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https://www.readbyqxmd.com/read/29692765/a-carbohydrate-moiety-of-secreted-stage-specific-glycoprotein-4-participates-in-host-cell-invasion-by-trypanosoma-cruzi-extracellular-amastigotes
#1
Pilar T V Florentino, Fernando Real, Cristina M Orikaza, Julia P C da Cunha, Francisca N L Vitorino, Esteban M Cordero, Tiago J P Sobreira, Renato A Mortara
Trypanosoma cruzi is the etiologic agent of Chagas' disease. It is known that amastigotes derived from trypomastigotes in the extracellular milieu are infective in vitro and in vivo . Extracellular amastigotes (EAs) have a stage-specific surface antigen called Ssp-4, a GPI-anchored glycoprotein that is secreted by the parasites. By immunoprecipitation with the Ssp-4-specific monoclonal antibodies (mAb) 2C2 and 1D9, we isolated the glycoprotein from EAs. By mass spectrometry, we identified the core protein of Ssp-4 and evaluated mRNA expression and the presence of Ssp-4 carbohydrate epitopes recognized by mAb1D9...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29688817/current-status-of-messenger-rna-delivery-systems
#2
Matthew G Stanton
Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results...
April 24, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29688138/antibody-responses-against-streptococcus-pneumoniae-haemophilus-influenzae-and-moraxella-catarrhalis-in-children-with-acute-respiratory-infection-with-or-without-nasopharyngeal-bacterial-carriage
#3
Dafne C Andrade, Igor C Borges, Maiara L Bouzas, Juliana R Oliveira, Helena Käyhty, Olli Ruuskanen, Cristiana Nascimento-Carvalho
BACKGROUND: We studied Immunoglobulin G (IgG) antibody responses against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in young children with acute viral type respiratory infection and analyzed the findings in a multivariate model including age, nasopharyngeal carriage of the tested bacteria and pneumococcal vaccination. METHODS: We included 227 children aged 6-23 months with acute respiratory infection. Nasopharyngeal aspirates were tested for bacterial carriage through detection of messenger RNA (mRNA) transcript with nCounter analysis...
April 24, 2018: Infectious Diseases
https://www.readbyqxmd.com/read/29684601/the-effect-of-intermittent-hypoxia-under-different-temperature-on-the-immunomodulation-in-streptococcus-agalactiae-vaccinated-nile-tilapia-oreochromis-niloticus
#4
Jing Wang, Dan-Qi Lu, Biao Jiang, Heng-Li Luo, Ge-Ling Lu, An-Xing Li
Dissolved oxygen (DO) and temperature are the potential immunomodulators in fish and play the important roles in regulating immunity. We studied the effect of intermittent hypoxia under different temperature on the immunomodulation in vaccinated Nile tilapia (Oreochromis niloticus). The expression of immune-related genes, enzymatic activities, histology, cumulative mortality, and S. agalactiae clearance were assessed. Study conditions were intermittently hypoxic (4.0 ± 1.0 mg/L DO) at 30 ± 0.5 °C or 35 ± 0...
April 20, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29683387/primary-transcriptome-analysis-reveals-importance-of-is-elements-for-the-shaping-of-the-transcriptional-landscape-of-bordetella-pertussis
#5
Fabian Amman, Alexandre D'Halluin, Rudy Antoine, Ludovic Huot, Ilona Bibova, Kristina Keidel, Stéphanie Slupek, Peggy Bouquet, Loïc Coutte, Ségolène Caboche, Camille Locht, Branislav Vecerek, David Hot
Bordetella pertussis is the causative agent of whooping cough, a respiratory disease still considered as a major public health threat and for which recent re-emergence has been observed. Constant reshuffling of Bordetella pertussis genome organization was observed during evolution. These rearrangements are essentially mediated by Insertion Sequences (IS), a mobile genetic elements present in more than 230 copies in the genome, which are supposed to be one of the driving forces enabling the pathogen to escape from vaccine-induced immunity...
April 23, 2018: RNA Biology
https://www.readbyqxmd.com/read/29681409/recombinant-bcg-rv2645-elicits-enhanced-protective-immunity-compared-to-bcg-in-vivo-with-induced-isgylation-related-genes-and-th1-and-th17-responses
#6
Wei Luo, Zilu Qu, Lingyun Zhang, Yan Xie, Fengling Luo, Yang Tan, Qin Pan, Xiao-Lian Zhang
There is a need to develop protective vaccines against tuberculosis (TB). Recently, we identified an immunodominant T-cell antigen, Rv2645, from the region of deletion 13 (RD13) of M. tuberculosis (M. tb) H37Rv, which is absent in Bacille Calmette-Guérin (BCG). Here, a recombinant BCG expressing Rv2645, namely, BCG::Rv2645, was constructed. Compared to BCG, we found that BCG::Rv2645 improved the antigen presentation capacity of dendritic cells (DCs) and elicited much stronger Th1 and Th17 responses, higher CD44high CD62low effector memory CD4+ T cells (TEM ), and fewer T regulated cells (Treg) and regulatory B10 in mice...
April 19, 2018: Vaccine
https://www.readbyqxmd.com/read/29679791/phosphorodiamidate-morpholino-targeting-the-5-untranslated-region-of-the-zikv-rna-inhibits-virus-replication
#7
Waldemar Popik, Atanu Khatua, James E K Hildreth, Benjamin Lee, Donald J Alcendor
BACKGROUND: Zika virus (ZIKV) infection has been associated with microcephaly in infants. Currently there is no treatment or vaccine. Here we explore the use of a morpholino oligonucleotide targeted to the 5' untranslated region (5'-UTR) of the ZIKV RNA to prevent ZIKV replication. METHODS: Morpholino DWK-1 inhibition of ZIKV replication in human glomerular podocytes was examined by qRT-PCR, reduction in ZIKV genome copy number, western blot analysis, immunofluorescence and proinflammatory cytokine gene expression...
April 18, 2018: Virology
https://www.readbyqxmd.com/read/29678225/synergistic-effect-of-co-stimulation-of-membrane-and-endosomal-tlrs-on-chicken-innate-immune-responses
#8
Sungwon Kim, Pete Kaiser, Dominika Borowska, Lonneke Vervelde
Toll-like receptor (TLR) ligands (TLR-Ls) are critical activators of immunity and are successfully being developed as vaccine adjuvants in both mammals and birds. In this study, we investigated the synergistic effect of co-stimulation of membrane and endosomal TLRs on the innate immune responses using chicken bone marrow-derived macrophages (BMMs), and studied the effect of age on the induction of innate responses. BMMs from 1 and 4-week-old birds were stimulated with Pam3Cys-SK4 (PCSK; TLR2), synthetic monophosphoryl lipid A (MPLA), Di[3-deoxy-d-manno-octulosonyl]-lipid A ammonium salt (KLA; TLR4), Gardiquimod, Resiquimod (R848; TLR7), CpG class B and C (TLR21)...
May 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29674503/dexamethasone-promotes-durable-factor-viii-specific-tolerance-in-hemophilia-a-mice-via-thymic-mechanisms
#9
Maria T Georgescu, Paul C Moorehead, Alice S van Velzen, Kate Nesbitt, Birgit M Reipert, Katharina N Steinitz, Maria Schuster, Christine Hough, David Lillicrap
The development of inhibitory antibodies to factor VIII is the most serious complication of replacement therapy in hemophilia A. Activation of the innate immune system during exposure to this protein contributes to inhibitor development. However, avoidance of factor VIII exposure during innate immune system activation by external stimuli (e.g. vaccines) has not been consistently shown to prevent inhibitors. We hypothesized that dexamethasone, a drug with potent anti-inflammatory effects, could prevent inhibitors by promoting immunologic tolerance to factor VIII in hemophilia A mice...
April 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29618645/feline-herpesvirus-1-fhv-1-us3-blocks-type-i-ifn-signal-pathway-by-targeting-irf3-dimerization-in-a-kinase-independent-manner
#10
Jin Tian, Yongxiang Liu, Xiaoxiao Liu, Xue Sun, Jikai Zhang, Liandong Qu
As a prevalent agent in cats, feline herpesvirus 1 (FHV-1) infection contributes to feline respiratory disease and acute and chronic conjunctivitis. FHV-1 can successfully evade the host innate immune response and persist for the lifetime of the cat. Several mechanisms of immune evasion by human herpesviruses have been elucidated, but the mechanism by FHV-1 remains unknown. In this study, we screened for FHV-1 ORFs responsible for inhibiting type I interferon (IFN) pathway with an IFN-β promoter reporter and an analysis of IFN-β mRNA levels in HEK 293T cells and CRFK feline cell line, and we identified the Ser/Thr kinase US3 as the most powerful inhibitor...
April 4, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29604449/the-mechanisms-of-ag85a-dna-vaccine-activates-rna-sensors-through-new-signal-transduction
#11
Jingbo Zhai, Qiubo Wang, Yunfeng Gao, Ran Zhang, Shengjun Li, Bing Wei, Yong You, Xun Sun, Changlong Lu
Low immunogenicity is one of the major problems limiting the clinical use for DNA vaccines, which makes it impossible to obtain a strong protective immune response after vaccination. In order to explore whether Ag85A DNA vaccine could mount more efficiently protective immune response through new RNA sensor and its signal transduction pathway of antigen presentation we designed and synthesized Ag85A gene fragment containing multiple points mutations and transfected the gene fragment into the dendritic cell line (DC2...
March 28, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29587627/obtaining-insights-from-high-dimensional-data-sparse-principal-covariates-regression
#12
Katrijn Van Deun, Elise A V Crompvoets, Eva Ceulemans
BACKGROUND: Data analysis methods are usually subdivided in two distinct classes: There are methods for prediction and there are methods for exploration. In practice, however, there often is a need to learn from the data in both ways. For example, when predicting the antibody titers a few weeks after vaccination on the basis of genomewide mRNA transcription rates, also mechanistic insights about the effect of vaccinations on the immune system are sought. Principal covariates regression (PCovR) is a method that combines both purposes...
March 27, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29580160/significant-transcriptome-and-cytokine-changes-in-hepatitis-b-vaccine-non-responders-revealed-by-genome-wide-comparative-analysis
#13
Shaohui Qiu, Peng He, Xin Fang, Haiqing Tong, Jingjing Lv, Jiaye Liu, Li Zhang, Xiangjun Zhai, Liying Wang, Zhongyu Hu, Yongli Yu
Individuals fail to elicit protective antibody after hepatitis B vaccination remain at risk for hepatitis B virus infection. Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) is essential to elucidate the characteristics of gene expression in non-responders. In this study, we enrolled seven responders who had received three injections and seven non-responders who had six injections of hepatitis B vaccine before. All the participants were then vaccinated with a three-dose boost regimen...
March 26, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29559570/uninfected-bystander-cells-impact-the-measurement-of-hiv-specific-antibody-dependent-cellular-cytotoxicity-responses
#14
Jonathan Richard, Jérémie Prévost, Amy E Baxter, Benjamin von Bredow, Shilei Ding, Halima Medjahed, Gloria G Delgado, Nathalie Brassard, Christina M Stürzel, Frank Kirchhoff, Beatrice H Hahn, Matthew S Parsons, Daniel E Kaufmann, David T Evans, Andrés Finzi
The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs)...
March 20, 2018: MBio
https://www.readbyqxmd.com/read/29554212/combined-immunotherapy-encompassing-intratumoral-poly-iclc-dendritic-cell-vaccination-and-radiotherapy-in-advanced-cancer-patients
#15
M E Rodríguez-Ruiz, J L Perez-Gracia, I Rodríguez, C Alfaro, C Oñate, G Pérez, I Gil-Bazo, A Benito, S Inogés, A López-Diaz de Cerio, M Ponz-Sarvise, L Resano, P Berraondo, B Barbés, S Martin-Algarra, A Gúrpide, M F Sanmamed, C de Andrea, A M Salazar, I Melero
BACKGROUND: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. PATIENTS AND METHODS: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24h with poly-ICLC (Hiltonol), TNF-α and IFN-α...
March 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29530809/expression-of-salmonella-typhimurium-and-escherichia-coli-flagellin-protein-and-its-functional-characterization-as-an-adjuvant
#16
Manoochehr Makvandi, Ali Teimoori, Mehdi Parsa Nahad, Ali Khodadadi, Mohammad Ghasemi Deh Cheshmeh, Milad Zandi
BACKGROUND: Flagellin is the major structural protein monomer of bacterial flagella. Flagellin through binding to its receptor and activation of antigen presenting cells stimulates the innate and adaptive immune responses. Flagellin is used as an effective systemic or mucosal adjuvant to stimulate the immune system. Recently, the therapeutic and protective role of flagellin in some infectious diseases and cancers has been investigated. In this study, we cloned the fliC genes from Salmonella typhimurium and Escherichia coli into pET-28a vector and investigated their expression in the prokaryotic system...
March 9, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29530062/potential-mediators-of-in-ovo-delivered-double-stranded-ds-rna-induced-innate-response-against-low-pathogenic-avian-influenza-virus-infection
#17
Hanaa Ahmed-Hassan, Mohamed Sarjoon Abdul-Cader, Upasama De Silva Senapathi, Maha Ahmed Sabry, Eman Hamza, Eva Nagy, Shayan Sharif, Mohamed Faizal Abdul-Careem
BACKGROUND: Toll like receptor (TLR) 3 is a critically important innate pattern recognizing receptor that senses many viral infections. Although, it has been shown that double stranded (ds) RNA can be used for the stimulation of TLR3 signaling pathway in a number of host-viral infection models, it's effectiveness as an antiviral agent against low pathogenic avian influenza virus (LPAIV) needs further investigation. METHODS: In this study, first, we delivered TLR3 ligand, dsRNA, in ovo at embryo day (ED)18 since in ovo route is routinely used for vaccination against poultry viral and parasitic infections and infected with H4N6 LPAIV 24-h post-treatment...
March 12, 2018: Virology Journal
https://www.readbyqxmd.com/read/29509510/epicutaneous-administration-of-the-pattern-recognition-receptor-agonist-polyinosinic-polycytidylic-acid-activates-the-mda5-mavs-pathway-in-langerhans-cells
#18
Pooja Tajpara, Christopher Schuster, Elisabeth Schön, Philip Kienzl, Martin Vierhapper, Michael Mildner, Adelheid Elbe-Bürger
Together with keratinocytes (KCs) and the dense network of Langerhans cells (LCs), the epidermis is an ideal portal for vaccine delivery. Pattern recognition receptor agonists, in particular polyinosinic-polycytidylic acid [p(I:C)], are promising adjuvant candidates for therapeutic vaccination to generate protective T-cell immunity. Here we established an ex vivo skin explant model to study the expression and activation of double-stranded RNA (dsRNA)-sensing pattern recognition receptors in LCs and KCs in human skin...
March 6, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29498010/therapeutic-oligonucleotides-in-cardiovascular-and-metabolic-diseases-insights-for-the-internist
#19
Domenico Girelli, Fabiana Busti, Giacomo Marchi, Nicola Martinelli, Oliviero Olivieri
The idea of using small RNA fragments (oligonucleotides) for therapeutic purposes dates back to the 1990s, following the landmark discoveries on the mechanisms of gene silencing and RNA-interference (RNA-i). However, the first applications in medicine were hampered by difficulties in chemical stabilization and efficient delivery to target tissues. Recent advances in chemical manipulation of oligonucleotides have, at least partially, bypassed such obstacles. In particular, conjugation with ligands for specific receptors allows the selective uptake of oligonucleotides by critical cells (e...
March 1, 2018: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/29468364/antitumor-in-situ-vaccination-effect-of-tnf%C3%AE-and-il-12-plasmid-dna-electrotransfer-in-a-murine-melanoma-model
#20
Urska Kamensek, Maja Cemazar, Ursa Lampreht Tratar, Katja Ursic, Gregor Sersa
Gene electrotransfer (GET) is one of the most efficient non-viral gene therapy approaches for the localized transfer of multiple genes into tumors in vivo; therefore, it is especially promising for delivering different cytokines that are toxic if administered systemically. In this study, we used concomitant intratumoral GET of two cytokines: tumor necrosis factor alpha (TNFα), a potent cytotoxic cytokine to induce in situ vaccination, and interleukin 12 (IL-12), an immunostimulatory cytokine to boost the primed local immune response into a systemic one...
February 21, 2018: Cancer Immunology, Immunotherapy: CII
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