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https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#1
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28436755/modes-of-action-for-mucosal-vaccine-adjuvants
#2
Taiki Aoshi
Vaccine adjuvants induce innate immune responses and the addition of adjuvants to the vaccine helps to induce protective immunity in the host. Vaccines utilizing live attenuated or killed whole pathogens usually contain endogenous adjuvants, such as bacterial cell wall products and their genomic nucleic acids, which act as pathogen-associated molecular patterns and are sufficient to induce adaptive immune responses. However, purified protein- or antigen-based vaccines, including component or recombinant vaccines, usually lose these endogenous innate immune stimulators, so the addition of an exogenous adjuvant is essential for the success of these vaccine types...
April 24, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28436425/monocyte-differentiation-and-antigen-presenting-functions
#3
REVIEW
Claudia V Jakubzick, Gwendalyn J Randolph, Peter M Henson
Monocytes develop in the bone marrow and represent the primary type of mononuclear phagocyte found in the blood. They were long thought of as a source for tissue macrophages, but recent studies indicate more complex roles for monocytes, both within the circulation and after their migration into tissues and lymphoid organs. In this Review, we discuss the newer concepts underlying the maturation of emigrating monocytes into different classes of tissue macrophages, as well as their potential functions, as monocyte-derived cells, in the tissues...
April 24, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28435136/chitosan-enhances-nanoparticle-delivery-from-the-reproductive-tract-to-target-draining-lymphoid-organs
#4
Jaehyung Park, Renuka Ramanathan, Linhchi Pham, Kim A Woodrow
To prime adaptive immune responses from the female reproductive tract (FRT), particulate antigens must be transported to draining lymph nodes (dLNs) since there are no local organized lymphoid structures equivalent to those found in the respiratory or gastrointestinal tracts. However, little is known about how to safely and effectively navigate successive barriers to transport such as crossing the epithelium and gaining access to migratory cells and lymphatic drainage that provide entry into dLNs. Here, we demonstrate that intravaginal pre-treatment with chitosan significantly facilitates translocation of nanoparticles (NPs) across the multilayered vaginal epithelium to target dLNs...
April 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28433944/evaluation-of-vaccinal-effectiveness-of-preparations-containing-membrane-antigens-of-leishmania-l-amazonensis-in-experimental-cutaneous-leishmaniasis-model
#5
João G Ribeiro, Amália S Ferreira, Sharon R A Macedo, Norton R D L P Rossi, Mayara C P da Silva, Rosane N M Guerra, Neuza B de Barros, Roberto Nicolete
American tegumentary leishmaniasis (ATL) is considered a neglected disease, for which an effective vaccine or an efficient diagnosis is not yet available and whose chemotherapeutic arsenal is threatened by the emergence of resistance by etiological agents such as Leishmania amazonensis. ATL is endemic in poor countries and has a high incidence in Brazil. Vaccines developed from native parasite fractions have led to the identification of defined antigenic subunits and the development of vaccine adjuvant technology...
April 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28431490/new-challenges-in-therapeutic-vaccines-against-hiv-infection
#6
Lorna Leal, Constanza Lucero, Josep M Gatell, Teresa Gallart, Montserrat Plana, Felipe García
There is a growing interest in developing curative strategies for HIV infection. Therapeutic vaccines are one of the most promising approaches. We will review the current knowledge and the new challenges in this research field. Areas covered: PubMed and ClinicalTrial.gov databases were searched to review the progress and prospects for clinical development of immunotherapies aimed to cure HIV infection. Dendritic cells (DC)-based vaccines have yielded the best results in the field. However, major immune-virologic barriers may hamper current vaccine strategies...
April 21, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28429211/influence-of-humic-acids-extracted-from-peat-by-different-methods-on-functional-activity-of-macrophages-in-vitro
#7
E S Trofimova, M V Zykova, A A Ligacheva, E Y Sherstoboev, V V Zhdanov, M V Belousov, M S Yusubov, S V Krivoshchekov, M G Danilets, A M Dygai
We studied activation of macrophages with humic acids extracted from peat of large deposits in the Tomsk region by two extraction methods: by hydroxide or sodium pyrophosphate. Humic acid of lowland peat types containing large amounts of aromatic carbon, phenolic and alcohol groups, carbohydrate residues and ethers, irrespectively of the extraction methods contained LPS admixture that probably determines their activating properties. Humic acid of upland peat types characterized by high content of carbonyl, carboxyl, and ester groups enhance NO production and reduce arginase expression, but these effects were minimized when sodium hydroxide was used as an extraction solvent...
April 20, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#8
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428556/treatment-of-donor-corneal-tissue-with-immunomodulatory-cytokines-a-novel-strategy-to-promote-graft-survival-in-high-risk-corneal-transplantation
#9
Maryam Tahvildari, Parisa Emami-Naeini, Masahiro Omoto, Alireza Mashaghi, Sunil K Chauhan, Reza Dana
Antigen-presenting cells (APCs) play an important role in transplant rejection and tolerance. In high-risk corneal transplantation, where the graft bed is inflamed and vascularized, immature APCs in the donor corneal stroma quickly mature and migrate to lymphoid tissues to sensitize host T cells. In this study, using a mouse model of corneal transplantation, we investigated whether enrichment of tolerogenic APCs (tolAPCs) in donor corneas can enhance graft survival in corneal allograft recipients with inflamed graft beds...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428369/single-cell-rna-seq-reveals-new-types-of-human-blood-dendritic-cells-monocytes-and-progenitors
#10
Alexandra-Chloé Villani, Rahul Satija, Gary Reynolds, Siranush Sarkizova, Karthik Shekhar, James Fletcher, Morgane Griesbeck, Andrew Butler, Shiwei Zheng, Suzan Lazo, Laura Jardine, David Dixon, Emily Stephenson, Emil Nilsson, Ida Grundberg, David McDonald, Andrew Filby, Weibo Li, Philip L De Jager, Orit Rozenblatt-Rosen, Andrew A Lane, Muzlifah Haniffa, Aviv Regev, Nir Hacohen
Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C(+) subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs)...
April 21, 2017: Science
https://www.readbyqxmd.com/read/28428120/pathogenesis-of-immune-thrombocytopenia
#11
REVIEW
Sylvain Audia, Matthieu Mahévas, Maxime Samson, Bertrand Godeau, Bernard Bonnotte
Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an abnormal T cell response, notably supported by splenic T follicular helper cells, that stimulates the proliferation and differentiation of autoreactive B cells. The antiplatelet autoantibodies they produce facilitate platelet phagocytosis by macrophages, essentially in the spleen. Macrophages contribute to the perpetuation of the auto-immune response as the main antigen-presenting cell during ITP. CD8(+) T cells also participate to thrombocytopenia by increasing platelet apoptosis...
April 17, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28427395/protein-antigen-of-bird-related-hypersensitivity-pneumonitis-in-pigeon-serum-and-dropping
#12
Tsuyoshi Shirai, Haruhiko Furusawa, Asuka Furukawa, Yuki Ishige, Keisuke Uchida, Yasunari Miyazaki, Yoshinobu Eishi, Naohiko Inase
BACKGROUND: Avian antigen is a common cause of hypersensitivity pneumonitis (HP). Inhalation challenge with pigeon serum and pigeon dropping extract (PDE) elicits a hypersensitivity reaction in patients with bird-related hypersensitivity pneumonitis (BRHP), but the antigenic components in these materials have yet to be fully elucidated. METHOD: Pigeon serum, pigeon intestine homogenates, and PDE were immunoblotted with serum samples from 8 patients with BRHP, 2 patients with summer-type HP, 2 patients with humidifier lung, and 3 healthy volunteers...
April 20, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28425917/tapbpr-bridges-udp-glucose-glycoprotein-glucosyltransferase-1-onto-mhc-class-i-to-provide-quality-control-in-the-antigen-presentation-pathway
#13
Andreas Neerincx, Clemens Hermann, Robin Antrobus, Andy van Hateren, Huan Cao, Nico Trautwein, Stefan Stevanović, Tim Elliott, Janet E Deane, Louise H Boyle
Recently we revealed that TAPBPR is a peptide exchange catalyst important for optimal peptide selection by MHC class I molecules. Here we asked if any other co-factors associate with TAPBPR which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive class I molecules...
April 20, 2017: ELife
https://www.readbyqxmd.com/read/28423736/laminarin-promotes-anti-cancer-immunity-by-the-maturation-of-dendritic-cells
#14
Kyeongeun Song, Li Xu, Wei Zhang, Yun Cai, Bian Jang, Junghwan Oh, Jun-O Jin
This research evaluates the effects of laminarin on the maturation of dendritic cells and on the in vivo activation of anti-cancer immunity. In vivo treatment of C56BL/6 mice with laminarin increased the expression levels of co-stimulatory molecules and the production of pro-inflammatory cytokines in spleen dendritic cells. Laminarin enhanced ovalbumin antigen presentation in spleen dendritic cells and promoted the proliferation of OT-I and OT-II T cells. Laminarin also induced the maturation of dendritic cells in tumor-draining lymph nodes and protected interferon-γ and tumor necrosis factor-α and proliferation of OT-I and OT-II T cells in tumors...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423025/determination-of-influenza-b-identity-and-potency-in-quadrivalent-inactivated-influenza-vaccines-using-lineage-specific-monoclonal-antibodies
#15
Swati Verma, Jackeline Soto, Anupama Vasudevan, Falko Schmeisser, Esmeralda Alvarado-Facundo, Wei Wang, Carol D Weiss, Jerry P Weir
Co-circulation of two antigenically and genetically distinct lineages of influenza B virus, represented by prototype viruses B/Victoria/2/1987 and B/Yamagata/16/1988, has led to the development of quadrivalent influenza vaccines that contain two influenza B antigens. The inclusion of two influenza B antigens presents challenges for the production and regulation of inactivated quadrivalent vaccines, including the potential for cross-reactivity of the reagents used in identity and potency assays because of the relative close relatedness of the hemagglutinin (HA) from the two virus lineages...
2017: PloS One
https://www.readbyqxmd.com/read/28421694/molecular-engineering-and-plant-expression-of-an-immunoglobulin-heavy-chain-scaffold-for-delivery-of-a-dengue-vaccine-candidate
#16
Mi-Young Kim, Craig Van Dolleweerd, Alastair Copland, Matthew John Paul, Sven Hofmann, Gina R Webster, Emily Julik, Ivonne Ceballos-Olvera, Jorge Reyes-Del Valle, Moon-Sik Yang, Yong-Suk Jang, Rajko Reljic, Julian K Ma
In order to enhance vaccine uptake by the immune cells in vivo, molecular engineering approach was employed to construct a Polymeric Immunoglobulin G Scaffold (PIGS) that incorporates multiple copies of an antigen and targets the Fc gamma receptors on antigen-presenting cells. These self-adjuvanting immunogens were tested in the context of dengue infection, for which there is currently no globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII) of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco plants and Chinese Ovary Hamster cells...
April 19, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28421248/indications-for-cellular-migration-from-the-central-nervous-system-to-its-draining-lymph-nodes-in-cd11c-gfp-bone-marrow-chimeras-following-eae
#17
Fridtjof Schiefenhövel, Kerstin Immig, Carolin Prodinger, Ingo Bechmann
The concept as to how the brain maintains its immune privilege has initially been based on observations that it is lacking classical lymph vessels and later, the absence of dendritic cells (DC). This view has been challenged by several groups demonstrating drainage/migration of injected tracers and cells into cervical lymph nodes (CLNs) and the presence of brain antigens in CLNs in the course of various brain pathologies. Using CD11c-diphtheria toxin receptor (DTR)-green fluorescent protein (GFP) transgenic (tg) mice, we have shown the existence of CD11c(+) cells, a main DC marker, within the brain parenchyma...
April 18, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28420873/viewing-immune-regulation-as-it-happens-in-vivo-imaging-for-investigation-of-regulatory-t-cell-function
#18
REVIEW
Michael J Hickey, Zachary Chow
Regulatory T cells (Tregs) play indispensable roles in the immune system, in limiting excessive or inappropriate immune and inflammatory responses. They achieve this function via effects on other immune cells in the secondary lymphoid system, and in peripheral locations such as skin, gut and bone marrow. As for the more extensively-studied cellular players in the immune system, particularly dendritic cells and conventional T cells, in vivo imaging of Tregs via two-photon or multiphoton microscopy (MPM) has been central to the development of understanding how these cells function...
April 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28419628/hla-hd-an-accurate-hla-typing-algorithm-for-next-generation-sequencing-data
#19
Shuji Kawaguchi, Koichiro Higasa, Masakazu Shimizu, Ryo Yamada, Fumihiko Matsuda
The accurate typing of HLA alleles is critical for a variety of medical applications, such as genomic studies of multifactorial diseases, including immune system and inflammation-related disorders, and donor selection in organ transplantation and regenerative medicine. Here we developed a new algorithm for determining HLA alleles using next-generation sequencing (NGS) results. The method consists of constructing an extensive dictionary of HLA alleles, precise mapping of the NGS reads, and calculating a score based on weighted read counts to select the most suitable pair of alleles...
April 16, 2017: Human Mutation
https://www.readbyqxmd.com/read/28419492/expression-and-trafficking-of-mhc-related-protein-1-mr1
#20
REVIEW
R Lamichhane, J E Ussher
MHC related protein 1 (MR1) is a non-polymorphic MHC class IB antigen presenting molecule that is the restricting molecule for mucosal associated invariant T (MAIT) cells, a prominent population of innate-like antibacterial T cells. The MAIT cell-MR1 axis represents a new paradigm in antigen presentation, with the MR1 ligand derived from vitamin B compounds or their metabolic precursors. Many bacteria and some fungi produce the activating ligand for MR1. In evolution, MR1 is highly conserved in most, but not all, mammals...
April 17, 2017: Immunology
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