Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.

Détails

Ressource 1Télécharger: BIB_C791C445724A.P001.pdf (1391.92 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_C791C445724A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.
Périodique
Plos One
Auteur(s)
Gómez C.E., Perdiguero B., Jiménez V., Filali-Mouhim A., Ghneim K., Haddad E.K., Quakkelaar E.D., Quakkerlaar E.D., Delaloye J., Harari A., Roger T., Dunhen T., Sékaly R.P., Melief C.J., Calandra T., Sallusto F., Lanzavecchia A., Wagner R., Pantaleo G., Esteban M.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2012
Volume
7
Numéro
4
Pages
e35485
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
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.
Mots-clé
AIDS Vaccines/immunology, Animals, Antibodies, Viral/blood, Antigen Presentation, Antigens, Viral/biosynthesis, Cell Proliferation, Cells, Cultured, Cross-Priming, Cytokines/metabolism, Dendritic Cells/immunology, Dendritic Cells/metabolism, Gene Expression, Gene Expression Profiling, HIV Envelope Protein gp120/immunology, HIV Infections/immunology, HIV Infections/prevention & control, HIV-1/immunology, Humans, Immunity, Active/genetics, Immunity, Innate/genetics, Mice, Mice, Inbred BALB C, Recombinant Proteins/biosynthesis, Signal Transduction/genetics, Systems Analysis, T-Lymphocytes/immunology, T-Lymphocytes/physiology, Vaccination, Vaccines, Synthetic/genetics, Vaccines, Synthetic/immunology, Vaccinia virus/genetics, Vaccinia virus/immunology, gag Gene Products, Human Immunodeficiency Virus/biosynthesis
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/07/2012 22:26
Dernière modification de la notice
09/05/2019 1:06
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