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https://www.readbyqxmd.com/read/28938115/a-human-bi-specific-antibody-against-zika-virus-with-high-therapeutic-potential
#1
Jiaqi Wang, Marco Bardelli, Diego A Espinosa, Mattia Pedotti, Thiam-Seng Ng, Siro Bianchi, Luca Simonelli, Elisa X Y Lim, Mathilde Foglierini, Fabrizia Zatta, Stefano Jaconi, Martina Beltramello, Elisabetta Cameroni, Guntur Fibriansah, Jian Shi, Taylor Barca, Isabel Pagani, Alicia Rubio, Vania Broccoli, Elisa Vicenzi, Victoria Graham, Steven Pullan, Stuart Dowall, Roger Hewson, Simon Jurt, Oliver Zerbe, Karin Stettler, Antonio Lanzavecchia, Federica Sallusto, Andrea Cavalli, Eva Harris, Shee-Mei Lok, Luca Varani, Davide Corti
Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28938099/plasmid-dna-launches-live-attenuated-japanese-encephalitis-virus-and-elicits-virus-neutralizing-antibodies-in-balb-c-mice
#2
Brian Nickols, Irina Tretyakova, Alexander Tibbens, Elena Klyushnenkova, Peter Pushko
We describe novel plasmid DNA that encodes the full-length Japanese encephalitis virus (JEV) genomic cDNA and launches live-attenuated JEV vaccine in vitro and in vivo. The synthetic cDNA based on the sequence of JEV SA14-14-2 live-attenuated virus was placed under transcriptional control of the cytomegalovirus major immediate-early promoter. The stability and yields of the plasmid in E. coli were optimized by inserting three synthetic introns that disrupted JEV cDNA in the structural and nonstructural genes...
September 19, 2017: Virology
https://www.readbyqxmd.com/read/28938005/recombinant-vaccines-of-a-cd4-t-cell-epitope-promote-efficient-control-of-paracoccidioides-brasiliensis-burden-by-restraining-primary-organ-infection
#3
Rodrigo Assunção Holanda, Julián Esteban Muñoz, Lucas Santos Dias, Leandro Buffoni Roque Silva, Julliana Ribeiro Alves Santos, Sthefany Pagliari, Érica Leandro Marciano Vieira, Tatiane Alves Paixão, Carlos Pelleschi Taborda, Daniel Assis Santos, Oscar Bruña-Romero
Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay...
September 22, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28936773/intranasal-delivery-of-duox2-dna-using-cationic-polymer-can-prevent-acute-influenza-a-viral-infection-in-vivo-lung
#4
Bong Jik Kim, Sung Woo Cho, Yung Jin Jeon, Sujin An, Ara Jo, Jae Hyun Lim, Dong-Young Kim, Tae-Bin Won, Doo Hee Han, Chae-Seo Rhee, Hyun Jik Kim
We studied the contribution of Duox2 in mucosal host defense against influenza A virus (IAV) infection in in vivo lung. We found that Duox2 was required for the induction of type I and III interferon (IFN)s and transient Duox2 overexpression using cationic polymer polyethyleneimine (PEI) leads to suppression of IAV infection in in vivo lung. Twenty mice (C57BL/6J) were anesthetized and challenged by intranasal administration of 213 pfu/30 μl of IAV (WS/33/H1N1), and IAV-infected mice were euthanized at 1, 3, 5, 7, 10, 14 days post infection (dpi)...
September 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28936557/adjuvant-activity-of-saponins-from-kazakhstani-plants-on-the-immune-responses-to-subunit-influenza-vaccine
#5
A S Turmagambetova, P G Alexyuk, A P Bogoyavlenskiy, I A Zaitseva, E S Omirtaeva, M S Alexyuk, N S Sokolova, V E Berezin
In recent years, there have been a number of reports on the successful use of immunostimulatory complexes with saponins and viral glycoproteins as veterinary vaccines and in clinical trials for human medicine. The saponins Algiox, Sapanox and Pangisan were isolated and purified by HPLC from Allochrusa gypsophiloides, Saponaria officinalis and Gypsophila paniculata plants in Kazakhstan and they proved to have low toxicity in experiments with mice, chickens and chicken embryos. Algiox, Sapanox and Pangisan can be used to create immunostimulatory complexes (ISCOMs) similar to saponin-Quil-A-containing ISCOMs both in structure and in immunostimulatory efficiency...
September 21, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28936484/cetylpyridinium-chloride-cpc-exhibits-potent-rapid-activity-against-influenza-viruses-in-vitro-and-in-vivo
#6
Daniel L Popkin, Sarah Zilka, Matthew Dimaano, Hisashi Fujioka, Cristina Rackley, Robert Salata, Alexis Griffith, Pranab K Mukherjee, Mahmoud A Ghannoum, Frank Esper
BACKGROUND: There is a continued need for strategies to prevent influenza. While cetylpyridinium chloride (CPC), a broad-spectrum antimicrobial agent, has an extensive antimicrobial spectrum, its ability to affect respiratory viruses has not been studied in detail. OBJECTIVES: Here, we evaluate the ability of CPC to disrupt influenza viruses in vitro and in vivo. METHODS: The virucidal activity of CPC was evaluated against susceptible and oseltamivir-resistant strains of influenza viruses...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28936471/analysis-of-hepatitis-c-virus-particle-heterogeneity-in-immunodeficient-human-liver-chimeric-fah-mice
#7
Ursula Andreo, Ype P de Jong, Margaret A Scull, Jing W Xiao, Koen Vercauteren, Corrine Quirk, Michiel C Mommersteeg, Sonia Bergaya, Arjun Menon, Edward A Fisher, Charles M Rice
BACKGROUND & AIMS: Hepatitis C virus (HCV) is a leading cause of chronic liver diseases and the most common indication for liver transplantation in the United States. HCV particles in the blood of infected patients are characterized by heterogeneous buoyant densities, likely owing to HCV association with lipoproteins. However, clinical isolates are not infectious in vitro and the relative infectivity of the particles with respect to their buoyant density therefore cannot be determined, pointing to the need for better in vivo model systems...
November 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28935758/scavenger-receptor-cd36-directs-nonclassical-monocyte-patrolling-along-the-endothelium-during-early-atherogenesis
#8
Paola M Marcovecchio, Graham D Thomas, Zbigniew Mikulski, Erik Ehinger, Karin A L Mueller, Amy Blatchley, Runpei Wu, Yury I Miller, Anh Tram Nguyen, Angela M Taylor, Coleen A McNamara, Klaus Ley, Catherine C Hedrick
OBJECTIVE: Nonclassical monocytes (NCM) function to maintain vascular homeostasis by crawling or patrolling along the vessel wall. This subset of monocytes responds to viruses, tumor cells, and other pathogens to aid in protection of the host. In this study, we wished to determine how early atherogenesis impacts NCM patrolling in the vasculature. APPROACH AND RESULTS: To study the role of NCM in early atherogenesis, we quantified the patrolling behaviors of NCM in ApoE(-/-) (apolipoprotein E) and C57BL/6J mice fed a Western diet...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28935594/self-replicating-rna-vaccine-functionality-modulated-by-fine-tuning-of-polyplex-delivery-vehicle-structure
#9
Thomas Démoulins, Thomas Ebensen, Kai Schulze, Pavlos C Englezou, Panagiota Milona, Maria Pelliccia, Carlos A Guzmán, Nicolas Ruggli, Kenneth C McCullough
The major limitations with large and complex self-amplifying RNA vaccines (RepRNA) are RNase-sensitivity and inefficient translation in dendritic cells (DCs). Condensing RepRNA with polyethylenimine (PEI) gave positive in vitro readouts, but was largely inferior to virus-like replicon particles (VRP) or direct electroporation. In the present study, we improved such polyplex formulation and determined that fine-tuning of the polyplex structure is essential for ensuring efficacious translation. Thereby, three parameters dominate: (i) PEI molecular weight (MW); (ii) RepRNA:PEI (weight:weight) ratio; and (iii) inclusion of cell penetrating peptides (CPPs)...
September 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28935568/genetically-engineered-oncolytic-newcastle-disease-virus-mediates-cytolysis-of-prostate-cancer-stem-like-cells
#10
Raghunath Shobana, Raghavendra Sumanth Pudupakam, Adria Allen, Moanaro Biswas, Nammalwar Sriranganathan
Oncolytic virotherapy is a promising novel approach that overcomes the limitations posed by radiation and chemotherapy. In this study, the oncolytic efficacy of a recombinant Newcastle disease virus (rNDV) BC-KLQL-GFP, against prostate cancer stem-like/tumor initiating cells was evaluated. Xenograft derived prostaspheres (XPS) induced tumor more efficiently than monolayer cell derived prostaspheres (MCPS) in nude mice. Primary and secondary XPS show enhanced self-renewal and clonogenic potential compared to MCPS...
September 18, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28935111/evaluation-of-virus-like-particle-based-tumor-associated-carbohydrate-immunogen-in-a-mouse-tumor-model
#11
Suttipun Sungsuwan, Xuanjun Wu, Xuefei Huang
Tumor-associated carbohydrate antigens (TACAs) are attractive targets for anticancer vaccine development. Due to the low immunogenicity of TACAs, a powerful carrier system is needed to boost immune responses. Virus-like particles (VLPs) are an exciting platform for delivering TACAs to the immune system. The high symmetry of VLPs enables the display of TACAs in an organized manner, which in turn can potently activate antibody secreting B cells, eliciting high titers of antiglycan IgG antibodies. In this chapter, the protocol for conjugating a prototypical TACA, the Tn antigen to a VLP, bacteriophage Qβ, is presented...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28934904/clonal-deletion-of-t-cell-repertoires-with-specific-t-cell-receptor-v%C3%AE-chains-by-two-endogenous-superantigens-in-nc-nga-mice
#12
Kozo Ohkusu-Tsukada, Teruyo Tsukada, Kimimasa Takahashi
Superantigens (SAgs) are powerful T-cell stimulatory proteins. Because an atopic dermatitis (AD) model NC/Nga mice had two endogenous SAgs, namely minor lymphocyte-stimulating locus-1(a) (Mls-1(a)) and mouse mammary tumor virus (MMTV)(SHN), SAg-responsive T-cells bearing Vβ5.1, Vβ6, Vβ8.1, Vβ8.2, Vβ8.3, Vβ9, and Vβ11 should be endogenously deleted. Here, we discuss that the endogenous SAgs-expression may be involved in AD-sensitivity in NC/Nga mice.
September 22, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28934479/targeted-reconstruction-of-t-cell-receptor-sequence-from-single-cell-rna-seq-links-cdr3-length-to-t-cell-differentiation-state
#13
Shaked Afik, Kathleen B Yates, Kevin Bi, Samuel Darko, Jernej Godec, Ulrike Gerdemann, Leo Swadling, Daniel C Douek, Paul Klenerman, Eleanor J Barnes, Arlene H Sharpe, W Nicholas Haining, Nir Yosef
The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934454/assessment-of-molecular-antigenic-and-pathological-features-of-canine-influenza-a-h3n2-viruses-that-emerged-in-the-united-states
#14
Joanna A Pulit-Penaloza, Natosha Simpson, Hua Yang, Hannah M Creager, Joyce Jones, Paul Carney, Jessica A Belser, Genyan Yang, Jessie Chang, Hui Zeng, Sharmi Thor, Yunho Jang, Mary Lea Killian, Melinda Jenkins-Moore, Alicia Janas-Martindale, Edward Dubovi, David E Wentworth, James Stevens, Terrence M Tumpey, C Todd Davis, Taronna R Maines
Background: A single subtype of canine influenza virus (CIV), A(H3N8), was circulating in the United States until a new subtype, A(H3N2), was detected in Illinois in spring 2015. Since then, this CIV has caused thousands of infections in dogs in multiple states. Methods: In this study, genetic and antigenic properties of the new CIV were evaluated. In addition, structural and glycan array binding features of the recombinant hemagglutinin were determined. Replication kinetics in human airway cells and pathogenesis and transmissibility in animal models were also assessed...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934453/an-adjuvanted-a-h5n1-subvirion-vaccine-elicits-virus-specific-antibody-response-and-improves-protection-against-lethal-influenza-viral-challenge-in-mouse-model-of-protein-energy-malnutrition
#15
Enitra N Jones, Samuel Amoah, Weiping Cao, Suryaprakash Sambhara, Shivaprakash Gangappa
Background: Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including influenza infection, but no studies have addressed the potential influences of PEM on the immunogenicity and protective efficacy of avian influenza A(H5N1) vaccine. Methods: We investigated the role of PEM on vaccine-mediated protection after a lethal challenge with recombinant A(H5N1) virus using isocaloric diets providing either adequate protein (AP; 18% protein) or very low protein (VLP; 2% protein) in an established murine model of influenza vaccination...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934386/expression-of-the-neuropathy-associated-mtmr2-gene-rescues-mtm1-associated-myopathy
#16
Matthieu A Raess, Belinda S Cowling, Dimitri L Bertazzi, Christine Kretz, Bruno Rinaldi, Jean-Marie Xuereb, Pascal Kessler, Norma B Romero, Bernard Payrastre, Sylvie Friant, Jocelyn Laporte
Myotubularins (MTMs) are active or dead phosphoinositides phosphatases defining a large protein family conserved through evolution and implicated in different neuromuscular diseases. Loss-of-function mutations in MTM1 cause the severe congenital myopathy called myotubular myopathy (or X-linked centronuclear myopathy) while mutations in the MTM1-related protein MTMR2 cause a recessive Charcot-Marie-Tooth peripheral neuropathy. Here we aimed to determine the functional specificity and redundancy of MTM1 and MTMR2, and to assess their abilities to compensate for a potential therapeutic strategy...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934369/in-vivo-activation-of-latent-hiv-with-a-synthetic-bryostatin-analog-effects-both-latent-cell-kick-and-kill-in-strategy-for-virus-eradication
#17
Matthew D Marsden, Brian A Loy, Xiaomeng Wu, Christina M Ramirez, Adam J Schrier, Danielle Murray, Akira Shimizu, Steven M Ryckbosch, Katherine E Near, Tae-Wook Chun, Paul A Wender, Jerome A Zack
The ability of HIV to establish a long-lived latent infection within resting CD4+ T cells leads to persistence and episodic resupply of the virus in patients treated with antiretroviral therapy (ART), thereby preventing eradication of the disease. Protein kinase C (PKC) modulators such as bryostatin 1 can activate these latently infected cells, potentially leading to their elimination by virus-mediated cytopathic effects, the host's immune response and/or therapeutic strategies targeting cells actively expressing virus...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934360/pkacs-attenuate-innate-antiviral-response-by-phosphorylating-visa-and-priming-it-for-march5-mediated-degradation
#18
Bing-Ru Yan, Lu Zhou, Ming-Ming Hu, Mi Li, Heng Lin, Yan Yang, Yan-Yi Wang, Hong-Bing Shu
Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits α and β as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes...
September 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934110/a-recombinant-measles-vaccine-with-enhanced-resistance-to-passive-immunity
#19
Emily Julik, Jorge Reyes-Del Valle
Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity...
September 21, 2017: Viruses
https://www.readbyqxmd.com/read/28933668/nasal-aluminum-oxy-hydroxide-enables-adsorbed-antigens-to-induce-specific-systemic-and-mucosal-immune-responses
#20
Haiyue Xu, Tinashe B Ruwona, Sachin G Thakkar, Yanping Chen, Mingtao Zeng, Zhengrong Cui
Some insoluble aluminum salts are commonly used in injectable vaccines as adjuvants to accelerate, prolong, or enhance the antigen-specific immune responses. Data from previous studies testing the nasal mucosal vaccine adjuvant activity of aluminum salts are conflicting. The present study is designed to further assess the feasibility of repurposing aluminum salts in injectable vaccines as nasal mucosal vaccine adjuvants. Using Alhydrogel®, the international scientific standard of aluminum (oxy)hydroxide gels, and ovalbumin or 3 × M2e-HA2, a synthetic influenza virus fusion protein, as antigens, we showed in a mouse model that when dosed intranasally Alhydrogel® enables antigens adsorbed on it to induce stronger antigen-specific immune responses in both serum samples (e...
September 21, 2017: Human Vaccines & Immunotherapeutics
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