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Immunization With Hiv Gag Targeted To Dendritic Cells Followed By Recombinant New York Vaccinia Virus Induces Robust T-Cell Immunity In Nonhuman Primates, Barbara J. Flynn, Kathrin Kastenmüller, Ulrike Wille-Reece Jan 2011

Immunization With Hiv Gag Targeted To Dendritic Cells Followed By Recombinant New York Vaccinia Virus Induces Robust T-Cell Immunity In Nonhuman Primates, Barbara J. Flynn, Kathrin Kastenmüller, Ulrike Wille-Reece

Publications

Protein vaccines, if rendered immunogenic, would facilitate vaccine development against HIV and other pathogens. We compared in nonhuman primates (NHPs) immune responses to HIV Gag p24 within 3G9 antibody to DEC205 ("DEC-HIV Gag p24"), an uptake receptor on dendritic cells, to nontargeted protein, with or without poly ICLC, a synthetic double stranded RNA, as adjuvant. Priming s.c. with 60 ?g of both HIV Gag p24 vaccines elicited potent CD4+ T cells secreting IL-2, IFN-γ, and TNF-α, which also proliferated. The responses increased with each of three immunizations and recognized multiple Gag peptides. DEC-HIV Gag p24 showed better cross-priming for …


Newcastle Disease Virus Expressing A Dendritic Cell-Targeted Hiv Gag Protein Induces A Potent Gag-Specific Immune Response In Mice, Jad Mammary, Frida Array, Qinshan Gao Jan 2011

Newcastle Disease Virus Expressing A Dendritic Cell-Targeted Hiv Gag Protein Induces A Potent Gag-Specific Immune Response In Mice, Jad Mammary, Frida Array, Qinshan Gao

Publications

Viral vaccine vectors have emerged as an attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine. Recombinant Newcastle disease virus (rNDV) stands out as a vaccine vector since it has a proven safety profile in humans, it is a potent inducer of both alpha interferon (IFN-α) and IFN-β) production, and it is a potent inducer of dendritic cell (DC) maturation. Our group has previously generated an rNDV vector expressing a codon-optimized HIV Gag protein and demonstrated its ability to induce a Gag-specific CD8+ T cell response in mice. In this report we demonstrate that the Gag-specific …


Flt3l Controls The Development Of Radiosensitive Dendritic Cells In The Meninges And Choroid Plexus Of The Steady-State Mouse Brain, Niroshana Anandasabapathy, Gabriel D. Victora, Matthew M. Meredith Jan 2011

Flt3l Controls The Development Of Radiosensitive Dendritic Cells In The Meninges And Choroid Plexus Of The Steady-State Mouse Brain, Niroshana Anandasabapathy, Gabriel D. Victora, Matthew M. Meredith

Publications

Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences …


Dendritic Cells Induce Antigen-Specific Regulatory T Cells That Prevent Graft Versus Host Disease And Persist In Mice, Uri Sela, Peter Olds, Andrew Park Jan 2011

Dendritic Cells Induce Antigen-Specific Regulatory T Cells That Prevent Graft Versus Host Disease And Persist In Mice, Uri Sela, Peter Olds, Andrew Park

Publications

Foxp3 + regulatory T cells (T reg cells) effectively suppress immunity, but it is not determined if antigen-induced T reg cells (iT reg cells) are able to persist under conditions of inflammation and to stably express the transcription factor Foxp3. We used spleen cells to stimulate the mixed leukocyte reaction (MLR) in the presence of transforming growth factor β (TGF-β) and retinoic acid. We found that the CD11c high dendritic cell fraction was the most potent at inducing high numbers of alloreactive Foxp3 + cells. The induced CD4 +CD25 +Foxp3 + cells appeared after extensive proliferation. When purified …


Snapshot: Dendritic Cells, Juliana Idoyaga, Ralph M. Steinman Jan 2011

Snapshot: Dendritic Cells, Juliana Idoyaga, Ralph M. Steinman

Publications

[No abstract available]


Synthetic Double-Stranded Rna Induces Innate Immune Responses Similar To A Live Viral Vaccine In Humans, Marina Caskey, François Lefebvre, Ali Filali-Mouhim Jan 2011

Synthetic Double-Stranded Rna Induces Innate Immune Responses Similar To A Live Viral Vaccine In Humans, Marina Caskey, François Lefebvre, Ali Filali-Mouhim

Publications

Adjuvants are critical for the success of vaccines. Agonists of microbial pattern recognition receptors (PRRs) are promising new adjuvant candidates. A mechanism through which adjuvants enhance immune responses is to stimulate innate immunity. We studied the innate immune response in humans to synthetic double-stranded RNA (polyinosinic:polycytidylic acid [poly IC] stabilized with poly-l-lysine [poly ICLC]), an agonist for toll-like receptor (TLR) 3, and the cytosolic RNA helicase MDA-5. Transcriptional analysis of blood samples from eight volunteers, after subcutaneous administration of poly ICLC, showed upregulation of genes involved in multiple innate immune pathways in all subjects, including interferon (IFN) and inflammasome signaling. …


Flt3 Signaling-Dependent Dendritic Cells Protect Against Atherosclerosis, Jae-Hoon Choi, Cheolho Cheong, Guillaume Darrasse-Jèze Jan 2011

Flt3 Signaling-Dependent Dendritic Cells Protect Against Atherosclerosis, Jae-Hoon Choi, Cheolho Cheong, Guillaume Darrasse-Jèze

Publications

Early events in atherosclerosis occur in the aortic intima and involve monocytes that become macrophages. We looked for these cells in the steady state adult mouse aorta, and surprisingly, we found a dominance of dendritic cells (DCs) in the intima. In contrast to aortic adventitial macrophages, CD11c +MHC II hi DCs were poorly phagocytic but were immune stimulatory. DCs were of two types primarily: classical Flt3-Flt3L signaling-dependent, CD103 +CD11b - DCs and macrophage-colony stimulating factor (M-CSF)-dependent, CD14 +CD11b +DC-SIGN + monocyte-derived DCs. Both types expanded during atherosclerosis. By crossing Flt3 -/- to Ldlr -/- atherosclerosis-prone mice, …