Open AccessSystems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C
Author(s) -
Carmen Elena Gómez,
Beatriz Perdiguero,
Victoria Jiménez,
Abdelali Filali-Mouhim,
Khader Ghneim,
Elias K. Haddad,
Esther D. Quakkerlaar,
Julie Delaloye,
Alexandre Harari,
Thierry Roger,
Thomas Dunhen,
Rafick Pierre Sékaly,
Cornelis J.M. Melief,
Thierry Calandra,
Federica Sallusto,
Antonio Lanzavecchia,
Ralf Wagner,
Giuseppe Pantaleo,
Mariano Esteban
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0035485
Subject(s) - modified vaccinia ankara , biology , virology , antigen , hiv vaccine , cd80 , immune system , cd8 , cd86 , t cell , hiv antigens , immunology , cytotoxic t cell , vaccinia , vaccine trial , virus , cd40 , vaccination , recombinant dna , in vitro , genetics , gene , viral disease
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.