Immunology and Infectious Disease Commons^™

Novel Neutralizing Antibody Assays For Recombinant Human Hookworm Na-Gst-1 Vaccine, Xi Chen, Brian Keegan, Peter J. Hotez, Jeffrey M. Bethony, Amar R. Jariwala

GW Research Days 2013

BACKGROUND

Necator Americanus, a human hookworm causes approximately 85% of the global hookworm infections. Hookworm ingest hemoglobin containing erythrocytes. Hemoglobin is further digested to Heme and Globin by hookworm's gut enzymes. Iron-containing Heme is a potent enzyme inhibitor and generates toxic reactive oxygen species which is toxic to hookworms. Hookworm's gut enzyme Na-GST-1 (Necator Americanus Glutathione S-Transferase-1) has been hypothesized to detoxify Heme. Na-GST-1 adjuvanted with Alhydrogel® is a new vaccine which is currently under clinical development. Na-GST-1 has two active sites, the ligand binding or Heme detoxification site (H-site) and the catalytic active glutathione binding …

American Society Of Parasitologists Newsletter, V. 35, No. 1, Spring 2013, Scott Lyell Gardner

American Society of Parasitologists: Newsletter

American Society of Parasitologists Newsletter, volume 35, number 1, Spring 2013

Protein Kinase C Delta Is A Substrate Of Tissue Transglutaminase And A Novel Autoantigen In Coeliac Disease, Greg Byrne, Michael Freeley, Con Feighery, Alex Whelan, Aideen Long

Articles

Post-translational modification of proteins by deamidation or transamidation by tissue transglutaminase (tTG) has been suggested as a possible mechanism for the development of autoimmunity. Sequence analysis of protein kinase C delta (PKCδ) identified an amino acid motif that suggested the possibility that PKCδ was a glutamine substrate of tTG and MALDI-TOF analysis of synthesised peptides from PKCδ proved that this was the case. Polymerisation experiments using recombinant tTG and biotinylated hexapeptide substrate incorporation assays demonstrated that PKCδ is a substrate for tTG-mediated transamidation. Elevated levels of anti-PKCδ antibodies were detected in sera from patients with coeliac disease (pb0.0001) but not …

Molecular Analysis Of The Localization And Function Of Caspase-Like Proteins In Dictyostelium Discoideum And The Parasitic Protozoan Acanthamoeba Castellanii, Entsar Jabbar Saheb Kano

Theses and Dissertations

Two novel families of caspase-like proteins, metacaspases and paracaspases, have been discovered but have remained poorly characterized. Metacaspase type-1 (Acmcp) has been identified in Acanthamoeba castellanii , which is an opportunistic protozoan parasite that causes several diseases in humans. On the other hand, paracaspase (Ddpcp) has been found in the protozoan Dictyostelium discoideum . D. discoideum is well-researched model organism that is appropriate for studying these caspase-like proteins. In this study, we investigated the localization and molecular function of metacaspase and paracaspase proteins by over-expressing them in D. discoideum . Separate cell lines over-expressing a GFP-tagged version of the full …

A Role For Interferon Stimulated Gene-15 (Isg15) During Chikungunya Virus Infection, Scott Werneke

All Theses and Dissertations (ETDs)

Abstract of the Dissertation

A Role for Interferon Stimulated Gene-15: ISG15) During Chikungunya Virus Infection

By

Scott William Werneke

Doctor of Philosophy in Biology and Biomedical Science

(Immunology)

Washington University in St. Louis, 2013

Professor Deborah J. Lenschow, Chairperson

Chikungunya fever is caused by Chikungunya virus: CHIKV), an infectious disease that is characterized by severe joint and muscle pain in humans. The latest outbreak of CHIKV, which began in 2005, has affected millions of people across India, Singapore, and the Indian Ocean Island region. Type I interferon: IFN), which mediates protection against many different viruses through the upregulation of interferon …

Tumor Antigens Revealed By Exome Seqeuncing Drive Editing Of Tumor Immunogenicity, Matthew David Vesely

All Theses and Dissertations (ETDs)

Accumulated data from animal models and human cancer patients strongly support the concept that immunity cannot only function as an extrinsic tumor suppressor, but also shape tumor immunogenicity. These observations led to the development of the cancer immunoediting hypothesis that stresses the dual host-protective and tumor-sculpting actions of immunity on developing cancers. We previously demonstrated important roles for lymphocytes and type I: IFN-α/β) and type II: IFN-γ) interferons in cancer immunoediting. In the present work, we confirmed the role of IFN-γ in sculpting tumor immunogenicity and provide evidence that antigens expressed by tumors drive the destructive or sculpting actions of …

Genetic And Epigenetic Interactions In In Vivo And In Vitro Reprogramming, Margaret Ashley Young

All Theses and Dissertations (ETDs)

In cancer pathogenesis and induced pluripotent stem: iPS) cell production, an essential step for reprogramming is acquisition of self-renewal. In hematopoietic cells, HOX genes are partially responsible for self-renewal, and HOX gene dysregulation commonly occurs in acute myeloid leukemia: AML). HOX dysregulation is seen in AML with translocations involving HOX genes themselves: e.g. NUP98-HOXA9) and with other disease-initiating translocations: e.g. MLL translocations and inv(16)). However, HOX genes are also highly expressed in many AML samples without translocations; the mechanism that causes "dysregulation" in these cases is unknown. Whole genome sequencing of 45 de novo AML genomes showed that recurrent mutations …

Hirsutella Sinensis Mycelium Suppresses Interleukin-1b And Interleukin-18 Secretion By Inhibiting Both Canonical And Non-Canonical Inflammasomes, Tsung-Teng Huang, Kowit-Yu Chong, David M. Ojcius, Yi-Hui Wu, Yun-Fei Ko, Cheng-Yeu Wu, Jan Martel, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Cordyceps sinensis is a medicinal mushroom used for centuries in Asian countries as a health supplement and tonic. Hirsutella sinensis—the anamorphic, mycelial form of C. sinensis—possesses similar properties, and is increasingly used as a health supplement. Recently, C. sinensis extracts were shown to inhibit the production of the pro-inflammatory cytokine IL-1β in lipopolysaccharide-treated macrophages. However, the molecular mechanism underlying this process has remained unclear. In addition, whether H. sinensis mycelium (HSM) extracts also inhibit the production of IL-1β has not been investigated. In the present study, the HSM extract suppresses IL-1β and IL-18 secretion, and ATP-induced activation of caspase-1. Notably, …

Batf3-Deficient Mice: Susceptibility To Toxoplasma Gondii And Responses To Il-12 Treatment In Vivo, Mona Mashayekhi

All Theses and Dissertations (ETDs)

CD8α+ dendritic cells are important in vivo for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, stimulation of IL-12 production by CD8α+ DCs has suggested a role for these cells in response to Toxoplasma gondii antigens, although no experiments have yet shown an in vivo requirement for these cells against T. gondii infection. Towards this goal, we examined T. gondii infection of Batf3-/- mice, which selectively lack only lymphoid-resident CD8α+ DCs and related peripheral CD103+ DCs. Batf3-/- mice were extremely susceptible to T. gondii infection, with defective priming of CD8+ T cells, and decreased production of IL-12 and …

Break Out: Urogenital Schistosomiasis And Schistosoma Haematobium Infection In The Post-Genomic Era, Paul J. Brindley, Peter J. Hotez

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Immunological And Reproductive Health Assessment In Herring Gulls And Black-Crowned Night Herons In The Hudson-Raritan Estuary, Keith A. Grasman, Kathy R. Echols, Thomas M. May, Paul H. Peterman

University Faculty Publications and Creative Works

Previous studies have shown inexplicable declines in breeding waterbirds within western New York/New Jersey Harbor between 1996 and 2002 and elevated polychlorinated dibenzo-p-dioxins and polychlorinated biphenyls (PCBs) in double-crested cormorant (Phalacrocorax auritus) eggs. The present study assessed associations between immune function, prefledgling survival, and selected organochlorine compounds and metals in herring gulls (Larus argentatus) and black-crowned night herons (Nycticorax nycticorax) in lower New York Harbor during 2003. In pipping gull embryos, lymphoid cells were counted in the thymus and bursa of Fabricius (sites of T and B lymphocyte maturation, respectively). The phytohemagglutinin (PHA) skin response assessed T cell function in …

Mechanisms Of Protective Activity Of West Nile Virus Anti-Envelope Antibodies In Vitro And In Vivo, Matthew Raymond Vogt

All Theses and Dissertations (ETDs)

West Nile virus: WNV) is a neurotropic flavivirus capable of causing severe disease and death in humans. Studies in mice have demonstrated that the humoral immune response against WNV limits primary infection and protects against a secondary challenge. Accordingly, passive transfer of immune serum or monoclonal antibodies: MAb) against the envelope: E) protein either prior to WNV infection or shortly thereafter is sufficient to protect mice from disease. The E protein is an immunodominant antigen in the antibody response to WNV infection, and the most potent neutralizing MAbs recognize an epitope on the lateral ridge of domain III: DIII-LR) of …

The Herpesvirus Vp1/2 Protein Is An Effector Of Dynein-Mediated Capsid Transport And Neuroinvasion, Sofia V. Zaichick, Kevin P. Bohannon, Ami Hughes, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Microtubule transport of herpesvirus capsids from the cell periphery to the nucleus is imperative for viral replication and, in the case of many alphaherpesviruses, transmission into the nervous system. Using the neuroinvasive herpesvirus, pseudorabies virus (PRV), we show that the viral protein 1/2 (VP1/2) tegument protein associates with the dynein/dynactin microtubule motor complex and promotes retrograde microtubule transport of PRV capsids. Functional activation of VP1/2 requires binding to the capsid protein pUL25 or removal of the capsid-binding domain. A proline-rich sequence within VP1/2 is required for the efficient interaction with the dynein/ dynactin microtubule motor complex as well as for …

Pathology In Practice, Timothy L. Cushing, David J. Steffen, Gerald E. Duhamel

School of Veterinary and Biomedical Sciences: Faculty Publications

A 1.5-year-old second-parity Large Black X Tamworth cross sow from a well-managed 20-sow, unvaccinated, pasture-raised herd of pigs in upstate New York aborted a litter of 7 variably mummified near-term fetuses and stillborn piglets. This sow had no signs of ill health other than abortion; it was housed in a group with 4 other sows and a 2-year-old Gloucestershire Old Spot boar. One of the stillborn piglets from this litter was submitted to the New York State Animal Health Diagnostic Center for necropsy; no placental tissue was submitted with the piglet. A second sow from this group had aborted a …

Review Of Haploporid (Trematoda) Genera With Ornate Muscularization In The Region Of The Oral Sucker, Including Four New Species And A New Genus, Eric E. Pulis, Robin M. Overstreet

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Species of the Haploporidae Nicoll, 1914 with elaborate muscularization of the oral sucker belong in three trematode genera, including three new species and a new genus from the intestine of fishes in Australian waters. Spiritestis Nagaty, 1948 is resurrected and S. herveyensis n. sp. is described from the mullet Moolgarda seheli (Forsskål) collected in Hervey Bay, Queensland, Australia; the latter differs from S. arabii Nagaty, 1948 in that the position of the genital pore is pharyngeal rather than post-pharyngeal and the geographical range is off Australia rather than the Red Sea. A new genus is proposed for two new species, …

Phi X 174, David J. Hall

Infectious Pathogens

Phi X 174 database number # 1CD3. Phi X 174 is a virus that infects bacteria and was the first DNA-based genome to be sequenced in 1977. This bacteriophage has a [+] circular single-stranded DNA genome. The assembly of the capsid has been successfully done in vitro and is the focus of many studies on self-assembly, drug delivery and nanotechnology.

Dengue Virus, David J. Hall

Infectious Pathogens

Dengue virus, database # 1THD Dengue fever, is an infectious tropical disease caused by the dengue virus and transmitted by mosquito. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases the disease develops into the life-threatening dengue hemorrhagic fever. Dengue is a positive strand RNA virus that is part of the flavivirus family. Dengue is an enveloped virus meaning it has a nucleocapsid protecting the RNA and the nucleocapsid is surrounded by lipids (hence the name enveloped).

Human Papilloma Virus 16, David J. Hall

Infectious Pathogens

Human Papilloma virus 16, database# 1DZL Infection by most papillomaviruses is either asymptomatic or causes small benign tumors, known as papillomas or warts (e.g. human papillomavirus HPV6 or HPV11). Papillomas caused by some types, however, such as human papillomaviruses 16 and 18, carry a risk of becoming cancerous. Human papilloma virus is a non-enveloped, double stranded, circular DNA virus.

Hepatitis B, David J. Hall

Infectious Pathogens

Hepatitis B, database # 2g33. Hepatitis B is an infectious inflammatory illness of the liver caused by the hepatitis B virus (HBV). Hepatitis B virus (HBV) is a member of the Hepadnavirus family.The virus particle, (virion) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein. These virions are 42 nM in diameter. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity.

Changes In Natural Killer Cell Activation And Function During Primary Hiv-1 Infection, Vivek Naranbhai, Marcus Altfeld, Salim S. Abdool Karim, Thumbi Ndung’U, Quarraisha Abdool Karim, William H. Carr

Publications and Research

Background: Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection.

Methodology/Principal Findings: Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, …

Impact Of Cryoablation On Tumor Immunity, Jesse Veenstra

Wayne State University Dissertations

Background and Objectives: Percutaneous cryoablation is a minimally invasive procedure for tumor debulking, which has the potential to initiate or amplify tumor immunity through the release of tumor-associated antigens and endogenous danger signals. However, enhanced immunity is rarely observed in treated patients, suggesting the need for mechanistic analysis. The goal is to determine how cryoablation affects tumor specific immunity and if the response can be improved through exogenous TLR9 stimulation.

Methodology: We evaluated anti-Her2/neu immunity following cryoablation in wt BALB/c and tolerant NeuT mice inoculated with neu or Her2 expressing mammary tumors TUBO and D2F2/E2 respectively. Mice were treated with …

Effects Of Treatment On Ige Responses Against Parasite Allergen-Like Proteins And Immunit To Reinfection In Childhood Schistosome And Hookworm Coinfections, Angela Pinot De Moira, Frances M. Jones, Shona Wilson, Edridah Tukahebwa, Colin M. Fitzsimmons, Joseph K. Mwatha, Jeffrey M. Bethony, Narcis B. Kabatereine, David W. Dunne

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Naturally occurring human immunity to both schistosomiasis and hookworm infection has been associated with IgE responses against parasite allergen-like proteins. Since the two helminths frequently coinfect the same individuals, there is growing advocacy for their concurrent treatment. However, both helminths are known to exert strong immunomodulatory effects; therefore, coinfected individuals could have immune responses different from those characteristically seen in monoinfected individuals. In this study, we measured changes in IgE, IgG1, and IgG4 responses to schistosome and hookworm antigens, including the allergen-like proteins Schistosoma mansoni tegumental-allergen-like 1 protein (SmTAL1), SmTAL2, and Necator americanus Ancylostoma-secreted protein-2 (Na-ASP-2), following concurrent …

Transcriptional Responses Of In Vivo Praziquantel Exposure In Schistosomes Identifies A Functional Role For Calcium Signalling Pathway Member Camkii, Hong You, Donald P. Mcmanus, Wei Hu, Michael J. Smout, Paul J. Brindley, Geoffrey N. Gobert

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Treatment for clinical schistosomiasis has relied centrally on the broad spectrum anthelmintic praziquantel; however, there is limited information on its mode of action or the molecular response of the parasite. This paper presents a transcriptional and functional approach to defining the molecular responses of schistosomes to praziquantel. Differential gene expression in Schistosoma japonicum was investigated by transcriptome-wide microarray analysis of adult worms perfused from infected mice after 0.5 to 24 hours after oral administration of sub-lethal doses of praziquantel. Genes up-regulated initially in male parasites were associated with “Tegument/Muscle Repair” and “Lipid/Ion Regulation” functions and were followed by “Drug Resistance” …

Serum 25-Hydroxyvitamin D Levels And C-Reactive Protein In Persons With Human Immunodeficiency Virus Infection, C. Anderson Johnson, Kalpana Poudel-Tandukar, Krishna C. Poudel, Masamine Jimba, Jun Kobayashi, Paula Palmer

CGU Faculty Publications and Research

Human immunodeficiency virus (HIV) infection has frequently been associated with vitamin D deficiency as well as chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D [25(OH)D] and high-sensitivity C-reactive protein (CRP) in a cohort of HIV-positive people. A cross-sectional survey was conducted among 316 HIV-positive people (181 men and 135 women) aged 16 to 60 years residing in the Kathmandu Valley, Nepal. Serum high-sensitivity CRP concentrations and serum 25(OH)D levels were measured by the latex agglutination nephelometry method and the competitive protein-binding assay, respectively. The relationship between serum CRP concentrations and 25(OH)D …

Patent Landscape Of Helminth Vaccines And Related Technologies, Jon R. Cavicchi, Stanley P. Kowalski, John Schroeder, Rayna Burke, Jillian Michaud-King

Law Faculty Scholarship

Executive Summary This report focuses on patent landscape analysis of technologies related to vaccines targeting parasitic worms, also known as helminths. These technologies include methods of formulating vaccines, methods of producing of subunits, the composition of complete vaccines, and other technologies that have the potential to aid in a global response to this pathogen. The purpose of this patent landscape study was to search, identify, and categorize patent documents that are relevant to the development of vaccines that can efficiently promote the development of protective immunity against helminths. The search strategy used keywords which the team felt would be general …

Title Page, Contents, Contributors For Estudios Científicos En El Estado De Hidalgo Y Zonas Aledañas, Volumen Ii, Griselda Pulido-Flores, Scott Monks

Estudios científicos en el estado de Hidalgo y zonas aledañas

Title Page

Contents

Contributors

Los Parásitos Y El Estudio De Su Biodiversidad: Un Enfoque Sobre Los Estimadores De La Riqueza De Especies, Christian E. Bautista-Hernández, Scott Monks, Griselda Pulido-Flores

Estudios científicos en el estado de Hidalgo y zonas aledañas

Durante años los parásitos fueron considerados únicamente como agentes patógenos que debían ser eliminados, sin considerar que son un componente importante de la biodiversidad, que son capaces de aportar información de sí mismos y de otros organismos. Existen estimadores de riqueza que predicen el número de especies para una comunidad a partir de la riqueza observada y de la abundancia de las especies o datos de incidencia; pueden ser estimadores paramétricos y no paramétricos. La comparación de la riqueza de especies entre componente de comunidades de parásitos frecuentemente pueden ser difícil de evaluar debido a que los datos no se …

Alloreactivity-Based Medical Conditions, Stanislav Vukmanovic, Margaret G. Petroff, Anne M. Stevens, Daniel Rukavina

Pediatrics Faculty Publications

No abstract provided.

El Uso De Helmintos Parásitos Como Bioindicadores En La Evaluación De La Calidad Del Agua: Lago De Tecocomulco Vs. Laguna De Metztitlán, Hidalgo, México, Scott Monks, Griselda Pulido-Flores, Christian E. Bautista-Hernández, Berenice Alemán-García, Jorge Falcón-Ordaz, Juan Carlos Gaytán-Oyarzún

Estudios científicos en el estado de Hidalgo y zonas aledañas

Como parte integral de la evaluación de la calidad ambiental del estado de Hidalgo, este estudio tiene énfasis en los helmintos parásitos de los peces y su uso como bioindicadores de la calidad de agua en Lago de Tecocomulco y Laguna de Metztitlán. Como parte del estudio, se obtuvieron los parámetros ecológicos de la infección para cada especie. En Lago Tecocomulco se registraron dos especies de digéneos (larvas), Posthodiplostomum sp. y Diplostomum sp. en el cerebro, los ojos y el mesenterio de dos especies de peces nativos de la zona (Chirostoma jordani y Girardinicthys viviparus); un céstodo (larva), …

Helmintos Parásitos De Algunos Roedores (Mammalia: Rodentia) En San Miguel De Allende, Tepeapulco, Hidalgo, México, Griselda Pulido-Flores, Scott Monks, Jorge Falcón-Ordaz

Estudios científicos en el estado de Hidalgo y zonas aledañas

Los helmintos son un componente de la biodiversidad, que proveen información sobre la historia natural de los hospederos, y de las relaciones tróficas. El conocimiento de la diversidad de roedores y sus parásitos en Hidalgo es escaso y puntual. Por la amplia distribución de los roedores, su adaptabilidad a los ambientes modificados y por el riesgo zoonótico que representan, es importante conocer la parasitofauna de estos hospederos. El objetivo del este trabajo fue registrar la helmintofauna de algunos roedores en San Miguel de Allende, Tepeapulco, Hidalgo, México. Entre agosto de 2005 y junio de 2007 se colectaron 19 roedores (12 …