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https://www.readbyqxmd.com/read/28435909/self-assembled-particulate-psaa-as-vaccine-against-streptococcus-pneumoniae-infection
#1
Majela González-Miro, Laura Rodríguez-Noda, Mildrey Fariñas-Medina, Dagmar García-Rivera, Vicente Vérez-Bencomo, Bernd H A Rehm
Streptococcus pneumoniae is a human pathogen responsible for the majority of childhood pneumonia and media otitis cases worldwide. The diversity of its capsular polysaccharides (CPS) results in more than 91 serotypes of which at least 23 are virulent. Various CPS conjugated to immunogenic carrier proteins are currently licensed and provide protection against the infection caused by the respective serotypes but not against new and emerging virulent serotypes. In this study, we considered the conserved protein antigen PsaA, the pneumococcal surface adhesin A, in order to overcome the limitations of CPS antigens...
April 2017: Heliyon
https://www.readbyqxmd.com/read/28429719/transiently-antigen-primed-b-cells-return-to-naive-like-state-in-absence-of-t-cell-help
#2
Jackson S Turner, Matangi Marthi, Zachary L Benet, Irina Grigorova
The perspective that naive B-cell recognition of antigen in the absence of T-cell help causes cell death or anergy is supported by in vivo studies of B cells that are continuously exposed to self-antigens. However, intravital imaging suggests that early B-cell recognition of large foreign antigens may be transient. Whether B cells are tolerized or can be recruited into humoural immune responses following such encounters is not clear. Here we show that in the presence of T-cell help, single transient antigen acquisition is sufficient to recruit B cells into the germinal centre and induce memory and plasma cell responses...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28428345/proliferation-of-primary-human-hepatocytes-and-prevention-of-hepatitis-b-virus-reinfection-efficiently-deplete-nuclear-cccdna-in-vivo
#3
Lena Allweiss, Tassilo Volz, Katja Giersch, Janine Kah, Giuseppina Raffa, Joerg Petersen, Ansgar W Lohse, Concetta Beninati, Teresa Pollicino, Stephan Urban, Marc Lütgehetmann, Maura Dandri
OBJECTIVE: The stability of the covalently closed circular DNA (cccDNA) in nuclei of non-dividing hepatocytes represents a key determinant of HBV persistence. Contrarily, studies with animal hepadnaviruses indicated that hepatocyte turnover can reduce cccDNA loads but knowledge on the proliferative capacity of HBV-infected primary human hepatocytes (PHHs) in vivo and the fate of cccDNA in dividing PHHs is still lacking. This study aimed to determine the impact of human hepatocyte division on cccDNA stability in vivo...
April 20, 2017: Gut
https://www.readbyqxmd.com/read/28425751/development-of-red-blood-cell-autoantibodies-following-treatment-with-checkpoint-inhibitors-a-new-class-of-anti-neoplastic-immunotherapeutic-agents-associated-with-immune-dysregulation
#4
Laura L Cooling, John Sherbeck, Jonathon C Mowers, Sheri L Hugan
Ipilimumab, nivolumab, and pembrolizumab represent a new class of immunotherapeutic drugs for treating patients with advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response to tumor antigens by inhibiting T-cell autoregulation. As a consequence, they can be associated with immune-related adverse events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective clinical chart review, including serologic, hematology, and chemistry laboratory results, of two patients who developed red blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor...
January 2017: Immunohematology
https://www.readbyqxmd.com/read/28424695/b-cell-tolerance-to-deiminated-histones-in-balb-c-c57bl-6-and-autoimmune-prone-mouse-strains
#5
Nishant Dwivedi, Annica Hedberg, Ying Yi Zheng, Indira Neeli, Minoru Satoh, Laurence Morel, Ole Petter Rekvig, Marko Radic
Deimination, a posttranslational modification of arginine to citrulline carried out by peptidylarginine deiminases, may compromise tolerance of self-antigens. Patients with connective tissue autoimmunity, particularly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or Felty's syndrome, present with autoantibodies to deiminated histones (dH), which thus form a category of antibodies to citrullinated protein antigens (ACPA). In general, ACPA are a sensitive diagnostic for RA and may form in response to the release of nuclear chromatin (DNA plus dH) from granulocytes, usually referred to as neutrophil extracellular traps...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28422790/particle-based-delivery-of-the-hiv-envelope-protein
#6
Benedikt Asbach, Ralf Wagner
PURPOSE OF REVIEW: A major focus in HIV vaccine research is the development of suitable antigens that elicit broadly neutralizing antibody responses targeting HIV's envelope protein (Env). Delivery of Env in a repetitive manner on particle-based carriers allows higher avidity interactions and is therefore expected to efficiently engage B cells, thus leading to affinity maturation that results in superior antibody responses characterized by improved breadth, potency, and durability. This review summarizes current work that is evaluating diverse types of such particulate carriers for Env delivery...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28421864/selfie-autoimmunity
#7
Haseeb Ahsan
The immune system provides protection to tissues damaged by infectious microrganisms or physical damage. In autoimmune diseases, the immune system recognizes and attacks its own tissues i.e., self-destruction. Various agents such as genetic factors and environmental triggers are thought to play a major role in the development of autoimmune diseases. A common feature of all autoimmune diseases is the presence of autoantibodies and inflammation, including mononuclear phagocytes, autoreactive T lymphocytes and autoantibody producing B cells (plasma cells)...
April 19, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/28421849/infliximab-crystal-structures-reveal-insights-into-self-association
#8
Thomas F Lerch, Penelope Sharpe, Stephen J Mayclin, Thomas E Edwards, Eunhee Lee, Hugh D Conlon, Sharon Polleck, Jason C Rouse, Yin Luo, Qin Zou
Aggregation and self-association in protein-based biotherapeutics are critical quality attributes that are tightly controlled by the manufacturing process. Aggregates have the potential to elicit immune reactions, including neutralizing anti-drug antibodies, which can diminish the drug's efficacy upon subsequent dosing. The structural basis of reversible self-association, a form of non-covalent aggregation in the native state, is only beginning to emerge for many biologics and is often unique to a given molecule...
April 19, 2017: MAbs
https://www.readbyqxmd.com/read/28421694/molecular-engineering-and-plant-expression-of-an-immunoglobulin-heavy-chain-scaffold-for-delivery-of-a-dengue-vaccine-candidate
#9
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/28421005/autoimmune-aspects-of-neurodegenerative-and-psychiatric-diseases-a-template-for-innovative-therapy
#10
REVIEW
Peter de Haan, Hans C Klein, Bert A 't Hart
Neurodegenerative and psychiatric diseases (NPDs) are today's most important group of diseases, surpassing both atherosclerotic cardiovascular disease and cancer in morbidity incidence. Although NPDs have a dramatic impact on our society because of their high incidence, mortality, and severe debilitating character, remarkably few effective interventions have become available. The current treatments, if available, comprise the lifelong intake of general immunosuppressants to delay disease progression or neurotransmitter antagonists/agonists to dampen undesired behaviors...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28416194/foxp3-reprograms-t-cell-metabolism-to-function-in-low-glucose-high-lactate-environments
#11
Alessia Angelin, Luis Gil-de-Gómez, Satinder Dahiya, Jing Jiao, Lili Guo, Matthew H Levine, Zhonglin Wang, William J Quinn, Piotr K Kopinski, Liqing Wang, Tatiana Akimova, Yujie Liu, Tricia R Bhatti, Rongxiang Han, Benjamin L Laskin, Joseph A Baur, Ian A Blair, Douglas C Wallace, Wayne W Hancock, Ulf H Beier
Immune cells function in diverse metabolic environments. Tissues with low glucose and high lactate concentrations, such as the intestinal tract or ischemic tissues, frequently require immune responses to be more pro-tolerant, avoiding unwanted reactions against self-antigens or commensal bacteria. T-regulatory cells (Tregs) maintain peripheral tolerance, but how Tregs function in low-glucose, lactate-rich environments is unknown. We report that the Treg transcription factor Foxp3 reprograms T cell metabolism by suppressing Myc and glycolysis, enhancing oxidative phosphorylation, and increasing nicotinamide adenine dinucleotide oxidation...
April 11, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28414197/engineering-of-a-self-adjuvanted-itep-delivered-ctl-vaccine
#12
Shuyun Dong, Tiefeng Xu, Peng Wang, Peng Zhao, Mingnan Chen
Cytotoxic T lymphocyte (CTL) epitope peptide-based vaccines are widely used in cancer and infectious disease therapy. We previously generated an immune-tolerant elastin-like polypeptides (iTEPs)-based carrier to deliver a peptide CTL vaccine and enhance the efficiency of the vaccine. To further optimize the vaccine carrier, we intended to potentiate its function by designing an iTEP-based carrier that was able to deliver adjuvant and a vaccine epitope as one molecule. Thus, we fused a 9-mer H100, a peptide derived from the high-mobility group box 1 protein (HMGB1) that could induce activation of dendritic cells (DCs), with an iTEP polymer to generate a new iTEP polymer named H100-iTEP...
April 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28411807/a-sensitive-and-disposable-indium-tin-oxide-based-electrochemical-immunosensor-for-label-free-detection-of-mage-1
#13
Burçak Demirbakan, Mustafa Kemal Sezgintürk
MAGE-1 (MAGE, for melanoma antigen), was identified by virtue of its processing and cell surface expression as a tumor-specific peptide bound to major histocompatibility complexes which was reactive with autolytic T cells. 3-Glycidoxypropyltrimethoxysilane (3-GOPS) is frequently employed for the preparation of dense heterometal hybrid polymers which are used, e.g., for hard coatings of organic polymers and contact lens materials in the optical industry. In this study, we have improved a new immunological biosensor with indium tin oxide (ITO)...
July 1, 2017: Talanta
https://www.readbyqxmd.com/read/28408118/a-novel-combined-vaccine-based-on-monochimeric-vlp-co-displaying-multiple-conserved-epitopes-against-enterovirus-71-and-varicella-zoster-virus
#14
Yangtao Wu, Rui Zhu, Longfa Xu, Yongchao Li, Shuxuan Li, Hai Yu, Shaowei Li, Hua Zhu, Tong Cheng, Ningshao Xia
Chicken pox and hand, foot and mouth disease (HFMD) are two major infectious diseases that mainly affect infants and children, causing significant morbidity annually. Varicella-zoster virus (VZV) and enterovirus 71 (EV71), respectively, are the principal epidemic pathogens causing these two diseases. To investigate the possibility of developing a novel combined vaccine to prevent chicken pox and HFMD, we constructed three chimeric virus-like particles (VLPs) (termed HBc-V/1/2, HBc-2/V/1 and HBc-1/2/V) based on the hepatitis B core antigen (HBc) carrier that display epitopes derived from VZV-gE, EV71-VP1, and EV71-VP2 in a varied tandem manner...
May 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28407054/procalcitonin-as-a-marker-of-etiology-in-adults-hospitalized-with-community-acquired-pneumonia
#15
Wesley H Self, Robert A Balk, Carlos G Grijalva, Derek J Williams, Yuwei Zhu, Evan J Anderson, Grant W Waterer, D Mark Courtney, Anna M Bramley, Christopher Trabue, Sherene Fakhran, Anne J Blaschke, Seema Jain, Kathryn M Edwards, Richard G Wunderink
Background: Recent trials suggest procalcitonin-based guidelines can reduce antibiotic use for respiratory infections. However, the accuracy of procalcitonin to discriminate between viral and bacterial pneumonia requires further dissection. Methods: We evaluated the association between serum procalcitonin concentration at hospital admission with pathogens detected in a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia...
April 12, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28404797/self-adjuvanting-c18-lipid-vinil-sulfone-pp2a-vaccine-study-of-the-induced-immunomodulation-against-trichuris-muris-infection
#16
M Gomez-Samblas, J J García-Rodríguez, M Trelis, D Bernal, F J Lopez-Jaramillo, F Santoyo-Gonzalez, S Vilchez, A M Espino, F Bolás-Fernández, A Osuna
Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis (rPP2A) was used for intranasal immunization in mice previously infected with Trichuris muris The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28397237/-progress-in-research-on-tlr7-gene-single-nucleotide-polymorphisms-and-copy-number-variations-in-autoimmune-diseases
#17
Jianxiong Xi, Qiming Zhang, Yanfeng Zou
Autoimmune diseases (AID) are a group of complex disorders due to antibodies acting on self-antigens causing damage to the body. AID has long been considered as the outcome of genetic and environmental interactions. In recent years, studies have shown that increased susceptibility to AID may be associated with single nucleotide polymorphisms and copy number variations of Toll like receptor 7 (TLR7) gene, which provided a clue to further understanding of the pathogenesis of AID. This paper provides a review of the recent advances in understanding of the roles of TLR7 gene single nucleotide polymorphisms and copy number variations in AID...
April 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28396662/the-role-of-dendritic-cell-maturation-in-the-induction-of-insulin-dependent-diabetes-mellitus
#18
REVIEW
Jacques C Mbongue, Hector A Nieves, Timothy W Torrez, William H R Langridge
Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans and are largely responsible for the initiation and guidance of innate and adaptive immune responses involved in maintenance of immunological homeostasis. Immature dendritic cells (iDCs) phagocytize pathogens and toxic proteins and in endosomal vesicles degrade them into small fragments for presentation on major histocompatibility complex (MHC) II receptor molecules to naïve cognate T cells (Th0). In addition to their role in stimulation of immunity, DCs are involved in the induction and maintenance of immune tolerance toward self-antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28388966/vaccination-with-poly-ic-lc-and-peptide-pulsed-autologous-dendritic-cells-in-patients-with-pancreatic-cancer
#19
Shikhar Mehrotra, Carolyn D Britten, Steve Chin, Elizabeth Garrett-Mayer, Colleen A Cloud, Mingli Li, Gina Scurti, Mohamed L Salem, Michelle H Nelson, Melanie B Thomas, Chrystal M Paulos, Andres M Salazar, Michael I Nishimura, Mark P Rubinstein, Zihai Li, David J Cole
BACKGROUND: Dendritic cells (DCs) enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, in conjunction with toll-like receptor (TLR)-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC). METHODS: We generated autologous DCs from the peripheral blood of HLA-A2(+) patients with PC. DCs were pulsed with three distinct A2-restricted peptides: 1) human telomerase reverse transcriptase (hTERT, TERT572Y), 2) carcinoembryonic antigen (CEA; Cap1-6D), and 3) survivin (SRV...
April 7, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28385374/central-immune-tolerance-depends-on-crosstalk-between-the-classical-and-alternative-nf-%C3%AE%C2%BAb-pathways-in-medullary-thymic-epithelial-cells
#20
Marc Riemann, Nico Andreas, Maria Fedoseeva, Elke Meier, Debra Weih, Helga Freytag, Ruth Schmidt-Ullrich, Ulf Klein, Zhao-Qi Wang, Falk Weih
Medullary thymic epithelial cells (mTECs) contribute to self-tolerance by expressing and presenting peripheral tissue antigens for negative selection of autoreactive T cells and differentiation of natural regulatory T cells. The molecular control of mTEC development remains incompletely understood. We here demonstrate by TEC-specific gene manipulation in mice that the NF-κB transcription factor subunit RelB, which is activated by the alternative NF-κB pathway, regulates development of mature mTECs in a dose-dependent manner...
April 3, 2017: Journal of Autoimmunity
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