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Neutralizing antibodies

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https://www.readbyqxmd.com/read/29353241/inhibition-of-endothelial-notch-signaling-impairs-fatty-acid-transport-and-leads-to-metabolic-and-vascular-remodeling-of-the-adult-heart
#1
Markus Jabs, Adam J Rose, Lorenz H Lehmann, Jacqueline Taylor, Iris Moll, Tjeerd P Sijmonsma, Stefanie E Herberich, Sven W Sauer, Gernot Poschet, Giuseppina Federico, Carolin Mogler, Eva-Maria Weis, Hellmut G Augustin, Minhong Yan, Norbert Gretz, Roland M Schmid, Ralf H Adams, Hermann-Joseph Gröne, Rüdiger Hell, Jürgen G Okun, Johannes Backs, Peter P Nawroth, Stephan Herzig, Andreas Fischer
Background -Nutrients are transported through endothelial cells before being metabolized in muscle cells. However, little is known about the regulation of endothelial transport processes. Notch signaling is a critical regulator of metabolism and angiogenesis during development. Here, we studied how genetic and pharmacological manipulation of endothelial Notch signaling in adult mice affects endothelial fatty acid transport, cardiac angiogenesis, and heart function. Methods -Endothelial-specific Notch inhibition was achieved by conditional genetic inactivation of Rbp-jκ in adult mice to analyze fatty acid metabolism and heart function...
January 20, 2018: Circulation
https://www.readbyqxmd.com/read/29353060/parathyroid-hormone-related-protein-contributes-to-early-healing-of-habu-snakevenom-induced-glomerulonephritis-in-mice
#2
Mazène Hochane, Denis Raison, Catherine Coquard, Claire Béraud, Sabrina Danilin, Audrey Bethry, Thierry Massfelder, Mariette Barthelmebs
Proliferative glomerulonephritis is characterized by local inflammation and mesangial cell deterioration, followed by mesangial proliferation and glomerular healing. Parathyroid-hormone-related peptide (PTHrP) is a mesangial cytokine-like growth factor implicated in mesangial proliferation and survival. No data are available about its role in glomerulonephritis. Herein, we analyzed the expression and role of PTHrP in glomerular inflammation and healing in an experimental model of glomerulonephritis induced by intravenous injection of Habu-snake venom in mice...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29351737/identifying-genome-wide-immune-gene-variation-underlying-infectious-disease-in-wildlife-populations-a-next-generation-sequencing-approach-in-the-gopher-tortoise
#3
Jean P Elbers, Mary B Brown, Sabrina S Taylor
BACKGROUND: Infectious disease is the single greatest threat to taxa such as amphibians (chytrid fungus), bats (white nose syndrome), Tasmanian devils (devil facial tumor disease), and black-footed ferrets (canine distemper virus, plague). Although understanding the genetic basis to disease susceptibility is important for the long-term persistence of these groups, most research has been limited to major-histocompatibility and Toll-like receptor genes. To better understand the genetic basis of infectious disease susceptibility in a species of conservation concern, we sequenced all known/predicted immune response genes (i...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29350181/a-single-continuous-metric-to-define-tiered-serum-neutralization-potency-against-hiv
#4
Peter Hraber, Bette Korber, Kshitij Wagh, David Montefiori, Mario Roederer
HIV-1 Envelope (Env) variants are grouped into tiers by their neutralization-sensitivity phenotype. This helped to recognize that tier-1 neutralization responses can be elicited readily, but do not protect against new infections. Tier-3 viruses are the least sensitive to neutralization. Because most circulating viruses are tier 2, vaccines that elicit neutralization responses against them are needed. While tier classification is widely used for viruses, a way to rate serum or antibody neutralization responses in comparable terms is needed...
January 19, 2018: ELife
https://www.readbyqxmd.com/read/29348820/effects-of-different-cytokines-on-immune-responses-of-rainbow-trout-in-a-virus-dna-vaccination-model
#5
Yongsheng Cao, Qiya Zhang, Liming Xu, Shaowu Li, Di Wang, Jingzhuang Zhao, Hongbai Liu, Jian Feng, Tongyan Lu
Seven rainbow trout cytokine genes (interleukin (IL)-2, IL-8, IL-15, IL-17, IL-1β, intracellular interferon (iIFN) 1a, and IFN-γ2) were evaluated for their adjuvant effects on a DNA vaccine, called pG, containing the glycoprotein gene of infectious hematopoietic necrosis virus (IHNV). Distinct DNA constructs in expression plasmid pcDNA3.1 encoding a cytokine gene were generated. Immunofluorescence assays in rainbow trout gonadal cells demonstrated successful protein expression from all these constructs. Subsequently, fish were immunized with pG alone or together with a cytokine expression plasmid...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29346585/maternal-vaccination-with-a-mono-component-pertussis-toxoid-vaccine-is-sufficient-to-protect-infants-in-a-baboon-model-of-whooping-cough
#6
Parul Kapil, James F Papin, Roman F Wolf, Lindsey I Zimmerman, Leslie D Wagner, Tod J Merkel
Background: Bordetella pertussis is a human pathogen responsible for serious respiratory illness. The disease is most severe in infants too young to be vaccinated with most hospitalizations and deaths occurring within this age group. The Advisory Committee on Immunization Practices recommended immunization of pregnant women to protect infants from birth until their first vaccination at six to eight weeks of age. We previously demonstrated that maternal vaccination with licensed acellular pertussis vaccines protected newborn baboons from disease...
January 15, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29346435/influenza-a-virus-hemagglutinin-glycosylation-compensates-for-antibody-escape-fitness-costs
#7
Ivan Kosik, William L Ince, Lauren E Gentles, Andrew J Oler, Martina Kosikova, Matthew Angel, Javier G Magadán, Hang Xie, Christopher B Brooke, Jonathan W Yewdell
Rapid antigenic evolution enables the persistence of seasonal influenza A and B viruses in human populations despite widespread herd immunity. Understanding viral mechanisms that enable antigenic evolution is critical for designing durable vaccines and therapeutics. Here, we utilize the primerID method of error-correcting viral population sequencing to reveal an unexpected role for hemagglutinin (HA) glycosylation in compensating for fitness defects resulting from escape from anti-HA neutralizing antibodies...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29345851/the-immunosuppressive-effects-of-cd4-cd25-regulatory-t-cells-on-dendritic-cells-in-patients-with-chronic-hepatitis-b
#8
Pei-Pei Zhou, Juan Xu, Ming-Jia Dai, Yin-Yue Shi, Gui-Ping Wu, Yuan Fang, Xue-Bing Yan
The characteristics and functions of CD4+ CD25+ regulatory T cells (Tregs) have been well defined in murine and human systems. However, the interaction or cross-talk between CD4+ CD25+ Tregs and dendritic cells (DCs) remains controversial. In this study, the effects of chronic hepatitis B (CHB) CD4+ CD25+ Tregs on the maturation and function of monocyte-derived DCs were examined. The results showed that CD4+ CD25+ render the DCs inefficient as antigen-presenting cells (APCs) despite prestimulation with CD40 ligand...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29345496/feedback-from-the-european-bioanalysis-forum-focus-workshop-on-current-analysis-of-immunogenicity-best-practices-and-regulatory-hurdles
#9
Joanne Goodman, Simon Cowen, Viswanath Devanarayan, David Egging, Thomas Emrich, Michaela Golob, Daniel Kramer, Jim McNally, James Munday, Robert Nelson, João A Pedras-Vasconcelos, Timo Piironen, Denise Sickert, Venke Skibeli, Marianne Scheel Fjording, Philip Timmerman
European Bioanalysis Forum Workshop, Lisbon, Spain, September 2016: At the recent European Bioanalysis Forum Focus Workshop, 'current analysis of immunogenicity: best practices and regulatory hurdles', several important challenges facing the bioanalytical community in relation to immunogenicity assays were discussed through a mixture of presentations and panel sessions. The main areas of focus were the evolving regulatory landscape, challenges of assay interferences from either drug or target, cut-point setting and whether alternative assays can be used to replace neutralizing antibody assays...
January 18, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29345344/differential-outcomes-of-tlr2-engagement-in-inflammation-induced-preterm-birth
#10
Monica Cappelletti, Matthew J Lawson, Calvin C Chan, Adrienne N Wilburn, Senad Divanovic
Preterm birth (PTB) is the leading cause of neonatal mortality worldwide. Infection and inflammation are considered main causes of PTB. Among multiple pathogens, Gram-positive bacteria are commonly linked with induction of PTB. Although activation of innate immune responses, via TLR2 engagement, by Gram-positive bacteria is a likely cause, whether induction of PTB depends on the potency of specific microbial components to induce Toll-like receptor (TLR)2-driven inflammation has not been elucidated. Here, we show that TLR2 activation by synthetic lipopeptides, Pam2Cys, and Pam3Cys specifically, variably influenced inflammation and subsequent induction of PTB...
December 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345064/tlr8-ligation-induces-apoptosis-of-monocytic-myeloid-derived-suppressor-cells
#11
Yushe Dang, Zina J Rutnam, Gregory Dietsch, Hailing Lu, Yi Yang, Robert Hershberg, Mary L Disis
Myeloid-derived suppressor cells (MDSCs) accumulate in tumors and the peripheral blood of cancer patients and demonstrate cancer-promoting activity across multiple tumor types. A limited number of agents are known to impact MDSC activity. TLR8 is expressed in myeloid cells. We investigated expression of TLR8 on MDSC and the effect of a TLR8 agonist, motolimod, on MDSC survival and function. TLR8 was highly expressed in monocytic MDSC (mMDSC) but absent in granulocytic MDSC (gMDSC). Treatment of human PBMC with motolimod reduced the levels of mMDSC in volunteers and cancer donors versus control (P < 0...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344664/crucial-role-of-ox40-ox40l-signaling-in-a-murine-model-of-asthma
#12
Wei Lei, Daxiong Zeng, Gaoqin Liu, Yehan Zhu, Jiajia Wang, Hongya Wu, Junhong Jiang, Jianan Huang
The aim of the present study was to explore the roles of OX40/OX40 ligand (OX40L) signaling and OX40+ T cells in ovalbumin (OVA)‑induced mouse asthma model. Asthma was induced by OVA exposure and subsequent co‑treatment with OX40L protein, neutralizing anti‑OX40L blocking antibody, OX40+ T cells or PBS. The protein expression levels of interleukin (IL)‑4, IL‑6, IL‑13, IL‑17, tumor necrosis factor (TNF)‑α and interferon (IFN)‑γ in bronchoalveolar lavage fluid (BALF) were examined using murine cytokine‑specific ELISA...
January 18, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344192/tslp-promotes-angiogenesis-of-human-umbilical-vein-endothelial-cells-by-strengthening-the-crosstalk-between-cervical-cancer-cells-and-eosinophils
#13
Bing Zhang, Chun-Yan Wei, Kai-Kai Chang, Jia-Jun Yu, Wen-Jie Zhou, Hui-Li Yang, Jun Shao, Jin-Jin Yu, Ming-Qing Li, Feng Xie
Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted by cervical cancer cells promotes angiogenesis and recruitment, and regulates the function of eosinophils (EOS). However, the function of TSLP in the crosstalk between EOS and vascular endothelial cells in cancer lesions remains unknown. The aim of the present study was to investigate the effect of EOS caused by TSLP in in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). The results of the present study revealed that recombinant human TSLP protein (rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF), but not fibroblast growth factors, in HL-60-eosinophils (HL-60E)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343577/cellular-and-humoral-immunity-protect-against-vaginal-zika-virus-infection-in-mice
#14
Jason M Scott, Tania J Lebratti, Justin M Richner, Xiaoping Jiang, Estefania Fernandez, Haiyan Zhao, Daved H Fremont, Michael S Diamond, Haina Shin
Zika virus (ZIKV), which can cause devastating disease in fetuses of infected pregnant women, can be transmitted by mosquito inoculation and sexual routes. Little is known about immune protection against sexually transmitted ZIKV. In this study, we show that previous infection through intravaginal or subcutaneous routes with a contemporary Brazilian strain of ZIKV can protect against subsequent intravaginal challenge with a homologous strain. Both routes of inoculation induced high titers of ZIKV-specific and neutralizing antibody in serum and the vaginal lumen...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343576/increased-epitope-complexity-correlated-with-antibody-affinity-maturation-and-a-novel-binding-mode-revealed-by-structures-of-rabbit-antibodies-against-the-third-variable-loop-v3-of-hiv-1-gp120
#15
Ruimin Pan, Yali Qin, Marisa Banasik, William Lees, Adrian J Shepherd, Michael W Cho, Xiang-Peng Kong
The V3 loop of HIV-1 gp120 is an immunodominant region targeted by neutralizing antibodies (nAbs). Despite limited breadth, better characterization of the structural details of the interactions between these nAbs and their target epitopes would enhance our understanding of the mechanism of neutralization and facilitate designing better immunogens to induce nAbs with greater breadth. Recently, we isolated two anti-V3 neutralizing monoclonal antibodies (mAbs), 10A3 and 10A37, from a rabbit immunized with gp120 of the M group consensus sequence...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343432/hiv-immunogens-affinity-is-key
#16
Savit Prabhu, Ian A Cockburn, Carola G Vinuesa
Generation of broadly neutralizing antibodies is a key aim of HIV vaccine design, but the precursor B cells are rare. Abbott et al. (2018) report that high affinity and avidity immunogens are required to promote maturation of low frequency B cells in germinal centers.
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29342954/a-built-in-cpg-adjuvant-in-rsv-f-protein-dna-vaccine-drives-a-th1-polarized-and-enhanced-protective-immune-response
#17
Yao Ma, Yue-Ying Jiao, Yun-Zhou Yu, Nan Jiang, Ying Hua, Xiu-Juan Zhang, Yuan-Hui Fu, Xiang-Lei Peng, Yan-Peng Zheng, Larry J Anderson, Jin-Sheng He
Human respiratory syncytial virus (RSV) is the most significant cause of acute lower respiratory infection in children. However, there is no licensed vaccine available. Here, we investigated the effect of five or 20 copies of C-Class of CpG ODN (CpG-C) motif incorporated into a plasmid DNA vaccine encoding RSV fusion (F) glycoprotein on the vaccine-induced immune response. The addition of CpG-C motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c mice immunized with the DNA vaccines...
January 15, 2018: Viruses
https://www.readbyqxmd.com/read/29342251/kinetics-of-serological-responses-in-critically-ill-patients-hospitalized-with-influenza-a-h1n1-pdm09-virus-infection-in-canada-2009-2011
#18
Melissa A Rolfes, F Liaini Gross, Brendan Flannery, Adrienne F A Meyers, Ma Luo, Nathalie Bastien, Robert A Fowler, Jacqueline M Katz, Min Z Levine, Anand Kumar, Timothy M Uyeki
Background: The kinetics of the antibody response during severe influenza are not well documented. Methods: Critically ill patients with influenza A(H1N1)pdm09 virus infection, confirmed by RT-PCR or seroconversion (≥4-fold rise in titers), during 2009-2011 in Canada were prospectively studied. Antibody titers in serially collected sera were determined using hemagglutinin inhibition (HAI) and microneutralization assays. Average antibody curves were estimated using linear mixed effects models and compared by patient outcome, age, and corticosteroid treatment...
January 12, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29341118/inhibition-of-the-fgl2-fc%C3%AE-riib-riii-immunosuppressive-pathway-enhances-antiviral-t-cell-and-b-cell-responses-leading-to-clearance-of-lcmv-cl-13
#19
Olga Klingberg, Ramzi Khattar, Kaveh Farrokhi, Dario Ferri, Nataliya Yavorska, Jianhua Zhang, Hassan Sadozai, Oyedele Adeyi, Andrzej Chruscinski, Gary A Levy, Nazia Selzner
Persistent viruses evade immune detection by interfering with virus-specific innate and adaptive antiviral immune responses. Fibrinogen-Like Protein-2 (FGL2) is a potent effector molecule of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) and exerts its immunosuppressive activity following ligation to its cognate receptor, FcγRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection caused by Lymphocytic Choriomeningitis Virus Clone-13 (LCMV cl-13) was assessed in this study. Chronically infected fgl2+/+ mice had increased plasma levels of FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on macrophages and dendritic cells (DC) and impaired production of neutralizing antibody...
January 17, 2018: Immunology
https://www.readbyqxmd.com/read/29340221/recombinant-antibodies-to-the-ebola-virus-glycoprotein
#20
A A Panina, I G Dementieva, T K Aliev, V A Toporova, D S Balabashin, M N Bokov, L P Pozdnyakova, O B Shchemchukova, D A Dolgikh, P G Sveshnikov, M P Kirpichnikov
Currently, there are no approved therapies for targeted prevention and treatment of Ebola hemorrhagic fever. In the present work, we describe the development of a eukaryotic expression system for the production of three full-length chimeric antibodies (IgG1-kappa isotypes) GPE118, GPE325, and GPE534 to the recombinant glycoprotein of the Ebola virus (EBOV GP), which is a key factor in the pathogenicity of the disease. The immunochemical properties of the obtained antibodies were studied by immunoblotting and indirect, direct, and competitive ELISA using the recombinant EBOV proteins rGPdTM, NP, and VP40...
October 2017: Acta Naturae
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