title: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Madrid, Spain.
authors.forename: Carmen Elena
authors.initials: CE
authors.lastname: Gómez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Perdiguero
authors.forename: Victoria
authors.initials: V
authors.lastname: Jiménez
authors.forename: Abdelali
authors.initials: A
authors.lastname: Filali-Mouhim
authors.forename: Khader
authors.initials: K
authors.lastname: Ghneim
authors.forename: Elias K
authors.initials: EK
authors.lastname: Haddad
authors.forename: Esther D
authors.initials: ED
authors.lastname: Quakkelaar
authors.forename: Esther D
authors.initials: ED
authors.lastname: Quakkerlaar
authors.forename: Julie
authors.initials: J
authors.lastname: Delaloye
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harari
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.forename: Thomas
authors.initials: T
authors.lastname: Duhen
authors.forename: Thomas
authors.initials: T
authors.lastname: Dunhen
authors.forename: Rafick P
authors.initials: RP
authors.lastname: Sékaly
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Thierry
authors.initials: T
authors.lastname: Calandra
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000096:biosynthesis; D049109:Cell Proliferation; D002478:Cells, Cultured; D045142:Cross-Priming; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D020869:Gene Expression Profiling; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007110:Immunity, Active / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D013597:Systems Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology / Q000821:virology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D054301:gag Gene Products, Human Immunodeficiency Virus; C514793:gp120 protein, Human immunodeficiency virus 1