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https://www.readbyqxmd.com/read/30098206/il-33-contributes-to-disease-severity-in-dengue-virus-infection-in-mice
#1
Rafael E Marques, Anne-Gaëlle Besnard, Isabelle Maillet, Caio T Fagundes, Danielle G Souza, Bernhard Ryffel, Mauro M Teixeira, Foo Y Liew, Rodrigo Guabiraba
The excessive inflammation often present in patients with severe dengue infection is considered both a hallmark of disease and a target for potential treatments. IL-33 is a pleiotropic cytokine with pro-inflammatory effects whose role in dengue has not been fully elucidated. Here we demonstrate that IL-33 plays a disease-exacerbating role during experimental dengue infection in immunocompetent mice. Mice infected with Dengue virus serotype 2 (DENV2) produced high levels of IL-33. DENV2-infected mice treated with recombinant IL-33 developed markedly more severe disease compared to untreated mice as assessed by mortality, granulocytosis, liver damage and pro-inflammatory cytokine production...
August 11, 2018: Immunology
https://www.readbyqxmd.com/read/30098095/stereospecific-%C3%AE-l-rhamnopyranosylations-using-organoboron-reagents-via-sni-type-mechanism
#2
Nobuya Nishi, Kazuhiro Sueoka, Kiyoko Iijima, Ryuichi Sawa, Daisuke Takahashi, Kazunobu Toshima
Stereospecific β-L-rhamnopyranosylations were conducted using a 1,2-anhydro-L-rhamnopyranose donor and mono-ol or diol acceptors in the presence of a glycosyl-acceptor-derived borinic or boronic ester. Reactions proceeded smoothly to provide the corresponding β-L-rhamnopyranosides (β-L-Rhap) with complete stereoselectivity in moderate to high yields without any further additives under mild conditions. Mechanistic studies of the borinic ester-mediated glycosylation using 13C kinetic isotope effect (KIE) measurements and DFT calculations were consistent with a concerted SNi mechanism with an exploded transition state...
August 11, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/30096340/inhibition-of-adenovirus-serotype-14-infection-by-octadecyloxyethyl-esters-of-s-3-hydroxy-2-phosphonomethoxy-propyl-nucleosides-in-vitro
#3
Yohichi Kumaki, John D Woolcott, Jason P Roth, Tyler Z Mclean, Donald F Smee, Dale L Barnard, Nadejda Valiaeva, James R Beadle, Karl Y Hostetler
The most common adenovirus serotypes 1, 3, 5 and 7 can cause respiratory infections, and serotypes 40 and 41 can cause gastrointestinal infections. Most adenovirus infections are mild or asymptomatic, but a re-emerged serotype, adenovirus 14, was reported to cause severe and fatal pneumonia in rare cases in people of all ages. Unfortunately, no antiviral compounds have yet been approved for the treatment of such adenovirus infections. Vaccines have been developed for only two serotypes, 4 and 7, to prevent acute respiratory diseases (ARD) in military personnel...
August 7, 2018: Antiviral Research
https://www.readbyqxmd.com/read/30096193/comparison-of-two-rapid-diagnostic-tests-during-a-large-dengue-virus-serotype-3-outbreak-in-the-solomon-islands-in-2013
#4
Li-Teh Liu, Tenneth Dalipanda, Rooney Jagilly, Ying-Hui Wang, Ping-Chang Lin, Ching-Yi Tsai, Wen-Ter Lai, Jih-Jin Tsai
Dengue virus (DENV) infection causes various clinical presentations, including asymptomatic infection, dengue with or without warning signs and severe dengue. An early and accurate diagnosis of DENV infection during the first few days of illness supports clinical management and significantly reduces dengue-associated mortality and morbidity. However, it is very difficult to confirm DENV infection in endemic regions without qualified dengue diagnostic laboratories. In this study, we evaluated the performance of two commercially available rapid diagnostic tests (RDTs) using serum samples collected in the Solomon Islands during the 2013 DENV-3 outbreak...
2018: PloS One
https://www.readbyqxmd.com/read/30095362/immunogenicity-of-a-candidate-ebola-hemorrhagic-fever-vaccine-in-mice-based-on-controlled-in-vitro-expression-of-ebolavirus-glycoprotein
#5
Deepak Kumar, Sulgey Gauthami, Madala Uma, Karthika Nagalekshmi, Pavuluri Panduranga Rao, Atanu Basu, Krishna M Ella, Nagendra R Hegde
Ebolavirus (EBOV) is the etiology of Ebola hemorrhagic fever (EHF). A major EHF outbreak in 2014-2015 in West Africa claimed >11,000 lives. A licensed vaccine is not available for EHF, although several vaccines have undergone clinical trials. We developed a human adenovirus (Ad) serotype 5-based candidate EHF vaccine based on controlled expression of the EBOV (Makona strain) glycoprotein (GP) as the immunogen. Two clones, AdGP72 and AdGP75, and a control Ad515 vector, were generated and tested for protein expression in vitro and immunogenicity in mice...
August 10, 2018: Viral Immunology
https://www.readbyqxmd.com/read/30093306/systemic-aav-micro-dystrophin-gene-therapy-for-duchenne-muscular-dystrophy
#6
REVIEW
Dongsheng Duan
Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by dystrophin gene mutation. Conceptually, replacing the mutated gene with a normal one would cure the disease. However, this task has encountered significant challenges due to the enormous size of the gene and the distribution of muscle throughout the body. The former creates a hurdle for viral vector packaging and the latter begs for whole-body therapy. To address these obstacles, investigators have invented the highly abbreviated micro-dystrophin gene and developed body-wide systemic gene transfer with adeno-associated virus (AAV)...
July 17, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/30092576/characterization-of-recombinant-adeno-associated-viral-transduction-and-safety-profiles-in-cardiomyocytes
#7
Jianzhong Ai, Yong He, Mingxia Zheng, Yi Wen, Huan Zhang, Fangyang Huang, Ye Zhu
BACKGROUND/AIMS: Cardiovascular diseases (CVD) are the leading causes for human mortality. However, the effective treatment for these diseases are still lacking. Currently, gene therapy could be a potential way for efficiently treating heart diseases. The aim of our study is to analyze the transduction efficacy and safety profile of recombinant adeno associated virus (AAV) serotype 9 for cardiomyocytes in vivo and in vitro. METHODS: We produced rAAV serotype 9 expressing enhanced green fluorescence protein (EGFP) driven by a cardiac troponin T (cTNT) promoter, and characterized its transduction efficiency in primary cultured cardiomyocytes in vitro, and in wild-type mouse heart tissue in vivo...
August 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30092029/blockade-of-dengue-virus-entry-into-myeloid-cells-by-endocytic-inhibitors-in-the-presence-or-absence-of-antibodies
#8
Ana C Carro, Luana E Piccini, Elsa B Damonte
BACKGROUND: Dengue is the most prevalent arthropod-borne viral human disease in tropical and subtropical regions, caused by four dengue virus (DENV) serotypes. In spite of the increasing global incidence, no specific antiviral therapy is available. Cells of the mononuclear phagocyte lineage are the main targets either for direct antibody (Ab)-independent or Ab-mediated human DENV infection, usually associated to the severe forms of disease. Since the virus entry may be a convenient therapeutic alternative, this study aimed to investigate the mode of DENV internalization into myeloid cells in the absence and presence of DENV Ab and evaluate the inhibitory activity of diverse biochemical inhibitors of endocytosis...
August 9, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/30090842/cerebrospinal-fluid-directed-raav9-rsatp7a-plus-subcutaneous-copper-histidinate-advance-survival-and-outcomes-in-a-menkes-disease-mouse-model
#9
Marie Reine Haddad, Eun-Young Choi, Patricia M Zerfas, Ling Yi, Diego Martinelli, Patricia Sullivan, David S Goldstein, Jose A Centeno, Lauren R Brinster, Martina Ralle, Stephen G Kaler
Menkes disease is a lethal neurodegenerative disorder of copper metabolism caused by mutations in an evolutionarily conserved copper transporter, ATP7A. Based on our prior clinical and animal studies, we seek to develop a therapeutic approach suitable for application in affected human subjects, using the mottled-brindled ( mo-br ) mouse model that closely mimics the Menkes disease biochemical and clinical phenotypes. Here, we evaluate the efficacy of low-, intermediate-, and high-dose recombinant adeno-associated virus serotype 9 (rAAV9)-ATP7A delivered to the cerebrospinal fluid (CSF), in combination with subcutaneous administration of clinical-grade copper histidinate (sc CuHis, IND #34,166)...
September 21, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/30089645/development-and-validation-of-13-plex-luminex-based-assay-for-measuring-human-serum-antibodies-to-streptococcus-pneumoniae-capsular-polysaccharides
#10
Danka Pavliakova, Peter C Giardina, Soraya Moghazeh, Shite Sebastian, Maya Koster, Viliam Pavliak, Andrew McKeen, Roger French, Kathrin U Jansen, Michael Pride
A Luminex-based direct immunoassay (dLIA) platform has been developed to replace the standardized pneumococcal enzyme-linked immunosorbent assay platform. The multiplex dLIA simultaneously measures the concentration of serum immunoglobulin G (IgG) antibodies specific for pneumococcal capsular polysaccharide (PnPS) serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. The assay uses poly-l-lysine (PLL)-conjugated PnPS, chemically coupled to spectrally distinct Luminex microspheres. Assay validation experiments were performed using residual human serum samples obtained from 13-valent pneumococcal conjugate vaccine (13vPnC) clinical studies...
August 8, 2018: MSphere
https://www.readbyqxmd.com/read/30089644/evaluation-of-a-validated-luminex-based-multiplex-immunoassay-for-measuring-immunoglobulin-g-antibodies-in-serum-to-pneumococcal-capsular-polysaccharides
#11
Charles Y Tan, Fred W Immermann, Shite Sebastian, Michael W Pride, Danka Pavliakova, Kelly A Belanger, Wendy Watson, Daniel A Scott, Mohinder Sidhu, Kathrin U Jansen, Peter C Giardina
This article describes the results of a study designed to bridge the World Health Organization (WHO) pneumococcal enzyme-linked immunosorbent assay (ELISA) platform to the validated Luminex-based 13-plex direct immunoassay (dLIA) platform developed by Pfizer, Inc. Both assay platforms quantify serotype-specific serum IgG antibodies (in micrograms per milliliter) against an international reference standard serum. The primary goal of this study was to determine if the dLIA is a suitable replacement for the ELISA to support clinical vaccine studies that include the evaluation of immune responses to serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F...
August 8, 2018: MSphere
https://www.readbyqxmd.com/read/30089105/characterization-of-strains-of-neisseria-meningitidis-causing-meningococcal-meningitis-in-mozambique-2014-implications-for-vaccination-against-meningococcal-meningitis
#12
Alcides Moniz Munguambe, António Eugénio Castro Cardoso de Almeida, Aquino Albino Nhantumbo, Charlotte Elizabeth Come, Tomás Francisco Zimba, José Paulo Langa, Ivano de Filippis, Eduardo Samo Gudo
INTRODUCTION: In sub Saharan Africa, the epidemiology, including the distribution of serogroups of strains of N. meningitidis is poorly investigated in countries outside "the meningitis belt". This study was conducted with the aim to determine the distribution of serogroups of strains of N. meningitidis causing meningococcal meningitis in children and adults in Mozambique. METHODS: A total of 106 PCR confirmed Neisseria meningitidis Cerebrospinal Fluid (CSF) samples or isolates were obtained from the biobank of acute bacterial meningitis (ABM) surveillance being implemented by the National Institute of Health, at three central hospitals in Mozambique, from January to December 2014...
2018: PloS One
https://www.readbyqxmd.com/read/30087049/how-cost-effective-is-switching-universal-vaccination-from-pcv10-to-pcv13-a-case-study-from-a-developing-country
#13
Carlos Castañeda-Orjuela, Fernando De la Hoz-Restrepo
BACKGROUND: Children immunization with pneumococcal conjugate vaccine (PCV) had profound public health effects across the globe. Colombian adopted PCV10 universal vaccination, but PCV incremental impact need to be revalued. The objective of this analysis was to estimate the cost-effectiveness of switch to PCV13 versus continue PCV10 in Colombian children. METHODS: A complete economic analysis was carried-out assessing potential epidemiological and economic impact of switching from PCV10 to PCV13...
August 4, 2018: Vaccine
https://www.readbyqxmd.com/read/30086792/characterization-of-peritoneal-cells-from-cats-with-experimentally-induced-feline-infectious-peritonitis-fip-using-rna-seq
#14
Rie Watanabe, Christina Eckstrand, Hongwei Liu, Niels C Pedersen
Laboratory cats were infected with a serotype I cat-passaged field strain of FIP virus (FIPV) and peritoneal cells harvested 2-3 weeks later at onset of lymphopenia, fever and serositis. Comparison peritoneal cells were collected from four healthy laboratory cats by peritoneal lavage and macrophages predominated in both populations. Differential mRNA expression analysis identified 5621 genes as deregulated in peritoneal cells from FIPV infected versus normal cats; 956 genes showed > 2.0 Log2 Fold Change (Log2 FC) and 1589 genes showed < -2...
August 7, 2018: Veterinary Research
https://www.readbyqxmd.com/read/30086789/human-adenovirus-load-in-respiratory-tract-secretions-are-predictors-for-disease-severity-in-children-with-human-adenovirus-pneumonia
#15
Leyun Xie, Bing Zhang, Jieying Zhou, Han Huang, Saizhen Zeng, Qin Liu, Zhiping Xie, Hanchun Gao, Zhaojun Duan, Lili Zhong
BACKGROUND: Pneumonia is a serious public health issue and is concerned around the world. This study is to investigate the association between viral load in children with human adenovirus (HAdV) pneumonia and disease severity. METHODS: A total of 1313 cases of children hospitalized in Hunan Provincial People's Hospital due to community acquired pneumonia (CAP) from April 2011 to May 2014 were enrolled in this study. Samples of nasopharyngeal aspirate were collected for the cohort...
August 7, 2018: Virology Journal
https://www.readbyqxmd.com/read/30086716/methods-to-discriminate-primary-from-secondary-dengue-during-acute-symptomatic-infection
#16
Thi Hanh Tien Nguyen, Hannah E Clapham, Khanh Lam Phung, Thanh Kieu Nguyen, The Trung DInh, Than Ha Quyen Nguyen, Van Ngoc Tran, Stephen Whitehead, Cameron Simmons, Marcel Wolbers, Bridget Wills
BACKGROUND: Dengue virus infection results in a broad spectrum of clinical outcomes, ranging from asymptomatic infection through to severe dengue. Although prior infection with another viral serotype, i.e. secondary dengue, is known to be an important factor influencing disease severity, current methods to determine primary versus secondary immune status during the acute illness do not consider the rapidly evolving immune response, and their accuracy has rarely been evaluated against an independent gold standard...
August 7, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/30086713/bilateral-osteomyelitis-and-liver-abscess-caused-by-hypervirulent-klebsiella-pneumoniae-a-rare-clinical-manifestation-case-report
#17
Emma Sturm, Alex Tai, Belinda Lin, Jason Kwong, Eugene Athan, Benjamin P Howden, Richard D Angliss, Rafik Asaid, James Pollard
BACKGROUND: Hypervirulent strains of Klebsiella pneumoniae are a recognized cause of a distinct invasive syndrome that results in pyogenic liver abscesses and metastatic complications, particularly in the Asia Pacific region. Reports of hypervirulent K.pneumoniae in Europe, the Americas and Australia indicate worldwide spread. We present a case of multi-focal osteomyelitis, a rarely described complication of hypervirulent K.pneumoniae in the medical literature. The prevalence of this condition in countries outside Asia may be expected to rise with increasing travel...
August 7, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/30086652/a-proposed-nomenclature-for-infectious-bursal-disease-virus-isolates
#18
Daral J Jackwood, Karel A Schat, Linda O Michel, Sjaak de Wit
Infectious bursal disease virus (IBDV) was initially identified in the USA. For decades, these viruses were not categorized using a typing system because they were considered to be antigenically and pathogenically similar. In the 1980s, a second major serotype, serotype 2, was found in turkeys. Classification of IBDV became more complex with the discovery of antigenic variant strains called "variants" in the United States and a highly virulent strain known as "very virulent" or vvIBDV identified in Europe...
August 8, 2018: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/30085094/genetic-fine-mapping-of-systemic-lupus-erythematosus-mhc-associations-in-europeans-and-african-americans
#19
Ken B Hanscombe, David L Morris, Janelle A Noble, Alexander T Dilthey, Philip Tombleson, Kenneth M Kaufman, Mary Comeau, Carl D Langefeld, Marta E Alarcon-Riquelme, Patrick M Gaffney, Chaim O Jacob, Kathy L Sivils, Betty P Tsao, Graciela S Alarcon, Elizabeth E Brown, Jennifer Croker, Jeff Edberg, Gary Gilkeson, Judith A James, Diane L Kamen, Jennifer A Kelly, Joseph McCune, Joan T Merrill, Michelle Petri, Rosalind Ramsey-Goldman, John D Reveille, Jane E Salmon, Hal Scofield, Tammy Utset, Daniel J Wallace, Michael H Weisman, Robert P Kimberly, John B Harley, Cathryn M Lewis, Lindsey A Criswell, Timothy J Vyse
Genetic variation within the major histocompatibility complex contributes substantial risk for systemic lupus erythematosus, but high gene density, extreme polymorphism, and extensive linkage disequilibrium have made fine mapping challenging. To address the problem, we compared two association techniques in two ancestrally diverse populations, African Americans (AA) and Europeans (EUR). We observed a greater number of HLA alleles in AA consistent with the elevated level of recombination in this population. In EUR we observed 50 different A-C-B-DRB1-DQA-DQB multilocus haplotype sequences per hundred individuals; in the AA sample, about double the number, 95 per hundred...
July 31, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/30084709/safety-tolerability-and-immunogenicity-of-a-novel-4-antigen-staphylococcus-aureus-vaccine-sa4ag-in-healthy-japanese-adults
#20
Megumi Inoue, Takuma Yonemura, James Baber, Yasuko Shoji, Masakazu Aizawa, David Cooper, Joseph Eiden, William C Gruber, Kathrin U Jansen, Annaliesa S Anderson, Alejandra Gurtman
A novel Staphylococcus aureus 4-antigen vaccine (SA4Ag) is under development, comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197 , recombinant protein clumping factor A (rmClfA), and recombinant manganese transporter protein C (MntC). We evaluated SA4Ag safety, tolerability, and immunogenicity in Japanese adults aged 20 to 64 and 65 to 85 years. A total of 136 healthy Japanese adults (68 per age group) were randomized 1:1 to receive single-dose SA4Ag or placebo intramuscularly (Day 1)...
August 7, 2018: Human Vaccines & Immunotherapeutics
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