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https://www.readbyqxmd.com/read/28544973/pegylation-of-a-tlr2-agonist-based-vaccine-delivery-system-improves-antigen-trafficking-and-the-magnitude-of-ensuing-antibody-and-cd8-t-cell-responses
#1
Toshiki Sekiya, Junya Yamagishi, John Henry V Gray, Paul G Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C Jackson, Brendon Y Chua
The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expressed on many antigen-presenting cells such as dendritic cells (DCs). Electrostatic association of R4Pam2Cys with soluble protein antigens significantly enhances their immunogenicity and there is evidence to suggest that reducing the size of suitably adjuvanted-antigen complexes in solution may further improve their immunostimulatory capabilities. In this study, we investigated how incorporation of polyethylene glycol (PEG) into R4Pam2Cys affects the size, activity and efficacy of formed antigen-lipopeptide complexes...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28542556/an-inactivated-hand-foot-and-mouth-disease-vaccine-using-the-enterovirus-71-c4a-strain-isolated-from-a-korean-patient-induces-a-strong-immunogenic-response-in-mice
#2
Hyun Ju In, Heeji Lim, Jung-Ah Lee, Hye Jin Kim, Jin-Won Kim, Ji-Yeon Hyeon, Sang-Gu Yeo, June-Woo Lee, Jung Sik Yoo, Young Ki Choi, Sang-Won Lee
Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD) frequently occurring in children. HFMD induced by EV71 can cause serious health problems and has been reported worldwide, particularly in the Asia-Pacific region. In this study, we assessed the immunogenicity of a formalin-inactivated HFMD vaccine using an EV71 strain (FI-EV71 C4a) isolated from a Korean patient. The vaccine candidate was evaluated in mice to determine the vaccination doses and vaccine schedules. BALB/c mice were intramuscularly administered 5, 10, or 20 μg FI-EV71 vaccine, followed by a booster 2 weeks later...
2017: PloS One
https://www.readbyqxmd.com/read/28540623/qsp-toolbox-computational-implementation-of-integrated-workflow-components-for-deploying-multi-scale-mechanistic-models
#3
Yougan Cheng, Craig J Thalhauser, Shepard Smithline, Jyotsna Pagidala, Marko Miladinov, Heather E Vezina, Manish Gupta, Tarek A Leil, Brian J Schmidt
Quantitative systems pharmacology (QSP) modeling has become increasingly important in pharmaceutical research and development, and is a powerful tool to gain mechanistic insights into the complex dynamics of biological systems in response to drug treatment. However, even once a suitable mathematical framework to describe the pathophysiology and mechanisms of interest is established, final model calibration and the exploration of variability can be challenging and time consuming. QSP models are often formulated as multi-scale, multi-compartment nonlinear systems of ordinary differential equations...
May 24, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28532811/bovine-vaccinia-inactivated-vaccinia-virus-vaccine-induces-protection-in-murine-model
#4
Ana Carolina Diniz Matos, Maria Isabel Maldonado Coelho Guedes, Izabelle Silva Rehfeld, Erica Azevedo Costa, Aristoteles Gomes Costa, Natalia Lopes da Silva, Andrey Pereira Lage, Zélia Inês Portela Lobato
Bovine vaccinia (BV), caused by Vaccinia virus (VACV), is a zoonosis characterized by exanthematous lesions on the teats of dairy cows and the milkers' hands. Since 1999, due to the occurrence of many BV outbreaks in dairy farms across all Brazilian regions, there is a need to improve the control and prevention measures of the disease. Vaccination is one of the major tools to prevent viral diseases, and it could be an alternative for BV prevention. The main objective of this study was the development of vaccine formulations against BV using the inactivated VACV strain GP2 as antigen combined with different adjuvants...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28529481/topical-ophthalmic-formulation-of-trichostatin-a-and-surr9-c84a-for-quick-recovery-post-alkali-burn-of-corneal-haze
#5
Kislay Roy, Chun Hei Antonio Cheung, Rupinder K Kanwar, Rajat Sandhir, Jagat R Kanwar
Alkali burn injury is a true ocular emergency of the conjunctiva and cornea that requires immediate precision. Lack of an immediate therapy can lead to a substantial damage in the ocular surface and anterior segment further causing visual impairment and disfigurement. We explored the regenerative capability of dominant negative survivin protein (SurR9-C84A) and histone deacetylase inhibitor trichostatin-A (TSA) in vivo, in a rat alkali burn model. A topical insult in rat eyes with NaOH led to degradation of the conjunctival and corneal epithelium...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28528626/colloid-particle-formulations-for-antimicrobial-applications
#6
REVIEW
Ahmed F Halbus, Tommy S Horozov, Vesselin N Paunov
Colloidal particles are being extensively studied in various antimicrobial applications due to their small size to volume ratio and ability to exhibit a wide spectrum of antibacterial, antifungal, antialgal and antiviral action. The present review focuses on various nanoparticles (NPs) of inorganic, organic and hybrid materials, and discusses some of the methods for their preparation as well as mechanisms of their antimicrobial action. We consider the antimicrobial applications of metal oxide nanoparticles (ZnO, MgO, CuO, Cu2O, Al2O3, TiO2, CeO2 and Y2O3), metal nanoparticles (NPs), such as copper, silver and gold, metal hydroxide NPs such as Mg(OH)2 as well as hybrid NPs made from biodegradable materials, such as chitosan, lignin and dextran, loaded with other antimicrobial agents...
May 12, 2017: Advances in Colloid and Interface Science
https://www.readbyqxmd.com/read/28527686/local-innate-responses-and-protective-immunity-after-intradermal-immunization-with-bovine-viral-diarrhea-virus-e2-protein-formulated-with-a-combination-adjuvant-in-cattle
#7
Sams M A Sadat, Marlene Snider, Ravendra Garg, Robert Brownlie, Sylvia van Drunen Littel-van den Hurk
Bovine viral diarrhea virus (BVDV) is one of the most serious pathogens in cattle. Recently, we developed a novel adjuvant platform (TriAdj) that includes a toll-like receptor 3 agonist, poly (I:C); an innate defense regulatory peptide; and water-soluble polymer, poly[di(sodiumcarboxylatoethylphenoxy)]-phosphazene (PCEP). To develop a needle-free intradermal (ID) subunit vaccine, the BVDV type-2 E2 protein was formulated with TriAdj, and immune protection was evaluated in calves against a BVDV-2 strain. Intradermal delivery of E2/TriAdj elicited robust virus neutralizing antibodies and cell-mediated immune responses including CD4(+) and CD8(+) T-cell responses...
May 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28514971/effects-of-organic-complexed-or-inorganic-co-cu-mn-and-zn-supplementation-during-a-45-day-preconditioning-period-on-productive-and-health-responses-of-feeder-cattle
#8
K D Lippolis, R F Cooke, L G T Silva, K M Schubach, A P Brandao, R S Marques, C K Larson, J R Russell, S A Arispe, T DelCurto, D W Bohnert
This experiment evaluated production and health parameters among cattle offered concentrates containing inorganic or organic complexed sources of supplemental Cu, Co, Mn and Zn during a 45-day preconditioning period. In total, 90 Angus×Hereford calves were weaned at 7 months (day -1), sorted by sex, weaning BW and age (261±2 kg; 224±2 days), and allocated to 18 drylot pens (one heifer and four steers per pen) on day 0; thus, all pens had equivalent initial BW and age. Pens were randomly assigned to receive a corn-based preconditioning concentrate containing: (1) Cu, Co, Mn and Zn sulfate sources (INR), (2) Cu, Mn, Co and Zn complexed organic source (AAC) or (3) no Cu, Co, Mn and Zn supplementation (CON)...
May 18, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28511853/immunologic-evaluation-of-10-different-adjuvants-for-use-in-vaccines-for-chickens-against-highly-pathogenic-avian-influenza-virus
#9
Nazir Ahmed Lone, Erica Spackman, Darrell Kapczynski
Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the best formulations for chickens, vaccines were prepared with beta-propiolactone (BPL) inactivated A/British Columbia/314514-1/2004 H7N3 LP AIV using ten commercially available or experimental adjuvants. Each vaccine formulation was evaluated for immunogenicity in chickens...
May 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28511142/tailoring-nanostructured-lipid-carriers-for-the-delivery-of-protein-antigens-physicochemical-properties-versus-immunogenicity-studies
#10
Thomas Courant, Emilie Bayon, Hei Lanne Reynaud-Dougier, Christian Villiers, Mathilde Menneteau, Patrice N Marche, Fabrice P Navarro
New vaccine formulations are still highly anticipated in the near-future to face incoming health challenges, such as emergence or reemergence of severe infectious diseases, immunosenescence associated with elderly or the spread of pathogens resistant to antibiotics. In particular, new nanoparticle-based adjuvants are promising for sub-unit vaccines in order to elicit potent and long lasting immune responses with a better control on their safety. In this context, an innovative delivery system of protein antigens has been designed based on the chemical grafting of the antigen onto the shell of Nanostructured Lipid Carriers (NLC)...
May 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28511059/development-and-validation-of-a-rapid-reversed-phase-hplc-method-for-the-quantification-of-monoclonal-antibody-bevacizumab-from-polyester-based-nanoparticles
#11
Flávia Sousa, Virgínia M F Gonçalves, Bruno Sarmento
Bevacizumab is a powerful human monoclonal antibody approved worldwide for treatment of several types of cancer and ocular diseases due to its potential as antiangiogenic drug. Nowadays, in order to improve the monoclonal antibody-based therapy, attempts have been focused in the formulation of these biomacromolecules into nanoparticles. Thus, the aim of this work was to develop and validate a reversed-phase high-performance liquid chromatography with fluorescence detection method for the determination of bevacizumab from nanoparticulate systems, according to the International Conference on Harmonization guidelines...
May 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28505457/molecular-and-biocompatibility-characterization-of-red-blood-cell-membrane-targeted-and-cell-penetrating-peptide-modified-polymeric-nanoparticles
#12
Kaustuv Sahoo, Sriharsha Karumuri, Rangika S Hikkaduwa Koralege, Nicholas H Flynn, Steve Hartson, Jing Liu, Joshua D Ramsey, Kaan Kalkan, Carey Pope, Ashish Ranjan
Red blood cells (RBCs) express a variety of immunomodulatory markers that enable the body to recognize them as self. We have shown that RBC membrane glycophorin A (GPA) receptor can mediate membrane attachment of protein therapeutics. A critical knowledge gap is whether attaching drug encapsulated nanoparticles (NPs) to GPA, and modification with cell penetration peptide (CPP) will impact binding, oxygenation and induce cellular stress. The objective of this study was to formulate copolymer-based NPs containing model fluorescent tagged bovine serum albumin (BSA) with GPA-specific targeting ligands such as ERY1 (ENPs), single chain variable antibody (scFv TER-119, SNPs), and low molecular weight protamine based CPP (LNPs) and determine their biocompatibility using a variety of complementary high-throughput in vitro assays...
May 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28504191/lethal-factor-antibodies-contribute-to-lethal-toxin-neutralization-in-recipients-of-anthrax-vaccine-precipitated
#13
Eric K Dumas, Lori Garman, Hannah Cuthbertson, Sue Charlton, Bassam Hallis, Renata J M Engler, Shyamal Choudhari, William D Picking, Judith A James, A Darise Farris
A major difference between two currently licensed anthrax vaccines is presence (United Kingdom Anthrax Vaccine Precipitated, AVP) or absence (United States Anthrax Vaccine Adsorbed, AVA) of quantifiable amounts of the Lethal Toxin (LT) component Lethal Factor (LF). The primary immunogen in both vaccine formulations is Protective Antigen (PA), and LT-neutralizing antibodies directed to PA are an accepted correlate of vaccine efficacy; however, vaccination studies in animal models have demonstrated that LF antibodies can be protective...
May 11, 2017: Vaccine
https://www.readbyqxmd.com/read/28502677/biophysical-study-of-bevacizumab-structure-and-bioactivity-under-thermal-and-ph-stresses
#14
Flávia Sousa, Bruno Sarmento, Maria Teresa Neves-Petersen
The evaluation of the structural stability and bioactivity of monoclonal antibodies (mAb) is a crucial step in the development of mAb therapeutic based products, since immunogenicity needs to be avoided. In the present work, a study was carried out to understand the changes on the structure and bioactivity of mAbs induced by different pH and temperature values. Structural changes of bevacizumab were monitored using fluorescence spectroscopy, circular dichroism (CD) and Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR)...
May 11, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28499553/nasal-delivery-of-protollin-adjuvanted-h5n1-vaccine-induces-enhanced-systemic-as-well-as-mucosal-immunity-in-mice
#15
Weiping Cao, Jin Hyang Kim, Adrian J Reber, Mary Hoelscher, Jessica A Belser, Xiuhua Lu, Jacqueline M Katz, Shivaprakash Gangappa, Martin Plante, David S Burt, Suryaprakash Sambhara
Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model...
June 5, 2017: Vaccine
https://www.readbyqxmd.com/read/28495581/dipicolinic-acid-as-a-novel-spore-inspired-excipient-for-antibody-formulation
#16
Iris L Batalha, Peng Ke, Esther Tejeda-Montes, Shahid Uddin, Christopher F van der Walle, Graham Christie
Ionic excipients are commonly used in aqueous therapeutic monoclonal antibody (mAb) formulations. Novel excipients are of industrial interest, with a recent focus on Arg salt forms and their application as viscosity reducing and stabilizing additives. Here, we report that the calcium salt of dipicolinic acid (DPA, pyridine-2,6-dicarboxylic acid), uniquely present in nature in the core of certain bacterial spores, reduces the viscosity of a mAb formulated at 150mg/mL, below that achieved by Arg hydrochloride at the same concentration (10mM)...
May 8, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28486309/rationale-for-therapeutic-drug-monitoring-of-biopharmaceuticals-in-inflammatory-diseases
#17
Gilles Paintaud, Christophe Passot, David Ternant, Bertolotto Antonio, Theodora Bejan-Angoulvant, Dora Pascual-Salcedo, Denis Mulleman
Biopharmaceuticals bring together a number of specific characteristics as compared with other drugs. However, as done for most drugs, an individual adjustment of their dose may be necessary. Similar to "chemical" drugs, biopharmaceuticals used in immuno-inflammatory diseases have a rather narrow therapeutic range, lack good early clinical or biological marker of response, have variable pharmacokinetics, and their serum concentration are most often related with response. Monoclonal antibodies (mAbs) have additional specific sources of pharmacokinetic variability...
May 5, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28484467/immunogenic-domains-and-secondary-structure-of-escherichia-coli-recombinant-secreted-protein-escherichia-coli-secreted-protein-b
#18
Bruna Alves Caetano, Letícia Barboza Rocha, Eneas Carvalho, Roxane Maria Fontes Piazza, Daniela Luz
Several pathogenic bacteria are able to induce the attaching and effacing (A/E) lesion. The A/E lesion is caused by effector proteins, such as Escherichia coli-secreted protein B (EspB), responsible together with Escherichia coli-secreted protein D for forming a pore structure on the host cell, which allows the translocation of effector proteins. Different variants of this protein can be found in E. coli strains, and during natural infection or when this protein is injected, this leads to variant-specific production of antibodies, which may not be able to recognize other variants of this bacterial protein...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28482882/targeted-sirna-delivery-reduces-nitric-oxide-mediated-cell-death-after-spinal-cord-injury
#19
Wen Gao, Jianming Li
BACKGROUND: Traumatic spinal cord injury (SCI) includes the primary insult as well as a sequela of biochemical and cellular cascades that amplifies the initial injury. This degenerative process, known as secondary injury, is often mediated by both reactive oxygen and nitrogen species released from damaged cells. Previous data suggests that dysregulated production of nitric oxide via inducible nitric oxide synthase (iNOS) is detrimental to spinal cord recovery. M1 macrophages have been implicated to overexpress iNOS post-SCI...
May 8, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28481911/adenovirus-vectored-novel-african-swine-fever-virus-antigens-elicit-robust-immune-responses-in-swine
#20
Shehnaz Lokhandwala, Suryakant D Waghela, Jocelyn Bray, Neha Sangewar, Chloe Charendoff, Cameron L Martin, Wisam S Hassan, Tsvetoslav Koynarski, Lindsay Gabbert, Thomas G Burrage, David Brake, John Neilan, Waithaka Mwangi
African Swine Fever Virus (ASFV) is a high-consequence transboundary animal pathogen that often causes hemorrhagic disease in swine with a case fatality rate close to 100%. Lack of treatment or vaccine for the disease makes it imperative that safe and efficacious vaccines are developed to safeguard the swine industry. In this study, we evaluated the immunogenicity of seven adenovirus-vectored novel ASFV antigens, namely A151R, B119L, B602L, EP402RΔPRR, B438L, K205R and A104R. Immunization of commercial swine with a cocktail of the recombinant adenoviruses formulated in adjuvant primed strong ASFV antigen-specific IgG responses that underwent rapid recall upon boost...
2017: PloS One
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