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Broad neutralizing antibody

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https://www.readbyqxmd.com/read/28732199/catch-shiny-droplets-in-suspension-finding-the-needle-in-a-haystack
#1
Nina V Hein-Fuchs, Renate König
In a recent issue of Cell Chemical Biology, Chaipan et al. (2017) described a high-throughput screening methodology to identify epitopes on HIV-1 particles recognized by broadly neutralizing antibodies. The approach utilizes a droplet-based microfluidics platform combining robust phenotypic single-virus sorting with next-generation sequencing of viral quasispecies.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28728075/immunological-tolerance-as-a-barrier-to-protective-hiv-humoral-immunity
#2
REVIEW
Kristin Ms Schroeder, Amanda Agazio, Raul M Torres
HIV-1 infection typically eludes antibody control by our immune system and is not yet prevented by a vaccine. While many viral features contribute to this immune evasion, broadly neutralizing antibodies (bnAbs) against HIV-1 are often autoreactive and it has been suggested that immunological tolerance may restrict a neutralizing antibody response. Indeed, recent Ig knockin mouse studies have shown that bnAb-expressing B cells are largely censored by central tolerance in the bone marrow. However, the contribution of peripheral tolerance in limiting the HIV antibody response by anergic and potentially protective B cells is poorly understood...
July 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28726771/rapid-elicitation-of-broadly-neutralizing-antibodies-to-hiv-by-immunization-in-cows
#3
Devin Sok, Khoa M Le, Melissa Vadnais, Karen Saye-Francisco, Joseph G Jardine, Jonathan Torres, Zachary T Berndsen, Leopold Kong, Robyn Stanfield, Jennifer Ruiz, Alejandra Ramos, Chi-Hui Liang, Patricia L Chen, Michael F Criscitiello, Waithaka Mwangi, Ian A Wilson, Andrew B Ward, Vaughn V Smider, Dennis R Burton
No immunogen to date has reliably elicited broadly neutralizing antibodies to HIV in humans or animal models. Advances in the design of immunogens (BG505 SOSIP) that antigenically mimic the HIV envelope glycoprotein (Env)(1) have improved the elicitation of potent isolate-specific antibody responses in rabbits(2) and macaques(3), but so far failed to induce broadly neutralizing antibodies. One possible contributor to this failure is that the relevant antibody repertoires are poorly suited to target somewhat occluded conserved epitope regions on Env relative to exposed variable epitopes...
July 20, 2017: Nature
https://www.readbyqxmd.com/read/28724768/synthetic-tlr4-and-tlr7-ligands-work-additively-via-myd88-to-induce-protective-antiviral-immunity-in-mice
#4
Peter H Goff, Tomoko Hayashi, Wenqian He, Shiyin Yao, Howard B Cottam, Gene S Tan, Brian Crain, Florian Krammer, Karen Messer, Minya Pu, Dennis A Carson, Peter Palese, Maripat Corr
We have previously demonstrated that the combination of synthetic small molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity protective against influenza viruses in homologous, heterologous and heterosubtypic murine challenge models. Combining TLR4 and TLR7 ligands balances Th1/Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function in vivo via their known receptors with negligible off-target effects to induce protective immunity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724616/marburg-virus-survivor-immune-responses-are-th1-skewed-with-limited-neutralizing-antibody-responses
#5
Spencer W Stonier, Andrew S Herbert, Ana I Kuehne, Ariel Sobarzo, Polina Habibulin, Chen V Abramovitch Dahan, Rebekah M James, Moses Egesa, Stephen Cose, Julius Julian Lutwama, Leslie Lobel, John M Dye
Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized...
July 19, 2017: Journal of Experimental Medicine
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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