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https://www.readbyqxmd.com/read/27916504/the-state-of-play-and-future-of-antibody-therapeutics
#1
REVIEW
Zehra Elgundi, Mouhamad Reslan, Esteban Cruz, Vicki Sifniotis, Veysel Kayser
It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries...
December 1, 2016: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/27916408/safety-tolerability-and-immunogenicity-of-a-4-antigen-staphylococcus-aureus-vaccine-sa4ag-results-from-a-first-in-human-randomised-placebo-controlled-phase-1-2-study
#2
Robert W Frenck, C Buddy Creech, Eric A Sheldon, David J Seiden, Martin K Kankam, James Baber, Edward Zito, Robin Hubler, Joseph Eiden, Joseph M Severs, Shite Sebastian, Jasdeep Nanra, Kathrin U Jansen, William C Gruber, Annaliesa S Anderson, Douglas Girgenti
BACKGROUND: A prophylactic Staphylococcus aureus four-antigen vaccine (SA4Ag) is under development for prevention of invasive S. aureus disease. A preliminary S. aureus three-antigen vaccine (SA3Ag) was reformulated to include a novel manganese transporter protein (MntC or rP305A). This study describes the first-in-human dose-finding, safety, and immunogenicity results for SA4Ag. METHODS: In this double-blind, sponsor-unblind, placebo-controlled, phase 1/2 study, 454 healthy adults aged 18-64years were randomised to receive a single dose of one of three formulations of SA4Ag with escalating dose levels of rP305A or placebo...
December 1, 2016: Vaccine
https://www.readbyqxmd.com/read/27911254/neutralizing-and-enhancing-antibody-responses-to-five-genotypes-of-dengue-virus-type-1-denv-1-in-denv-1-patients
#3
Atsushi Yamanaka, Meng Ling Moi, Tomohiko Takasaki, Ichiro Kurane, Eiji Konishi
Dengue virus has four distinct serotypes, DENV-1-4, with 4-6 genotypes in each serotype. The World Health Organization recommends tetravalent formulations including one genotype of each serotype as safe and effective dengue vaccines. Here, we investigated the impact of genotype on the neutralizing antibody responses to DENV-1 in humans. Convalescent sera collected from patients with primary infection of DENV-1 were examined for neutralizing antibody against single-round infectious particles of the five DENV-1 genotypes (GI-GV)...
December 2, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902896/the-efficacy-of-chitosan-adjuvanted-mycoplasma-gallisepticum-bacterin-in-chickens
#4
Arithat Limsatanun, Jiroj Sasipreeyajan, Somsak Pakpinyo
Mycoplasma gallisepticum (MG) is one of the major pathogens that cause respiratory signs in the poultry industry. To control MG infection, vaccination is the useful procedure. In this study, MG vaccine was developed by using the local Thai MG isolate (AHRL 20/52). Chitosan, a polysaccharide adjuvant derived from crustaceans, has been successfully used in various vaccines. The objectives of this study were to prepare MG bacterins by using chitosan, serving as an adjuvant, to determine protection against the field Thai MG isolate and to evaluate tissue reaction at the injection site...
December 2016: Avian Diseases
https://www.readbyqxmd.com/read/27902762/presenting-influenza-a-m2e-antigen-on-recombinant-spores-of-bacillus-subtilis
#5
Tomasz Łęga, Paulina Weiher, Michał Obuchowski, Dawid Nidzworski
Effective vaccination against influenza virus infection is a serious problem mainly due to antigenic variability of the virus. Among many of investigated antigens, the extracellular domain of the M2 protein (M2e) features high homology in all strains of influenza A viruses and antibodies against M2e and is protective in animal models; this makes it a potential candidate for generation of a universal influenza vaccine. However, due to the low immunogenicity of the M2e, formulation of a vaccine based on this antigen requires some modification to induce effective immune responses...
2016: PloS One
https://www.readbyqxmd.com/read/27901071/staphylococcus-aureus-dependent-septic-arthritis-in-murine-knee-joints-local-immune-response-and-beneficial-effects-of-vaccination
#6
Alessia Corrado, Paolo Donato, Silvia Maccari, Raffaella Cecchi, Tiziana Spadafina, Letizia Arcidiacono, Simona Tavarini, Chiara Sammicheli, Donatello Laera, Andrea Guido Oreste Manetti, Paolo Ruggiero, Bruno Galletti, Sandra Nuti, Ennio De Gregorio, Sylvie Bertholet, Anja Seubert, Fabio Bagnoli, Giuliano Bensi, Emiliano Chiarot
Staphylococcus aureus is the major cause of human septic arthritis and osteomyelitis, which deserve special attention due to their rapid evolution and resistance to treatment. The progression of the disease depends on both bacterial presence in situ and uncontrolled disruptive immune response, which is responsible for chronic disease. Articular and bone infections are often the result of blood bacteremia, with the knees and hips being the most frequently infected joints showing the worst clinical outcome. We report the development of a hematogenous model of septic arthritis in murine knees, which progresses from an acute to a chronic phase, similarly to what occurs in humans...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27894306/first-phase-i-human-clinical-trial-of-a-killed-whole-hiv-1-vaccine-demonstration-of-its-safety-and-enhancement-of-anti-hiv-antibody-responses
#7
Eunsil Choi, Chad J Michalski, Seung Ho Choo, Gyoung Nyoun Kim, Elizabeth Banasikowska, Sangkyun Lee, Kunyu Wu, Hwa-Yong An, Anthony Mills, Stefan Schneider, U Fritz Bredeek, Daniel R Coulston, Shilei Ding, Andrés Finzi, Meijuan Tian, Katja Klein, Eric J Arts, Jamie F S Mann, Yong Gao, C Yong Kang
BACKGROUND: Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus...
November 28, 2016: Retrovirology
https://www.readbyqxmd.com/read/27892866/effectiveness-of-a-bhv-1-befv-bivalent-vaccine-against-bovine-herpesvirus-type-1-infection-in-cattle
#8
Yao-Chi Chung, Hsiu-Yen Shen, Li-Ting Cheng, Shyh-Shyan Liu, Chun-Yen Chu
Bovine herpesvirus type 1 (BHV-1) causes acute febrile respiratory diseases (infectious bovine rhinotracheitis, IBR), decreased milk production, weight loss and abortion. Bovine ephemeral fever virus (BEFV) causes acute febrile respiratory disease, with pulmonary emphysema and pulmonary edema as the main signs. These viruses infect domesticated herds and lead to significant economic losses. In our previous study, an inactivated BHV-1 and BEFV bivalent vaccine was formulated with water-in-oil-in-water adjuvant, and vaccine efficacy was evaluated in guinea pigs...
October 13, 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/27890399/a-partially-purified-outer-membrane-protein-virb9-1-for-low-cost-nanovaccines-against-anaplasma-marginale
#9
Liang Zhao, Antonino S Cavallaro, David Wibowo, Bing Zhang, Jun Zhang, Neena Mitter, Chengzhong Yu, Chun-Xia Zhao, Anton P J Middelberg
Anaplasma marginale is a devastating tick-borne pathogen causing anaplasmosis in cattle and results in significant economic loss to the cattle industry worldwide. Currently, there is no widely accepted vaccine against A. marginale. New generation subunit vaccines against A. marginale, which are much safer, more efficient and cost-effective, are in great need. The A. marginale outer membrane protein VirB9-1 is a promising antigen for vaccination. We previously have shown that soluble recombinant VirB9-1 protein can be expressed and purified from Escherichia coli and induce a high level of humoral and cellular immunity in mice...
November 24, 2016: Vaccine
https://www.readbyqxmd.com/read/27890396/structure-based-design-of-broadly-protective-group-a-streptococcal-m-protein-based-vaccines
#10
James B Dale, Pierre R Smeesters, Harry S Courtney, Thomas A Penfound, Claudia M Hohn, Jeremy C Smith, Jerome Y Baudry
BACKGROUND: A major obstacle to the development of broadly protective M protein-based group A streptococcal (GAS) vaccines is the variability within the N-terminal epitopes that evoke potent bactericidal antibodies. The concept of M type-specific protective immune responses has recently been challenged based on the observation that multivalent M protein vaccines elicited cross-reactive bactericidal antibodies against a number of non-vaccine M types of GAS. Additionally, a new "cluster-based" typing system of 175M proteins identified a limited number of clusters containing closely related M proteins...
November 24, 2016: Vaccine
https://www.readbyqxmd.com/read/27882487/delivery-of-small-interfering-rna-to-inhibit-vascular-endothelial-growth-factor-in-zebrafish-using-natural-brain-endothelia-cell-secreted-exosome-nanovesicles-for-the-treatment-of-brain-cancer
#11
Tianzhi Yang, Brittany Fogarty, Bret LaForge, Salma Aziz, Thuy Pham, Leanne Lai, Shuhua Bai
Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p < 0...
November 23, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27874029/an-anti-tnf-%C3%AE-antibody-mimetic-to-treat-ocular-inflammation
#12
Hanieh Khalili, Richard W Lee, Peng T Khaw, Steve Brocchini, Andrew D Dick, David A Copland
Infliximab is an antibody that neutralizes TNF-α and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpFinfliximab was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximab maintained binding affinity for both human and murine recombinant TNF-α...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872686/engineering-translation-in-mammalian-cell-factories-to-increase-protein-yield-the-unexpected-use-of-long-non-coding-sineup-rnas
#13
REVIEW
Silvia Zucchelli, Laura Patrucco, Francesca Persichetti, Stefano Gustincich, Diego Cotella
Mammalian cells are an indispensable tool for the production of recombinant proteins in contexts where function depends on post-translational modifications. Among them, Chinese Hamster Ovary (CHO) cells are the primary factories for the production of therapeutic proteins, including monoclonal antibodies (MAbs). To improve expression and stability, several methodologies have been adopted, including methods based on media formulation, selective pressure and cell- or vector engineering. This review presents current approaches aimed at improving mammalian cell factories that are based on the enhancement of translation...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27871990/multifunctional-gold-nanoparticles-a-nanovectorization-tool-for-the-targeted-delivery-of-novel-chemotherapeutic-agents
#14
Alexandra R Fernandes, João Jesus, Pedro Martins, Sara Figueiredo, Daniela Rosa, Luísa M R D R S Martins, Maria Luísa Corvo, Manuela C Carvalheiro, Pedro M Costa, Pedro V Baptista
Due to their small size and unique properties, multifunctional nanoparticles arise as versatile delivery systems easily grafted with a vast array of functional moieties, such as anticancer cytotoxic chemotherapeutics and targeting agents. Here, we formulated a multifunctional gold-nanoparticle (AuNP) system composed of a monoclonal antibody against epidermal growth factor receptor (EGFR) (anti-EGFR D-11) for active targeting and a Co(II) coordination compound [CoCl(H2O)(phendione)2][BF4] (phendione=1,10-phenanthroline-5,6-dione) (TS265) with proven antiproliferative activity towards cancer cells (designated as TargetNanoTS265)...
November 18, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27867431/the-avise-lupus-test-and-cell-bound-complement-activation-products-aid-the-diagnosis-of-systemic-lupus-erythematosus
#15
James Mossell, John A Goldman, Derren Barken, Roberta Vezza Alexander
BACKGROUND: Systemic lupus erythematosus (SLE) is a multifaceted disease, and its diagnosis may be challenging. A blood test for the diagnosis of SLE, the Avise Lupus test, has been recently commercialized and validated in clinical studies. OBJECTIVES: To evaluate the use of the Avise Lupus test by community rheumatologists. METHODS: The study is a longitudinal, case-control, retrospective review of medical charts. Cases had a positive test result, and controls had a negative result; all patients were anti-nuclear antibodies (ANA) positive but negative for SLE-specific autoantibodies...
2016: Open Rheumatology Journal
https://www.readbyqxmd.com/read/27866769/modular-virus-like-particles-for-sublingual-vaccination-against-group-a-streptococcus
#16
Arjun Seth, Il Gyu Kong, Su-Hyun Lee, Jin-Young Yang, Yong-Soo Lee, Yeji Kim, Nani Wibowo, Anton P J Middelberg, Linda H L Lua, Mi-Na Kweon
Infection with Group A streptococcus (GAS)-an oropharyngeal pathogen-leads to mortality and morbidity, primarily among developing countries and indigenous populations in developed countries. The development of safe and affordable GAS vaccines is challenging, due to the presence of various unique GAS serotypes, antigenic variation within the same serotype, and potential auto-immune responses. In the present study, we evaluated the use of a sublingual freeze-dried (FD) formulation based on immunogenic modular virus-like particles (VLPs) carrying the J8 peptide (J8-VLPs) as a potential safe and cost-effective GAS vaccine for inducing protective systemic and mucosal immunity...
December 12, 2016: Vaccine
https://www.readbyqxmd.com/read/27866765/safety-tolerability-and-immunogenicity-of-a-single-dose-4-antigen-or-3-antigen-staphylococcus-aureus-vaccine-in-healthy-older-adults-results-of-a-randomised-trial
#17
C Buddy Creech, Robert W Frenck, Eric A Sheldon, David J Seiden, Martin K Kankam, Edward T Zito, Douglas Girgenti, Joseph M Severs, Frederick W Immermann, Lisa K McNeil, David Cooper, Kathrin U Jansen, William Gruber, Joseph Eiden, Annaliesa S Anderson, James Baber
BACKGROUND: The decline in immune function with age is a challenge to vaccine development. Following an initial study in adults aged 18-64years, this study evaluated the safety and immunogenicity of Staphylococcus aureus (S. aureus) 4-antigen (SA4Ag) and 3-antigen (SA3Ag) vaccine in older adults. SA3Ag included capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to the nontoxic mutant form of diphtheria toxin (CRM197) and a recombinant version of clumping factor A (ClfA)...
November 17, 2016: Vaccine
https://www.readbyqxmd.com/read/27866015/diversity-selection-screening-and-quantitative-structure-activity-relationships-of-osmolyte-like-additive-effects-on-the-thermal-stability-of-a-monoclonal-antibody
#18
Olubukayo-Opeyemi Oyetayo, Oscar Méndez-Lucio, Andreas Bender, Hans Kiefer
Solvents used for therapeutic proteins in downstream processing and in formulations often contain stabilizing additives that inhibit denaturation and aggregation. Such additives are mostly selected based on their positive effect on thermal stability of the protein, and are often derived from naturally occuring osmolytes. To better understand the structural basis underlying the effect of additives, we selected a diverse library of compounds comprising 79 compounds of the polyol, amino acid and methylamine chemical classes and determined the effect of each compound on thermal stability of a monoclonal antibody as a function of compound concentration...
November 16, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27865266/ability-of-an-oral-formulation-of-afoxolaner-to-protect-dogs-from-borrelia-burgdorferi-infection-transmitted-by-wild-ixodes-scapularis-ticks
#19
C F Baker, J W McCall, S D McCall, M D Drag, E B Mitchell, S T Chester, D Larsen
A randomized, blinded, negative controlled study was conducted to determine whether treatment with afoxolaner (NexGard(®), Merial, Inc.) would prevent the transmission of Borrelia burgdorferi to dogs by wild caught Ixodes scapularis ticks. Twenty healthy dogs were randomly assigned to two groups of ten dogs each. Ten dogs were treated orally on Day 0 at a dose near the minimum recommended dose of afoxolaner of 2.5mg/kg (actual doses 2.5-3.1mg/kg) and ten control dogs were not treated. On Day 28, each dog was infested with approximately 50 adult unfed wild caught I...
December 2016: Comparative Immunology, Microbiology and Infectious Diseases
https://www.readbyqxmd.com/read/27862374/safety-and-effectiveness-of-a-single-and-repeat-intramuscular-injection-of-a-gnrh-vaccine-gonacon%C3%A2-in-adult-female-domestic-cats
#20
L M Vansandt, M A Kutzler, A E Fischer, K N Morris, W F Swanson
Sterilization is a key strategy to reduce the number of domestic cats entering and killed in shelters each year. However, surgical sterilization is expensive and labour-intensive and cannot fully address the 70 million free-roaming cats estimated to exist in the United States. GonaCon™ is a gonadotropin-releasing hormone vaccine originally developed for use as a wildlife immunocontraceptive. An earlier formulation was tested in domestic cats and found to be safe and effective for long-term contraception. However, the current Environmental Protection Agency (EPA)-registered formulation consists of a different antigen-carrier protein and increased antigen concentration and has never been tested in cats...
November 15, 2016: Reproduction in Domestic Animals, Zuchthygiene
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