Volume 2.43 | Nov 5

Immunology of Infectious Disease News 2.43 November 5, 2014
Immunology of Infectious Disease News
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Host Genetic Diversity Enables Ebola Hemorrhagic Fever Pathogenesis and Resistance
Scientists show that mice from the Collaborative Cross exhibit distinct disease phenotypes following mouse-adapted Ebola virus infection. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, likely mediated by the susceptibility allele Tek. [Science] Full Article | Press Release
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A Spaetzle-Like Role for Nerve Growth Factor β in Vertebrate Immunity to Staphylococcus aureus
Nerve growth factor β was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. [Science] Abstract

Autophagy Is Essential for Effector CD8+ T Cell Survival and Memory Formation
Researchers report that autophagy was dynamically regulated in virus-specific CD8+ T cells during acute infection of mice with lymphocytic choriomeningitis virus. In contrast to the current paradigm, autophagy decreased in activated proliferating effector CD8+ T cells and was then upregulated when the cells stopped dividing just before the contraction phase. [Nat Immunol] Abstract

CD28 Expression Is Required after T Cell Priming for Helper T Cell Responses and Protective Immunity to Infection
Investigators show that continued CD28 expression is important for effector CD4+ T cells following infection; maintained CD28 is required for the expansion of T helper type 1 cells, and for the differentiation and maintenance of T follicular helper cells during viral infection. [eLife] Abstract | Full Article

Failure of Antigen-Specific CD4+ T Cell Recruitment to the Kidney during Systemic Candidiasis
Using Ag-loaded immunoliposomes to artificially reverse the defective migration of Ag-specific CD4+ T cells into infected kidneys, scientists show that recruited cells polarize toward a Th17 phenotype in the kidney and are protective during fungal infection. [J Immunol] Abstract | Full Article

CD4+ T Cell Help Is Dispensable for Protective CD8+ T Cell Memory against Mousepox following Vaccinia Virus Immunization
Researchers show that CD4+ T helper cells play a role but are not essential for the maintenance, proliferation and effector differentiation of polyclonal memory CD8+ T cells after infection with wild type vaccinia virus WR. [J Virol] Abstract


CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells
Scientists used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigated the sources of the increased viral burden and the lifespan of productively infected cells. [PLoS Pathog] Full Article | Press Release

Multiplexing 7 miRNA-Based shRNAs to Suppress HIV Replication
The authors describe a simple strategy to express a large number of miRNA-based shRNAs (shRNA-miR) using minimal flanking sequences from multiple endogenous miRNAs. The lentiviral construct was pseudotyped with HIV-1 envelope to allow transduction of both resting and activated primary CD4 T cells. Unlike single shRNA-miRs, the 7shRNA-miR transduced T cells nearly abrogated HIV-1 infection in vitro. [Mol Ther] Abstract

Virological and Immunological Characterization of Novel NYVAC-Based HIV/AIDS Vaccine Candidates Expressing Clade C Trimeric Soluble gp140(ZM96) and Gag(ZM96)-Pol-Nef(CN54) as VLPs
Analysis of the immune responses elicited in mice after homologous NYVAC prime/NYVAC boost immunization shows that recombinant viruses induced polyfunctional Env-specific CD4 or Gag-specific CD8 T cell responses. [J Virol] Abstract

Reconstitution of Intestinal CD4 and Th17 T Cells in Antiretroviral Therapy Suppressed HIV-Infected Subjects: Implication for Residual Immune Activation from the Results of a Clinical Trial
Researchers examined intestinal and peripheral CD4+ T-cell subsets reconstitution under combined antiretroviral therapy (cART) and systemic immune activation markers. Eight months of cART increased intestinal CD4+ and Th17 cells and reduced levels of T-cell activation and proliferation. [PLoS One] Full Article

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Antibody Persistence and T-Cell Balance: Two Key Factors Confronting HIV Vaccine Development
The authors discuss the evidence illustrating the poor persistence of antibody responses to Env, the envelope glycoprotein of HIV-1, and the related problem of CD4+ T-cell responses that compromise vaccine efficacy by creating excess cellular targets of HIV-1 infection. [Proc Natl Acad Sci USA] Full Article

Dissecting the Dendritic Cell Controversy in Chronic Hepatitis B Virus Infection
The authors summarize multiple studies investigating dendritic cell function in chronic hepatitis B virus patients to determine whether common observations can be drawn. [Cell Mol Immunol] Abstract

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Novel Nanofiber-Based Technology Could Help Prevent HIV/AIDS Transmission
Scientists have developed a novel topical microbicide loaded with hyaluronic acid nanofibers that could potentially prevent transmission of the human immunodeficiency virus (HIV) through the vaginal mucosa. [Press release from the American Association of Pharmaceutical Sciences (AAPS) discussing research presented at the 2014 AAPS Annual Meeting and Exposition, San Diego] Press Release

Model by NIH Grantees Explains Why HIV Prevention Dosing Differs by Sex
A mathematical model developed by NIH grantees predicts that women must take the antiretroviral medication Truvada daily to prevent HIV infection via vaginal sex, whereas just two doses per week can protect men from HIV infection via anal sex. This finding helps explain why two large clinical trials testing HIV pre-exposure prophylaxis in women failed to show efficacy. [National Institute of Allergy and Infectious Diseases] Press Release

Positive Clinical Results Indicate Vaccine Candidate Is Highly Efficacious against Bacterial Diarrhea
New results from a safety and immunogenicity study, which included a challenge phase to test efficacy, indicate that a live attenuated enterotoxigenic Escherichia coli vaccine candidate, given in combination with a novel adjuvant, provided significant protection against disease. [PATH] Press Release

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Profectus BioSciences Receives $9.5 Million Department of Defense Funding to Manufacture Trivalent VesiculoVax™-Vectored Vaccine to Protect against All Ebola and Marburg Viruses
Profectus BioSciences, Inc. announced that the Department of Defense has contracted the manufacture and IND-enabling preclinical testing of the Profectus trivalent Ebola/Marburg vaccine. [Profectus BioSciences, Inc.] Press Release

Affinivax Launches Novel Conjugate Vaccine for Global Impact on Infectious Diseases
Affinivax Inc. announced its launch with a $4 million investment from the Bill & Melinda Gates Foundation. Proceeds from the funding will be used to develop Affinivax’s multiple antigen presenting system technology platform and enable the development of novel vaccines to protect children and adults in both the developed and developing worlds, with an initial focus on the company’s lead drug program for Streptococcus pneumoniae. [Affinivax Inc.] Press Release

Hemispherx Biopharma and United States Army Medical Research Institute of Infectious Diseases (USAMRIID) Collaborate on Alferon® and Ampligen® Against the Ebola Virus
Hemispherx Biopharma, Inc. has been informed by USAMRIID scientists that they have in vitro data indicating that Alferon® successfully protected human cells against the Ebola virus. [Hemispherx Biopharma, Inc.] Press Release

TNI BioTech, Inc., through Its Wholly Owned Subsidiary TNI BioTech International Ltd., Announces Start of a Bridging Trial in Nigeria for HIV/AIDS
TNI BioTech, Inc. announced the initiation of a 90-day bridging trial in Nigeria of Lodonal™ in patients with HIV/AIDS. The bridging trial goal is to supplement clinical data submitted to the National Agency for Food and Drug Administration and Control to confirm safety, tolerability and efficacy in the local population. [TNI BioTech, Inc.] Press Release
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NEW Immunology of Fungal Infections
January 18-23, 2015
Galveston, United States

NEW Cell & Gene Therapy Forum 2015
January 26-28, 2015
Washington DC, United States

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NEW Postdoctoral Fellowship – Universal Influenza Vaccine Development (National Institute of Allergy and Infectious Diseases)

NEW Postdoctoral Fellow – B Cell Responses Induced by HPV Vaccines (Leidos Biomedical Research, Inc.)

NEW Postdoctoral Position – Viral Pathogenesis (The Scripps Research Institute)

Postdoctoral Scientist – Host Genetic Factors and Activity of Endogenous Retroviruses (Medical Research Council)

Postdoctoral Research Fellow – Mucosal Immune System in Chronic and Infectious Disease (Griffith Health Institute)

Postdoctoral Research Fellow – Immune Responses to HSV (Fred Hutchinson Cancer Research Center)

Associate Professor – Molecular Immunology (Chiba University)

Research Fellow – Gene Expression of Immune Cells in Response to Infection (The University of Nottingham)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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