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vaccines and autoimmunity

G MuŽíková, R Laga
Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers...
October 20, 2016: Physiological Research
J M Greene, P Dash, S Roy, C McMurtrey, W Awad, J S Reed, K B Hammond, S Abdulhaqq, H L Wu, B J Burwitz, B F Roth, D W Morrow, J C Ford, G Xu, J Y Bae, H Crank, A W Legasse, T H Dang, H Y Greenaway, M Kurniawan, M C Gold, M J Harriff, D A Lewinsohn, B S Park, M K Axthelm, J J Stanton, S G Hansen, L J Picker, V Venturi, W Hildebrand, P G Thomas, D M Lewinsohn, E J Adams, J B Sacha
Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts...
October 19, 2016: Mucosal Immunology
Brandon Coder, Weikan Wang, Liefeng Wang, Zhongdao Wu, Qichuan Zhuge, Dong-Ming Su
The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process...
October 11, 2016: Oncotarget
Jae Hee Cheon
Remarkable advances have been made in the treatment of inflammatory bowel disease (IBD) since the introduction of anti-tumor necrosis factor (TNF)-α agents, especially for patients who are refractory to or cannot tolerate conventional therapies. Currently, infliximab, adalimumab, and golimumab are available in the East Asian medical market, and these agents have been shown to be effective for inducing and maintaining long-term remission of IBD. Despite their clinical benefits, anti-TNF therapy can also lead to increased vulnerability to infections, development of autoimmune diseases and malignancy, and decreased immunogenicity of vaccinations...
October 10, 2016: Journal of Gastroenterology and Hepatology
Craig A Beam, Colleen MacCallum, Kevan C Herold, Diane K Wherrett, Jerry Palmer, Johnny Ludvigsson
AIMS/HYPOTHESIS: GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. METHODS: In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine)...
October 4, 2016: Diabetologia
Michael Schumann, Lydia Lebenheim
Celiac disease occurs as a result of a T-cell-dependent immune reaction on gluten peptides. It is a complex genetic disorder that is mediated by an unknown number of genes, of which more than 50 have been identified in whole genome association studies. The genetic component helps identify oligosymptomatic or even subclinical celiacs by screening first-degree relatives and patients suffering from other autoimmune diseases. To offer sensitive as well as specific diagnostics for celiac disease (serology and small intestinal histology) some general rules should be followed including performing diagnostics only when patients are on a gluten-containing diet or after an appropriate re-exposition...
September 2016: Deutsche Medizinische Wochenschrift
Catherine W Cai, Jennifer R Blase, Xiuli Zhang, Christopher S Eickhoff, Daniel F Hoft
Th17 cells are a subset of CD4+ T cells known to play a central role in the pathogenesis of many autoimmune diseases, as well as in the defense against some extracellular bacteria and fungi. However, Th17 cells are not believed to have a significant function against intracellular infections. In contrast to this paradigm, we have discovered that Th17 cells provide robust protection against Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas disease. Th17 cells confer significantly stronger protection against T...
October 2016: PLoS Pathogens
Li Ding, Yuan Meng, Hui-Yi Zhang, Wen-Chao Yin, Yi Yan, Yun-Peng Cao
Active amyloid-β (Aβ) immunotherapy is effective in preventing Aβ deposition, facilitating plaque clearance, and improving cognitive functions in mouse models of Alzheimer's disease (AD). Developing a safe and effective AD vaccine requires a delicate balance between inducing adequate humoral immune responses and avoiding T cell-mediated autoimmune responses. In this study, we designed 2 peptide epitope vaccines, Aβ3-10-KLH and 5Aβ3-10, prepared respectively by coupling Aβ3-10 to the immunogenic carrier protein keyhole limpet hemocyanin (KLH) or by joining 5 Aβ3-10 epitopes linearly in tandem...
September 28, 2016: Neuroscience Letters
Daniel Fernandez-Ruiz, Wei Yi Ng, Lauren E Holz, Joel Z Ma, Ali Zaid, Yik Chun Wong, Lei Shong Lau, Vanessa Mollard, Anton Cozijnsen, Nicholas Collins, Jessica Li, Gayle M Davey, Yu Kato, Sapna Devi, Roghieh Skandari, Michael Pauley, Jonathan H Manton, Dale I Godfrey, Asolina Braun, Szun Szun Tay, Peck Szee Tan, David G Bowen, Friedrich Koch-Nolte, Björn Rissiek, Francis R Carbone, Brendan S Crabb, Mireille Lahoud, Ian A Cockburn, Scott N Mueller, Patrick Bertolino, Geoffrey I McFadden, Irina Caminschi, William R Heath
In recent years, various intervention strategies have reduced malaria morbidity and mortality, but further improvements probably depend upon development of a broadly protective vaccine. To better understand immune requirement for protection, we examined liver-stage immunity after vaccination with irradiated sporozoites, an effective though logistically difficult vaccine. We identified a population of memory CD8(+) T cells that expressed the gene signature of tissue-resident memory T (Trm) cells and remained permanently within the liver, where they patrolled the sinusoids...
September 17, 2016: Immunity
Jeffrey T Guptill, Vern C Juel, Janice M Massey, Amanda C Anderson, Manisha Chopra, John S Yi, Ehsanollah Esfandiari, Tim Buchanan, Bryan Smith, Paul Atherfold, Emma Jones, James F Howard
An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation...
August 11, 2016: Autoimmunity
Fanny Kryczanowsky, Verena Raker, Edith Graulich, Matthias P Domogalla, Kerstin Steinbrink
Dendritic cells (DCs) are key regulators of protective immune responses and tolerance to (self-)Ags. Therefore, the scientific rationale for the use of tolerogenic DC therapy in the fields of allergies, autoimmunity, and transplantation medicine is strong. In this study, we analyzed the tolerogenic capacity of IL-10-modulated DC (IL-10DC) subpopulations to identify a DC subset that combines potent immunosuppressive activities with valuable immune properties for clinical implementation. IL-10DCs consist of two phenotypically distinct subpopulations: CD83(high)CCR7(+) IL-10DCs and CD83(low)CCR7(-) IL-10DCs...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yunier Rodríguez-Álvarez, Yanelys Morera-Díaz, Haydee Gerónimo-Pérez, Jorge Castro-Velazco, Rafael Martínez-Castillo, Pedro Puente-Pérez, Vladimir Besada-Pérez, Eugenio Hardy-Rando, Araceli Chico-Capote, Klaudia Martínez-Cordovez, Alicia Santos-Savio
BACKGROUND: Interleukin-15 is an immunostimulatory cytokine overexpressed in several autoimmune and inflammatory diseases such as Rheumatoid Arthritis, psoriasis and ulcerative colitis; thus, inhibition of IL-15-induced signaling could be clinically beneficial in these disorders. Our approach to neutralize IL-15 consisted in active immunization with structurally modified human IL-15 (mhIL-15) with the aim to induce neutralizing antibodies against native IL-15. In the present study, we characterized the antibody response in Macaca fascicularis, non-human primates that were immunized with a vaccine candidate containing mhIL-15 in Aluminum hydroxide (Alum), Montanide and Incomplete Freund's Adjuvant...
September 26, 2016: BMC Immunology
Soheila Alyasin, Marzieh Adab, Asieh Hosseinpour, Reza Amin, Maryam Babaei
BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease which is characterized by B-cell abnormality and auto-antibody generation. Since bacterial infections are the most important causes of mortality in these patients, pneumococcal vaccination is recommended for children with SLE. OBJECTIVE: To investigate humoral immunity and specific-antibody formation in response to a 23-valent polysaccharide pneumococcal vaccination in SLE children and asthmatic control group...
September 2016: Iranian Journal of Immunology: IJI
Elham Behzadi, Raheleh Halabian, Hamideh Mahmoodzadeh Hosseini, Abbas Ali Imani Fooladi
DNA vaccination -a third generation vaccine-is a modern approach to stimulate humoral and cellular responses against different diseases such as infectious diseases, cancer and autoimmunity. These vaccines are composed of a gene that encodes sequences of a desired protein under control of a proper (eukaryotic or viral) promoter. Immune response following DNA vaccination is influenced by the route and the dose of injection. In addition, antigen presentation following DNA administration has three different mechanisms including antigen presentation by transfected myocytes, transfection of professional antigen presenting cells (APCs) and cross priming...
September 23, 2016: Microbial Pathogenesis
William Crowe, Philip J Allsopp, Gene E Watson, Pamela J Magee, J J Strain, David J Armstrong, Elizabeth Ball, Emeir M McSorley
Autoimmune diseases result from an interplay of genetic predisposition and factors which stimulate the onset of disease. Mercury (Hg), a well-established toxicant, is an environmental factor reported to be linked with autoimmunity. Hg exists in several chemical forms and is encountered by humans in dental amalgams, certain vaccines, occupational exposure, atmospheric pollution and seafood. Several studies have investigated the effect of the various forms of Hg, including elemental (Hg(0)), inorganic (iHg) and organic mercury (oHg) and their association with autoimmunity...
September 23, 2016: Autoimmunity Reviews
Martina Ahlmann, Georg Hempel
Cyclophosphamide is an alkylating agent belonging to the group of oxazaphosporines. As cyclophosphamide is in clinical use for more than 40 years, there is a lot of experience using this drug for the treatment of cancer and as an immunosuppressive agent for the treatment of autoimmune and immune-mediated diseases. Besides antimitotic and antireplicative effects, cyclophosphamide has immunosuppressive as well as immunomodulatory properties. Cyclophosphamide shows selectivity for T cells and is therefore now frequently used in tumour vaccination protocols and to control post-transplant allo-reactivity in haplo-identical unmanipulated bone marrow after transplantation...
October 2016: Cancer Chemotherapy and Pharmacology
Isaak Quast, Benjamin Peschke, Jan D Lünemann
Immunoglobulin gamma (IgG) antibodies are key effector proteins of the immune system. They recognize antigens with high specificity and are indispensable for immunological memory following pathogen exposure or vaccination. The constant, crystallizable fragment (Fc) of IgG molecules mediates antibody effector functions such as complement-dependent cytotoxicity, antibody-mediated cellular cytotoxicity, and antibody-dependent cell-mediated phagocytosis. These functions are regulated by a single N-linked, biantennary glycan of the heavy chain, which resides just below the hinge region, and the presence of specific sugar moieties on the glycan has profound implications on IgG effector functions...
September 17, 2016: Cellular and Molecular Life Sciences: CMLS
Ming Xiang, Tingting Liu, Wanyue Tan, Hongyu Ren, Hua Li, Junjun Liu, Hui Cao, Qi Cheng, Xiulan Liu, Hucheng Zhu, Yali Tuo, Jianping Wang, Yonghui Zhang
: The central purpose of this study was to investigate therapeutic effects of the botanical derivative kinsenoside (KD) in experimental autoimmune hepatitis (AIH). Treatment with KD substantially reduced hepatic histopathological damage, induced by lymphocyte infiltration and pro-inflammatory cytokines, in ConA-induced T cell-mediated hepatitis, and in dendritic cells loaded with hepatocellular carcinoma cells (DC/Hepa1-6) induced murine AIH. Interactions between immune cells after KD treatment in AIH were detected by anti-CD8 antibody blocking, CD8(+) T cells sorting, and vaccinated mice with KD-pretreated DCs in a DC/Hepa1-6 model...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jung-Rok Lee, D James Haddon, Nidhi Gupta, Jordan V Price, Grace M Credo, Vivian K Diep, Kyunglok Kim, Drew A Hall, Emily C Baechler, Michelle Petri, Madoo Varma, Paul J Utz, Shan X Wang
Autoantibodies are a hallmark of autoimmune diseases such as lupus and have the potential to be used as biomarkers for diverse diseases, including immunodeficiency, infectious disease, and cancer. More precise detection of antibodies to specific targets is needed to improve diagnosis of such diseases. Here, we report the development of reusable peptide microarrays, based on giant magnetoresistive (GMR) nanosensors optimized for sensitively detecting magnetic nanoparticle labels, for the detection of antibodies with a resolution of a single post-translationally modified amino acid...
September 16, 2016: ACS Nano
Jared Klarquist, Kristen Tobin, Peyman Farhangi Oskuei, Steven W Henning, Manuel F Fernandez, Emilia R Dellacecca, Flor C Navarro, Jonathan M Eby, Shilpak Chatterjee, Shikhar Mehrotra, Joseph I Clark, I Caroline Le Poole
T regulatory cells (Treg) avert autoimmunity but their increased levels in melanoma confer a poor prognosis. To explore the basis for Treg accumulation in melanoma, we evaluated chemokine expression in patients. A 5-fold increase was documented in the Treg chemoattractants CCL22 and CCL1 in melanoma-affected skin versus unaffected skin, as accompanied by infiltrating FoxP3+ T cells. In parallel, there was a ~2-fold enhancement in expression of CCR4 in circulating Treg but not T effector cells. We hypothesized that redirecting Treg away from tumors might suppress autoimmune side-effects caused by immune checkpoint therapeutics now used widely in the clinic...
September 12, 2016: Cancer Research
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