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Neutralizing antibodies

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https://www.readbyqxmd.com/read/28107434/anti-mrka-monoclonal-antibodies-reveal-distinct-structural-and-antigenic-features-of-mrka
#1
Qun Wang, Yan Chen, Romana Cvitkovic, Meghan E Pennini, Chew Shun Chang, Mark Pelletier, Jessica Bonnell, Adem C Koksal, Herren Wu, William F Dall'Acqua, C Kendall Stover, Xiaodong Xiao
Antibody therapy against antibiotics resistant Klebsiella pneumoniae infections represents a promising strategy, the success of which depends critically on the ability to identify appropriate antibody targets. Using a target-agnostic strategy, we recently discovered MrkA as a potential antibody target and vaccine antigen. Interestingly, the anti-MrkA monoclonal antibodies isolated through phage display and hybridoma platforms all recognize an overlapping epitope, which opens up important questions including whether monoclonal antibodies targeting different MrkA epitopes can be generated and if they possess different protective profiles...
2017: PloS One
https://www.readbyqxmd.com/read/28106886/loss-of-menin-in-osteoblast-lineage-affects-osteocyte-osteoclast-crosstalk-causing-osteoporosis
#2
Peng Liu, Sooyeon Lee, Jeanette Knoll, Alexander Rauch, Susanne Ostermay, Julia Luther, Nicole Malkusch, Ulf H Lerner, Mario M Zaiss, Mona Neven, Rainer Wittig, Martina Rauner, Jean-Pierre David, Philippe Bertolino, Chang X Zhang, Jan P Tuckermann
During osteoporosis bone formation by osteoblasts is reduced and/or bone resorption by osteoclasts is enhanced. Currently, only a few factors have been identified in the regulation of bone integrity by osteoblast-derived osteocytes. In this study, we show that specific disruption of menin, encoded by multiple endocrine neoplasia type 1 (Men1), in osteoblasts and osteocytes caused osteoporosis despite the preservation of osteoblast differentiation and the bone formation rate. Instead, an increase in osteoclast numbers and bone resorption was detected that persisted even when the deletion of Men1 was restricted to osteocytes...
January 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28106836/the-astrovirus-capsid-a-review
#3
REVIEW
Carlos F Arias, Rebecca M DuBois
Astroviruses are enterically transmitted viruses that cause infections in mammalian and avian species. Astroviruses are nonenveloped, icosahedral viruses comprised of a capsid protein shell and a positive-sense, single-stranded RNA genome. The capsid protein undergoes dramatic proteolytic processing both inside and outside of the host cell, resulting in a coordinated maturation process that affects cellular localization, virus structure, and infectivity. After maturation, the capsid protein controls the initial phases of virus infection, including virus attachment, endocytosis, and genome release into the host cell...
January 19, 2017: Viruses
https://www.readbyqxmd.com/read/28105852/the-effect-of-isoprinosine-treatment-on-persistent-infection-of-balb-c-mice-infected-with-murine-gammaherpesvirus-68-mhv-68
#4
O Janíčková, L Ančicová, K Briestenská, J Mistríková
We demonstrated the positive effect of Isoprinosine treatment on persistent infection of Balb/c mice with MHV-68. Increased number of leukocytes, increased percentage of neutrophils, elevated levels of virus-neutralizing (VN) antibodies, reduced number of atypical lymphocytes and reduced virus titers were detected in the examined organs after a 14-day treatment. The positive effect of Isoprinosine therapy vanished after 120-150 days. After this interval, we demonstrated lower numbers of leukocytes, lower levels of VN antibodies and an increased number of atypical lymphoid monocytes in the Isoprinosine-treated group...
January 19, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28105588/nogo-a-antibodies-for-progressive-multiple-sclerosis
#5
Benjamin V Ineichen, Patricia S Plattner, Nicolas Good, Roland Martin, Michael Linnebank, Martin E Schwab
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair...
January 19, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28104688/mice-with-a-deficiency-in-clec-2-are-protected-against-deep-vein-thrombosis
#6
Holly Payne, Tatyana Ponomaryov, Steve P Watson, Alexander Brill
Deep vein thrombosis (DVT) with its major complication, pulmonary embolism, is a global health problem. Mechanisms of DVT remain incompletely understood. Platelets play a role in DVT but the impact of specific platelet receptors remains unclear. Platelet C-type lectin-like receptor 2 (CLEC-2) is known to maintain the physiological state of blood vasculature under inflammatory conditions. DVT is a thromboinflammatory disorder developing largely as sterile inflammation in the vessel wall. We hypothesized therefore that CLEC-2 might play a role in DVT...
January 19, 2017: Blood
https://www.readbyqxmd.com/read/28103319/an-hsv-2-trivalent-vaccine-is-immunogenic-in-rhesus-macaques-and-highly-efficacious-in-guinea-pigs
#7
Sita Awasthi, Lauren M Hook, Carolyn E Shaw, Bapi Pahar, Jacob A Stagray, David Liu, Ronald S Veazey, Harvey M Friedman
A genital herpes vaccine is urgently needed to prevent pain and suffering, reduce the incidence of neonatal herpes, and decrease the risk of HIV acquisition and transmission that accompanies genital infection. We evaluated a trivalent HSV-2 subunit antigen vaccine administered with CpG and alum in rhesus macaques and guinea pigs. The vaccine contains glycoproteins C, D and E (gC2, gD2, gE2) to block virus entry by gD2 and immune evasion by gC2 and gE2. In rhesus macaques, the trivalent vaccine induced plasma and mucosa neutralizing antibodies, antibodies that block gC2 and gE2 immune evasion activities, and stimulated CD4 T cell responses...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28103139/endotoxin-neutralization-by-an-o-antigen-specific-monoclonal-antibody-a-potential-novel-therapeutic-approach-against-klebsiella-pneumoniaest258
#8
Valéria Szijártó, Luis M Guachalla, Katharina Hartl, Cecília Varga, Adriana Badarau, Irina Mirkina, Zehra C Visram, Lukas Stulik, Christine A Power, Eszter Nagy, Gábor Nagy
Klebsiella pneumoniae ST258 is a globally distributed multi-drug resistant pathogen responsible for severe invasive infections. In this study, the different virulence potential of K. pneumoniae ST258 isolates in endotoxin susceptible versus resistant animal models was shown. Furthermore, ST258 clinical isolates were found highly sensitive to the bactericidal effect of naive animal and human serum. These observations imply that LPS, released from the rapidly lysed bacteria, may contribute to the high mortality associated with ST258 bacteremia cases...
January 19, 2017: Virulence
https://www.readbyqxmd.com/read/28102671/structural-analysis-of-glycosylated-intact-hiv-1-gp120-b12-antibody-complex-using-hydroxyl-radical-protein-footprinting
#9
Xiaoyan Li, Oliver C Grant, Keigo Ito, Aaron Wallace, Shixia Wang, Peng Zhao, Lance Wells, Shan Lu, Robert J Woods, Joshua S Sharp
Glycoprotein gp120 is a surface antigen and virulence factor of the human immunodeficiency virus-1 (HIV-1). Broadly neutralizing antibodies (bNAbs) that are reactive to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system due to its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions...
January 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28102191/a-broadly-protective-therapeutic-antibody-against-influenza-b-virus-with-two-mechanisms-of-action
#10
Ning Chai, Lee R Swem, Summer Park, Gerald Nakamura, Nancy Chiang, Alberto Estevez, Rina Fong, Lynn Kamen, Elviza Kho, Mike Reichelt, Zhonghua Lin, Henry Chiu, Elizabeth Skippington, Zora Modrusan, Jeremy Stinson, Min Xu, Patrick Lupardus, Claudio Ciferri, Man-Wah Tan
Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28100831/coexistence-of-potent-hiv-1-broadly-neutralizing-antibodies-and-antibody-sensitive-viruses-in-a-viremic-controller
#11
Natalia T Freund, Haoqing Wang, Louise Scharf, Lilian Nogueira, Joshua A Horwitz, Yotam Bar-On, Jovana Golijanin, Stuart A Sievers, Devin Sok, Hui Cai, Julio C Cesar Lorenzi, Ariel Halper-Stromberg, Ildiko Toth, Alicja Piechocka-Trocha, Harry B Gristick, Marit J van Gils, Rogier W Sanders, Lai-Xi Wang, Michael S Seaman, Dennis R Burton, Anna Gazumyan, Bruce D Walker, Anthony P West, Pamela J Bjorkman, Michel C Nussenzweig
Some HIV-1-infected patients develop broad and potent HIV-1 neutralizing antibodies (bNAbs) that when passively transferred to mice or macaques can treat or prevent infection. However, bNAbs typically fail to neutralize coexisting autologous viruses due to antibody-mediated selection against sensitive viral strains. We describe an HIV-1 controller expressing HLA-B57*01 and HLA-B27*05 who maintained low viral loads for 30 years after infection and developed broad and potent serologic activity against HIV-1. Neutralization was attributed to three different bNAbs targeting nonoverlapping sites on the HIV-1 envelope trimer (Env)...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100773/targeted-fc%C3%AE-r-mediated-clearance-by-a-biparatopic-bispecific-antibody
#12
Srinath Kasturirangan, G Jonah Rainey, Linda Xu, Xinwei Wang, Alyse Portnoff, Tracy Chen, Christine Fazenbaker, Helen Zhong, Jared Bee, Zhutian Zeng, Craig Jenne, Herren Wu, Changshou Gao
Soluble ligands have commonly been targeted by antibody therapeutics for cancers and other diseases. While monoclonal antibodies targeting such ligands can block their interactions with their cognate receptors, they can also significantly increase the half-life of their ligands by FcRn-mediated antibody recycling, thereby evading ligand renal clearance and requiring increasingly high antibody doses to neutralize the increasing pool of target. To overcome this issue, we generated a bispecific/biparatopic antibody (BiSAb) that targets two different epitopes on IL-6 to block IL-6 mediated signaling...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100620/overexpression-of-il-7-extends-the-humoral-immune-response-induced-by-rabies-vaccination
#13
Yingying Li, Ming Zhou, Zhaochen Luo, Yachun Zhang, Min Cui, Huanchun Chen, Zhen F Fu, Ling Zhao
: Rabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programmes for domestic animals. However, traditional inactivated vaccines used in animals are costly and have a relatively low efficiency, which impedes their extensive use in developing countries. There is therefore an urgent need to develop single-dose and long-lasting rabies vaccines. However, little information is available regarding the mechanisms underlying immunological memory, which can broaden humoral responses following rabies vaccination...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100617/differences-in-glycoprotein-complex-gpc-receptor-binding-site-accessibility-prompt-poor-cross-reactivity-of-neutralizing-antibodies-between-closely-related-arenaviruses
#14
Rachel B Brouillette, Elisabeth K Phillips, Natarajan Ayithan, Wendy Maury
: The glycoprotein complex (GPC) of arenaviruses, composed of stable signal peptide (SSP), GP1, and GP2, is the only antigen correlated with antibody-mediated neutralization. However, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. Two closely related Clade B viruses, Machupo virus (MACV) and Junín virus (JUNV), have near identical overall GPC architecture and share a host receptor, transferrin receptor 1...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100616/the-v3-loop-of-hiv-1-env-determines-viral-susceptibility-to-ifitm3-impairment-of-viral-infectivity
#15
Yimeng Wang, Qinghua Pan, Shilei Ding, Zhen Wang, Jingyou Yu, Andrés Finzi, Shan-Lu Liu, Chen Liang
: Interferon inducible transmembrane proteins (IFITMs) inhibit a broad spectrum of viruses including HIV-1. IFITM proteins deter HIV-1 entry when expressed in target cells and also impair HIV-1 infectivity when expressed in virus producer cells. However, little is known about how viruses resist IFITM inhibition. In this study, we have investigated the susceptibilities of different primary isolates of HIV-1 to the inhibition of viral infectivity by IFITMs. Our results demonstrate that the infectivity of different HIV-1 primary isolates including transmitted founder viruses is diminished by IFITM3 to various levels, with strain AD8-1 exhibiting strong resistance...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28099492/priming-cross-protective-bovine-viral-diarrhea-virus-specific-immunity-using-live-vectored-mosaic-antigens
#16
Shehnaz Lokhandwala, Xin Fang, Suryakant D Waghela, Jocelyn Bray, Leo M Njongmeta, Andy Herring, Karim W Abdelsalam, Christopher Chase, Waithaka Mwangi
Bovine viral diarrhea virus (BVDV) plays a key role in bovine respiratory disease complex, which can lead to pneumonia, diarrhea and death of calves. Current vaccines are not very effective due, in part, to immunosuppressive traits and failure to induce broad protection. There are diverse BVDV strains and thus, current vaccines contain representative genotype 1 and 2 viruses (BVDV-1 & 2) to broaden coverage. BVDV modified live virus (MLV) vaccines are superior to killed virus vaccines, but they are susceptible to neutralization and complement-mediated destruction triggered by passively acquired antibodies, thus limiting their efficacy...
2017: PloS One
https://www.readbyqxmd.com/read/28097809/cancer-associated-fibroblasts-promote-m2-polarization-of-macrophages-in-pancreatic-ductal-adenocarcinoma
#17
Aibin Zhang, Yigang Qian, Zhou Ye, Haiyong Chen, Haiyang Xie, Lin Zhou, Yan Shen, Shusen Zheng
Pancreatic ductal adenocarcinoma (PDAC) is characterized by remarkable desmoplasia with infiltration of distinct cellular components. Cancer-associated fibroblasts (CAFs) has been shown to be among the most prominent cells and played a significant role in shaping the tumor microenvironment by interacting with other type of cells. Here, we aimed to investigate the effect of CAFs in modulating phenotype of tumor-associated macrophages (TAM). Under treatment of CAFs conditioned medium (CM) or direct co-culture with CAFs, monocytes exhibited enhanced expression of CD206 and CD163 compared with control group (P < 0...
January 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28096331/one-step-design-of-a-stable-variant-of-the-malaria-invasion-protein-rh5-for-use-as-a-vaccine-immunogen
#18
Ivan Campeotto, Adi Goldenzweig, Jack Davey, Lea Barfod, Jennifer M Marshall, Sarah E Silk, Katherine E Wright, Simon J Draper, Matthew K Higgins, Sarel J Fleishman
Many promising vaccine candidates from pathogenic viruses, bacteria, and parasites are unstable and cannot be produced cheaply for clinical use. For instance, Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is essential for erythrocyte invasion, is highly conserved among field isolates, and elicits antibodies that neutralize in vitro and protect in an animal model, making it a leading malaria vaccine candidate. However, functional RH5 is only expressible in eukaryotic systems and exhibits moderate temperature tolerance, limiting its usefulness in hot and low-income countries where malaria prevails...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095930/quantitative-risk-assessment-of-the-introduction-of-rabies-into-japan-through-the-importation-of-dogs-and-cats-worldwide
#19
N C L Kwan, K Sugiura, Y Hosoi, A Yamada, E L Snary
Japan has been free from rabies since 1958. A strict import regimen has been adopted since 2004 consisting of identification of an animal with microchip, two-time rabies vaccination, neutralizing antibody titration test and a waiting period of 180 days. The present study aims to quantitatively assess the risk of rabies introduction into Japan through the international importation of dogs and cats and hence provide evidence-based recommendations to strengthen the current rabies prevention system. A stochastic scenario tree model was developed and simulations were run using @RISK...
January 18, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28095712/current-views-on-the-potential-for-development-of-a-hiv-vaccine
#20
Kristen W Cohen, Nicole Frahm
Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic. Areas covered: This review summarizes past HIV vaccine efficacy trials and current vaccine strategies as well as new approaches about to move into first-in-human trials. Expert opinion: Despite many setbacks in early HIV vaccine efficacy trials, the success of RV144 has provided the glimmer of hope necessary to invigorate the vaccine field, and has led to the development of a large number of vaccine strategies aiming at inducing an array of different immune responses...
January 18, 2017: Expert Opinion on Biological Therapy
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