Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.
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 immu...
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2012
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oai:doaj.org-article:d2fbd70e5f1c483eba57e0bcefc85a232021-11-18T07:21:36ZSystems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.1932-620310.1371/journal.pone.0035485https://doaj.org/article/d2fbd70e5f1c483eba57e0bcefc85a232012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22536391/?tool=EBIhttps://doaj.org/toc/1932-6203Based 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.Carmen Elena GómezBeatriz PerdigueroVictoria JiménezAbdelali Filali-MouhimKhader GhneimElias K HaddadEsther D QuakkelaarJulie DelaloyeAlexandre HarariThierry RogerThomas DuhenRafick P SékalyCornelis J M MeliefThierry CalandraFederica SallustoAntonio LanzavecchiaRalf WagnerGiuseppe PantaleoMariano EstebanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35485 (2012) |
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| spellingShingle |
Medicine R Science Q Carmen Elena Gómez Beatriz Perdiguero Victoria Jiménez Abdelali Filali-Mouhim Khader Ghneim Elias K Haddad Esther D Quakkelaar Julie Delaloye Alexandre Harari Thierry Roger Thomas Duhen Rafick P Sékaly Cornelis J M Melief Thierry Calandra Federica Sallusto Antonio Lanzavecchia Ralf Wagner Giuseppe Pantaleo Mariano Esteban Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C. |
| description |
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. |
| format |
article |
| author |
Carmen Elena Gómez Beatriz Perdiguero Victoria Jiménez Abdelali Filali-Mouhim Khader Ghneim Elias K Haddad Esther D Quakkelaar Julie Delaloye Alexandre Harari Thierry Roger Thomas Duhen Rafick P Sékaly Cornelis J M Melief Thierry Calandra Federica Sallusto Antonio Lanzavecchia Ralf Wagner Giuseppe Pantaleo Mariano Esteban |
| author_facet |
Carmen Elena Gómez Beatriz Perdiguero Victoria Jiménez Abdelali Filali-Mouhim Khader Ghneim Elias K Haddad Esther D Quakkelaar Julie Delaloye Alexandre Harari Thierry Roger Thomas Duhen Rafick P Sékaly Cornelis J M Melief Thierry Calandra Federica Sallusto Antonio Lanzavecchia Ralf Wagner Giuseppe Pantaleo Mariano Esteban |
| author_sort |
Carmen Elena Gómez |
| title |
Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C. |
| title_short |
Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C. |
| title_full |
Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C. |
| title_fullStr |
Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C. |
| title_full_unstemmed |
Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C. |
| title_sort |
systems analysis of mva-c induced immune response reveals its significance as a vaccine candidate against hiv/aids of clade c. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/d2fbd70e5f1c483eba57e0bcefc85a23 |
| work_keys_str_mv |
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