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https://www.readbyqxmd.com/read/28636463/optimization-of-an-anti-her2-nanobody-expression-using-the-taguchi-method
#1
Alireza Farasat, Fatemeh Rahbarizadeh, Davoud Ahmadvand, Fatemeh Yazdian
Despite being widely used in immunotherapy of cancer, whole antibodies are limited by several disadvantages. This has led to the advent of novel biomolecules such as nanobodies. Taguchi method is a statistical experimental design to study the effect of multiple variables in biological processes. In an effort to overexpress a recombinant anti-HER2 nanobody, we carried out a detailed study to find optimal condition of temperature, induction, culture media, vector and host strain, using Taguchi methodology. A total of 16 various experiments were designed...
June 21, 2017: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/28634286/conjugate-vaccine-immunotherapy-for-substance-use-disorder
#2
REVIEW
Paul T Bremer, Kim D Janda
Substance use disorder, especially in relation to opioids such as heroin and fentanyl, is a significant public health issue and has intensified in recent years. As a result, substantial interest exists in developing therapeutics to counteract the effects of abused drugs. A promising universal strategy for antagonizing the pharmacology of virtually any drug involves the development of a conjugate vaccine, wherein a hapten structurally similar to the target drug is conjugated to an immunogenic carrier protein...
July 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28633319/immunotherapy-targeting-adenosine-synthase-a-decreases-severity-of-staphylococcus-aureus-infection-in-mouse-model
#3
Bao-Zhong Zhang, JianPiao Cai, Bin Yu, Lifeng Xiong, Qiubin Lin, Xiao-Yan Yang, Chen Xu, SongYue Zheng, Richard Yi-Tsun Kao, Konghung Sze, Kwok-Yung Yuen, Jian-Dong Huang
Staphylococcus aureus (S. aureus) is a severe pathogen found in the community and in hospitals. Most notably, Methicillin-resistant S. aureus (MRSA) is resistant to almost all antibiotics, which is a growing public health concern. The emergence of drug-resistant strains has prompted the search for alternative treatments such as immunotherapeutic approaches. Previous research showed that S. aureus exploit the immunomodulatory attributes of adenosine to escape host immunity. In this study, we investigated adenosine synthase A (AdsA), a S...
June 13, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28625520/immunogenicity-of-pulsatile-release-plga-microspheres-for-single-injection-vaccination
#4
Rohiverth Guarecuco, Jennifer Lu, Kevin J McHugh, James J Norman, Lavanya S Thapa, Emily Lydon, Robert Langer, Ana Jaklenec
The World Health Organization's Expanded Programme on Immunization has led to a dramatic rise in worldwide vaccination rates over the past 40years, yet 19.4 million infants remain underimmunized each year. Many of these infants have received at least one vaccine dose but may remain unprotected because they did not receive subsequent booster doses due to logistical challenges. This study aimed to develop injectable controlled release microparticles with kinetics that mimic common vaccine dosing regimens consisting of large antigen doses administered periodically over the course of months in order to eliminate the need for boosters...
June 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28623267/a-new-paradigm-for-antiangiogenic-therapy-through-controlled-release-of-bevacizumab-from-plga-nanoparticles
#5
Flávia Sousa, Andrea Cruz, Pedro Fonte, Inês Mendes Pinto, Maria Teresa Neves-Petersen, Bruno Sarmento
Monoclonal antibodies have deserved a remarkable interest for more than 40 years as a vital tool for the treatment of various diseases. Still, there is a raising interest to develop advanced monoclonal antibody delivery systems able to tailor pharmacokinetics. Bevacizumab is a humanized immunoglobulin IgG1 used in antiangiogenic therapies due to its capacity to inhibit the interaction between vascular endothelial growth factor and its receptor. However, bevacizumab-based antiangiogenic therapy is not always effective due to poor treatment compliance associated to multiples administrations and drug resistance...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621571/targeted-nanotechnologies-for-cancer-intervention-a-patent-review-2010-2016
#6
Priyamvada Pradeep, Pradeep Kumar, Yahya E Choonara, Viness Pillay
In recent years, several active targeting nanostrategies have been patented for application in cancer theranostics. The versatility of nanostructures in terms of composition, manufacturability, functionalization, and matrix formation make them ideal for carrying large dose of bioactive contents, high density of targeting ligands on their surface, efficient delivery to the site of interest, and capable of forming multicomponent platforms. Areas covered: The patents were classified into polymeric and non-polymeric nanostructures and their applicability in addressing the targeting paradigm related to cancer intervention was explored...
June 16, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28617076/characterization-of-highly-concentrated-antibody-solution-a-toolbox-for-the-description-of-protein-long-term-solution-stability
#7
Marie-Therese Schermeyer, Anna K Wöll, Bas Kokke, Michel Eppink, Jürgen Hubbuch
High protein titers are gaining importance in biopharmaceutical industry. A major challenge in the development of highly concentrated mAb solutions is their long-term stability and often incalculable viscosity. The complexity of the molecule itself, as well as the various molecular interactions, make it difficult to describe their solution behavior. To study the formulation stability, long- and short-range interactions and the formation of complex network structures have to be taken into account. For a better understanding of highly concentrated solutions, we combined established and novel analytical tools to characterize the effect of solution properties on the stability of highly concentrated mAb formulations...
June 15, 2017: MAbs
https://www.readbyqxmd.com/read/28615298/combination-treatment-with-orlistat-containing-nanoparticles-and-taxanes-is-synergistic-and-enhances-microtubule-stability-in-taxane-resistant-prostate-cancer-cells
#8
Joshua J Souchek, Amanda L Davis, Tanner K Hill, Megan B Holmes, Bowen Qi, Pankaj K Singh, Steven J Kridel, Aaron M Mohs
Taxane-based therapy provides a survival benefit in patients with metastatic prostate cancer, yet the median survival is less than 20 months in this setting due in part to taxane-associated resistance. Innovative strategies are required to overcome chemoresistance for improved patient survival. Here, NanoOrl, a new experimental nanoparticle formulation of the FDA-approved drug, orlistat, was investigated for its cytotoxicity in taxane-resistant prostate cancer utilizing two established taxane-resistant (TxR) cell lines...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28614662/investigating-liquid-liquid-phase-separation-of-a-monoclonal-antibody-using-solution-state-nmr-spectroscopy-effect-of-arg%C3%A2-glu-and-arg%C3%A2-hcl
#9
Priscilla Kheddo, Jack E Bramham, Rebecca J Dearman, Shahid Uddin, Christopher F van der Walle, Alexander P Golovanov
Liquid-liquid phase separation (LLPS) of monoclonal antibody (mAb) formulations involves spontaneous separation into dense (protein-rich) and diluted (protein-lean) phases, and should be avoided in the final drug product. Understanding the factors leading to LLPS, and ways to predict and prevent it would therefore be highly beneficial. Here we describe the link between LLPS behavior of an IgG1 mAb ('mAb5'), its solubility and parameters extracted using (1)H NMR spectroscopy, for various formulations. We show that the formulations demonstrating least LLPS lead to the largest mAb5 NMR signal intensities...
June 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28596770/a-phase-1-human-immunodeficiency-virus-vaccine-trial-for-cross-profiling-the-kinetics-of-serum-and-mucosal-antibody-responses-to-cn54gp140-modulated-by-two-homologous-prime-boost-vaccine-regimens
#10
Sven Kratochvil, Paul F McKay, Jakub T Kopycinski, Cynthia Bishop, Peter John Hayes, Luke Muir, Christopher L Pinder, Deniz Cizmeci, Deborah King, Yoann Aldon, Bruce D Wines, P Mark Hogarth, Amy W Chung, Stephen J Kent, Kathrin Held, Christof Geldmacher, Len Dally, Nelson S Santos, Tom Cole, Jill Gilmour, Sarah Fidler, Robin J Shattock
A key aspect to finding an efficacious human immunodeficiency virus (HIV) vaccine is the optimization of vaccine schedules that can mediate the efficient maturation of protective immune responses. In the present study, we investigated the effect of alternate booster regimens on the immune responses to a candidate HIV-1 clade C CN54gp140 envelope protein, which was coadministered with the TLR4-agonist glucopyranosyl lipid A-aqueous formulation. Twelve study participants received a common three-dose intramuscular priming series followed by a final booster at either 6 or 12 months...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28596090/liposomes-containing-monophosphoryl-lipid-a-and-qs-21-serve-as-an-effective-adjuvant-for-soluble-circumsporozoite-protein-malaria-vaccine-fmp013
#11
Christopher J Genito, Zoltan Beck, Timothy W Phares, Fanta Kalle, Keith J Limbach, Maureen E Stefaniak, Noelle B Patterson, Elke S Bergmann-Leitner, Norman C Waters, Gary R Matyas, Carl R Alving, Sheetij Dutta
Malaria caused by Plasmodium falciparum continues to threaten millions of people living in the tropical parts of the world. A vaccine that confers sterile and life-long protection remains elusive despite more than 30years of effort and resources invested in solving this problem. Antibodies to a malaria vaccine candidate circumsporozoite protein (CSP) can block invasion and can protect humans against malaria. We have manufactured the Falciparum Malaria Protein-013 (FMP013) vaccine based on the nearly full-length P...
June 5, 2017: Vaccine
https://www.readbyqxmd.com/read/28593474/high-throughput-prediction-approach-for-monoclonal-antibody-aggregation-at-high-concentration
#12
Mitja Zidar, Ana Šušterič, Miha Ravnik, Drago Kuzman
PURPOSE: Characterization of the monoclonal antibody aggregation process and identification of stability factors that could be used as indicators of aggregation propensity with an emphasis on a large number of samples and low protein material consumption. METHODS: Differential scanning calorimetry, dynamic light scattering and size exclusion chromatography were used as the main methodological approaches. Conformational stability, colloidal stability and aggregation kinetics were assessed for two different IgG monoclonal antibody (mAbs) subclasses...
June 7, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28592534/comprehensive-cross-clade-characterization-of-antibody-mediated-recognition-complement-mediated-lysis-and-cell-mediated-cytotoxicity-of-hiv-1-envelope-specific-antibodies-towards-the-eradication-of-the-hiv-1-reservoir
#13
Shariq Mujib, Jun Liu, A K M Nur-Ur Rahman, Jordan A Schwartz, Phil Bonner, Feng Yun Yue, Mario A Ostrowski
Immunotherapy with passive administration of broadly neutralizing HIV-1 envelope-specific antibodies (bnAbs) in the setting of established infection in vivo has yielded mixed results. The contribution of different antibodies toward the direct elimination of infected cells is poorly understood. Here, we determined the ability of twelve well-characterized anti-HIV-1 neutralizing antibodies to recognize and eliminate primary CD4 T cells infected with HIV-1, belonging to clades A, B, C and D, via antibody-dependent complement-mediated lysis (ADCML) and antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28579233/a-phase-2-randomized-observer-blind-placebo-controlled-dose-ranging-trial-of-aluminum-adjuvanted-respiratory-syncytial-virus-f-particle-vaccine-formulations-in-healthy-women-of-childbearing-age
#14
Allison August, Gregory M Glenn, Eloi Kpamegan, Somia P Hickman, Dewal Jani, Hanxin Lu, D Nigel Thomas, Judy Wen, Pedro A Piedra, Louis F Fries
OBJECTIVE: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules. METHODS: Placebo, or vaccine with 60μg or 120μg RSV F protein and 0...
June 1, 2017: Vaccine
https://www.readbyqxmd.com/read/28579231/optimized-production-and-purification-of-coxsackievirus-b1-vaccine-and-its-preclinical-evaluation-in-a-mouse-model
#15
Minna M Hankaniemi, Olli H Laitinen, Virginia M Stone, Amirbabak Sioofy-Khojine, Juha A E Määttä, Pär G Larsson, Varpu Marjomäki, Heikki Hyöty, Malin Flodström-Tullberg, Vesa P Hytönen
Coxsackie B viruses are among the most common enteroviruses, causing a wide range of diseases. Recent studies have also suggested that they may contribute to the development of type 1 diabetes. Vaccination would provide an effective way to prevent CVB infections, and the objective of this study was to develop an efficient vaccine production protocol for the generation of novel CVB vaccines. Various steps in the production of a formalin-inactivated Coxsackievirus B1 (CVB1) vaccine were optimized including the Multiplicity Of Infection (MOI) used for virus amplification, virus cultivation time, type of cell growth medium, virus purification method and formulation of the purified virus...
June 1, 2017: Vaccine
https://www.readbyqxmd.com/read/28578824/improving-the-malaria-transmission-blocking-activity-of-a-plasmodium-falciparum-48-45-based-vaccine-antigen-by-spytag-spycatcher-mediated-virus-like-display
#16
Susheel K Singh, Susan Thrane, Christoph M Janitzek, Morten A Nielsen, Thor G Theander, Michael Theisen, Ali Salanti, Adam F Sander
Malaria is a devastating disease caused by Plasmodium parasites, resulting in almost 0.5 million deaths per year. The Pfs48/45 protein exposed on the P. falciparum sexual stages is one of the most advanced antigen candidates for a transmission-blocking (TB) vaccine in the clinical pipeline. However, it remains essential to identify an optimal vaccine formulation that can facilitate induction of a long-lasting TB anti-Pfs48/45 response. Here we report on the development and evaluation of two Pfs48/45-based virus-like particle (VLP) vaccines generated using the AP205 SpyTag/Catcher VLP system...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28575696/regiospecific-radiolabelling-of-nanofitin-on-ni-magnetic-beads-with-18-f-fbem-and-in-vivo-pet-studies
#17
Sylvestre Dammicco, Marine Goux, Christian Lemaire, Guillaume Becker, Mohamed Ali Bahri, Alain Plenevaux, Mathieu Cinier, André Luxen
INTRODUCTION: Nanofitins are low molecular weight, single chain and cysteine-free protein scaffolds able to selectively bind a defined biological target. They derive from Sac7d bacterial protein family and are highly stable over a wide range of pH (0-13) and temperature (Tm ~80°C). Their extreme stability, low cost of production and high tolerability for chemical coupling make Nanofitins a very interesting alternative to antibodies and their fragments. Here, a hexahistidine tagged model Nanofitin (H4) directed against hen egg white lysozyme was radiolabelled and injected in mice to provide a baseline biodistribution and pharmacokinetic profiles to support future Nanofitin development programs...
April 27, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28575080/immunization-of-a-wild-koala-population-with-a-recombinant-chlamydia-pecorum-major-outer-membrane-protein-momp-or-polymorphic-membrane-protein-pmp-based-vaccine-new-insights-into-immune-response-protection-and-clearance
#18
Marion Desclozeaux, Amy Robbins, Martina Jelocnik, Shahneaz Ali Khan, Jon Hanger, Volker Gerdts, Andrew Potter, Adam Polkinghorne, Peter Timms
We assessed the effects of two different single-dose anti-Chlamydia pecorum (C. pecorum) vaccines (containing either Major Outer Membrane Protein (3MOMP) or Polymorphic Membrane Protein (Pmp) as antigens) on the immune response of a group of wild koalas. Both vaccines elicited a systemic humoral response as seen by the production of anti-chlamydial IgG antibodies in more than 90% of vaccinated koalas. A mucosal immune response was also observed, with an increase in Chlamydia-specific mucosal IgG and/or IgA antibodies in some koalas post-vaccination...
2017: PloS One
https://www.readbyqxmd.com/read/28574716/development-of-a-clinically-viable-heroin-vaccine
#19
Paul T Bremer, Joel E Schlosburg, Matthew L Banks, Floyd F Steele, Bin Zhou, Justin L Poklis, Kim D Janda
Heroin is a highly abused opioid and incurs a significant detriment to society worldwide. In an effort to expand the limited pharmacotherapy options for opioid use disorders, a heroin conjugate vaccine was developed through comprehensive evaluation of hapten structure, carrier protein, adjuvant and dosing. Immunization of mice with an optimized heroin-tetanus toxoid (TT) conjugate formulated with adjuvants alum and CpG oligodeoxynucleotide (ODN) generated heroin 'immunoantagonism', reducing heroin potency by >15-fold...
June 2, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28570837/high-throughput-screening-and-analysis-of-charge-variants-of-monoclonal-antibodies-in-multiple-formulations
#20
Larysa Alekseychyk, Cheng Su, Gerald W Becker, Michael J Treuheit, Vladimir I Razinkov
Among different biopharmaceutical products, monoclonal antibodies (mAbs) show a high level of complexity, including heterogeneity due to differences in size, hydrophobicity, charge, and so forth. Such heterogeneity can be related to both cell-based production and any of the stages of purification, storage, and delivery that the mAb is subjected to. Choosing the right formulation composition providing both physical and chemical stabilities can be a very challenging process, especially when done in the limited time frame required for a typical drug development cycle...
June 1, 2017: SLAS Discovery
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