Elena Gomez, Carmen and Perdiguero, Beatriz and Jimenez, Victoria and Filali-Mouhim, Abdelali and Ghneim, Khader and Haddad, Elias K. and Quakkerlaar, Esther D. and Delaloye, Julie and Harari, Alexandre and Roger, Thierry and Dunhen, Thomas and Sekaly, Rafick P. and Melief, Cornelis J. M. and Calandra, Thierry and Sallusto, Federica and Lanzavecchia, Antonio and Wagner, Ralf and Pantaleo, Giuseppe and Esteban, Mariano (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. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-CELL RESPONSES; POXVIRUS VECTORS MVA; VIRUS ANKARA; DENDRITIC CELLS; HIV-1 INFECTION; PHASE-1 SAFETY; DNA PRIME; IMMUNOGENICITY; NYVAC; ANTIGENS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 May 2020 05:49 |
| Last Modified: | 18 May 2020 05:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18877 |
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