title: Loading dendritic cells with PLA-p24 nanoparticles or MVA expressing HIV genes induces HIV-1-specific T cell responses.
abstract: Since recent data suggest that nanoparticles and modified vaccinia ankara (MVA) vectors could play a pivotal role in HIV-1 therapeutics and vaccine design, in an ex vivo model of human monocyte-derived dendritic cells (MDDCs), we compared two different loading strategies with HIV-1 vaccine vehicles, either viral or synthetic derived. We used polylactic acid (PLA) colloidal biodegradable particles, coated with HIV Gag antigens (p24), and MVA expressing Gag (rMVA-gag and rMVA-gag/trans membrane) or Tat, Nef and Rev genes (rMVA tat+rev and rMVA nef). PLA-p24 captured by MDDCs from HIV-1 individuals induced a slight degree of MDDC maturation, cytokine and chemokine secretion and migration towards a gradient of CCL19 chemokine and highly increased HIV-specific CD8(+) T-cell proliferation compared with p24 alone. After complete maturation induction of PLA-p24-pulsed MDDCs, maximal migration towards a gradient of CCL19 chemokine and induction of HIV-specific T-cell proliferation (two-fold higher for CD4(+) than CD8(+)) and cytokine secretion (IFN-γ and IL-2) in the co-culture were observed. Upon exposure to MVA-gag, MDDCs produced cytokines and chemokines and maintained their capacity to migrate to a gradient of CCL19. MDDCs infected with MVA-gag and MVA-gag trans-membrane were able to induce HIV-specific CD8(+) proliferation and secretion of IFN-γ, IL-2, IL-6 and TNF-α. We conclude that both HIV antigens loading strategies (PLA-p24 nanoparticles or MVA expressing HIV genes) induce HIV-1-specific T-cell responses, which are able to kill autologous gag-expressing cells. Thus, they are plausible candidates for the development of anti-HIV vaccines.
authors.affiliation: Service of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain; AIDS Research Group, and Catalonian Center for HIV Vaccines (HIVACAT), Barcelona, Spain. Electronic address: ncliment@clinic.ub.es.
authors.forename: Núria
authors.initials: N
authors.lastname: Climent
authors.affiliation: Institut de Biology et Chimie des Protéines, UMR5305, UCBL, 7 Passage du Vercors, 69367 Lyon Cedex 07, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Munier
authors.affiliation: Department of Microbiology and Parasitology, Pharmacy Faculty, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Piqué
authors.affiliation: AIDS Research Group, and Catalonian Center for HIV Vaccines (HIVACAT), Barcelona, Spain; Infectious Diseases and AIDS Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.affiliation: Institut de Biology et Chimie des Protéines, UMR5305, UCBL, 7 Passage du Vercors, 69367 Lyon Cedex 07, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pavot
authors.affiliation: Institut de Biology et Chimie des Protéines, UMR5305, UCBL, 7 Passage du Vercors, 69367 Lyon Cedex 07, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Primard
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Casanova
authors.affiliation: AIDS Research Group, and Catalonian Center for HIV Vaccines (HIVACAT), Barcelona, Spain; Infectious Diseases and AIDS Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Institut de Biology et Chimie des Protéines, UMR5305, UCBL, 7 Passage du Vercors, 69367 Lyon Cedex 07, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.affiliation: Service of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain; AIDS Research Group, and Catalonian Center for HIV Vaccines (HIVACAT), Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D019344:Lactic Acid / Q000494:pharmacology; D053758:Nanoparticles; D011091:Polyesters; D011108:Polymers / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; C515460:CCL19 protein, human; D054415:Chemokine CCL19; D015488:HIV Antigens; D016655:HIV Core Protein p24; C573415:IFNG protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; D011091:Polyesters; D011108:Polymers; D014614:Vaccines, Synthetic; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D019344:Lactic Acid; C033616:poly(lactide); D007371:Interferon-gamma
keywords: Cytokines; HIV core protein p24; HIV immunogens; Human CD4(+) T and CD8(+) T-cells; Human monocytes derived-dendritic cells; MVA; Polylactic acid (PLA) particles; Proliferation