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https://www.readbyqxmd.com/read/28330110/sequence-based-approach-for-rapid-identification-of-cross-clade-cd8-t-cell-vaccine-candidates-from-all-high-risk-hpv-strains
#1
Krishna P Singh, Neeraj Verma, Bashir A Akhoon, Vishal Bhatt, Shishir K Gupta, Shailendra K Gupta, Suchi Smita
Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28328161/synthesis-in-vitro-evaluation-and-68-ga-radiolabeling-of-cdp1-towards-pet-ct-imaging-of-bacterial-infection
#2
Jyotibon Dutta, Sooraj Baijnath, Anou M Somboro, Savania Nagiah, Fernando Albericio, Beatriz G de la Torre, Biljana Marjanovic-Painter, Jan Rijn Zeevaart, Mike Sathekge, Hendrik G Kruger, Anil Chuturgoon, Tricia Naicker, Thomas Ebenhan, Thavendran Govender
Bacterial infections are a major concern in the human health sector due to poor diagnosis and development of multi drug resistant strains. PET/CT provides a means for the noninvasive detection and localization of the infectious foci; however, the radiotracers available are either cumbersome to prepare or their exact contribution towards the imaging is not yet established. Human antimicrobial peptides are of interest for development as PET radiotracers as they are an integral component of the immune system, non-immunogenic towards the recipient and show selectivity towards pathogens such as bacteria...
March 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28327965/carbon-dating-cancer-defining-the-chronology-of-metastatic-progression-in-colorectal-cancer
#3
H Lote, I Spiteri, L Ermini, A Vatsiou, A Roy, A McDonald, N Maka, M Balsitis, N Bose, M Simbolo, A Mafficini, A Lampis, J C Hahne, F Trevisani, Z Eltahir, G Mentrasti, C Findlay, Eaj Kalkman, M Punta, B Werner, S Lise, A Aktipis, C Maley, M Greaves, C Braconi, J White, M Fassan, A Scarpa, A Sottoriva, N Valeri
Background: HASH(0x379c320) Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but lack of chronological references makes dating the exact onset of tumours very challenging. Patients and Methods: HASH(0x37a1a30) Here we describe the case of a colorectal cancer patient presenting with synchronous lung metastasis and metachronous thyroid, chest wall and urinary tract metastases over the course of five years...
February 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327944/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#4
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327674/quantitation-of-the-immunodominant-33-mer-peptide-from-%C3%AE-gliadin-in-wheat-flours-by-liquid-chromatography-tandem-mass-spectrometry
#5
Kathrin Schalk, Christina Lang, Herbert Wieser, Peter Koehler, Katharina Anne Scherf
Coeliac disease (CD) is triggered by the ingestion of gluten proteins from wheat, rye, and barley. The 33-mer peptide from α2-gliadin has frequently been described as the most important CD-immunogenic sequence within gluten. However, from more than 890 published amino acid sequences of α-gliadins, only 19 sequences contain the 33-mer. In order to make a precise assessment of the importance of the 33-mer, it is necessary to elucidate which wheat species and cultivars contain the peptide and at which concentrations...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327531/porcine-dendritic-cells-as-an-in-vitro-model-to-assess-the-immunological-behaviour-of-streptococcus-suis-subunit-vaccine-formulations-and-the-polarizing-effect-of-adjuvants
#6
Léa Martelet, Sonia Lacouture, Guillaume Goyette-Desjardins, Guy Beauchamp, Charles Surprenant, Marcelo Gottschalk, Mariela Segura
An in vitro porcine bone marrow-derived dendritic cell (DC) culture was developed as a model for evaluating immune polarization induced by adjuvants when administered with immunogens that may become vaccine candidates if appropriately formulated. The swine pathogen Streptococcus suis was chosen as a prototype to evaluate proposed S. suis vaccine candidates in combination with the adjuvants Poly I:C, Quil A ®, Alhydrogel ®, TiterMax Gold ® and Stimune ®. The toll-like receptor ligand Poly I:C and the saponin Quil A ® polarized swine DC cytokines towards a type 1 phenotype, with preferential production of IL-12 and TNF-α...
March 22, 2017: Pathogens
https://www.readbyqxmd.com/read/28327300/rbaltmip-a-recombinant-alpha-type-myotoxin-inhibitor-from-bothrops-alternatus-rhinocerophis-alternatus-snake-as-a-potential-candidate-to-complement-the-antivenom-therapy
#7
Norival A Santos-Filho, Tiago S Sousa, Johara Boldrini-França, Ludier K Santos-Silva, Danilo L Menaldo, Flávio Henrique-Silva, Adélia C O Cintra, Helen J Laure, Carla C N Mamede, Fábio Oliveira, Thalita B Riul, Marcelo Dias-Baruffi, José C Rosa, Suely V Sampaio
Phospholipase A2 inhibitors (PLIs) are important targets in the search and development of new drugs. This study aimed at evaluating the potential of an alpha-type phospholipase A2 inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake in its recombinant form (rBaltMIP) to complement the conventional antivenom therapy. Biochemical experiments showed that rBaltMIP presented pI 5.8 and molecular masses of ∼21 kDa by SDS-PAGE and 19.57 kDa by MALDI/TOF MS. After tryptic peptides sequencing, the results were compared with other PLIs available in databases, showing 100% identity between rBaltMIP and its native inhibitor BaltMIP and from 92% to 96% identity with other inhibitors...
December 15, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28326768/air-pollution-and-climate-change-effects-on-allergies-in-the-anthropocene-abundance-interaction-and-modification-of-allergens-and-adjuvants
#8
Kathrin Reinmuth-Selzle, Christopher J Kampf, Kurt Lucas, Naama Lang-Yona, Janine Fröhlich-Nowoisky, Manabu Shiraiwa, Pascale Sylvie Jeanne Lakey, Senchao Lai, Fobang Liu, Anna Theresa Kunert, Kira Ziegler, Fangxia Shen, Rossella Sgarbanti, Bettina Weber, Iris Bellinghausen, Joachim Saloga, Michael G Weller, Albert Duschl, Detlef Schuppan, Ulrich Pöschl
Air pollution and climate change are potential drivers for the increasing burden of allergic diseases. The molecular mechanisms by which air pollutants and climate parameters may influence allergic diseases, however, are complex and elusive. This article provides an overview of physical, chemical and biological interactions between air pollution, climate change, allergens, adjuvants and the immune system, addressing how these interactions may promote the development of allergies. We reviewed and synthesized key findings from atmospheric, climate, and biomedical research...
March 22, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28326559/a-phase-1-study-to-evaluate-the-safety-and-ldl-cholesterol-lowering-effects-of-rg7652-a-fully-human-monoclonal-antibody-against-proprotein-convertase-subtilisin-kexin-type-9
#9
Amos Baruch, Diana Luca, Robert S Kahn, Kyra J Cowan, Maya Leabman, Nageshwar R Budha, Cecilia P C Chiu, Yan Wu, Daniel Kirchhofer, Andrew Peterson, John C Davis, Whittemore G Tingley
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) downregulates low-density lipoprotein (LDL) receptors, thereby leading to a rise in circulating LDL cholesterol (LDL-C). RG7652 is a fully human monoclonal antibody against PCSK9. This placebo-controlled, phase 1 ascending-dose study in healthy subjects evaluated the safety of RG7652 and its efficacy as a potential LDL-C-lowering drug. HYPOTHESIS: Anti-PCSK9 antibody therapy safely and effectively reduces LDL-C...
March 22, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28325477/nano-sized-soluplus%C3%A2-polymeric-micelles-enhance-the-induction-of-tetanus-toxin-neutralising-antibody-response-following-transcutaneous-immunisation-with-tetanus-toxoid
#10
Manolya Saydam, Woei Ping Cheng, Nathan Palmer, Robert Tierney, Robert Francis, Kirsty MacLellan-Gibson, Ambreen Khan, Fatme Mawas
The use of Soluplus® polymeric micelles as a novel adjuvant for tetanus toxoid (TTxd) in transcutaneous immunisation was evaluated. TTxd was added to Soluplus® polymeric micelles to form TTxd-Soluplus® nano-aggregates with a size of 68nm. Non-adjuvanted TTxd commonly induces very poor antibody response by the transcutaneous route. However, in this study, the use of TTxd-Soluplus® resulted in a significant increase in the antibody response to TTxd, which was similar to that induced in the presence of CPG-oligodeoxynucleotides (CPG-ODNs) adjuvant...
March 18, 2017: Vaccine
https://www.readbyqxmd.com/read/28325291/systemic-rala-inos-nanoparticles-a-potent-gene-therapy-for-metastatic-breast-cancer-coupled-as-a-biomarker-of-treatment
#11
Cian M McCrudden, John W McBride, Joanne McCaffrey, Ahlam A Ali, Nicholas J Dunne, Vicky L Kett, Jonathan A Coulter, Tracy Robson, Helen O McCarthy
This study aimed to determine the therapeutic benefit of a nanoparticular formulation for the delivery of inducible nitric oxide synthase (iNOS) gene therapy in a model of breast cancer metastasis. Nanoparticles comprising a cationic peptide vector, RALA, and plasmid DNA were formulated and characterized using a range of physiochemical analyses. Nanoparticles complexed using iNOS plasmids and RALA approximated 60 nm in diameter with a charge of 25 mV. A vector neutralization assay, performed to determine the immunogenicity of nanoparticles in immunocompetent C57BL/6 mice, revealed that no vector neutralization was evident...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325151/adipose-tissue-derived-pericytes-for-cartilage-tissue-engineering
#12
Jin Xin Zhang, Chun Yan Du, Wei Min Guo, Pan Li, Shu Yun Liu, Zhi Guo Yuan, Jian Hua Yang, Xun Sun, He Yong Yin, Quan Yi Guo, Chen Fu Zhou
Mesenchymal stem cells (MSCs) represent a promising alternative source for cartilage tissue engineering. However, MSC culture is labor-intensive, so these cells cannot be applied immediately to regenerate cartilage for clinical purposes. Risks during the ex vivo expansion of MSCs, such as infection and immunogenicity, can be a bottleneck in their use in clinical tissue engineering. As a novel stem cell source, pericytes are generally considered to be the origin of MSCs. Pericytes do not have to undergo time-consuming ex vivo expansion because they are uncultured cells...
March 21, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28324619/identification-of-a-herv-k-env-surface-peptide-highly-recognized-in-ra-patients-a-cross-sectional-case-control-study
#13
G Mameli, G L Erre, E Caggiu, S Mura, D Cossu, Marco Bo, M L Cadoni, A Piras, N Mundula, E Colombo, G Buscetta, G Passiu, L A Sechi
Endogenous Retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been recently reported to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su 19-37 , env-su 109-26 , env-su 164-186 , env-su 209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity...
March 21, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28324011/a-novel-fc-fgf21-with-improved-resistance-to-proteolysis-increased-affinity-towards-%C3%AE-klotho-and-enhanced-efficacy-in-mice-and-cynomolgus-monkeys
#14
Shanaka Stanislaus, Randy Hecht, Junming Yie, Todd Hager, Michael Hall, Chris Spahr, Wei Wang, Jennifer Weiszmann, Yang Li, Liying Deng, Dwight Winters, Stephen Smith, Lei Zhou, Yuesheng Li, Murielle M Véniant, Jing Xu
FGF21 is a natural hormone that modulates glucose, lipid, and energy metabolism. Previously, we engineered an Fc fusion FGF21 variant with two mutations, Fc-FGF21(RG), to extend the half-life and reduce aggregation and in vivo degradation of FGF21. We now describe a new variant developed to reduce the extreme C-terminal degradation and improve the binding affinity to β-Klotho. We demonstrate, by introducing one additional mutation located at the C-terminus of FGF21 (A180E) that the new molecule, Fc-FGF21(RGE), has gained many improved attributes...
January 26, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323513/transmembrane-tnf-dependent-uptake-of-anti-tnf-antibodies
#15
Arun Deora, Subramanya Hegde, Jacqueline Lee, Chee-Ho Choi, Qing Chang, Cheryl Lee, Lucia Eaton, Hua Tang, Dongdong Wang, David Lee, Mark Michalak, Medha Tomlinson, Qingfeng Tao, Nidhi Gaur, Bohdan Harvey, Shaun McLoughlin, Boris Labkovsky, Tariq Ghayur
TNF-alpha (TNF), a pro-inflammatory cytokine is synthesized as a 26 kDa protein, anchors in the plasma membrane as transmembrane TNF (TmTNF), and is subjected to proteolysis by the TNF-alpha converting enzyme (TACE) to release the 15 kDa form of soluble TNF (sTNF). TmTNF and sTNF interact with two distinct receptors, TNF-R1 (p55) and TNF-R2 (p75), to mediate the multiple biological effects of TNF described to date. Several anti-TNF biologics that bind to both forms of TNF and block their interactions with the TNF receptors are now approved for the treatment of a variety of immune-mediated diseases...
March 21, 2017: MAbs
https://www.readbyqxmd.com/read/28322916/prediction-and-reduction-of-the-aggregation-of-monoclonal-antibodies
#16
Rob van der Kant, Anne R Karow-Zwick, Joost Van Durme, Michaela Blech, Rodrigo Gallardo, Daniel Seeliger, Kerstin Aßfalg, Pieter Baatsen, Griet Compernolle, Ann Gils, Joey M Studts, Patrick Schulz, Patrick Garidel, Joost Schymkowitz, Frederic Rousseau
Protein aggregation remains a major area of focus in the production of monoclonal antibodies. Improving the intrinsic properties of antibodies can improve manufacturability, attrition rates, safety, formulation, titers, immunogenicity and solubility. Here, we explore the potential of predicting and reducing the aggregation propensity of monoclonal antibodies, based on the identification of aggregation-prone regions (APRs) and their contribution to the thermodynamic stability of the protein. Although APRs are thought to occur in the antigen binding region to drive hydrophobic binding with antigen, we were able to rationally design variants that display a marked decrease in aggregation propensity while retaining antigen binding through the introduction of artificial aggregation gatekeeper residues...
March 17, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28322894/inflammation-and-immunogenicity-limit-the-utility-of-the-rabbit-as-a-nonclinical-species-for-ocular-biologic-therapeutics
#17
Christina L Zuch de Zafra, Vito G Sasseville, Steven Matsumoto, Christian Freichel, Mark Milton, Timothy K MacLachlan, Cindy Farman, Iona Raymond, Swati Gupta, Ronald Newton, Elke-Astrid Atzpodien, Evan A Thackaberry
The nonclinical safety evaluation of therapeutic drug candidates is commonly conducted in two species (rodent and non-rodent) in keeping with international health authority guidance. Biologic drugs typically have restricted species cross-reactivity, necessitating the evaluation of safety in non-human primates and thus limiting the utility of lower order species. Safety studies of cross-reactive ocular biologic drug candidates have been conducted in rabbits as a second toxicology species, despite the fact that rabbits are not a rodent species...
March 16, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28321224/specific-igg-antibodies-react-to-mimotopes-of-bk-polyomavirus-a-small-dna-tumor-virus-in-healthy-adult-sera
#18
Silvia Pietrobon, Ilaria Bononi, Elisa Mazzoni, Francesca Lotito, Marco Manfrini, Andrea Puozzo, Federica Destro, Giovanni Guerra, Pier Francesco Nocini, Fernanda Martini, Mauro G Tognon
BK polyomavirus (BKPyV) was isolated in 1971 from the urine of a kidney transplant patient. Soon after its identification, BKPyV was characterized as a kidney-tropic virus, which is responsible of a significant fraction of the rejection of transplant kidney in the host. Moreover, in experimental conditions, BKPyV is able to transform different types of animal and human cells and to induce tumors of different histotypes in experimental animals. BKPyV DNA sequences have been detected in healthy individuals and cancer patients using polymerase chain reaction/Shouthern blot hybridization methods...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28321220/adjusted-particle-size-eliminates-the-need-of-linkage-of-antigen-and-adjuvants-for-appropriated-t-cell-responses-in-virus-like-particle-based-vaccines
#19
Ariane C Gomes, Anna Flace, Philippe Saudan, Franziska Zabel, Gustavo Cabral-Miranda, Aadil El Turabi, Vania Manolova, Martin F Bachmann
Since the discovery of the first virus-like particle (VLP) derived from hepatitis B virus in 1980 (1), the field has expanded substantially. Besides successful use of VLPs as safe autologous virus-targeting vaccines, the powerful immunogenicity of VLPs has been also harnessed to generate immune response against heterologous and even self-antigens (2-4). Linking adjuvants to VLPs displaying heterologous antigen ensures simultaneous delivery of all vaccine components to the same antigen-presenting cells. As a consequence, antigen-presenting cells, such as dendritic cells, will process and present the antigen displayed on VLPs while receiving costimulatory signals by the VLP-incorporated adjuvant...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320976/a-study-on-the-efficacy-of-the-recombinant-yersinia-adhesin-a-vaccine-against-yersiniosis-in-the-early-phase
#20
Kosuke Tsugo, Shin/Ichi Nakamura, Hiroko Yamanaka, Yumi Une
Yersinia pseudotuberculosis (Y. ptb) is a zoonotic pathogenic bacterial species of the family Enterobacteriaceae and causes yersiniosis, an acute intestinal infection in humans and animals. Y. ptb is often implicated in lethal epidemics in zoo animals and reductions in the breeding population, but a valid prevention method has not been established. Therefore, this study aimed to develop a vaccine for yersiniosis control. The immunogenicity of one of the adhesion factors involved in pathogenic mechanisms of Y...
March 20, 2017: Journal of Veterinary Medical Science
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