Immunology of Infectious Disease News Volume 5.24 | Jun 21 2017

TOP STORY

Human Virus-Derived Small RNAs Can Confer Antiviral Immunity in Mammals

Using human enterovirus 71 (HEV71) as a model, investigators showed HEV71 3A protein as an authentic viral suppressor of RNA interference (RNAi) during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. [Immunity] Abstract | Graphical Abstract

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Inflammatory Ly6C^high Monocytes Protect against Candidiasis through IL-15-Driven NK Cell/Neutrophil Activation

Scientists used a murine model of systemic candidiasis to explore the role of inflammatory Ly6C^high monocytes in NK cell-mediated neutrophil activation during the innate immune response against Candida albicans. They found that efficient anti-Candida immunity required a collaborative response between the spleen and kidney, which relied on type I interferon-dependent IL-15 production by spleen inflammatory Ly6C^high monocytes to drive efficient activation and GM-CSF release by spleen NK cells; this in turn was necessary to boost the Candida killing potential of kidney neutrophils. [Immunity] Abstract | Graphical Abstract

Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis

Investigators examined CD4 T cell responses to two leading tuberculosis vaccine antigens, ESAT-6 and Ag85B, in Mycobacterium tuberculosis (Mtb)-infected mice and in vaccinated humans with and without underlying Mtb infection. In both species, Mtb infection drove ESAT-6-specific T cells to be more differentiated than Ag85B-specific T cells. [Cell Host Microbe] Full Article | Graphical Abstract

Multiple Layers of Heterogeneity and Subset Diversity in Human MAIT Cell Responses to Distinct Microorganisms and to Innate Cytokines

The authors found that mucosa-associated invariant T (MAIT) cell responses against Escherichia coli and Candida albicans displayed microbe-specific polyfunctional response profiles, antigen sensitivity, and response magnitudes. MAIT cell effector responses against E. coli and C. albicans displayed differential MR1 dependency and TCR β-chain bias, consistent with possible divergent antigen subspecificities between these bacterial and fungal organisms. [Proc Natl Acad Sci USA] Full Article

Mito-Xenophagic Killing of Bacteria Is Coordinated by a Metabolic Switch in Dendritic Cells

Scientists showed that TNF-α controls a pathway by driving cytosolic phospholipase 2-mediated arachidonic acid (AA) production. AA then impaired mitochondrial function, which disturbed the development and integrity of energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promoted dendritic cell survival. [Sci Rep] Full Article

Memory-Phenotype CD4⁺ T Cells Spontaneously Generated under Steady-State Conditions Exert Innate T_H1-Like Effector Function

Researchers showed that memory-phenotype (MP) cells are autonomously generated from peripheral naïve cells in the absence of infectious stimulation in a T cell receptor– and CD28–dependent manner. They further demonstrated that MP cells contain a T-bet^hi subpopulation that is continuously generated by environmental IL-12 and rapidly produces interferon-γ in response to IL-12 in the absence of pathogen recognition. [Sci Immunol] Full Article

HIV

Clonal Expansion of Genome-Intact HIV-1 in Functionally Polarized Th1 CD4⁺ T Cells

Investigators performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4⁺ T cells, and subsets of functionally polarized memory CD4⁺ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4⁺ T cells harboring intact HIV-1. [J Clin Invest] Full Article

Follicular Regulatory T Cells Are Highly Permissive to R5-Tropic HIV-1

Scientists found follicular regulatory T cells (TFRs) were more permissive than follicular helper T cells to R5-tropic HIV-1 ex vivo. TFR expressed more CCR5 and CD4, and supported higher frequencies of viral fusion. [J Virol] Abstract

Simultaneous Knockout of CXCR4 and CCR5 Genes in CD4⁺ T Cells via CRISPR/Cas9 Confers Resistance to Both X4- and R5-Tropic HIV-1 Infection

Researchers ablated the CCR5 and CXCR4 genes in human CD4⁺ cell lines and primary CD4⁺ T cells, simultaneously, using CRISPR/Cas9, a well-developed, highly efficient genetic engineering tool. The efficiency of gene modification was as high as 55% for CCR5 and 36% for CXCR4 in CD4⁺ cell lines through infection of a single lentiviral vector, which were markedly protected from both HIV-1_NL4-3 and HIV-1_YU-2 infection. [Hum Gene Ther] Abstract

Increasing Procaspase 8 Expression Using Repurposed Drugs to Induce HIV Infected Cell Death in Ex Vivo Patient Cells

One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. Investigators tested whether increasing procaspase 8 levels in CD4 T cells would produce more Casp8p41 following HIV reactivation, causing more reactivated cells to die. [PLoS One] Full Article

Type I Interferons Suppress Viral Replication but Contribute to T Cell Depletion and Dysfunction during Chronic HIV-1 Infection

Scientists used a monoclonal antibody to block interferon-α/β receptor (IFNAR) 1 signaling during persistent HIV-1 infection in humanized mice. They discovered that, during chronic HIV-1 infection, IFNAR blockade increased viral replication, which was correlated with elevated T cell activation. [JCI Insight] Full Article

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Systems Immunology: Just Getting Started

Systems-biology approaches in immunology take various forms. The authors review strategies for measuring a broad swath of immunological functions as a means of discovering previously unknown relationships and phenomena and as a powerful way of understanding the immune system as a whole. [Nat Immunol] Abstract

The Role of IL-6 in Host Defence against Infections: Immunobiology and Clinical Implications

Clinical studies of IL-6 inhibitors, mainly tocilizumab, reveal that their use is associated with an increased rate of both serious and opportunistic infections generally in the range observed with other non-IL-6 directed biologic therapies. Targeting IL-6 has several other important clinical implications related to diagnosis, management and prevention of infectious diseases. [Nat Rev Rheumatol] Abstract

Visit our reviews page to see a complete list of reviews in the immunology of infectious disease research field.

GSK Presents Positive Results from Phase III Revaccination Study of Its Candidate Shingles Vaccine Shingrix

GSK will be presenting new results from a clinical study showing that its candidate vaccine for the prevention of herpes zoster (shingles) in people aged 50 years or older, Shingrix, induces a strong immune response in older adults who have previously been vaccinated against shingles with the currently available live-attenuated zoster vaccine. [Press release from GlaxoSmithKline plc. discussing research to be presented at the US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) Meeting, Atlanta] Press Release

INTERCEPT Blood System Highlighted at the International Society of Blood Transfusion (ISBT)

Cerus Corporation announced results of 16 abstracts presenting experiences with the INTERCEPT Blood System for platelets, plasma, and red blood cells. [Press release from Cerus Corporation discussing research presented at the 27^th Regional Congress of the International Society of Blood Transfusion (ISBT), Copenhagen] Press Release

NanoViricides Abstract Accepted for Poster Presentation

NanoViricides, Inc. announced that its late-breaking abstract submission has been accepted for a poster presentation. Dr. Brian Friedrich, Senior Virologist of the company, will present the company’s work on the evaluation of nanoviricides drug candidates for effectiveness against the shingles virus. [Press release from NanoViricides, Inc. (PR Newswire Association LLC.) discussing research presented at the 36^th Annual Meeting of the American Society of Virology (ASV), Madison] Press Release

SerImmune Inc. Announces Discovery and Development Collaboration with Merck

SerImmune Inc. announced a research and development collaboration agreement with a subsidiary of Merck. “This collaboration provides strong validation of our immune repertoire characterization platform following Merck’s participation in our financing,” said Patrick Daugherty, CEO of SerImmune. “We look forward to working with the scientists at Merck, to apply our unique platform to advance Merck’s pre-clinical development efforts in infectious diseases.” [SerImmune Inc. (PR Newswire Association LLC.)] Press Release

$3.6 Million NIH Grant Awarded to NYBC Scientist for Research on River Blindness Vaccine

New York Blood Center (NYBC) announced that researcher Dr. Sara Lustigman, Head of Laboratory of Molecular Parasitology at NYBC’s Lindsley F. Kimball Research Institute, has obtained a five-year, $3.6 million grant to put into action a strategic plan to create a preventative vaccine for River Blindness, with the ultimate goal of eliminating the disease from Sub-Saharan Africa. [New York Blood Center] Press Release

Seqirus Announces next Major Advancement in Cell-Based Influenza Vaccine Technology

Seqirus announced the next major advancement in the use of cell-based technology at its state-of-the art manufacturing facility in Holly Springs, North Carolina. Seqirus has successfully produced cell-based influenza vaccine at commercial scale using a candidate vaccine virus that has been isolated and grown in cells, rather than in eggs. [Seqirus] Press Release

Pfizer Begins Phase I Clinical Trial to Evaluate Investigational Group B Streptococcus Vaccine

Pfizer Inc. announced that it has started a Phase I trial in healthy volunteers of PF-06760805, an investigational vaccine designed to help protect against Group B Streptococcus (GBS) infection. In newborns, GBS manifests as sepsis, pneumonia, and meningitis, with potentially fatal outcomes for some, and long-lasting neurological damage in 46 to 50 percent of those infected. [Pfizer Inc.] Press Release

NanoBio and Porton Biopharma Receive Approval to Advance next Generation Anthrax Vaccine

NanoBio Corporation announced the progression of a novel intranasal anthrax vaccine into a pre-clinical IND-enabling toxicology study funded by the U.S. National Institute of Health’s National Institute of Allergy and Infectious Diseases. The vaccine combines NanoBio’s novel intranasal nanoemulsion adjuvant with recombinant protective antigen for anthrax from Porton Biopharma Ltd. Following the pre-clinical toxicology study, the vaccine will progress to a Phase I clinical trial. [NanoBio Corporation] Press Release

Ligand’s Partner Melinta Therapeutics Announces U.S. FDA Approval of Baxdela^™ (Delafloxacin) for Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Ligand Pharmaceuticals Incorporated’s partner Melinta Therapeutics announced that the U.S. Food and Drug Administration (FDA) has approved Baxdela^™, indicated in adults for the treatment of ABSSSI caused by susceptible bacteria. [Ligand Pharmaceuticals Incorporated] Press Release

Prof. Jamal Tazi, Inventor of ABX464, ABIVAX’s Lead Drug Candidate for Inducing a Functional Cure for HIV, Awarded the CNRS Medal of Innovation 2017

ABIVAX congratulates Prof. Jamal Tazi, inventor of ABX464, ABIVAX’s lead drug candidate for inducing a functional cure for HIV, and member of its Executive Committee, on receiving the CNRS Medal of Innovation 2017. [ABIVAX] Press Release

University of Tokyo Scientist Hit by Anonymous Allegations Fights Back

Last September, anonymous allegations of questionable data and images in 22 papers by six prominent groups at the prestigious University of Tokyo prompted the school to set up an investigating committee. Now, even before the panel completes its investigation, one of the accused researchers has mounted a staunch defense of his work, with a point-by-point rebuttal of the allegations and an apology for mistakes confirmed in several of the questioned papers. [ScienceInsider] Editorial

China Cracks Down on Fake Peer Reviews

The Chinese government is going on the offensive against scientists who dupe journals by creating fraudulent reviews of submitted papers. A coalition of agencies led by the science ministry announced that the government would suspend the grants of researchers involved in such fraud, which surfaced earlier this year when a cancer journal retracted 107 research papers from Chinese authors. [Nature News] Editorial

Strengthened US Sanctions on Cuba Disappoint Scientists

US President Donald Trump announced that he would strengthen travel and trade restrictions against Cuba, reversing his predecessor’s attempts to normalize relations with the country. The move is a blow to scientists who hoped that former president Barack Obama’s push to relax US restrictions on Cuba would make it easier for researchers there to travel and to collaborate with colleagues in the United States. [Nature News] Editorial

NEW Keystone Symposia: Malaria – From Innovation to Eradication
June 26, 2017
Online

NEW 12^th Asia Pacific Travel Health Conference
March 21-24, 2018
Bangkok, Thailand

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Researcher – Orbivirus (The Pirbright Institute)

NEW Postdoctoral Position – Infectious Diseases Pathogenesis (Massachusetts General Hospital & Harvard Medical School)

Research Associate – HIV Immunology (University College London)

Postdoctoral Scientist – HIV-1 and Malaria Vaccine Research (Center for Infectious Disease Research)

Postdoctoral Position – HIV in T Cells (Ludwig-Maximilians-Universität München)

Scientist – Immunology, Infectious Diseases (Regeneron)

Physician Scientist – Molecular Basis of Microbial Pathogenesis (Virginia Commonwealth University)

Research Scientist – Microbiology/Molecular Biology (Day Zero Diagnostics)

Lab Aide – Infectious Disease Sciences Program (Fred Hutchinson Cancer Research Center)

Cell Biology Scientists – T Cells Responsive to Various Infectious Disease Targets (Immunocore)

Scientist I/II – Analytical Development (KBI Biopharma)

Staff Clinician Position – Laboratory of Clinical Infectious Diseases (National Institute of Allergy and Infectious Diseases)

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