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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

C. Gómez,B. Perdiguero,V. Jiménez,A. Filali‐Mouhim,K. Ghneim,E. Haddad,E. Quakkerlaar,J. Delaloye,A. Harari,T. Roger,T. Duhem,R. Sékaly,C. Melief,T. Calandra,F. Sallusto,A. Lanzavecchia,R. Wagner,G. Pantaleo,M. Esteban

Published 2012 in Retrovirology

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. Citation: Gómez CE, Perdiguero B, Jiménez V, Filali-Mouhim A, Ghneim K, et al. (2012) Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C. PLoS ONE 7(4): e35485. doi:10.1371/journal.pone.0035485 Editor: Clive M. Gray, University of Cape Town, South Africa Received February 16, 2012; Accepted March 16, 2012; Published April 19, 2012 Copyright: 2012 Gómez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was conducted as part of the Poxvirus T Cell Vaccine Discovery Consortium (PTVDC) under the Collaboration for AIDS Vaccine Discovery with support from the Bill & Melinda Gates Foundation and by Spanish grant SAF 2008-02036. JD was supported by a grant from the Swiss National Science Foundation (number 313600-115680). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: mesteban@cnb.csic.es

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