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https://www.readbyqxmd.com/read/28336300/development-of-topical-delivery-systems-for-flightless-neutralizing-antibody
#1
Hanif Haidari, Qian Zhang, Elizabeth Melville, Zlatko Kopecki, Yunmei Song, Allison J Cowin, Sanjay Garg
Flightless I (Flii) is an actin remodelling protein important for cytoskeletal regulation and cellular processes including migration, proliferation and adhesion. Previous studies have clearly identified Flii as a novel therapeutical target for improved wound repair and have demonstrated Flii regulation using Flii neutralizing antibodies (FnAb) in different models of wound healing in vivo. Here we describe the development of an optimised topical delivery system that can neutralize Flii activity in the epidermis...
March 20, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#2
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28335329/nanoparticle-based-delivery-of-anaplasma-marginale-membrane-proteins-virb9-1-and-virb10-produced-in-the-pichia-pastoris-expression-system
#3
Bing Zhang, Antonio S Cavallaro, Karishma T Mody, Jun Zhang, James R Deringer, Wendy C Brown, Timothy J Mahony, Chengzhong Yu, Neena Mitter
Bovine anaplasmosis or cattle-tick fever is a tick-borne haemolytic disease caused by the rickettsial haemoparasite Anaplasma marginale in tropical and subtropical areas of the world. While difficult to express, the proteins VirB9-1 and VirB10 are immunogenic components of the outer membrane type IV secretion system that have been identified as candidate antigens for vaccines targeting of A. marginale. Soluble VirB9-1 and VirB10 were successfully expressed using Pichia pastoris. When formulated with the self-adjuvanting silica vesicles, SV-100 (diameter: 50 nm, and pore entrance size: 6 nm), 200 µg of VirB9-1 and VirB10 were adsorbed per milligram of nanoparticle...
November 5, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28333964/optimizing-ultrasound-molecular-imaging-of-secreted-frizzled-related-protein-2-expression-in-angiosarcoma
#4
James K Tsuruta, Nicholas P Schaub, Juan D Rojas, Jason Streeter, Nancy Klauber-DeMore, Paul Dayton
Secreted frizzled related protein 2 (SFRP2) is a tumor endothelial marker expressed in angiosarcoma. Previously, we showed ultrasound molecular imaging with SFRP2-targeted contrast increased average video pixel intensity (VI) of angiosarcoma vessels by 2.2 ± 0.6 VI versus streptavidin contrast. We hypothesized that redesigning our contrast agents would increase imaging performance. Improved molecular imaging reagents were created by combining NeutrAvidin™-functionalized microbubbles with biotinylated SFRP2 or IgY control antibodies...
2017: PloS One
https://www.readbyqxmd.com/read/28322916/prediction-and-reduction-of-the-aggregation-of-monoclonal-antibodies
#5
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/28321813/harnessing-the-immune-system-against-leukemia-monoclonal-antibodies-and-checkpoint-strategies-for-aml
#6
Lucia Masarova, Hagop Kantarjian, Guillermo Garcia-Mannero, Farhad Ravandi, Padmanee Sharma, Naval Daver
Acute myeloid leukemia (AML) is the most common leukemia among adults and is associated with a poor prognosis, especially in patients with adverse prognostic factors, older age, or relapsed disease. The last decade has seen a surge in successful immune-based therapies in various solid tumors; however, the role of immune therapies in AML remains poorly defined. This chapter describes the rationale, clinical data, and toxicity profiles of immune-based therapeutic modalities in AML including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD1/PDL1 or CTLA4...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28320753/do-memory-b-cells-form-secondary-germinal-centers-impact-of-antibody-class-and-quality-of-memory-t-cell-help-at-recall
#7
Louise J McHeyzer-Williams, Chad Dufaud, Michael G McHeyzer-Williams
Antigen recall can clearly induce a germinal center (GC) reaction. What has become an issue for debate are the origins of the antigen-specific B cells that form memory-response GCs (mGCs). Using antigen labeling and adoptive transfer, memory B cells expressing different antibody class can give rise to mGCs with differing efficiency. Here, we will argue that the range of class-specific memory responses reported across multiple systems represents the spectrum of memory B-cell fate and function. While the formulation of recall immunogen and location of mGCs have an important role, we propose that effective cognate regulation is the key variable influencing recall outcome...
March 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28319364/a-new-spin-on-antibody-drug-conjugates-trastuzumab-fulvestrant-colloidal-drug-aggregates-target-her2-positive-cells
#8
Ahil N Ganesh, Christopher Mclaughlin, Da Duan, Brian K Shoichet, Molly S Shoichet
While the formation of colloidal aggregates leads to artifacts in early drug discovery, their composition makes them attrac-tive as nanoparticle formulations for targeted drug delivery as the entire nanoparticle is composed of drug. The typical tran-sient stability of colloidal aggregates has inhibited exploiting this property. To overcome this limitation, we investigated a series of proteins to stabilize colloidal aggregates of the chemotherapeutic, fulvestrant, including: bovine serum albumin, a generic human immunoglobulin G, and trastuzumab, a therapeutic anti-human epidermal growth factor receptor 2 anti-body...
March 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28316602/toll-like-receptor-ligand-based-vaccine-adjuvants-require-intact-myd88-signaling-in-antigen-presenting-cells-for-germinal-center-formation-and-antibody-production
#9
Munir M Mosaheb, Michael L Reiser, Lee M Wetzler
Vaccines are critical in the fight against infectious diseases, and immune-stimulating adjuvants are essential for enhancing vaccine efficacy. However, the precise mechanisms of action of most adjuvants are unknown. There is an urgent need for customized and adjuvant formulated vaccines against immune evading pathogens that remain a risk today. Understanding the specific role of various cell types in adjuvant-induced protective immune responses is vital for an effective vaccine design. We have investigated the role of cell-specific MyD88 signaling in vaccine adjuvant activity in vivo, using Neisserial porin B (PorB), a TLR2 ligand-based adjuvant, compared with an endosomal TLR9 ligand (CpG) and toll-like receptor (TLR)-independent (alum, MF59) adjuvants...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28316436/antibody-titers-in-group-o-platelet-donors
#10
Anita Amar Tendulkar, Puneet Ashok Jain, Sanjay Velaye
BACKGROUND AND OBJECTIVES: The occurrence of hemolysis due to transfusion of ABO plasma-incompatible platelets (PLTs) is challenging. There has been no consensus for critical antibody titers in the transfusion community. This study was conducted to understand the trends of anti-A and anti-B antibody titer levels in O group donors and to identify any specific patterns of distribution in relation to age and gender. MATERIALS AND METHODS: A total of 1635 Group O PLT donors were randomly selected for this prospective study...
January 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28304250/tranexamic-acid-and-supportive-measures-to-treat-wasting-marmoset-syndrome
#11
Takuro Yoshimoto, Kimie Niimi, Eiki Takahashi
Wasting marmoset syndrome (WMS) has high incidence and mortality rates and is one of the most important problems in captive common marmoset (Callithrix jacchus) colonies. Despite several reports on WMS, little information is available regarding its reliable treatment. We previously reported that marmosets with WMS had high serum levels of matrix metalloproteinase 9 (MMP9). MMP9 is thought to be a key enzyme in the pathogenesis of inflammatory bowel disease, the main disease state of WMS, and is activated by plasmin, a fibrinolytic factor...
December 1, 2016: Comparative Medicine
https://www.readbyqxmd.com/read/28302407/immunogenicity-and-safety-of-an-as03-adjuvanted-h7n1-vaccine-in-adults-65years-of-age-and-older-a-phase-ii-observer-blind-randomized-controlled-trial
#12
Anuradha Madan, Murdo Ferguson, Paul Rheault, David Seiden, Azhar Toma, Damien Friel, Jyoti Soni, Ping Li, Bruce L Innis, Anne Schuind
BACKGROUND: H7 influenza strains can cause severe and often fatal human infections, especially in the elderly. This phase II, observer-blind, randomized trial (www.ClinicalTrials.gov: NCT01949090) assessed the immunogenicity and safety of a novel AS03-adjuvanted H7N1 vaccine that may serve as a model H7-subtype vaccine. METHODS: 360 adults ≥65years of age in stable health received either 1 of 4 adjuvanted A/mallard/Netherlands/12/2000 split virion vaccine formulations (3...
March 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28301509/genome-wide-association-mapping-in-winter-barley-for-grain-yield-and-culm-cell-wall-polymer-content-using-the-high-throughput-compp-technique
#13
Andrea Bellucci, Alessandro Tondelli, Jonatan U Fangel, Anna Maria Torp, Xin Xu, William G T Willats, Andrew Flavell, Luigi Cattivelli, Søren K Rasmussen
A collection of 112 winter barley varieties (Hordeum vulgare L.) was grown in the field for two years (2008/09 and 2009/10) in northern Italy and grain and straw yields recorded. In the first year of the trial, a severe attack of barley yellow mosaic virus (BaYMV) strongly influenced final performances with an average reduction of ~ 50% for grain and straw harvested in comparison to the second year. The genetic determination (GD) for grain yield was 0.49 and 0.70, for the two years respectively, and for straw yield GD was low in 2009 (0...
2017: PloS One
https://www.readbyqxmd.com/read/28301280/panblok-h1-advax-h1n1-2009pdm-vaccine-insights-into-rapid-development-of-an-delta-inulin-adjuvanted-recombinant-pandemic-influenza-vaccine
#14
Yoshikazu Honda-Okubo, Harinda Rajapaksha, Dimitar Sajkov, David Gordon, Manon M J Cox, Nikolai Petrovsky
Timely vaccine supply is critical during influenza pandemics but is impeded by current virus-based manufacturing methods. The 2009 H1N1/2009pdm 'swine flu' pandemic reinforced the need for innovation in pandemic vaccine design. We report on insights gained during rapid development of a pandemic vaccine based on recombinant haemagglutinin (rHA) formulated with Advax™ delta inulin adjuvant (Panblok-H1/Advax). Panblok-H1/Advax was designed and manufactured within 1 month of the pandemic declaration by WHO and successfully entered human clinical testing in under 3 months from first isolation and sequencing of the novel pandemic virus, requiring several major challenges to be overcome...
February 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28292243/injectable-drug-loaded-nanocarriers-for-lung-cancer-treatments
#15
Huang-Ping Yu, Ibrahim A Aljuffali, Jia-You Fang
Different types of injectable nanoparticles, including metallic nanoparticles, polymeric nanocarriers, dendrimers, liposomes, niosomes, and lipid nanoparticles, have been employed to load drugs for lung delivery. Nanoparticles used for lung delivery offer some benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tumor targeting, and minimal side effects. In recent years, the concept of using injectable nanocarriers as vehicles for drug delivery has attracted increasing attention...
2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28289411/immunogenicity-of-a-bivalent-adjuvanted-glycoconjugate-vaccine-against-salmonella-typhimurium-and-salmonella-enteritidis
#16
Fabio Fiorino, Simona Rondini, Francesca Micoli, Luisa Lanzilao, Renzo Alfini, Francesca Mancini, Calman A MacLennan, Donata Medaglini
Salmonella enterica serovars Typhimurium and Enteritidis are the predominant causes of invasive non-typhoidal Salmonella (iNTS) disease. Considering the co-endemicity of S. Typhimurium and S. Enteritidis, a bivalent vaccine formulation against both pathogens is necessary for protection against iNTS disease, thus investigation of glycoconjugate combination is required. In the present work, we investigated the immune responses induced by S. Typhimurium and S. Enteritidis monovalent and bivalent glycoconjugate vaccines adjuvanted with aluminum hydroxide (alum) only or in combination with cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28288639/rhesus-macaque-and-mouse-models-for-down-selecting-circumsporozoite-protein-based-malaria-vaccines-differ-significantly-in-immunogenicity-and-functional-outcomes
#17
Timothy W Phares, Anthony D May, Christopher J Genito, Nathan A Hoyt, Farhat A Khan, Michael D Porter, Margot DeBot, Norman C Waters, Philippe Saudan, Sheetij Dutta
BACKGROUND: Non-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. Transgenic rodent parasites expressing genes of human Plasmodium are now routinely used for efficacy studies of human malaria vaccines. Mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are sufficient to move a vaccine candidate into the clinic...
March 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28284602/a-novel-chimeric-protein-composed-of-recombinant-mycoplasma-hyopneumoniae-antigens-as-a-vaccine-candidate-evaluated-in-mice
#18
Natasha Rodrigues de Oliveira, Sérgio Jorge, Charles Klazer Gomes, Caroline Rizzi, Violetta Dias Pacce, Thais Farias Collares, Leonardo Garcia Monte, Odir Antônio Dellagostin
Enzootic Pneumonia (EP) is caused by the Mycoplasma hyopneumoniae pathogenic bacteria, and it represents a significant respiratory disease that is responsible for major economic losses within the pig industry throughout the world. The bacterins that are currently commercially available have been proven to offer only partial protection against M. hyopneumoniae, and the development of more efficient vaccines is required. Several recombinant antigens have been evaluated via different immunization strategies and have been found to be highly immunogenic...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28278283/enhanced-control-of-mycobacterium-tuberculosis-extrapulmonary-dissemination-in-mice-by-an-arabinomannan-protein-conjugate-vaccine
#19
Rafael Prados-Rosales, Leandro Carreño, Tingting Cheng, Caroline Blanc, Brian Weinrick, Adel Malek, Todd L Lowary, Andres Baena, Maju Joe, Yu Bai, Rainer Kalscheuer, Ana Batista-Gonzalez, Noemi A Saavedra, Leticia Sampedro, Julen Tomás, Juan Anguita, Shang-Cheng Hung, Ashish Tripathi, Jiayong Xu, Aharona Glatman-Freedman, Williams R Jacobs, John Chan, Steven A Porcelli, Jacqueline M Achkar, Arturo Casadevall
Currently there are a dozen or so of new vaccine candidates in clinical trials for prevention of tuberculosis (TB) and each formulation attempts to elicit protection by enhancement of cell-mediated immunity (CMI). In contrast, most approved vaccines against other bacterial pathogens are believed to mediate protection by eliciting antibody responses. However, it has been difficult to apply this formula to TB because of the difficulty in reliably eliciting protective antibodies. Here, we developed capsular polysaccharide conjugates by linking mycobacterial capsular arabinomannan (AM) to either Mtb Ag85b or B...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28277097/towards-functional-antibody-based-vaccines-to-prevent-pre-erythrocytic-malaria-infection
#20
Brandon Sack, Stefan H I Kappe, D Noah Sather
An effective malaria vaccine would be considered a milestone of modern medicine, yet has so far eluded research and development efforts. This can be attributed to the extreme complexity of the malaria parasites, presenting with a multi-stage life cycle, high genome complexity and the parasite's sophisticated immune evasion measures, particularly antigenic variation during pathogenic blood stage infection. However, the pre-erythrocytic (PE) early infection forms of the parasite exhibit relatively invariant proteomes, and are attractive vaccine targets as they offer multiple points of immune system attack...
March 1, 2017: Expert Review of Vaccines
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