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Broadly neutralizing antibodies

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https://www.readbyqxmd.com/read/28716884/which-dengue-vaccine-approach-is-the-most-promising-and-should-we-be-concerned-about-enhanced-disease-after-vaccination-the-challenges-of-a-dengue-vaccine
#1
Gavin Screaton, Juthathip Mongkolsapaya
A dengue vaccine has been pursued for more than 50 years and, unlike other flaviviral vaccines such as that against yellow fever, progress has been slow. In this review, we describe progress toward the first licensed dengue vaccine Dengvaxia, which does not give complete protection against disease. The antibody response to the dengue virion is reviewed, highlighting immunodominant yet poorly neutralizing responses in the context of a highly dynamic structurally flexible dengue virus particle. Finally, we review recent evidence for cross-reactivity between antibody responses to Zika and dengue viruses, which may further complicate the development of broadly protective dengue virus vaccines...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28705932/use-of-a-neutralizing-antibody-helps-identify-structural-features-critical-for-binding-of-clostridium-difficile-toxin-tcda-to-the-host-cell-surface
#2
Heather K Kroh, Ramyavardhanee Chandrasekaran, Kim Rosenthal, Rob Woods, Xiaofang Jin, Melanie D Ohi, Andrew C Nyborg, G Jonah Rainey, Paul Warrener, Benjamin W Spiller, D Borden Lacy
Clostridium difficile is a clinically significant pathogen that causes mild-to-severe (and often recurrent) colon infections. Disease symptoms stem from the activities of two large, multi-domain toxins known as TcdA and TcdB. The toxins can bind, enter, and perturb host cell function through a multi-step mechanism of receptor binding, endocytosis, pore formation, autoproteolysis, and glucosyltransferase-mediated modification of host substrates. Monoclonal antibodies that neutralize toxin activity provide a survival benefit in preclinical animal models and prevent recurrent infections in human clinical trials...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28701866/inhibitory-effects-of-ginsenosides-on-basic-fibroblast-growth-factor-induced-melanocyte-proliferation
#3
Ji Eun Lee, Jong Il Park, Cheol Hwan Myung, Jae Sung Hwang
BACKGROUND: UV-B-exposed keratinocytes secrete various paracrine factors. Among these factors, basic fibroblast growth factor (bFGF) stimulates the proliferation of melanocytes. Ginsenosides, the major active compounds of ginseng, are known to have broad pharmacological effects. In this study, we examined the antiproliferative effects of ginsenosides on bFGF-induced melanocyte proliferation. METHODS: We investigated the inhibitory effects of Korean Red Ginseng and ginsenosides from Panax ginseng on bFGF-induced proliferation of melan-a melanocytes...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28700571/open-and-closed-structures-reveal-allostery-and-pliability-in-the-hiv-1-envelope-spike
#4
Gabriel Ozorowski, Jesper Pallesen, Natalia de Val, Dmitry Lyumkis, Christopher A Cottrell, Jonathan L Torres, Jeffrey Copps, Robyn L Stanfield, Albert Cupo, Pavel Pugach, John P Moore, Ian A Wilson, Andrew B Ward
For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication. The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion. Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness...
July 12, 2017: Nature
https://www.readbyqxmd.com/read/28698284/breaching-peripheral-tolerance-promotes-the-production-of-hiv-1-neutralizing-antibodies
#5
Kristin M S Schroeder, Amanda Agazio, Pamela J Strauch, Sean T Jones, Scott B Thompson, Michael S Harper, Roberta Pelanda, Mario L Santiago, Raul M Torres
A subset of characterized HIV-1 broadly neutralizing antibodies (bnAbs) are polyreactive with additional specificities for self-antigens and it has been proposed immunological tolerance may present a barrier to their participation in protective humoral immunity. We address this hypothesis by immunizing autoimmune-prone mice with HIV-1 Envelope (Env) and characterizing the primary antibody response for HIV-1 neutralization. We find autoimmune mice generate neutralizing antibody responses to tier 2 HIV-1 strains with alum treatment alone in the absence of Env...
July 11, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28696188/evolution-of-cross-neutralizing-antibodies-and-mapping-epitope-specificity-in-plasma-of-chronic-hiv-1-infected-antiretroviral-therapy-na%C3%A3-ve-children-from-india
#6
Muzamil A Makhdoomi, Lubina Khan, Sanjeev Kumar, Heena Aggarwal, Ravinder Singh, Rakesh Lodha, Mohit Singla, Bimal K Das, Sushil K Kabra, Kalpana Luthra
Delineating the factors leading to the development of broadly neutralizing antibodies (bnAbs) during natural HIV-1 infection and dissecting their epitope specificities generates useful information for vaccine design. This is the first longitudinal study to assess the plasma-neutralizing antibody response and neutralizing determinants in HIV-1-infected children from India. We enrolled 26 and followed up 20 antiretroviral therapy (ART)-naïve, asymptomatic, chronic HIV-1-infected children. Five (19.2 %) baseline and 10 (50 %) follow-up plasma samples neutralized ≥50 % of subtypes A, B and C tier 2 viruses at an ID50 titre ≥150...
July 12, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28696158/immunization-with-hiv-1-envelope-t20-encoding-dna-vaccines-elicits-cross-clade-neutralizing-antibody-responses
#7
S Stenler, K E Lundin, L Hansen, S Petkov, N Mozafari, M Isaguliants, P Blomberg, C I E Smith, D M Goldenberg, C-H Chang, K Ljungberg, J Hinkula, B Wahren
BACKGROUND: Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid...
July 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28679958/fc-functional-antibodies-in-humans-with-severe-h7n9-and-seasonal-influenza
#8
Hillary A Vanderven, Lu Liu, Fernanda Ana-Sosa-Batiz, Thi Ho Nguyen, Yanmin Wan, Bruce Wines, P Mark Hogarth, Danielle Tilmanis, Arnold Reynaldi, Matthew S Parsons, Aeron C Hurt, Miles P Davenport, Tom Kotsimbos, Allen C Cheng, Katherine Kedzierska, Xiaoyan Zhang, Jianqing Xu, Stephen J Kent
BACKGROUND: Both seasonal and novel avian influenza viruses can result in severe infections requiring hospitalization. Anti-influenza antibodies (Abs) with Fc-mediated effector functions, such as Ab-dependent cellular cytotoxicity (ADCC), are of growing interest in control of influenza but have not previously been studied during severe human infections. As such, the objective of this study was to examine Fc-mediated Ab functions in humans hospitalized with influenza infection. METHODS: Serum Ab response was studied in subjects hospitalized with either pandemic H7N9 avian influenza virus in China (n = 18) or circulating seasonal influenza viruses in Melbourne, Australia (n = 16)...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28679760/co-operation-between-strain-specific-and-broadly-neutralizing-responses-limited-viral-escape-and-prolonged-exposure-of-the-broadly-neutralizing-epitope
#9
Colin Anthony, Talita York, Valerie Bekker, David Matten, Philippe Selhorst, Roux-Cil Ferreria, Nigel J Garrett, Salim S Abdool Karim, Lynn Morris, Natasha T Wood, Penny L Moore, Carolyn Williamson
V3-glycan targeting broadly neutralizing antibodies (bNAbs) are a focus of HIV-1 vaccine development. Understanding the viral dynamics that stimulate the development of these antibodies can provide insights for immunogen design. We used a deep sequencing approach, together with neutralization phenotyping, to investigate the rate and complexity of escape from V3-glycan directed bNAbs, compared to overlapping early strain-specific neutralizing antibody (ssNAb) responses to the V3/C3 region in donor CAP177. Escape from the ssNAb response occurred rapidly, via a N334 to N332 glycan switch, which took just 7...
July 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28669616/clostridium-difficile-chimeric-toxin-receptor-binding-domain-vaccine-induced-protection-against-different-strains-in-active-and-passive-challenge-models
#10
Jing-Hui Tian, Gregory Glenn, David Flyer, Bin Zhou, Ye Liu, Eddie Sullivan, Hua Wu, James F Cummings, Larry Elllingsworth, Gale Smith
Clostridium difficile is the number one cause of nosocomial antibiotic-associated diarrhea in developed countries. Historically, pathogenesis was attributed two homologous glucosylating toxins, toxin-A (TcdA) and toxin-B (TcdB). Over the past decade, however, highly virulent epidemic strains of C. difficile (B1/NAP1/027) have emerged and are linked to an increase in morbidity and mortality. Increased virulence is attributed to multiple factors including: increased production of A- and B-toxins; production of binary toxin (CDT); and the emergence of more toxic TcdB variants (TcdB(027))...
July 24, 2017: Vaccine
https://www.readbyqxmd.com/read/28669387/amplification-and-selection-of-prrsv-activated-vdj-repertoires-in-pigs-secreting-distinct-neutralizing-antiboidies
#11
Nanhua Chen, Benjamin R Trible, Raymond R R Rowland
Neutralizing antibodies (nAbs) play an important role in protective immunity against porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the characterization of PRRSV nAb repertoires is rarely investigated. In this study, we developed a swine VDJ amplification method and selection criteria for the characterization of PRRSV-activated VDJ repertoires. According to clonal expansion theory, two separated aliquots of lymph nodes from pigs producing different PRRSV nAbs were utilized to determine the activated B-cell repertoires...
July 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28667249/conformational-heterogeneity-of-the-hiv-envelope-glycan-shield
#12
Mingjun Yang, Jing Huang, Raphael Simon, Lai-Xi Wang, Alexander D MacKerell
To better understand the conformational properties of the glycan shield covering the surface of the HIV gp120/gp41 envelope (Env) trimer, and how the glycan shield impacts the accessibility of the underlying protein surface, we performed enhanced sampling molecular dynamics (MD) simulations of a model glycosylated HIV Env protein and related systems. Our simulation studies revealed a conformationally heterogeneous glycan shield with a network of glycan-glycan interactions more extensive than those observed to date...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28663207/is-it-possible-to-develop-a-universal-influenza-virus-vaccine-immunogenetic-considerations-underlying-b-cell-biology-in-the-development-of-a-pan-subtype-influenza-a-vaccine-targeting-the-hemagglutinin-stem
#13
Sarah F Andrews, Barney S Graham, John R Mascola, Adrian B McDermott
Current influenza vaccines preferentially generate B-cell responses to the variable hemagglutinin (HA) head. Focusing vaccine-induced antibody responses on epitopes in the conserved HA stem may provide better protection against future drifted and pandemic strains. Understanding the basis for the dominant HA head and subdominant HA stem-specific responses at the level of B-cell activation and differentiation will be critical for designing vaccines that induce sustained stem-specific responses. Identifying antibody lineages with broad neutralizing activity against influenza A viruses and defining the structural mode of recognition for germline precursors of those antibodies will also guide future immunogen design...
June 29, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28660781/variability-in-biological-behaviour-pathogenicity-protectotype-and-induction-of-virus-neutralizing-antibodies-by-different-vaccination-programs-to-infectious-bronchitis-virus-genotype-q1-strains-from-chile
#14
J J de Wit, R Dijkman, P Guerrero, J Calvo, A Gonzalez, H Hidalgo
In the period from July 2008 to 2010 a disease episode resulting in serious economic losses in the major production area of the Chilean poultry industry were reported. These losses were associated with respiratory problems, increase of condemnations, drops in egg production and nephritis in breeders, laying hens and broilers due to infections with infectious bronchitis virus (IBV). Twenty-five IBV isolates were genotyped and 4 strains were selected for further testing by pathotyping and protectotyping. Twenty-four IBV isolates were of the Q1 genotype...
June 29, 2017: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/28658672/identification-of-a-novel-hiv-1-neutralizing-antibody-from-a-crf07_bc-infected-chinese-donor
#15
Youxiang Sun, Yuanyuan Qiao, Yuanmei Zhu, Huihui Chong, Yuxian He
The identification of human monoclonal antibodies (mAbs) able to neutralize a broad spectrum of primary HIV-1 isolates is highly important for understanding the immune response of HIV-1 infection and developing vaccines and therapeutics. In this study, we isolated a novel human mAb termed Y498 from a phage display antibody library constructed with the PBMC samples of a CRF07_BC-infected Chinese donor whose sera exhibited broadly neutralizing activity. Y498 cross-reacted with diverse Env antigens and neutralized 30% of 70 tested HIV-1 isolates...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28651892/construction-of-a-recombinant-full-length-membrane-associated-igg-library
#16
Zehua Sun, Shiqiang Lu, Zheng Yang, Jingjing Li, Mei-Yun Zhang
HIV/AIDS has become a global pandemic. Development of an effective HIV-1 vaccine eliciting broadly neutralizing monoclonal antibodies (bnmAbs) remains a big challenge. Before an effective vaccine comes out, passive treatment for prevention and protection of HIV-1 infection may alleviate the burden caused by the pandemic. Numerous bnmAbs have been isolated against different epitopes in HIV-1 envelope glycoprotein via phage/yeast display, EBV-immortalization, single cell sorting and micro neutralization. Recombinant antibody library with extended diversity and enlarged size of units are applicable by phage/yeast display and mammalian cell display for monoclonal antibody isolation...
June 24, 2017: Virus Research
https://www.readbyqxmd.com/read/28648617/a-perspective-on-the-structural-and-functional-constraints-for-immune-evasion-insights-from-influenza-virus
#17
REVIEW
Nicholas C Wu, Ian A Wilson
Influenza virus evolves rapidly to constantly escape from natural immunity. Most humoral immune responses to influenza virus target the hemagglutinin (HA) glycoprotein, which is the major antigen on the surface of the virus. The HA is composed of a globular head domain for receptor binding and a stem domain for membrane fusion. The major antigenic sites of HA are located in the globular head subdomain, which is highly tolerant of amino acid substitutions and continual addition of glycosylation sites. Nonetheless, the evolution of the receptor-binding site and the stem region on HA is severely constrained by their functional roles in engaging the host receptor and in mediating membrane fusion, respectively...
June 23, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28645240/engineered-expression-of-broadly-neutralizing-antibodies-against-human-immunodeficiency-virus
#18
Maham Ahmad, Osama M Ahmed, Bruce Schnepp, Philip R Johnson
This review discusses recent progress made in developing a vaccine and novel treatments for human immunodeficiency virus (HIV). It highlights the shortcomings of the RV144 vaccination trial [ALVAC-HIV (vCP1521) and AIDSVAX B/E] and the current standard of care and proposes that engineered expression of broadly neutralizing antibodies (bNAbs) against HIV-1 could overcome these shortcomings. Current developments in three major lines of research on HIV prevention and treatment using bNAbs are reviewed: firstly, the use of sequential immunogens to activate B cells to express bNAbs; secondly, the delivery of novel and extremely potent bNAbs through passive administration; and finally, the use of gene transfer using adeno-associated viral vectors to deliver bNAbs...
June 23, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28637924/vp4-and-vp7-specific-antibodies-mediate-heterotypic-immunity-to-rotavirus-in-humans
#19
Nitya Nair, Ningguo Feng, Lisa K Blum, Mrinmoy Sanyal, Siyuan Ding, Baoming Jiang, Adrish Sen, John M Morton, Xiao-Song He, William H Robinson, Harry B Greenberg
Human rotaviruses (RVs) are the leading cause of severe diarrhea in young children worldwide. The molecular mechanisms underlying the rapid induction of heterotypic protective immunity to RV, which provides the basis for the efficacy of licensed monovalent RV vaccines, have remained unknown for more than 30 years. We used RV-specific single cell-sorted intestinal B cells from human adults, barcode-based deep sequencing of antibody repertoires, monoclonal antibody expression, and serologic and functional characterization to demonstrate that infection-induced heterotypic immunoglobulins (Igs) primarily directed to VP5*, the stalk region of the RV attachment protein, VP4, are able to mediate heterotypic protective immunity...
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28632942/the-glycans-mediated-mechanism-on-the-interactions-of-gp120-with-cd4-and-antibody-insights-from-molecular-dynamics-simulation
#20
Yan Zhang, Yuzhen Niu, Jia Qi Tian, Xuewei Liu, Xiaojun Yao, Huanxiang Liu
N-linked glycans such as 234 and 276 gp120 glycans are vital components of HIV evasion from humoral immunity and important for HIV-1 neutralization of many broadly neutralizing antibodies (bNAbs). However, it is unknown the action mechanism of two glycans. To investigate the roles of the glycans on the interactions of gp120 with CD4 and antibody, molecular dynamics simulations based on gp120-CD4-8ANC195 complex with 234 and 276 gp120 glycans, 234 gp120 glycan, 276 gp120 glycan and without glycan were performed...
June 20, 2017: Chemical Biology & Drug Design
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