology
Immunity, Active genetics
Systems Analysis
Vaccinia virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22536391
- Full Text :
- https://doi.org/10.1371/journal.pone.0035485