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

Gómez, Carmen Elena; Perdiguero, Beatriz; Jiménez, Victoria; Filali-Mouhim, Abdelali; Ghneim, Khader; Haddad, Elias K.; Quakkerlaar, Esther D.; Delaloye, Julie; Harari, Alexandre; Roger, Thierry; Dunhen, Thomas; Sékaly, Rafick P.; Melief, Cornelis J. M.; Calandra, Thierry; Sallusto, Federica; Lanzavecchia, Antonio; Wagner, Ralf; Pantaleo, Giuseppe; Esteban, Mariano

doi:10.1371/journal.pone.0035485

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Journal article

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

Gómez, Carmen Elena Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Madrid, Spain
Perdiguero, Beatriz Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Madrid, Spain
Jiménez, Victoria Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Madrid, Spain
Filali-Mouhim, Abdelali Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, Florida, United States of America
Ghneim, Khader Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, Florida, United States of America
Haddad, Elias K. Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, Florida, United States of America
Quakkerlaar, Esther D. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
Delaloye, Julie Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland - University of Lausanne, Lausanne, Switzerland
Harari, Alexandre Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Roger, Thierry Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland - University of Lausanne, Lausanne, Switzerland
Dunhen, Thomas Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Sékaly, Rafick P. Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, Florida, United States of America
Melief, Cornelis J. M. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
Calandra, Thierry Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland -University of Lausanne, Lausanne, Switzerland
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Wagner, Ralf University of Regensburg, Regensburg, Germany
Pantaleo, Giuseppe Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Esteban, Mariano Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Madrid, Spain

19.04.2012

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Plos one. - 2012, vol. 7, no. 4, p. e35485

English 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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