Volume 4.17 | May 2

Immunology of Infectious Disease News 4.17 May 4, 2016
Immunology of Infectious Disease News
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Ebola Vaccine: Promising Phase I Trials
The clinical Phase I trial of a potential vaccine against the dreaded Ebola virus has been successfully completed at four partner sites in Africa and Europe. The safety of the tested vaccine “rVSV-ZEBOV”, which induces persistent antibodies against the virus, has been confirmed. [Press release from the German Center for Infection Research discussing online prepublication in The New England Journal of Medicine]
Press Release | Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Unique Human Immune Signature of Ebola Virus Disease in Guinea
Researchers evaluated the physiology of the human T cell immune response in Ebola virus disease (EVD) patients at the time of admission and longitudinally until discharge or death. Through the use of multiparametric flow cytometry, they identified an immune signature that is unique in EVD fatalities. [Nature] Abstract

Topoisomerase 1 Inhibition Suppresses Inflammatory Genes and Protects from Death by Inflammation
Investigators identified topoisomerase 1 (Top1) as a positive regulator of RNA polymerase II transcriptional activity at pathogen-induced genes. Depletion or chemical inhibition of Top1 suppressed the host response against Influenza and Ebola viruses as well as bacterial products. [Science]
Abstract | Press Release 1 | Press Release 2

Maternal-Derived Hepatitis B Virus e Antigen Alters Macrophage Function in Offspring to Drive Viral Persistence after Vertical Transmission
Scientists developed a mouse model to study the effect of maternal hepatitis B virus (HBV) infection on HBV persistence in offspring and found that HBV carried by the mother impaired CD8+ T cell responses to HBV in her offspring, resulting in HBV persistence. [Immunity] Abstract | Graphical Abstract | Press Release

IRF7 Inhibition Prevents Destructive Innate Immunity—A Target for Nonantibiotic Therapy of Bacterial Infections
Scientists identified the transcription factor interferon regulatory factor 7 (IRF-7), a heterodimer partner of IRF-3, as a target for non–antibiotics-based therapy of bacterial infections. They identified IRF-7 as a target for immunomodulatory therapy. [Sci Transl Med] Abstract | Press Release

Transcriptome Signature for Dampened Th2 Dominance in Acellular Pertussis Vaccine-Induced CD4+ T Cell Responses through TLR4 Ligation
Transcriptomics analysis was performed on purified CD4+ T cells of control and vaccinated mice after in vitro restimulation with acellular pertussis vaccine antigens. Multiple key factors in T helper (Th) differentiation, including transcription factors, cytokines, and receptors, were identified within the differentially expressed genes. [Sci Rep] Full Article


Initiation of Immune Tolerance–Controlled HIV gp41 Neutralizing B Cell Lineages
In germline knock-in mice, broadly neutralizing antibody precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M. [Sci Transl Med] Abstract | Press Release

Public T Cell Receptors Confer High-Avidity CD4 Responses to HIV Controllers
To identify the molecular determinants that underlie this response, investigators characterized the T cell receptor (TCR) repertoire directed at Gag293, the most immunoprevalent CD4 epitope in the HIV-1 capsid. Transfer of these TCRs to healthy donor CD4+ T cells conferred high antigen sensitivity and polyfunctionality, thus recapitulating key features of the controller CD4 response. [J Clin Invest] Full Article

Modification of the HIV-Specific CD8+ T-Cell Response in an HIV Elite Controller after Chikungunya Virus Infection
Researchers evaluated the impact of Chikungunya virus (CHIKV) infection on the quality of the HIV-specific CD8+ T-cell (CTL) response in an HIV elite controller. The results showed that the phenotype and function of HIV-specific CTLs were modified in temporal association with an HIV viral load blip that followed CHIKV infection. [AIDS] Abstract

Early CD4+ T Cell Responses Are Associated with Subsequent CD8+ T Cell Responses to an rAd5-Based Prophylactic Prime-Boost HIV Vaccine Strategy
Scientists hypothesized that the IFN-γ producing cytotoxic CD8+ T cell responses could be predicted by early IL-2 producing CD4+ helper T cell responses, and evaluated this hypothesis using data from a Phase I/II prophylactic HIV vaccine trial. [PLoS One] Full Article

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Local Innate Immune Responses in the Vaccine Adjuvant-Injected Muscle
The authors focus on the initial innate immune events that occur locally at the site of intramuscular vaccine delivery, and how they are influenced by clinically approved vaccine adjuvants. [Clin Transl Immunol] Full Article

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Inovio Pharmaceuticals Showcases Its Broad Pipeline of DNA-Based Immunotherapies, Vaccines and dMAbs
Inovio Pharmaceuticals, Inc. announced it will exhibit the breadth and promise of its cancer and infectious disease immunotherapy, vaccine and DNA-based monoclonal antibody (dMAb) pipeline in ten presentations. [Press release from Inovio Pharmaceuticals, Inc. discussing research to be presented at the 19th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), Washington, DC] Press Release

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Inovio Partners with National Cancer Institute and Mayo Clinic to Initiate Hepatitis C Immunotherapy Clinical Trial
Inovio Pharmaceuticals, Inc. announced its immunotherapy for hepatitis C (INO-8000) will be evaluated in a Phase I trial in chronically infected patients who are not receiving other hepatitis C virus treatments. [Inovio Pharmaceuticals, Inc.] Press Release

Probing Resistance
Boston College microbial systems biologist Tim van Opijnen has been awarded a five-year, $10 million grant by the National Institutes of Health to lead a multidisciplinary team that will study the role of the immune system in the emergence of antibiotic-resistant bacteria. [Boston College] Press Release

Positive CHMP Opinion for CAZ AVI in the EU for Serious Bacterial Infections
AstraZeneca announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion, recommending the approval of a new antibiotic, CAZ AVI powder. CAZ AVI is being developed to treat a broad range of Gram-negative bacterial infections that are increasingly resistant to antibiotics. [AstraZeneca] Press Release
Funding Decline for a U.S. Government HIV/AIDS Initiative Raises Concerns
A U.S. government agency whose mission is to help save the lives of people around the world living with HIV and AIDS has seen a steep drop in funding for an important part of its budget. [UCLA] Editorial

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Therapeutic Goods Administration (Australia)
NEW Pediatric Infectious Diseases 2016
June 20-23, 2016
Hilton Head Island, United States

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NEW Faculty Positions – Immunology and Host-Microbe Interactions (Ohio State University)

NEW Research Positions – Basic Medical Sciences (Zhejiang University)

NEW Postdoctoral Position – Immunity and Pathogenesis (Sanford Burnham Prebys Medical Discovery Institute)

NEW Postdoctoral Position – Immunology (Erasmus MC)

Research Technologist – T Cell Immunology (STEMCELL Technologies Inc.)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Scientist – Bioengineering (STEMCELL Technologies Inc.)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Research Positions – Infection and Immunity (Columbia University)

Principal Investigators – Infectious Diseases (CCID)

Administrative Head – Vaccine and Infectious Disease (Fred Hutchinson Cancer Research Center)

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