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.