177 research outputs found
Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus
BACKGROUND:Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease. DESIGN:Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated i.m. on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology. RESULTS:All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence. CONCLUSIONS:These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated
Norwalk Virus Shedding after Experimental Human Infection
Noroviruses are shed in feces up to 8 weeks after infection
Helium beam shadowing for high spatial resolution patterning of antibodies on microstructured diagnostic surfaces
We have developed a technique for the high-resolution, self-aligning, and high-throughput patterning of antibody binding functionality on surfaces by selectively changing the reactivity of protein-coated surfaces in specific regions of a workpiece with a beam of energetic helium particles. The exposed areas are passivated with bovine serum albumin (BSA) and no longer bind the antigen. We demonstrate that patterns can be formed (1) by using a stencil mask with etched openings that forms a patterned exposure, or (2) by using angled exposure to cast shadows of existing raised microstructures on the surface to form self-aligned patterns. We demonstrate the efficacy of this process through the patterning of anti-lysozyme, anti-Norwalk virus, and anti-Escherichia coli antibodies and the subsequent detection of each of their targets by the enzyme-mediated formation of colored or silver deposits, and also by binding of gold nanoparticles. The process allows for the patterning of three-dimensional structures by inclining the sample relative to the beam so that the shadowed regions remain unaltered. We demonstrate that the resolution of the patterning process is of the order of hundreds of nanometers, and that the approach is well-suited for high throughput patterning
Invasive Mold Infections Following Hurricane Harvey-Houston, Texas
BACKGROUND: Characterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making.
METHODS: We assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status.
RESULTS: IMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 cases) (rate ratio, 1.48 [95% confidence interval, 1.10-2.00]), largely driven by surveillance IMI cases.
CONCLUSIONS: IMI incidence likely increased following Hurricane Harvey and outcomes for IMI patients were severe. Patient and clinician education on IMI prevention and identification is warranted, particularly as the frequency of extreme weather events increases due to climate change
Effects of Child and Maternal Histo-Blood Group Antigen Status on Symptomatic and Asymptomatic Enteric Infections in Early Childhood
Funding Information: Financial support. This work was funded by the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project funded by the Bill & Melinda Gates Foundation (BMGF) (BMGF-47075), the Foundation for the National Institutes of Health, and the National Institutes of Health, Fogarty International Center, whereas additional support was obtained from BMGF for the examination of host innate factors on enteric disease risk and enteropathy (Grants OPP1066146 and OPP1152146; to M. N. K.). Additional funding was obtained from teh Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Johns Hopkins School of Medicine (to M. N. K) and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institues of health 1UL1TR001079. Acknowledgments. We thank the participants, their families, and the study community for their dedicated time and effort to better the understanding the transmission and more enduring impact of enteric infections in early childhood. We also thank the following: Jan Vinje (Centers for Disease Control and Prevention) for critical input and manuscript review; Dr. Leah Jager for consultation regarding the statistical analysis; Dr. Ben Jann (University of Bern, Switzerland) for guidance in generating the figures; Christine Szymanski for insight and encouragement, particularly regarding Campylobacter infection and disease patency; Chris Damman and Anita Zaidi for input on early iterations of the analysis; and Dick Guerrant for final reflections.Peer reviewe
Flotation Immunoassay: Masking the Signal from Free Reporters in Sandwich Immunoassays
In this work, we demonstrate that signal-masking reagents together with appropriate capture antibody carriers can eliminate the washing steps in sandwich immunoassays. A flotation immunoassay (FI) platform was developed with horseradish peroxidase chemiluminescence as the reporter system, the dye Brilliant Blue FCF as the signal-masking reagent, and buoyant silica micro-bubbles as the capture antibody carriers. Only reporters captured on micro-bubbles float above the dye and become visible in an analyte-dependent manner. These FIs are capable of detecting proteins down to attomole levels and as few as 106 virus particles. This signal-masking strategy represents a novel approach to simple, sensitive and quantitative immunoassays in both laboratory and point-of-care settings
A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity
Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed a conserved epitope, away from the HBGA binding site, fully accessible only when VP1 transitions to a “raised” conformation in the capsid. Together with dynamic light scattering and electron microscopy of the GII.4 VLPs, our studies suggest a mechanism in which M4 accesses the epitope by altering the conformational dynamics of the capsid and triggering its disassembly to neutralize GII.4 infection.Instituto de VirologíaFil: Salmen, Wilhelm. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Hu, Liya. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnologicas; ArgentinaFil: Bok, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chaimongkol, Natthawan. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Ettayebi, Khalil. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Sosnovtsev, Stanislav V. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Soni, Kaundal. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Ayyar, B. Vijayalakshmi. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Shanker, Sreejesh. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Neill, Frederick H. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Sankaran, Banumathi. Berkeley Center for Structural Biology. Molecular Biophysics and Integrated Bioimaging. Lawrence Berkeley Laboratory; Estados UnidosFil: Atmar, Robert L. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Atmar, Robert L. Baylor College of Medicine. Department of Medicine; Estados UnidosFil: Estes, Mary K. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Estes, Mary K. Baylor College of Medicine. Department of Medicine; Estados UnidosFil: Green, Kim Y. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virologia e Innovaciones Tecnologicas (IVIT); ArgentinaFil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Prasad, B. V. Venkataram. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Prasad, B. V. Venkataram. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados Unido
Human Norovirus Histo-Blood Group Antigen (HBGA) Binding Sites Mediate the Virus Specific Interactions with Lettuce Carbohydrates
Lettuce is often implicated in human norovirus (HuNoV) foodborne outbreaks. We identified H-like histo-blood group antigens (HBGAs) on lettuce leaves as specific binding moieties for virus-like particles (VLPs) of HuNoV GII.4/HS194/2009 strain. The objective of this study was to determine whether HuNoV-lettuce binding is mediated through the virus HBGA binding sites (HBS). Toward this objective, VLPs of historical HuNoV GII.4 strains (1987, 1997, 2002, 2004 and 2006) with known natural mutations in their HBS, two newly generated VLP mutants of GII.4/HS194/2009 (D374A and G443A) and a VLP mutant (W375A) of GI.1/Norwalk/1968 along with its wild type VLPs, which displays distinct HBS, were investigated for their binding to lettuce. ELISA revealed that historical GII.4 strains binding to lettuce was dependent on their HBGAs profiles. The VLP mutants D374A and G443A lost binding to HBGAs and displayed no to minimal binding to lettuce, respectively. The VLPs of GI.1/Norwalk/1968 strain bound to lettuce through an H-like HBGA and the binding was inhibited by fucosidase digestion. Mutant W375A which was previously shown not to bind to HBGAs, displayed significantly reduced binding to lettuce. We conclude that the binding of HuNoV GII.4 and GI.1 strains to lettuce is mediated through the virus HBS
Norwalk Virus–specific Binding to Oyster Digestive Tissues
Specific binding of virus to oysters can selectively concentrate a human pathogen
Biodiversity on Broadway - Enigmatic Diversity of the Societies of Ants (Formicidae) on the Streets of New York City
Each year, a larger proportion of the Earth's surface is urbanized, and a larger proportion of the people on Earth lives in those urban areas. The everyday nature, however, that humans encounter in cities remains poorly understood. Here, we consider perhaps the most urban green habitat, street medians. We sampled ants from forty-four medians along three boulevards in New York City and examined how median properties affect the abundance and species richness of native and introduced ants found on them. Ant species richness varied among streets and increased with area but was independent of the other median attributes measured. Ant assemblages were highly nested, with three numerically dominant species present at all medians and additional species present at a subset of medians. The most common ant species were the introduced Pavement ant (Tetramorium caespitum) and the native Thief ant (Solenopsis molesta) and Cornfield ant (Lasius neoniger). The common introduced species on the medians responded differently to natural and disturbed elements of medians. Tetramorium caespitum was most abundant in small medians, with the greatest edge/area ratio, particularly if those medians had few trees, whereas Nylanderia flavipes was most abundant in the largest medians, particularly if they had more trees. Many of the species encountered in Manhattan were similar to those found in other large North American cities, such that a relatively small subset of ant species probably represent most of the encounters humans have with ants in North America
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