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Immune engineering

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https://www.readbyqxmd.com/read/28106821/a-protective-vaccine-against-chlamydia-genital-infection-using-vault-nanoparticles-without-an-added-adjuvant
#1
Janina Jiang, Guangchao Liu, Valerie A Kickhoefer, Leonard H Rome, Lin-Xi Li, Stephen J McSorley, Kathleen A Kelly
Chlamydia trachomatis genital infection is the most common sexually transmitted bacterial disease, causing a significant burden to females due to reproductive dysfunction. Intensive screening and antibiotic treatment are unable to completely prevent female reproductive dysfunction, thus, efforts have become focused on developing a vaccine. A major impediment is identifying a safe and effective adjuvant which induces cluster of differentiation 4 (CD4) cells with attributes capable of halting genital infection and inflammation...
January 19, 2017: Vaccines
https://www.readbyqxmd.com/read/28103055/the-discovery-and-development-of-the-crispr-system-in-applications-in-genome-manipulation
#2
Veronica Lau, James R Davie
The clustered regularly interspaced short palindromic repeat (CRISPR) associated 9 (Cas9) system is a microbial adaptive immune system that has been recently developed for genomic engineering. From the moment the CRISPR system was discovered in Escherichia coli, the drive to understand the mechanism prevailed, leading to rapid advancement in the knowledge and applications of the CRISPR system. With the ability to characterize and understand the function of the Cas9 endonuclease came the ability to adapt the CRISPR-Cas9 system for use in a variety of applications and disciplines ranging from agriculture to biomedicine...
October 28, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28100467/an-essential-role-of-cbl-and-cbl-b-ubiquitin-ligases-in-mammary-stem-cell-maintenance
#3
Bhopal Mohapatra, Neha Zutshi, Wei An, Benjamin Goetz, Priyanka Arya, Timothy A Bielecki, Insha Mustaq, Matthew D Storck, Jane L Meza, Vimla Band, Hamid Band
CBL and CBL-B ubiquitin ligases are negative regulators of tyrosine kinase signaling with established roles in the immune system. However, their physiological roles in epithelial tissues are unknown. Here we used the MMTV-Cre-mediated Cbl gene deletion on a Cbl-b-null background as well as a tamoxifen-inducible mammary stem cell (MaSC)-specific Cbl/Cbl-b double knockout (DKO), using Lgr5-GFP-CreERT, to demonstrate a mammary epithelial cell-autonomous requirement of CBL and CBL-B in the maintenance of MaSCs...
January 18, 2017: Development
https://www.readbyqxmd.com/read/28098169/ifn-%C3%AE-regulates-human-dental-pulp-stem-cells-behavior-via-nf-%C3%AE%C2%BAb-and-mapk-signaling
#4
Xinyao He, Wenkai Jiang, Zhirong Luo, Tiejun Qu, Zhihua Wang, Ningning Liu, Yaqing Zhang, Paul R Cooper, Wenxi He
During caries, dental pulp expresses a range of pro-inflammatory cytokines in response to the infectious challenge. Interferon gamma (IFN-γ) is a dimerized soluble cytokine, which is critical for immune responses. Previous study has demonstrated that IFN-γ at relative high concentration (100 ng/mL) treatment improved the impaired dentinogenic and immunosuppressive regulatory functions of disease-derived dental pulp stem cells (DPSCs). However, little is known about the regulatory effects of IFN-γ at relative low concentration on healthy DPSC behavior (including proliferation, migration, and multiple-potential differentiation)...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096848/immunogenicity-and-efficacy-of-live-l-tarentolae-expressing-kmp11-ntgp96-gfp-fusion-as-a-vaccine-candidate-against-experimental-visceral-leishmaniasis-caused-by-l-infantum
#5
Vahid Nasiri, Abdolhossein Dalimi, Fatemeh Ghaffarifar, Azam Bolhassani
BACKGROUND: The aim of present study was to evaluate the protective efficacy of live recombinant L. tarentolae expressing KMP11-NTGP96-GFP fusion as candidates for live engineered recombinant vaccine against visceral leishmaniasis in BALB/c mice. METHODS: KMP-11 and NT-GP96 genes cloned into the pJET1.2/blunt cloning vector and then into pEGFP-N1 expression vector. The KMP-11, NT-GP96 and GFP fused in pEGFP-N1 and subcloned into Leishmanian pLEXSY-neo vector. Finally this construct was transferred to L...
April 2016: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#6
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28095489/transgenic-expression-of-the-anti-parasitic-factor-tep1-in-the-malaria-mosquito-anopheles-gambiae
#7
Gloria Volohonsky, Ann-Katrin Hopp, Mélanie Saenger, Julien Soichot, Heidi Scholze, Jens Boch, Stéphanie A Blandin, Eric Marois
Mosquitoes genetically engineered to be resistant to Plasmodium parasites represent a promising novel approach in the fight against malaria. The insect immune system itself is a source of anti-parasitic genes potentially exploitable for transgenic designs. The Anopheles gambiae thioester containing protein 1 (TEP1) is a potent anti-parasitic protein. TEP1 is secreted and circulates in the mosquito hemolymph, where its activated cleaved form binds and eliminates malaria parasites. Here we investigated whether TEP1 can be used to create malaria resistant mosquitoes...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28092363/mouse-models-of-uv-induced-melanoma-genetics-pathology-and-clinical-relevance
#8
Chi-Ping Day, Rachel Marchalik, Glenn Merlino, Helen Michael
Melanocytes, a neural crest cell derivative, produce pigment to protect keratinocytes from ultraviolet radiation (UVR). Although melanocytic lesions such as nevi and cutaneous malignant melanomas are known to be associated with sun exposure, the role of UVR in oncogenesis is complex and has yet to be clearly elucidated. UVR appears to have a direct mutational role in inducing or promoting melanoma formation as well as an indirect role through microenvironmental changes. Recent advances in the modeling of human melanoma in animals have built platforms upon which prospective studies can begin to investigate these questions...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28090564/hepatocyte-toll-like-receptor-5-promotes-bacterial-clearance-and-protects-mice-against-high-fat-diet-induced-liver-disease
#9
Lucie Etienne-Mesmin, Matam Vijay-Kumar, Andrew T Gewirtz, Benoit Chassaing
BACKGROUND & AIMS: Innate immune dysfunction can promote chronic inflammatory diseases of the liver. For example, mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) show microbial dysbiosis and predisposition to high-fat diet (HFD)-induced hepatic steatosis. The extent to which hepatocytes play a direct role in detecting bacterial products in general, or flagellin in particular, is poorly understood. In the present study, we investigated the role of hepatocyte TLR5 in recognizing flagellin, policing bacteria, and protecting against liver disease...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28087528/engineering-mycobacteria-for-the-production-of-self-assembling-biopolyesters-displaying-mycobacterial-antigens-for-use-as-tuberculosis-vaccine
#10
Jason W Lee, Natalie A Parlane, Bernd H A Rehm, Bryce M Buddle, Axel Heiser
: Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. Recently, engineered polyhydroxyalkanoate (PHA) biobeads produced in both E. coli and Lactococcus lactis displaying mycobacterial antigens were found to induce significant cell mediated immune responses in mice. We observed that such PHA beads contained host cell proteins as impurities which we hypothesized to have the potential to induce immunity...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28081143/engineered-aedes-aegypti-jak-stat-pathway-mediated-immunity-to-dengue-virus
#11
Natapong Jupatanakul, Shuzhen Sim, Yesseinia I Angleró-Rodríguez, Jayme Souza-Neto, Suchismita Das, Kristin E Poti, Shannan L Rossi, Nicholas Bergren, Nikos Vasilakis, George Dimopoulos
We have developed genetically modified Ae. aegypti mosquitoes that activate the conserved antiviral JAK/STAT pathway in the fat body tissue, by overexpressing either the receptor Dome or the Janus kinase Hop by the blood feeding-induced vitellogenin (Vg) promoter. Transgene expression inhibits infection with several dengue virus (DENV) serotypes in the midgut as well as systemically and in the salivary glands. The impact of the transgenes Dome and Hop on mosquito longevity was minimal, but it resulted in a compromised fecundity when compared to wild-type mosquitoes...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28077675/post-hoc-assessment-of-the-immunogenicity-of-bioengineered-factor-viia-demonstrates-the-use-of-preclinical-tools
#12
Kasper Lamberth, Stine Louise Reedtz-Runge, Jonathan Simon, Ksenia Klementyeva, Gouri Shankar Pandey, Søren Berg Padkjær, Véronique Pascal, Ileana R León, Charlotte Nini Gudme, Søren Buus, Zuben E Sauna
Immunogenicity is an important consideration in the licensure of a therapeutic protein because the development of neutralizing anti-drug antibodies (ADAs) can affect both safety and efficacy. Neoantigens introduced by bioengineering of a protein drug are a particular cause for concern. The development of a bioengineered recombinant factor VIIa (rFVIIa) analog was discontinued after phase 3 trials because of the development of ADAs. The unmodified parent molecule (rFVIIa), on the other hand, has been successfully used as a drug for more than two decades with no reports of immunogenicity in congenital hemophilia patients with inhibitors...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077318/alcohol-microbiome-life-style-influence-alcohol-and-non-alcoholic-organ-damage
#13
REVIEW
Manuela G Neuman, Samuel W French, Samir Zakhari, Stefen Malnick, Helmut K Seitz, Lawrence B Cohen, Mikko Salaspuro, Andreea Voinea Griffin, Andrei Barasch, Irina A Kirpich, Paul G Thomes, Laura W Schrum, Terrence M Donohue, Kusum Kharbanda, Marcus Cruz, Mihai Opris
This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, onJune 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealedthe basic aspects of alcohol metabolism that may be responsible for the development of liver diseaseas well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases...
January 7, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28076778/axl-mediates-zika-virus-entry-in-human-glial-cells-and-modulates-innate-immune-responses
#14
Laurent Meertens, Athena Labeau, Ophelie Dejarnac, Sara Cipriani, Laura Sinigaglia, Lucie Bonnet-Madin, Tifenn Le Charpentier, Mohamed Lamine Hafirassou, Alessia Zamborlini, Van-Mai Cao-Lormeau, Muriel Coulpier, Dorothée Missé, Nolwenn Jouvenet, Ray Tabibiazar, Pierre Gressens, Olivier Schwartz, Ali Amara
ZIKA virus (ZIKV) is an emerging pathogen responsible for neurological disorders and congenital microcephaly. However, the molecular basis for ZIKV neurotropism remains poorly understood. Here, we show that Axl is expressed in human microglia and astrocytes in the developing brain and that it mediates ZIKV infection of glial cells. Axl-mediated ZIKV entry requires the Axl ligand Gas6, which bridges ZIKV particles to glial cells. Following binding, ZIKV is internalized through clathrin-mediated endocytosis and traffics to Rab5+ endosomes to establish productive infection...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28075558/immunological-principles-guiding-the-rational-design-of-particles-for-vaccine-delivery
#15
Katelyn T Gause, Adam K Wheatley, Jiwei Cui, Yan Yan, Stephen J Kent, Frank Caruso
Despite the immense public health successes of immunization over the past century, effective vaccines are still lacking for globally important pathogens such as human immunodeficiency virus, malaria, and tuberculosis. Exciting recent advances in immunology and biotechnology over the past few decades have facilitated a shift from empirical to rational vaccine design, opening possibilities for improved vaccines. Some of the most important advancements include (i) the purification of subunit antigens with high safety profiles, (ii) the identification of innate pattern recognition receptors (PRRs) and cognate agonists responsible for inducing immune responses, and (iii) developments in nano- and microparticle fabrication and characterization techniques...
January 11, 2017: ACS Nano
https://www.readbyqxmd.com/read/28075126/cell-conditioned-protein-coronas-on-engineered-particles-influence-immune-responses
#16
Qiong Dai, Junling Guo, Yan Yan, Ching-Seng Ang, Nadja Bertleff-Zieschang, Frank Caruso
A protein corona, which forms on engineered particles as soon as they are introduced into biological environments, is known to provide particles with a "biological identity". Protein coronas derived from various biological environments have been demonstrated to alter the cell internalization mechanism, to diminish targeting ability and to induce nanoparticle aggregation. So far, most of these studies have challenged engineered particles with a static biological environment. However, the extracellular environment is highly dynamic due to the process termed "cell-conditioning", in which cells deplete and secrete biomolecules...
January 11, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28072880/characterisation-of-early-life-fecal-microbiota-in-susceptible-and-healthy-pigs-to-post-weaning-diarrhoea
#17
Samir Dou, Pascale Gadonna-Widehem, Véronique Rome, Dounia Hamoudi, Larbi Rhazi, Lyes Lakhal, Thibaut Larcher, Narges Bahi-Jaber, Arturo Pinon-Quintana, Alain Guyonvarch, Isabelle L E Huërou-Luron, Latifa Abdennebi-Najar
Early-life microbial exposure is of particular importance to growth, immune system development and long-lasting health. Hence, early microbiota composition is a promising predictive biomarker for health and disease but still remains poorly characterized in regards to susceptibility to diarrhoea. In the present study, we aimed to assess if gut bacterial community diversity and composition during the suckling period were associated with differences in susceptibility of pigs to post-weaning diarrhoea. Twenty piglets from 5 sows (4 piglets / litter) were weaned in poor housing conditions to challenge their susceptibility to post-weaning diarrhoea...
2017: PloS One
https://www.readbyqxmd.com/read/28069500/solution-blow-spinning-fibres-new-immunologically-inert-substrates-for-the-analysis-of-cell-adhesion-and-motility
#18
Rafaella T Paschoalin, Bruna Traldi, Gülcan Aydin, Juliano E Oliveira, Stephan Rütten, Luiz H C Mattoso, Martin Zenke, Antonio Sechi
The control of cell behaviour through material geometry is appealing as it avoids the requirement for complex chemical surface modifications. Significant advances in new technologies have been made to the development of polymeric biomaterials with controlled geometry and physico-chemical properties. Solution blow spinning technique has the advantage of ease of use allowing the production of nano or microfibres and the direct fibre deposition on any surface in situ. Yet, in spite of these advantages, very little is known about the influence of such fibres on biological functions such as immune response and cell migration...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28069025/interaction-of-biomedical-nanoparticles-with-the-pulmonary-immune-system
#19
REVIEW
Fabian Blank, Kleanthis Fytianos, Emilie Seydoux, Laura Rodriguez-Lorenzo, Alke Petri-Fink, Christophe von Garnier, Barbara Rothen-Rutishauser
Engineered nanoparticles (NPs) offer site-specific delivery, deposition and cellular uptake due to their unique physicochemical properties and were shown to modulate immune responses. The respiratory tract with its vast surface area is an attractive target organ for innovative immunomodulatory therapeutic applications by pulmonary administration of such NPs, enabling interactions with resident antigen-presenting cells (APCs), such as dendritic cells and macrophages. Depending on the respiratory tract compartment, e...
January 9, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28068879/electrospun-template-architecture-and-composition-regulate-neutrophil-netosis-in-vitro-and-in-vivo
#20
Allison E Fetz, Indira Neeli, Isaac A Rodriguez, Marko Z Radic, Gary Bowlin
Mounting evidence indicates that neutrophils, first responders to an implanted biomaterial, prime the microenvironment for recruited immune cells by secreting factors and releasing neutrophil extracellular traps (NETs) through NETosis. In this study, we investigated the role of electrospun template architecture and composition in regulating NETosis. Electrospun polydioxanone (PDO), collagen type I (COL), and blended PDO-COL templates (PC) were fabricated with small (0.25-0.35µm) and large (1.0-2.00µm) diameter fibers...
January 9, 2017: Tissue Engineering. Part A
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