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https://www.readbyqxmd.com/read/29329817/isothermal-chemical-denaturation-as-a-complimentary-tool-to-overcome-limitations-of-thermal-differential-scanning-fluorimetry-in-predicting-physical-stability-of-protein-formulations
#1
Hristo Svilenov, Uroš Markoja, Gerhard Winter
Various stability indicating techniques find application in the early stage development of novel therapeutic protein candidates. Some of these techniques are used to select formulation conditions that provide high protein physical stability. Such approach is highly dependent on the reliability of the stability indicating technique used. In this work, we present a formulation case study where we evaluate the ability of differential scanning fluorimetry (DSF) and isothermal chemical denaturation (ICD) to predict the physical stability of a model monoclonal antibody during accelerated stability studies...
January 9, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29328968/in-vitro-examination-of-an-oleosome-based-sun-protection-product-on-the-influence-of-uvb-induced-inflammation-markers-in-human-epidermal-skin-equivalent-tissue-model
#2
James V Gruber, Robert Holtz, Soo In Yang
In vitro human epidermal skin equivalent tissues (MatTek EpiDerm™) were employed to examine the influence of UVB radiation on various established inflammation markers in the presence of topically applied sunscreens. MatTek EpiDerm™ tissues were treated with 2.0mg/cm2 of an Experimental oleosome-based SPF 30 product or a commercial SPF 30 beach product. Tissues were irradiated with 300mJ/cm2 of UVB radiation. Inflammatory cytokines IL-1α, IL-6 and IL-8 as well as arachidonic acid cascade marker PGE2 were examined via ELISA-based antibody detection...
December 28, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29328884/evaluation-of-g2-citric-acid-based-dendrimer-as-an-adjuvant-in-veterinary-rabies-vaccine
#3
Vahid Asgary, Alireza Shoari, Majid Afshar Moayad, Mehdi Shafiee Ardestani, Razieh Bigdeli, Leila Ghazizadeh, Mohammad Sadeq Khosravy, Erfan Panahnejad, Alireza Janani, Rouzbeh Bashar, Maliheh Abedi, Reza Ahangari Cohan
For induction of an appropriate immune response, especially in the case of an inactivated vaccine, the use of an adjuvant is crucial. In this study, adjuvanticity effect of G2 dendrimer in veterinary rabies vaccine has been investigated. A nonlinear globular G2 dendrimer comprising citric acid and polyethylene glycol 600 (PEG-600) was synthesized and the toxicity was studied in vitro on the J774A.1 cell line. The adjuvanticity effect of the dendrimer was then investigated on rabies virus in NMRI mice as a model...
January 2018: Viral Immunology
https://www.readbyqxmd.com/read/29326066/novel-everolimus-loaded-nanocarriers-for-topical-treatment-of-murine-experimental-autoimmune-uveoretinitis-eau
#4
Maren Kasper, Doris Gabriel, Michael Möller, Dirk Bauer, Lena Wildschütz, Herve Courthion, Michael R R Böhm, Martin Busch, Karin Loser, Solon Thanos, Robert Gurny, Arnd Heiligenhaus
In the present study, therapeutic effect of topically applied everolimus (EV)-loaded methoxy-poly(ethylene-glycol)-hexyl substituted poly (lactic acid) (mPEGhexPLA) nanocarriers on experimental autoimmune uveitis (EAU) were investigated. EAU was induced in B10.RIII mice via immunization with human interphotoreceptor retinoid-binding protein peptide 161-180 (hIRBPp161-180) in complete Freund's adjuvant. Everolimus-loaded mPEGhexPLA (EV/mPEGhexPLA) nanocarriers were prepared by using a solvent evaporation method...
January 8, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29317163/investigations-into-the-efficacy-of-multi-component-cocaine-vaccines
#5
Atsushi Kimishima, Margaret E Olson, Kim D Janda
Although cocaine addiction remains a serious health and societal problem in the United States, no FDA-approved treatment has been developed. Vaccines offer an exciting strategy for the treatment of cocaine addiction; however, vaccine formulations need to be optimized to improve efficacy. Herein, we examine the effectiveness of a tricomponent cocaine vaccine, defined as having its hapten (GNE) and adjuvant (cytosine-guanine oligodeoxynucleotide 1826, CpG ODN 1826) covalently linked via the immunogenic protein ovalbumin (OVA)...
December 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29316978/in-vivo-testing-of-novel-vaccine-prototypes-against-actinobacillus-pleuropneumoniae
#6
Fabio Antenucci, Cyrielle Fougeroux, Alannah Deeney, Cathrine Ørskov, Andrew Rycroft, Peter Johannes Holst, Anders Miki Bojesen
Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a Gram-negative bacterium that represents the main cause of porcine pleuropneumonia in pigs, causing significant economic losses to the livestock industry worldwide. A. pleuropneumoniae, as the majority of Gram-negative bacteria, excrete vesicles from its outer membrane (OM), accordingly defined as outer membrane vesicles (OMVs). Thanks to their antigenic similarity to the OM, OMVs have emerged as a promising tool in vaccinology. In this study we describe the in vivo testing of several vaccine prototypes for the prevention of infection by all known A...
January 9, 2018: Veterinary Research
https://www.readbyqxmd.com/read/29315762/effect-of-apoptosis-associated-speck-like-protein-containing-a-caspase-recruitment-domain-on-vaccine-efficacy-overcoming-the-effects-of-its-deficiency-with-aluminum-hydroxide-adjuvant
#7
Deuk-Ki Lee, Eun-Young Lee, Ryoon-Ho Kim, Hye-Won Kwak, Joo Young Kim, Hun Kim, Kyung-Won Kang, Sang-Myeong Lee, Jong-Hwan Park, Jun Chang, Jae-Hwan Nam
Host factors such as nutritional status and immune cell state are important for vaccine efficacy. Inflammasome activation may be important for triggering vaccine-induced humoral and cell-mediated immune responses. Formulations with alum as a typical adjuvant to overcome the effects of host factors have recently been shown to induce inflammasome activation, which augments vaccine efficacy. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is one of main components of inflammasomes, but it is not clear whether ASC affects the vaccine-induced immune response...
January 8, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29315487/using-extensional-flow-to-reveal-diverse-aggregation-landscapes-for-three-igg1-molecules
#8
Leon F Willis, Amit Kumar, John Dobson, Nick Bond, David Lowe, Richard Turner, Sheena E Radford, Nikil Kapur, David J Brockwell
Monoclonal antibodies (mAbs) currently dominate the biopharmaceutical sector due to their potency and efficacy against a range of disease targets. These proteinaceous therapeutics are, however, susceptible to unfolding, mis-folding and aggregation by environmental perturbations. Aggregation thus poses an enormous challenge to biopharmaceutical development, production, formulation and storage. Hydrodynamic forces have also been linked to aggregation, but the ability of different flow fields (e.g. shear and extensional flow) to trigger aggregation has remained unclear...
January 8, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29303684/patterns-of-exposure-of-carnivores-to-selected-pathogens-in-the-betampona-natural-reserve-landscape-madagascar
#9
Fidisoa Rasambainarivo, Mamy Navalona Andriamihajarivo, Edward Dubovi, Patricia G Parker
Carnivores of Madagascar are at increased risk of extinction due to anthropogenic loss of habitat, hunting, and interactions with introduced carnivores. Interactions between introduced and native animals also present the potential for introduction of pathogens into new geographic areas or host species. Here, we provide serologic data regarding pathogen exposure of domestic and native carnivores from the Betampona Natural Reserve Landscape, a protected area in eastern Madagascar. For the Eupleridae, we found limited evidence of exposure to viruses from domestic animals but greater prevalence for Toxoplasma gondii (39%) and Leptospira interrogans (40%)...
January 5, 2018: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/29300203/evolving-criteria-for-the-diagnosis-of-antibody-mediated-rejection-in-renal-allografts
#10
Mark Haas
PURPOSE OF REVIEW: To review changes in the Banff schema for antibody-mediated renal allograft rejection over the past decade, including key revisions agreed upon during and immediately subsequent to the 2017 Banff Conference on Allograft Pathology. RECENT FINDINGS: The original Banff schema for diagnosis of acute and chronic active antibody-mediated rejection (ABMR) in renal allografts was formulated at the 2001 and 2007 Banff Conferences, and required histologic (primarily microvascular inflammation and transplant glomerulopathy), immunohistologic (C4d in peritubular capillaries), and serologic [circulating donor-specific antibodies (DSA)] evidence for a definitive diagnosis of ABMR...
January 2, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29299701/effects-of-drying-process-on-an-igg1-monoclonal-antibody-using-solid-state-hydrogen-deuterium-exchange-with-mass-spectrometric-analysis-sshdx-ms
#11
Ehab M Moussa, Nathan E Wilson, Qi Tony Zhou, Satish K Singh, Sandeep Nema, Elizabeth M Topp
PURPOSE: Lyophilization and spray drying are widely used to manufacture solid forms of therapeutic proteins. Lyophilization is used to stabilize proteins vulnerable to degradation in solution, whereas spray drying is mainly used to prepare inhalation powders or as an alternative to freezing for storing bulk drug substance. Both processes impose stresses that may adversely affect protein structure, stability and bioactivity. Here, we compared lyophilization with and without controlled ice nucleation, and spray drying for their effects on the solid-state conformation and matrix interactions of a model IgG1 monoclonal antibody (mAb)...
January 3, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29296883/innate-transcriptional-effects-by-adjuvants-on-the-magnitude-quality-and-durability-of-hiv-envelope-responses-in-nhps
#12
Joseph R Francica, Daniel E Zak, Caitlyn Linde, Emilio Siena, Carrie Johnson, Michal Juraska, Nicole L Yates, Bronwyn Gunn, Ennio De Gregorio, Barbara J Flynn, Nicholas M Valiante, Padma Malyala, Susan W Barnett, Pampi Sarkar, Manmohan Singh, Siddhartha Jain, Margaret Ackerman, Munir Alam, Guido Ferrari, Georgia D Tomaras, Derek T O'Hagan, Alan Aderem, Galit Alter, Robert A Seder
Adjuvants have a critical role for improving vaccine efficacy against many pathogens, including HIV. Here, using transcriptional RNA profiling and systems serology, we assessed how distinct innate pathways altered HIV-specific antibody responses in nonhuman primates (NHPs) using 8 clinically based adjuvants. NHPs were immunized with a glycoprotein 140 HIV envelope protein (Env) and insoluble aluminum salts (alum), MF59, or adjuvant nanoemulsion (ANE) coformulated with or without Toll-like receptor 4 (TLR4) and 7 agonists...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288093/notorious-but-not-understood-how-liquid-air-interfacial-stress-triggers-protein-aggregation
#13
Ellen Koepf, Simon Eisele, Rudolf Schroeder, Gerald Brezesinski, Wolfgang Friess
Protein aggregation is a major challenge in the development of biopharmaceuticals. As the pathways of aggregation are manifold, good understanding of the mechanisms behind is essential. Particularly, the presence of liquid-air interfaces has been identified to trigger the formation of large protein particles. Investigations of two monoclonal antibodies (IgGs) at the liquid-air interface exhibited the formation of a highly compressible film. An inhomogeneous protein distribution across the interface with areas of increased packing density was discovered by Brewster-Angle microscopy...
December 26, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29281112/modified-mrna-based-vaccines-elicit-robust-immune-responses-and-protect-guinea-pigs-from-ebola-virus-disease
#14
Michelle Meyer, Eric Huang, Olga Yuzhakov, Palaniappan Ramanathan, Giuseppe Ciaramella, Alexander Bukreyev
Most current Ebola virus (EBOV) vaccine candidates are based on viral vectors, some of which cause side effects or require complex manufacturing. Modified mRNA vaccines are easily produced, safe, and are highly immunogenic. We developed 2 mRNA vaccines based on the EBOV envelope glycoprotein, which differed by the nature of signal peptide for improved glycoprotein post-translational translocation. The mRNAs were formulated with lipid nanoparticles to facilitate delivery. Vaccination of guinea pigs induced EBOV-specific IgG and neutralizing antibody responses and 100% survival after EBOV infection...
December 21, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29280507/soybean-oil-containing-ginseng-saponins-as-adjuvants-promotes-production-of-cytokines-and-enhances-immune-responses-to-foot-and-mouth-disease-vaccine
#15
Cenrong Zhang, Wei Xu, Jian Chen, Ran Guan, Shicheng Bi, Haibo Jin, Xuemei Cui, Fushan Shi, Songhua Hu
The adjuvant effect of soybean oil containing ginseng root saponins (SO-GS-R) on the immune response to foot-and-mouth disease vaccine (FMDV) in mice was investigated in this study. When immunized with FMDV antigen emulsified in an SO-GS-R formulation, mice generated remarkably higher serum antibody and cytokine responses than mice immunized with FMDV antigen alone. To elucidate the mechanisms underlying the adjuvant effect of SO-GS-R, we measured cytokines in the serum and muscle tissue after intramuscular injection of SO-GS-R...
December 27, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/29280061/antifungal-activity-of-oral-tragacanth-acrylic-acid-amphotericin-b-carrier-for-systemic-candidiasis-in-vitro-and-in-vivo-study
#16
Heba A Mohamed, Rasha R Radwan, Amany I Raafat, Amr El-Hag Ali
In an effort to increase the oral bioavailability of Amphotericin B (AmB), a pH-sensitive drug carrier composed of Tragacanth (Trag) and acrylic acid (AAc) was prepared using γ-irradiation. The swelling behavior of (Trag/AAc) hydrogels was characterized as a function of pH and ionic strength of the swelling medium. The obtained swelling indices revealed the ability of the prepared hydrogel to protect a loaded drug in stomach-simulated medium (Fickian behavior) and to release such drug in intestinal-simulated medium (non-Fickian behavior)...
December 27, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29251413/serologic-genetic-and-clinical-associations-with-increased-healthcare-resource-utilization-in-inflammatory-bowel-disease
#17
Phillip Gu, Anshika Kapur, Dalin Li, Talin Haritunians, Eric Vasiliauskas, David Q Shih, Stephan R Targan, Brennan M R Spiegel, Dermot P B McGovern, Jeanne T Black, Gil Y Melmed
BACKGROUND: Inflammatory bowel diseases (IBD) are associated with significant morbidity and economic burden. The highly variable course of IBD creates a need for accurate predictors of clinical outcomes and health resource utilization (HRU) to guide treatment decisions early in the disease course. OBJECTIVE: We aimed to identify clinical, serologic and/or genetic markers associated with inpatient resource utilization in patients with ulcerative colitis (UC) and Crohn's disease (CD)...
December 18, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/29243216/lipid-a-adjuvanted-chylomicron-mimicking-solid-fat-nanoemulsions-for-immunization-against-hepatitis-b
#18
Sunita Minz, Ravi Shankar Pandey
Traditional parenteral recombinant hepatitis B virus (HBV) vaccines have effectively reduced the disease burden despite being able to induce seroprotective antibody titers in 5-10% vaccinated individuals (non-responders). Moreover, an estimated 340 million chronic HBV cases are in need of treatment. Development of safe, stable, and more effective hepatitis B vaccine formulation would address these challenges. Recombinant hepatitis B surface antigen (rHBsAg) entrapped solid fat nanoemulsions (SFNs) containing monophosphoryl lipid A (MPLA) that was prepared and optimized by quality by design (QbD) using response surface methodology (RSM), i...
December 14, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29243106/quantitative-validation-of-immunofluorescence-and-lectin-staining-using-reduced-clarity-acrylamide-formulations
#19
D M Krolewski, V Kumar, B Martin, R Tomer, K Deisseroth, R M Myers, A F Schatzberg, F S Lee, J D Barchas, W E Bunney, H Akil, S J Watson
The CLARITY technique enables three-dimensional visualization of fluorescent-labeled biomolecules in clarified intact brain samples, affording a unique view of molecular neuroanatomy and neurocircuitry. It is therefore, essential to find the ideal combination for clearing tissue and detecting the fluorescent-labeled signal. This method requires the formation of a formaldehyde-acrylamide fixative-generated hydrogel mesh through which cellular lipid is removed with sodium dodecyl sulfate. Several laboratories have used differential acrylamide and detergent concentrations to achieve better tissue clearing and antibody penetration, but the potential effects upon fluorescent signal retention is largely unknown...
December 14, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29241186/strengthening-gastric-cancer-therapy-by-trastuzumab-conjugated-nanoparticles-with-simultaneous-encapsulation-of-anti-mir-21-and-5-fluorouridine
#20
Nan Hu, Jun Feng Yin, Ze Ji, Yidong Hong, Puyuan Wu, Baoxiang Bian, Ziyan Song, Rutian Li, Qin Liu, Fenglei Wu
BACKGROUND/AIMS: MicroRNA-21 is an oncogenic miR (oncomiR) frequently elevated in gastric cancer (GC). Overexpression of miR-21 decreases the sensitivity of GC cells to 5-fluorouridine (5-Fu) and trastuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including anti-miRNA oligonucleotides (AMOs). This study is a continuation of earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target GC with HER2 receptor over-expression using anti-miRNA-21 (AMO-21) and 5-Fu...
December 12, 2017: Cellular Physiology and Biochemistry
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