Immunology of Infectious Disease News Volume 4.43 | Nov 2 2016

TOP STORY

Protective Neutralizing Influenza Antibody Response in the Absence of T Follicular Helper Cells

Researchers found that IgG2 antibodies predominated in the response to vaccination with inactivated influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAV strains, even in mice that lacked T follicular helper cells and germinal centers. [Nat Immunol] Abstract

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Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions

Scientists employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. [Nat Immunol] Abstract

Evaluating Frequency and Quality of Pathogen-Specific T Cells

Researchers report a new technique to determine the frequency and potency of antigen-specific CD8 T cells. The assay measures changes of intracellular Ca2⁺ in real time by fluorescent microscopy in individual CD8 T cells responding to cognate peptides. [Nat Commun] Full Article

ZIKA Virus Elicits p53 Activation and Genotoxic Stress in Human Neural Progenitors Similar to Mutations Involved in Severe Forms of Genetic Microcephaly and p53

The authors explored the possible similarities between transcriptional responses induced by Zika virus (ZIKV) in human neural progenitors and those elicited by three different genetic mutations leading to severe forms of microcephaly in mice. They found that the strongest similarity between all these conditions is the activation of common P53 downstream genes. [Cell Death Dis] Full Article

HCV Core Protein Inhibits Polarization and Activity of Both M1 and M2 Macrophages through the TLR2 Signaling Pathway

Researchers tested whether hepatitis C virus core protein (HCVc) affects human blood-derived monocyte differentiating into macrophages. Results showed that HCVc inhibits monocyte differentiation to either M1 or M2 macrophages through TLR2, associated with impaired STATs signaling pathway. [Sci Rep] Full Article

An Extract from Taxodium distichum Targets Hemagglutinin- and Neuraminidase-Related Activities of Influenza Virus In Vitro

After screening different plant extracts with potential anti-influenza activity, a water extract of Taxodium distichum stems (TDSWex) showed excellent activity against influenza viruses. The EC₅₀ of TDSWex was 0.051 ± 0.024 mg/mL against influenza virus A/WSN/33. [Sci Rep] Full Article

Respective IL-17A Production by γδ T and Th17 Cells and Its Implication in Host Defense against Chlamydial Lung Infection

Investigators found that γδT cells and Th17 cells are the major producers of IL-17A at the early and later stages of chlamydial infection, respectively. Depletion of γδT cells in vivo at the early postinfection stage, when most γδT cells produce IL-17A, failed to alter Th1 responses and bacterial clearance. [Mol Immunol] Abstract

HIV

Cryo-EM Structure of a CD4-Bound Open HIV-1 Envelope Trimer Reveals Structural Rearrangements of the gp120 V1V2 Loop

Researchers present an 8.9-Å cryo-electron microscopy structure of a BG505 HIV-1 envelope (Env)-sCD4-17b-8ANC195 complex, which reveals large structural rearrangements in gp120, but small changes in gp41, compared with closed Env structures. [Proc Natl Acad Sci USA] Abstract

Expression of HIV-1 Matrix Protein p17 and Association with B-Cell Lymphoma in HIV-1 Transgenic Mice

The authors investigated which viral proteins are associated with the development of leukemia/lymphoma in the Tg26 mouse model, and performed microarray analysis on RNA from spleen and lymph nodes to identify potential mechanisms of lymphomagenesis. Of the viral proteins examined, only expression of HIV-1 matrix protein p17 was associated with leukemia/lymphoma development and was highly expressed in bone marrow before disease. [Proc Natl Acad Sci USA] Full Article

Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001

Scientists report on the production and analysis of HIV-1 Env-specific human monoclonal antibodies (hMAbs) isolated from vaccinees in the DP6-001 trial. For this initial report, 13 hMAbs from four vaccinees in the DP6-001 trial showed broad binding to gp120 proteins of diverse subtypes both autologous and heterologous to vaccine immunogens. [J Virol] Abstract

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HIV-Associated Opportunistic CNS Infections: Pathophysiology, Diagnosis and Treatment

The authors discuss several of the most common CNS opportunistic infections: cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, tuberculous meningitis, cryptococcal meningitis and cytomegalovirus infection, with an emphasis on clinical pearls, pathological findings, MRI findings and treatment. Moreover, they discuss the risk factors, pathophysiology and management of immune reconstitution inflammatory syndrome. [Nat Rev Neurol] Abstract

Tuberculosis

In many low-income and middle-income countries, tuberculosis (TB) continues to be a major cause of morbidity and mortality, and drug-resistant TB is a major concern in many settings. Although several new TB diagnostics have been developed, including rapid molecular tests, there is a need for simpler point-of-care tests. [Nat Rev Dis Primers] Full Article

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New Data for VIBATIV^® (Telavancin) Reported

Theravance Biopharma, Inc. announced the presentation of positive new data from several studies of VIBATIV^® (Telavancin), the company’s proprietary FDA-approved antibiotic. Results of the studies included reporting of high clinical cure rates in patients with osteomyelitis, greater in vitro potency against challenging MRSA pathogens as compared to other commercialized antibiotics, and similarities in the overall healthcare costs and renal function impact for VIBATIV as compared to vancomycin. [Press release from Theravance Biopharma, Inc. discussing research presented at IDWeek^™ 2016, New Orleans] Press Release

Theravance Biopharma Presents Interim Data from Ongoing Telavancin Observational Use Registry (TOUR™)

Theravance Biopharma, Inc. announced the presentation of interim data from the company’s ongoing TOUR^™ study. TOUR is designed to assess how VIBATIV^® (telavancin) is being used by healthcare practitioners to treat patients in real-world settings. An initial review of data from the first 200 patients enrolled in TOUR demonstrated clinical response rates of 74% in a range of difficult-to-treat infection types including the drug’s approved indications of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) and complicated skin & skin structure infections. [Press release from Theravance Biopharma, Inc. discussing research presented at IDWeek^™ 2016, New Orleans] Press Release

Data Highlight Risk Factors for Carbapenem Resistance Among Patients Hospitalized for Serious Infections

Allergan plc presented new data identifying hospitalized patients with serious infections due to Enterobactericaeae who are at greater risk for having carbapenem-resistant Enterobacteriaceae infections. [Press release from Allergan plc discussing research presented at IDWeek^™ 2016, New Orleans] Press Release

GSK Presents New Data for Shingles Candidate Vaccine

GSK announced new data for its shingles candidate vaccine Shingrix^™. The data examined co-administration of GSK’s candidate vaccine with the flu vaccine; a flexible dosing schedule; and the vaccine’s impact on quality of life. [Press release from GSK discussing research presented at IDWeek^™ 2016, New Orleans] Press Release

BD MAX^™ Vaginal Panel Receives FDA Market Authorization to Detect Most Common Causes of Vaginal Infections

Becton, Dickinson and Company announced U.S. Food and Drug Administration (FDA) market authorization for a first-of-its-kind molecular test to detect the most common causes for vaginitis. Laboratories and clinicians will now have the ability to use a single test to detect microorganisms responsible for Bacterial Vaginosis, Trichomoniasis and Vulvovaginal Candidiasis, also known as a yeast infection, which are the most common infectious causes of vaginitis. [Becton, Dickinson and Company] Press Release

Results from Shire’s Phase II Study of Maribavir Showed Activity against CMV Infection in Patients Undergoing Transplant

Shire plc presented data from a Phase II study evaluating maribavir, an investigational antiviral agent studied in patients with cytomegalovirus (CMV) infection undergoing hematopoietic stem cell transplant or solid organ transplant who are resistant or refractory to ganciclovir or foscarnet, drugs currently used to treat these infections. [Shire plc] Press Release

Fimbrion Therapeutics Pioneers Anti-Virulence Solutions to Treat UTIs

Fimbrion Therapeutics, Inc. recently obtained an exclusive license to patented technology from Washington University to develop small molecule drugs, known as mannosides, for the treatment and prevention of UTIs. [Fimbrion Therapeutics, Inc.] Press Release

Publisher Pulls 58 Articles by Iranian Scientists over Authorship Manipulation

A tranche of 58 articles authored by 282 Iran-based researchers were retracted by a leading scientific publisher, which said it had found signs that the peer review and publication processes had been compromised. [Nature News] Editorial

Young Scientists Ditch Postdocs for Biotech Start-Ups

There is a vanguard of young biomedical scientists who have started companies instead of taking the conventional academic path and pursuing postdoctoral studies after their PhDs. Among the factors driving this change are an infusion of money into early-stage biotech investing, the emergence of biotech incubators and the scarcity of academic jobs in science. [Nature News] Editorial

Beyond Trump vs Clinton: A Scientist’s Guide to the US Election

Choices that voters make will influence other levels of government — and some of these decisions will steer the course of science and science policy. [Nature News] Editorial

NEW Keystone Symposium: Mononuclear Phagocytes in Health, Immune Defense and Disease
April 30-May 4, 2017
Austin, United States

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NEW Project Research Scientist – Malaria Research (The Francis Crick Institute)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Infection and Immunity (University of Oxford)

Lecturer/Senior Lecturer/Reader – Immunology/Bacteriology (University of Bristol)

Research Specialist – Stem Cell Biology (University of Pittsburgh)

PhD Prize Studentships (University of Oxford)

Senior Postdoctoral Research Scientist – Genetics (University of Oxford)

Postdoctoral Position – Immunology (Klinikum der Universität München)

Faculty Positions – Immunology (Ohio State University)

Postdoctoral Positions – Mucosal, Innate and Adaptive Immunity (UT Southwestern Medical Center)

Faculty Position – Senior Immunologist (Fred Hutchinson Cancer Research Center)

Research Position – Immunotherapy Approach to Treat HIV Infection (California Institute of Technology)

Faculty Position – Immunology (Vanderbilt University Medical Center)

Postdoctoral Fellow – Mucosal Immunology (University of Utah)

Postdoctoral Research Fellow – Quantitative Infectious Disease Methods (Fred Hutchinson Cancer Research Center)

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