Journal article
Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C
PloS one, v 7(4), pp e35485-e35485
19 Apr 2012
PMID: 22536391
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C
- Creators
- Carmen Elena Gómez - University of Cape TownBeatriz Perdiguero - University of Cape TownVictoria Jiménez - University of Cape TownAbdelali Filali-Mouhim - Vaccine & Gene Therapy Institute of FloridaKhader Ghneim - Vaccine & Gene Therapy Institute of FloridaElias K. Haddad - University of Cape TownEsther D. Quakkerlaar - Leiden University Medical CenterJulie Delaloye - University Hospital of LausanneAlexandre Harari - University Hospital of LausanneThierry Roger - University Hospital of LausanneThomas Dunhen - University of Cape TownRafick P. Sékaly - Vaccine & Gene Therapy Institute of FloridaCornelis J. M. Melief - Leiden University Medical CenterThierry Calandra - University Hospital of LausanneFederica Sallusto - Institute for Research in BiomedicineAntonio Lanzavecchia - Institute for Research in BiomedicineRalf Wagner - University of RegensburgGiuseppe Pantaleo - University Hospital of LausanneMariano Esteban - University of Cape Town
- Publication Details
- PloS one, v 7(4), pp e35485-e35485
- Publisher
- Public Library of Science
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000305336200045
- Scopus ID
- 2-s2.0-84859856404
- Other Identifier
- 991020100198604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology