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Neutralizing antibodies

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https://www.readbyqxmd.com/read/28239654/flow-virometric-sorting-and-analysis-of-hiv-quasispecies-from-plasma
#1
Thomas Musich, Jennifer C Jones, Brandon F Keele, Lisa M Miller Jenkins, Thorsten Demberg, Thomas S Uldrick, Robert Yarchoan, Marjorie Robert-Guroff
Flow cytometry is utilized extensively for cellular analysis, but technical limitations have prevented its routine application for characterizing virus. The recent introduction of nanoscale fluorescence-activated cytometric cell sorting now allows analysis of individual virions. Here, we demonstrate staining and sorting of infectious HIV. Fluorescent antibodies specific for cellular molecules found on budding virions were used to label CCR5-tropic Bal HIV and CXCR4-tropic NL4.3 HIV Env-expressing pseudovirions made in THP-1 cells (monocyte/macrophage) and H9 cells (T cells), respectively...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28238904/proteomic-toxicological-and-immunogenic-characterization-of-mexican-west-coast-rattlesnake-crotalus-basiliscus-venom-and-its-immunological-relatedness-with-the-venom-of-central-american-rattlesnake-crotalus-simus
#2
Álvaro Segura, María Herrera, Francisco Reta Mares, Claudia Jaime, Andrés Sánchez, Mariángela Vargas, Mauren Villalta, Aarón Gómez, José María Gutiérrez, Guillermo León
: The venom of the Mexican west-coast rattlesnake (Crotalus basiliscus) was characterized for its protein composition, toxicological profile and immunogenic properties. This venom is composed of 68% Zn(2+)-dependent metalloproteinases (SVMPs), 14% phospholipases A2 (PLA2s), 11% serine proteinases, 4% SVMPs-inhibitor tripeptides (SVMP-ITs), 2% bradykinin-potentiating peptides (BPPs), 0.6% cysteine-rich secretory proteins (CRISPs), and 0.2% l-amino acid oxidases (LAAOs). SVMPs present in the venom are responsible for azocasein hydrolysis and hemorrhagic activity, but their contribution to the lethal activity of the venom in mice is masked by the neurotoxic activity of PLA2s, which in addition are also responsible for myotoxic activity...
February 23, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28237764/evaluation-of-a-novel-multi-immunogen-vaccine-strategy-for-targeting-4e10-10e8-neutralizing-epitopes-on-hiv-1-gp41-membrane-proximal-external-region
#3
Saikat Banerjee, Heliang Shi, Marisa Banasik, Hojin Moon, William Lees, Yali Qin, Andrew Harley, Adrian Shepherd, Michael W Cho
The membrane proximal external region (MPER) of HIV-1 gp41 is targeted by broadly neutralizing antibodies (bnAbs) 4E10 and 10E8. In this proof-of-concept study, we evaluated a novel multi-immunogen vaccine strategy referred to as Incremental, Phased Antigenic Stimulation for Rapid Antibody Maturation (IPAS-RAM) to induce 4E10/10E8-like bnAbs. Rabbits were immunized sequentially, but in a phased manner, with three immunogens that are progressively more native (gp41-28×3, gp41-54CT, and rVV-gp160DH12). Although nAbs were not induced, epitope-mapping analyses indicated that IPAS-RAM vaccination was better able to target antibodies towards the 4E10/10E8 epitopes than homologous prime-boost immunization using gp41-28×3 alone...
February 23, 2017: Virology
https://www.readbyqxmd.com/read/28237499/mers-cov-spike-nanoparticles-protect-mice-from-mers-cov-infection
#4
Christopher M Coleman, Thiagarajan Venkataraman, Ye V Liu, Gregory M Glenn, Gale E Smith, David C Flyer, Matthew B Frieman
The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice...
February 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28236535/impaired-expression-and-function-of-tlr8-in-chronic-hbv-infection-and-its-association-with-treatment-responses-during-peg-ifn-%C3%AE-2a-antiviral-therapy
#5
Guangying Deng, Jun Ge, Chao Liu, Jinke Pang, Zuxiong Huang, Jie Peng, Jian Sun, Jinlin Hou, Xiaoyong Zhang
BACKGROUND AND AIM: Toll-like receptor 8 (TLR8) plays an important role in controlling chronic viral infections. However, the role of TLR8 in chronic hepatitis B virus (HBV) infection is poorly understood. In this study, we aimed to investigate the expression and function of TLR8 in peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B (CHB) patients and its alteration during peg-IFN-α-2a therapy. METHODS: We evaluated TLR8 expression and antiviral function in vitro by real-time RT-PCR and flow cytometry analysis using fresh PBMCs obtained from CHB patients compared to healthy controls...
February 21, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28231271/applying-antibody-sensitive-hypervariable-region-1-deleted-hepatitis-c-virus-to-the-study-of-escape-pathways-of-neutralizing-human-monoclonal-antibody-ar5a
#6
Rodrigo Velázquez-Moctezuma, Mansun Law, Jens Bukh, Jannick Prentoe
Hepatitis C virus (HCV) is a major cause of end-stage liver diseases. With 3-4 million new HCV infections yearly, a vaccine is urgently needed. A better understanding of virus escape from neutralizing antibodies and their corresponding epitopes are important for this effort. However, for viral isolates with high antibody resistance, or antibodies with moderate potency, it remains challenging to induce escape mutations in vitro. Here, as proof-of-concept, we used antibody-sensitive HVR1-deleted (ΔHVR1) viruses to generate escape mutants for a human monoclonal antibody, AR5A, targeting a rare cross-genotype conserved epitope...
February 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28230658/engineering-antibody-like-inhibitors-to-prevent-and-treat-hiv-1-infection
#7
Matthew R Gardner, Michael Farzan
PURPOSE OF REVIEW: Here we discuss recently developed HIV-1 entry inhibitors that can target multiple epitopes on the HIV-1 envelope glycoprotein (Env), with an emphasis on eCD4-Ig. Some of these inhibitors are more potent and broader than any single antibody characterized to date. We also discuss the use of recombinant adeno-associated virus (rAAV) vectors as a platform for long-term expression of these inhibitors. RECENT FINDINGS: Much of the exterior of HIV-1 Env can be targeted by broadly neutralizing antibodies (bNAbs)...
February 21, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28230657/stabilized-hiv-1-envelope-glycoprotein-trimers-for-vaccine-use
#8
Max Medina-Ramírez, Rogier W Sanders, Quentin J Sattentau
PURPOSE OF REVIEW: To provide an update on the latest developments in the field of HIV-1 antibody-based soluble envelope glycoprotein (Env) trimer design for vaccine use. RECENT FINDINGS: The development of soluble native-like HIV-1 Env trimer immunogens has moved the field of antibody-based vaccine design forward dramatically over the past few years with refinement of various stabilizing approaches. However, despite this progress, significant challenges remain...
February 21, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28230656/role-of-nonneutralizing-antibodies-in-vaccines-and-or-hiv-infected-individuals
#9
Luzia Mayr, Bin Su, Christiane Moog
PURPOSE OF REVIEW: Increased body of evidence gathered over time indicate that antibodies are capable of many inhibitory mechanisms, virus neutralization being just one of them. Nonneutralizing antibodyactivities interfering with HIV replication can also lead to a decrease in viral load and even in-vivo protection. RECENT FINDINGS: It was previously believed that neutralizing antibodies can achieve sterilizing protection mainly by using their neutralization capacities against the infecting virus directly at the portal of virus entry...
February 21, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28230655/lessons-learned-from-human-hiv-vaccine-trials
#10
Justin Pollara, David Easterhoff, Genevieve G Fouda
PURPOSE OF REVIEW: The ability to induce broadly neutralizing antibody (bNAb) responses is likely essential for development of a globally effective HIV vaccine. Unfortunately, human vaccine trials conducted to date have failed to elicit broad plasma neutralization of primary virus isolates. Despite this limitation, in-depth analysis of the vaccine-induced memory B-cell repertoire can provide valuable insights into the presence and function of subdominant B-cell responses, and identify initiation of antibody lineages that may be on a path towards development of neutralization breadth...
February 21, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28230186/glycan-independent-binding-and-internalization-of-human-igm-to-fcmr-its-cognate-cellular-receptor
#11
Katy A Lloyd, Jiabin Wang, Britta C Urban, Daniel M Czajkowsky, Richard J Pleass
IgM is the first antibody to be produced in immune responses and plays an important role in the neutralization of bacteria and viruses. Human IgM is heavily glycosylated, featuring five N-linked glycan sites on the μ chain and one on the J-chain. Glycosylation of IgG is known to modulate the effector functions of Fcγ receptors. In contrast, little is known about the effect of glycosylation on IgM binding to the human Fcμ receptor (hFCMR). In this study, we identify the Cμ4 domain of IgM as the target of hFCMR, and show that binding and internalization of IgM by hFCMR is glycan-independent...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230168/phylogenetic-characterizations-of-highly-mutated-ev-b106-recombinants-showing-extensive-genetic-exchanges-with-other-ev-b-in-xinjiang-china
#12
Yang Song, Yong Zhang, Qin Fan, Hui Cui, Dongmei Yan, Shuangli Zhu, Haishu Tang, Qiang Sun, Dongyan Wang, Wenbo Xu
Human enterovirus B106 (EV-B106) is a new member of the enterovirus B species. To date, only three nucleotide sequences of EV-B106 have been published, and only one full-length genome sequence (the Yunnan strain 148/YN/CHN/12) is available in the GenBank database. In this study, we conducted phylogenetic characterisation of four EV-B106 strains isolated in Xinjiang, China. Pairwise comparisons of the nucleotide sequences and the deduced amino acid sequences revealed that the four Xinjiang EV-B106 strains had only 80...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228587/prophylactic-herpes-simplex-virus-2-hsv-2-vaccines-adjuvanted-with-stable-emulsion-and-toll-like-receptor-9-agonist-induce-a-robust-hsv-2-specific-cell-mediated-immune-response-protect-against-symptomatic-disease-and-reduce-the-latent-viral-reservoir
#13
Michael T Hensel, Jason D Marshall, Michael R Dorwart, Darren S Heeke, Eileen Rao, Padmaja Tummala, Li Yu, Gary H Cohen, Roselyn J Eisenberg, Derek D Sloan
Several prophylactic vaccines targeting HSV-2 have failed in the clinic to demonstrate a sustained depression in viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies, their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the neutralizing antibody (nAb) targets gD and gB, the novel T cell antigen and tegument protein UL40, and we compared this to a whole-inactivated virus vaccine (FI-HSV-2)...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228578/proof-of-concept-randomized-trial-of-the-monoclonal-antibody-gsk249320-versus-placebo-in-stroke-patients
#14
Steven C Cramer, Lori A Enney, Colleen K Russell, Monica Simeoni, Thomas R Thompson
BACKGROUND AND PURPOSE: One class of poststroke restorative therapy focuses on promoting axon outgrowth by blocking myelin-based inhibitory proteins such as myelin-associated glycoprotein. The purpose of the current study was to extend preclinical and clinical findings of GSK249320, a humanized monoclonal antibody to myelin-associated glycoprotein with disabled Fc region, to explore effects on motor outcomes post-stroke. METHODS: In this phase IIb double-blind, randomized, placebo-controlled study, patients at 30 centers with ischemic stroke 24 to 72 hours prior and gait deficits were randomized to 2 IV infusions of GSK249320 or placebo...
February 22, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28228559/targeting-influenza-virus-hemagglutinin-to-xcr1-dendritic-cells-in-the-absence-of-receptor-mediated-endocytosis-enhances-protective-antibody-responses
#15
Arnar Gudjonsson, Anna Lysén, Sreekumar Balan, Vibeke Sundvold-Gjerstad, Catharina Arnold-Schrauf, Lisa Richter, Espen S Bækkevold, Marc Dalod, Bjarne Bogen, Even Fossum
Targeting Ags to conventional dendritic cells can enhance Ag-specific immune responses. Although most studies have focused on the induction of T cell responses, the mechanisms by which targeting improves Ab responses are poorly understood. In this study we present data on the use of human XCL1 (hXCL1) and hXCL2 fusion vaccines in a murine model. We show that the human chemokines bound type 1 conventional dendritic cells (cDC1), and that immunization with influenza virus hemagglutinin fused to hXCL1 or hXCL2 induced full protection against influenza challenge...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28228321/immunization-of-bighorn-sheep-against-mannheimia-haemolytica-with-a-bovine-herpesvirus-1-vectored-vaccine
#16
Sai A Batra, Sudarvili Shanthalingam, Gaetano Donofrio, Gary J Haldorson, Shafiqul Chowdhury, Stephen N White, Subramaniam Srikumaran
Mannheimia haemolytica is an important pathogen of pneumonia in bighorn sheep (BHS), consistently causing 100% mortality under experimental conditions. Leukotoxin is the critical virulence factor of M. haemolytica. In a 'proof of concept' study, a vaccine containing leukotoxin and surface antigens of M. haemolytica induced 100% protection in BHS, but required multiple booster doses. Vaccination of wildlife is difficult. BHS, however, can be vaccinated at the time of transplantation, but administration of booster doses is impossible...
February 19, 2017: Vaccine
https://www.readbyqxmd.com/read/28228179/serological-evidence-of-lyssavirus-infection-among-bats-in-nagaland-a-north-eastern-state-in-india
#17
R S Mani, D P Dovih, M A Ashwini, B Chattopadhyay, P K Harsha, K M Garg, S Sudarshan, R Puttaswamaiah, U Ramakrishnan, S N Madhusudana
Bats are known to be reservoirs of several medically important viruses including lyssaviruses. However, no systematic surveillance for bat rabies has been carried out in India, a canine rabies endemic country with a high burden of human rabies. Surveillance for rabies virus (RABV) infection in bats was therefore carried out in Nagaland, a north-eastern state in India at sites with intense human-bat interfaces during traditional bat harvests. Brain tissues and sera from bats were tested for evidence of infection due to RABV...
February 23, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28225819/lipid-interactions-and-angle-of-approach-to-the-hiv-1-viral-membrane-of-broadly-neutralizing-antibody-10e8-insights-for-vaccine-and-therapeutic-design
#18
Adriana Irimia, Andreia M Serra, Anita Sarkar, Ronald Jacak, Oleksandr Kalyuzhniy, Devin Sok, Karen L Saye-Francisco, Torben Schiffner, Ryan Tingle, Michael Kubitz, Yumiko Adachi, Robyn L Stanfield, Marc C Deller, Dennis R Burton, William R Schief, Ian A Wilson
Among broadly neutralizing antibodies to HIV, 10E8 exhibits greater neutralizing breadth than most. Consequently, this antibody is the focus of prophylactic/therapeutic development. The 10E8 epitope has been identified as the conserved membrane proximal external region (MPER) of gp41 subunit of the envelope (Env) viral glycoprotein and is a major vaccine target. However, the MPER is proximal to the viral membrane and may be laterally inserted into the membrane in the Env prefusion form. Nevertheless, 10E8 has not been reported to have significant lipid-binding reactivity...
February 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28225652/dna-vaccination-partially-protects-muskellunge-against-viral-hemorrhagic-septicemia-virus-vhsv-ivb
#19
Elena V Millard, Ashley M Bourke, Scott E LaPatra, Travis O Brenden, Scott D Fitzgerald, Mohamed Faisal
A DNA vaccine containing the glycoprotein (G) gene of the North American viral hemorrhagic septicemia virus (VHSV) genotype IVb was developed to evaluate the immune response of fish following vaccination and evaluate its efficacy in protecting a susceptible species, the Muskellunge Esox masquinongy, against VHSV-IVb challenge. Seven weeks (539 degree-days) following vaccination with 10 μg of either pVHSivb-G or a control plasmid, Muskellunge were challenged by immersion with 10(5) plaque-forming units (pfu)/mL of VHSV-IVb...
March 2017: Journal of Aquatic Animal Health
https://www.readbyqxmd.com/read/28225449/ifn-%C3%AE-augments-natural-killer-mediated-antibody-dependent-cellular-cytotoxicity-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-major-histocompatibility-complex-class-1-downregulation
#20
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct natural killer (NK) cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon major histocompatibility complex class 1 (MHC-1) downregulation capacity. Here, we investigated if antibody-dependent cellular cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α prestimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1-infected patients (ART-suppressed or elite controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1-infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
March 13, 2017: AIDS
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