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Neutralizing antibodies

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https://www.readbyqxmd.com/read/28938115/a-human-bi-specific-antibody-against-zika-virus-with-high-therapeutic-potential
#1
Jiaqi Wang, Marco Bardelli, Diego A Espinosa, Mattia Pedotti, Thiam-Seng Ng, Siro Bianchi, Luca Simonelli, Elisa X Y Lim, Mathilde Foglierini, Fabrizia Zatta, Stefano Jaconi, Martina Beltramello, Elisabetta Cameroni, Guntur Fibriansah, Jian Shi, Taylor Barca, Isabel Pagani, Alicia Rubio, Vania Broccoli, Elisa Vicenzi, Victoria Graham, Steven Pullan, Stuart Dowall, Roger Hewson, Simon Jurt, Oliver Zerbe, Karin Stettler, Antonio Lanzavecchia, Federica Sallusto, Andrea Cavalli, Eva Harris, Shee-Mei Lok, Luca Varani, Davide Corti
Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28938099/plasmid-dna-launches-live-attenuated-japanese-encephalitis-virus-and-elicits-virus-neutralizing-antibodies-in-balb-c-mice
#2
Brian Nickols, Irina Tretyakova, Alexander Tibbens, Elena Klyushnenkova, Peter Pushko
We describe novel plasmid DNA that encodes the full-length Japanese encephalitis virus (JEV) genomic cDNA and launches live-attenuated JEV vaccine in vitro and in vivo. The synthetic cDNA based on the sequence of JEV SA14-14-2 live-attenuated virus was placed under transcriptional control of the cytomegalovirus major immediate-early promoter. The stability and yields of the plasmid in E. coli were optimized by inserting three synthetic introns that disrupted JEV cDNA in the structural and nonstructural genes...
September 19, 2017: Virology
https://www.readbyqxmd.com/read/28935894/strain-dependent-neutralization-reveals-antigenic-variation-of-human-parechovirus-3
#3
Eveliina Karelehto, Sabine van der Sanden, James A Geraets, Aušra Domanska, Lonneke van der Linden, Dionne Hoogendoorn, Gerrit Koen, Hetty van Eijk, Shabih Shakeel, Tim Beaumont, Menno de Jong, Dasja Pajkrt, Sarah J Butcher, Katja C Wolthers
Human parechovirus 3 (HPeV3), a member of the Picornavirus family, is frequently detected worldwide. However, the observed seropositivity rates for HPeV3 neutralizing antibodies (nAbs) vary from high in Japan to low in the Netherlands and Finland. To study if this can be explained by technical differences or antigenic diversity among HPeV3 strains included in the serological studies, we determined the neutralizing activity of Japanese and Dutch intravenous immunoglobulin batches (IVIG), a rabbit HPeV3 hyperimmune polyclonal serum, and a human HPeV3-specific monoclonal antibody (mAb) AT12-015, against the HPeV3 A308/99 prototype strain and clinical isolates from Japan, the Netherlands and Australia, collected between 1989 and 2015...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935478/development-and-validation-of-a-cell-based-assay-for-the-detection-of-neutralizing-antibodies-against-recombinant-insulins
#4
Sanjukta Chatterjee, Laxmikant Vashishta, Vinit S Waichale, Vivek G Nayak, Ramakrishnan Melarkode, Charles M Donnelly, Patrick T Vallano, Narendra Chirmule, Nilanjan Sengupta
Recombinant biopharmaceuticals can induce generation of anti-drug antibodies, which could potentially neutralize therapeutic drug activity. In this report, we describe development and validation of a cell-based assay for detection of neutralizing antibodies (Nab) against insulin and insulin analogues. In order to achieve clinically meaningful sensitivity the method used an early signalling event, insulin induced insulin receptor phosphorylation as the endpoint. Percentage insulin receptor phosphorylation in cell lysates was measured using ECL based ELISA...
September 18, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28935113/directed-evolution-of-glycopeptides-using-mrna-display
#5
Satoru Horiya, Jennifer K Bailey, Isaac J Krauss
Directed evolution is a useful method for the discovery of nucleic acids, peptides, or proteins that have desired binding abilities or functions. Because of the abundance and importance of glycosylation in nature, directed evolution of glycopeptides and glycoproteins is also highly desirable. However, common directed evolution platforms such as phage-, yeast-, or mammalian-cell display are limited for these applications by several factors. Glycan structure at each glycosylation site is not genetically encoded, and yeast and mammalian cells produce a heterogeneous mixture of glycoforms at each site on the protein...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28933684/screening-of-primary-gp120-immunogens-to-formulate-the-next-generation-polyvalent-dna-prime-protein-boost-hiv-1-vaccines
#6
Shixia Wang, Te-Hui Wu, Anthony Hackett, Veronica Efros, Yan Wang, Dong Han, Aaron Wallace, Yuxin Chen, Guangnan Hu, Shuying Liu, Paul Clapham, James Arthos, David Montefiori, Shan Lu
Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28933665/characterization-of-serum-anti-diphtheria-antibody-activity-following-administration-of-equine-anti-toxin-for-suspected-diphtheria
#7
Heidi L Smith, Greg Saia, Maria Lobikin, Tejpratap Tiwari, Su-Chun Cheng, Deborah C Molrine
There is a global shortage of equine-derived diphtheria anti-toxin (DAT) for diphtheria treatment. There are few existing data on serum antibody concentrations and neutralizing activity post-treatment to support development of new therapeutics. Antibody concentrations were quantified by ELISA and anti-toxin neutralizing activity by cytotoxicity assay in serum from four patients receiving DAT for suspected diphtheria. Using linear mixed effects modeling, estimated mean (SE) half-life was 78.2 (20.0) hours. Maximum serum neutralizing activity ranged from 28...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28933644/development-and-optimization-of-a-sensitive-pseudovirus-based-assay-for-hiv-1-neutralizing-antibodies-detection-using-a3r5-cells
#8
Qingqing Chen, Jianhui Nie, Weijin Huang, Yanmei Jiao, Lan Li, Tong Zhang, Juan Zhao, Hao Wu, Youchun Wang
Sensitive assays for HIV-1 neutralizing antibody detection are urgently needed for vaccine immunogen optimization and identification of protective immune response levels. In this study, we developed an easy-to-use HIV-1 pseudovirus neutralization assay based on a human CD4(+) lymphoblastoid cell line A3R5 by employing a high efficient pseudovirus production system. Optimal conditions for cell counts, infection time, virus dose and concentration of DEAE-dextran were tested and identified. For T-cell line-adapted tier 1 virus strains, significantly higher inhibitory efficiency was observed for both monoclonal neutralizing antibody (4 fold) and plasma (2 fold) samples in A3R5 than those in TZM-bl assay...
September 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28933132/effects-of-secukinumab-on-serum-adipocytokines-preliminary-data
#9
A Fassio, D Gatti, P Gisondi, G Girolomoni, O Viapiana, A Giollo, M Zamboni, M Rossini, L Idolazzi
Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects joints, connective tissues and the axial skeleton. Metabolic syndrome is an independent risk factor for psoriasis (Pso) development and is associated with more severe forms of Pso. Adipocytokines are secreted by white adipose tissue and are thought to link obesity with the development of metabolic and cardiovascular diseases. Secukinumab is a new monoclonal antibody with a different mechanism of action. This antibody selectively binds to and neutralizes interleukin-17 (IL-17) and it has shown efficacy in the treatment of PsA...
September 21, 2017: Reumatismo
https://www.readbyqxmd.com/read/28932227/targeted-delivery-of-neutralizing-anti-c5-antibody-to-renal-endothelium-prevents-complement-dependent-tissue-damage
#10
Paolo Durigutto, Daniele Sblattero, Stefania Biffi, Luca De Maso, Chiara Garrovo, Gabriele Baj, Federico Colombo, Fabio Fischetti, Antonio F Di Naro, Francesco Tedesco, Paolo Macor
Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28931763/reversible-retinal-vessel-closure-from-vegf-induced-leukocyte-plugging
#11
Yuanyuan Liu, Jikui Shen, Seth D Fortmann, Jiangxia Wang, Dietmar Vestweber, Peter A Campochiaro
Clinical trials in patients with macular edema due to diabetic retinopathy or retinal vein occlusion (RVO) have shown that suppression of VEGF not only improves macular edema, but also reopens closed retinal vessels, prevents progression of vessel closure, and improves retinopathy. In this study, we show the molecular basis for those clinical observations. Increased retinal levels of VEGF in mice cause plugging of retinal vessels with leukocytes, vessel closure, and hypoxia. Suppression of VEGF reduces leukocyte plugging, causing reperfusion of closed vessels...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931691/vertical-transmission-of-hepatitis-c-virus-variable-transmission-bottleneck-and-evidence-of-mid-gestation-in-utero-infection
#12
Sébastien Fauteux-Daniel, Ariane Larouche, Virginie Calderon, Jonathan Boulais, Chanel Béland, Doris G Ransy, Marc Boucher, Valérie Lamarre, Normand Lapointe, Isabelle Boucoiran, Armelle Le Campion, Hugo Soudeyns
Hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and childbirth. However, the timing and precise biologic mechanisms that are involved in this process are incompletely understood, as are the determinants that influence transmission of particular HCV variants. Here we report results of a longitudinal assessment of HCV quasispecies diversity and composition in 5 cases of vertical HCV transmission, including 3 women coinfected with HIV-1. The population structure of HCV variant spectra based on E2 envelope gene sequences (nucleotide positions 1491-1787), including hypervariable regions 1 and 2, was characterized using next-generation sequencing and median joining network analysis...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931687/a-dna-vaccine-that-targets-hemagglutinin-to-antigen-presenting-cells-protects-mice-against-h7-influenza
#13
Tor Kristian Andersen, Fan Zhou, Rebecca Cox, Bjarne Bogen, Gunnveig Grødeland
Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we have constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1)...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931679/pathogenic-correlates-of-the-simian-immunodeficiency-virus-siv-associated-b-cell-dysfunction
#14
Egidio Brocca-Cofano, David Kuhrt, Basile Siewe, Cuiling Xu, George S Haret-Richter, Jodi Craigo, Celia Labranche, David C Montefiori, Alan Landay, Cristian Apetrei, Ivona Pandrea
We compared and contrasted pathogenic (pigtailed macaques-PTMs) and nonpathogenic (African green monkeys-AGMs) SIVsab infections to assess the significance of the B-cell dysfunction observed in SIV/HIV infection. We report that the loss of B cells is specifically associated with the pathogenic SIV infection, while in the nonpathogenic natural hosts B cells rapidly increase in both LNs and intestine. SIV-associated B-cell dysfunction associated to the pathogenic SIV infection is characterized by loss of naïve B cells; loss of resting memory B cells due to their redistribution to the gut; increases of the activated B cells and circulating tissue-like memory B cells and expansion of the B regulatory cells...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931655/protection-against-a-mixed-shiv-challenge-by-a-broadly-neutralizing-antibody-cocktail
#15
Boris Julg, Po-Ting Liu, Kshitij Wagh, William M Fischer, Peter Abbink, Noe B Mercado, James B Whitney, Joseph P Nkolola, Katherine McMahan, Lawrence J Tartaglia, Erica N Borducchi, Shreeya Khatiwada, Megha Kamath, Jake A LeSuer, Michael S Seaman, Stephen D Schmidt, John R Mascola, Dennis R Burton, Bette T Korber, Dan H Barouch
HIV-1 sequence diversity presents a major challenge for the clinical development of broadly neutralizing antibodies (bNAbs) for both therapy and prevention. Sequence variation in critical bNAb epitopes has been observed in most HIV-1-infected individuals and can lead to viral escape after bNAb monotherapy in humans. We show that viral sequence diversity can limit both the therapeutic and prophylactic efficacy of bNAbs in rhesus monkeys. We first demonstrate that monotherapy with the V3 glycan-dependent antibody 10-1074, but not PGT121, results in rapid selection of preexisting viral variants containing N332/S334 escape mutations and loss of therapeutic efficacy in simian-HIV (SHIV)-SF162P3-infected rhesus monkeys...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28931639/trispecific-broadly-neutralizing-hiv-antibodies-mediate-potent-shiv-protection-in-macaques
#16
Ling Xu, Amarendra Pegu, Ercole Rao, Nicole Doria-Rose, Jochen Beninga, Krisha McKee, Dana M Lord, Ronnie R Wei, Gejing Deng, Mark Louder, Stephen D Schmidt, Zachary Mankoff, Lan Wu, Mangaiarkarasi Asokan, Christian Beil, Christian Lange, Wulf Dirk Leuschner, Jochen Kruip, Rebecca Sendak, Young Do Kwon, Tongqing Zhou, Xuejun Chen, Robert T Bailer, Keyun Wang, Misook Choe, Lawrence J Tartaglia, Dan H Barouch, Sijy O'Dell, John-Paul Todd, Dennis R Burton, Mario Roederer, Mark Connors, Richard A Koup, Peter D Kwong, Zhi-Yong Yang, John R Mascola, Gary J Nabel
The development of an effective AIDS vaccine has been challenging due to viral genetic diversity and the difficulty in generating broadly neutralizing antibodies (bnAbs). Here, we engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: 1) the CD4 binding site, 2) the membrane proximal external region (MPER) and 3) the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to human bnAbs, and conferred complete immunity against a mixture of SHIVs in non-human primates (NHP) in contrast to single bnAbs...
September 20, 2017: Science
https://www.readbyqxmd.com/read/28931425/neutralizing-immune-responses-induced-by-oligomeric-h5n1-hemagglutinins-from-plants
#17
Hoang Trong Phan, Thuong Thi Ho, Ha Hoang Chu, Trang Huyen Vu, Ulrike Gresch, Udo Conrad
Plant-based transient expression is an alternative platform to produce hemagglutinin-based subunit vaccines. This production system provides not only fast and effective response in the context of a pandemic but also enables the supply of big volume vaccines at low cost. Crude plant extracts containing influenza hemagglutinin are considered to use as vaccine sources because of avoidance of related purification steps resulting in low cost production allowing veterinary applications. Highly immunogenic influenza hemagglutinins are urgently required to meet these pre-conditions...
September 20, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28931127/single-visit-rabies-pre-exposure-priming-induces-a-robust-anamnestic-antibody-response-after-simulated-post-exposure-vaccination-results-of-a-dose-finding-study
#18
Emile F F Jonker, Leonardus G Visser
Background: The current standard 3-dose intramuscular rabies PrEP schedule suffers from a number of disadvantages that severely limit accessibility and availability. The cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages. Methods: Volunteers ( N  = 30) were randomly assigned to 4 study arms: 1 standard dose intramuscular (IM) dose of PVRV (purified Vero cell rabies vaccine, Verorab), and 1/5th, 2/5th or 3/5th- fractional intradermal (ID) dose of PVRV in a single visit...
September 1, 2017: Journal of Travel Medicine
https://www.readbyqxmd.com/read/28930978/influenza-a-virus-studies-in-a-mouse-model-of-infection
#19
Laura Rodriguez, Aitor Nogales, Luis Martínez-Sobrido
Influenza viruses cause over 500,000 deaths worldwide(1) and are associated with an annual cost of 12 - 14 billion USD in the United States alone considering direct medical and hospitalization expenses and work absenteeism(2). Animal models are crucial in Influenza A virus (IAV) studies to evaluate viral pathogenesis, host-pathogen interactions, immune responses, and the efficacy of current and/or novel vaccine approaches as well as antivirals. Mice are an advantageous small animal model because their immune system is evolutionarily similar to that found in humans, they are available from commercial vendors as genetically identical subjects, there are multiple strains that can be exploited to evaluate the genetic basis of infections, and they are relatively inexpensive and easy to manipulate...
September 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930686/antibody-27f3-broadly-targets-influenza-a-group-1-and-2-hemagglutinins-through-a-further-variation-in-vh1-69-antibody-orientation-on-the-ha-stem
#20
Shanshan Lang, Jia Xie, Xueyong Zhu, Nicholas C Wu, Richard A Lerner, Ian A Wilson
Antibodies that target both group 1 and group 2 influenza A viruses are valuable for therapeutic and vaccine development, but only a few have been reported to date. Here, we describe a new VH1-69 antibody 27F3 that broadly recognizes heterosubtypic hemagglutinins (HAs) from both group 1 and group 2 influenza A viruses. Structural characterization of 27F3 Fab with A/California/04/2009 (H1N1) hemagglutinin illustrates that 27F3 shares the key binding features observed in other VH1-69 antibodies to the HA stem...
September 19, 2017: Cell Reports
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