Immunology of Infectious Disease News Volume 8.21 | Jun 3 2020

TOP STORY

During Aspergillus Infection, Monocyte-Derived DCs, Neutrophils, and Plasmacytoid DCs Enhance Innate Immune Defense through CXCR3-Dependent Crosstalk

Aspergillus-infected murine monocyte-derived dendritic cells (DCs) and neutrophils recruited plasmacytoid DCs to the lung by releasing the CXCR3 ligands, CXCL9 and CXCL10, in a Dectin-1 and Card9- and type I and III interferon signaling-dependent manner, respectively. [Cell Host Microbe] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

SARS-CoV-2

Two Linear Epitopes on the SARS-CoV-2 Spike Protein That Elicit Neutralising Antibodies in COVID-19 Patients

Researchers report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that were recognized by sera from COVID-19 convalescent patients. One was specific to SARS-CoV-2, which was located in close proximity to the receptor binding domain. [Nat Commun] Full Article

Structural and Biochemical Characterization of nsp12-nsp7-nsp8 Core Polymerase Complex from SARS-CoV-2

The authors describe the near-atomic resolution structure of the SARS-CoV-2 polymerase complex, consisting of nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembled the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases, and suggested the mechanism for activation by cofactors. [Cell Rep] Abstract | Full Article | Graphical Abstract

Neutrophil Extracellular Traps in COVID-19

Investigators report that sera from patients with COVID-19 had elevated levels of cell-free DNA, myeloperoxidase-DNA, and citrullinated histone H3; the latter two were highly specific markers of neutrophil extracellular traps. [JCI Insight] Abstract | Full Article

Proteolytic Cleavage of the SARS-CoV-2 Spike Protein and the Role of the Novel S1/S2 Site

Scientists investigated the potential role of this novel S1/S2 cleavage site and present direct biochemical evidence for proteolytic processing by a variety of proteases. They discuss these findings in the context of the origin of SARS-CoV-2, viral stability and transmission. [iScience] Abstract | Full Article | Graphical Abstract

MORE IMMUNOLOGY OF INFECTIOUS DISEASE

Ecto-NTPDase CD39 Is a Negative Checkpoint That Inhibits Follicular Helper Cell Generation

The authors found that T follicular helper (Tfh) generation was inversely linked to the expression of the ecto-NTPDase CD39 that modified purinergic signaling. The lineage-determining transcription factor BCL6 inhibited CD39 expression, while increased Tfh frequencies were found in individuals with a germline polymorphism preventing transcription of ENTPD1, encoding CD39. [J Clin Invest] Full Article | Graphical Abstract

Plasma-Derived Extracellular Vesicles from Plasmodium vivax Patients Signal Spleen Fibroblasts via NF-kB Facilitating Parasite Cytoadherence

Investigators demonstrated that plasma-derived extracellular vesicles (EVs) from Plasmodium vivax patients were preferentially uptaken by human spleen fibroblasts as compared to the uptake of EVs from healthy individuals. [Nat Commun] Full Article

Malaria Parasites Regulate Intra-Erythrocytic Development Duration via Serpentine Receptor 10 to Coordinate with Host Rhythms

Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, researchers revealed that 57% of Plasmodium chabaudi genes exhibited daily rhythms in transcription and 58% of these genes lost transcriptional rhythmicity when the intra-erythrocytic developmental cycle was out-of-synchrony with host rhythms. [Nat Commun] Full Article

Antibody-Induced Internalization of Retroviral Envelope Glycoproteins Is a Signal Initiation Event

Investigators examined the impact of endogenous retroviral envelope glycoprotein expression and interaction with host proteins, particularly antibodies, on the cell, independently of retroviral infection. [PLoS Pathog] Full Article

Opsonization-Enhanced Antigen Presentation by MR1 Activates Rapid Polyfunctional MAIT Cell Responses Acting as an Effector Arm of Humoral Antibacterial Immunity

Researchers investigated the interplay between mucosa-associated invariant T (MAIT) cell-mediated antibacterial effector functions and the humoral immune response. IgG opsonization of the model microbe Escherichia coli with pooled human sera markedly enhanced the capacity of monocytic APC to stimulate MAIT cells. [J Immunol] Abstract

Lipid Nanoparticle Formulation Increases Efficiency of DNA-Vectored Vaccines/Immunoprophylaxis in Animals Including Transchromosomic Bovines

Scientists demonstrated that neutralizing antibodies produced in rabbits and non-human primates injected with lipid nanoparticle-formulated Andes virus or Zika virus DNA vaccines were elevated over unformulated vaccine. [Sci Rep] Full Article

CD137 Costimulation Enhances the Antiviral Activity of Vγ9Vδ2-T Cells against Influenza Virus

Scientists found that the expression of CD137 was inducible in Vγ9Vδ2-T cells following antigenic stimulation. CD137⁺Vγ9Vδ2-T cells displayed more potent antiviral activity against influenza virus than their CD137⁻ counterparts in vitro and in Rag2^-/-γc^-/- mice. [Signal Transduct Target Ther] Full Article

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Type I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19

The authors describe the recent progress in our understanding of both type I and type III interferon (IFN)-mediated innate antiviral responses against human coronaviruses and discuss the potential use of IFNs as a treatment strategy for COVID-19. [Cell Host Microbe] Full Article

Immune Response in COVID-19: Addressing a Pharmacological Challenge by Targeting Pathways Triggered by SARS-CoV-2

While a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. [Signal Transduct Target Ther] Full Article

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Relief Therapeutics and NeuroRx Announce Enrollment of First Patients with RLF- 100 in Phase IIb/III Clinical Trial in Patients with COVID-19 Associated Acute Respiratory Distress

Holding AG and its US partner, NeuroRx, Inc. announced treatment of the first patients with RLF-100 at the University of Miami Miller School of Medicine, Fla. This is part of a Phase IIb/III clinical trial to assess RLF-100 as a treatment for Acute Respiratory Distress Syndrome in COVID-19 patients on mechanical ventilation. [Relief Therapeutics] Press Release

Moderna Announces First Participants in Each Age Cohort Dosed in Phase II Study of mRNA Vaccine (mRNA-1273) against Novel Coronavirus

Moderna, Inc. announced that the first participants in each age cohort have been dosed in the company’s Phase II study of its mRNA vaccine candidate against the novel coronavirus. [Moderna, Inc.] Press Release

Ashvattha Therapeutics Subsidiary Orpheris Announces FDA Agreement to Initiate Phase II Study Evaluating OP-101 in Severe COVID-19 Patients

Orpheris announced the FDA has agreed to a Phase II clinical study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of OP-101 in patients with severe COVID-19. [Ashvattha Therapeutics] Press Release

Apellis Initiates Phase I/II Study of APL-9 in Patients with Severe COVID-19

Apellis Pharmaceuticals, Inc. announced that the company has initiated a Phase I/II clinical study of APL-9, an investigational C3 inhibitor designed for acute interventions, in COVID-19 patients with respiratory failure including acute respiratory distress syndrome. [Apellis Pharmaceuticals, Inc.] Press Release

A Mysterious Company’s Coronavirus Papers in Top Medical Journals May Be Unraveling

The Lancet results on chloroquine and hydroxychloroquine have begun to unravel-and Surgisphere, which provided patient data for two other high-profile COVID-19 papers, has come under withering online scrutiny from researchers and amateur sleuths. [ScienceInsider] Editorial

Operation Warp Speed Selects Billionaire Scientist’s COVID-19 Vaccine for Monkey Tests

Billionaire scientist and businessman Patrick Soon-Shiong announced in a 27 May investor call and press release that an experimental vaccine being developed by two of his companies is on the short list of 14 candidates being evaluated by Operation Warp Speed, the Trump administration’s push to deliver 300 million doses of safe and effective COVID-19 vaccines by January 2021. [ScienceInsider] Editorial

What’s the Risk that Animals Will Spread the Coronavirus?

Soon after the new coronavirus started spreading around the globe, reports emerged of cases in animals – pet cats in Hong Kong, tigers in a New York City zoo and mink on farms in the Netherlands. Now researchers are urgently trying to discover which species can catch the virus, and whether they can pass it to people. [Nature News] Editorial

India Expands Use of Controversial Drug for Coronavirus despite Safety Concerns

As safety concerns prompt several countries to reconsider the controversial use of a malaria drug to treat COVID-19, India’s government is recommending that front-line workers take the medicine to prevent infection. [Nature News] Editorial

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NEW Postdoctoral Fellow – Host-Viral Interactions (Thomas Jefferson Universtiy)

Postdoctoral Fellowship – Vaccinations (Brigham and Women’s Hospital)

Postdoctoral Researcher – Pathogenic Fungi (Leibniz Institute for Natural Product Research and Infection Biology)

Postdoctoral Researcher – Peptide-Based Antibiotics (University of Copenhagen)

Postdoctoral Fellow – Innate Lymphocytes and Influenza Pathogenesis (Oklahoma Medical Research Foundation)

Postdoctoral Fellow – Bacterial Infection (Seattle Children’s Research Institute)

Postdoctoral Researcher – Human Pathogenicity and Fungi (Hans Knöll Institute)

Research Fellow – Infectious Disease (The Lundquist Institute)

Director – Malaria Research (Johns Hopkins University)

Chair – Department of Microbiology and Immunology (Western University)

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