Immunology of Infectious Disease News Volume 8.04 | Feb 5 2020

TOP STORY

Potent Zika and Dengue Cross-Neutralizing Antibodies Induced by Zika Vaccination in a Dengue-Experienced Donor

Using a unique Zika virus (ZIKV) virion-based sorting strategy, the authors isolated and characterized multiple antibodies, including one termed MZ4, which targeted a novel site of vulnerability centered on the Envelope domain I/III linker region and protected mice from viremia and viral dissemination following ZIKV or dengue virus challenge. [Nat Med] Abstract

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Combination Anti-HIV-1 Antibody Therapy Is Associated with Increased Virus-Specific T Cell Immunity

Researchers documented increased HIV-1 Gag-specific CD8⁺ T cell responses in the peripheral blood of nine study participants who were infected with HIV-1 with suppressed blood viremia, while receiving broadly neutralizing antibodies therapy during antiretroviral therapy interruption. [Nat Med] Abstract

Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebola Virus Neutralization

Investigators systematically analyzed the antibody repertoire in human survivors and identified a pair of potently neutralizing monoclonal antibodies (mAbs) that cooperatively bound to the ebolavirus glycoprotein. High-resolution structures revealed that in a two-antibody cocktail, molecular mimicry was a major feature of mAb-glycoprotein interactions. [Immunity] Abstract | Graphical Abstract

Targeting p53 and Histone Methyltransferases Restores Exhausted CD8⁺ T Cells in HCV Infection

Researchers showed that in early hepatitis C virus (HCV) infection, exhaustion-committed virus-specific CD8⁺ T cells displayed a marked upregulation of transcription associated with impaired glycolytic and mitochondrial functions, that were linked to enhanced ataxia-telangiectasia mutatedand p53 signaling. [Nat Commun] Full Article

Neonatal Rhesus Macaques Have Distinct Immune Cell Transcriptional Profiles Following HIV Envelope Immunization

Trimeric forms of HIV-1 envelope (Env) immunogens elicited increased gp120- and gp41-specific antibodies more rapidly in neonatal macaques than adult macaques. Transcriptome analyses of neonatal versus adult immune cells after Env vaccination revealed that neonatal macaques had higher levels of the apoptosis regulator BCL2 in T cells and lower levels of the immunosuppressive IL-10 receptor alpha mRNA transcripts in T cells, B cells, NK cells, and monocytes. [Cell Rep] Full Article | Graphical Abstract

The Deubiquitinase OTUB1 Augments NF-κB-Dependent Immune Responses in Dendritic Cells in Infection and Inflammation by Stabilizing UBC13

The authors reveal that the deubiquitinase OTU domain, ubiquitin aldehyde binding 1 (OTUB1) was upregulated in dendritic cells (DCs) upon murine Toxoplasma gondii infection and lipopolysaccharide challenge. Stimulation of DCs with the TLR11/12 ligand T. gondii profilin and the TLR4 ligand lipopolysaccharide induced an increase in nuclear factor-κB activation in OTUB1-competent cells, resulting in elevated IL-6, IL-12, and tumor necrosis factor production, which was also observed upon the specific stimulation of TLR2, TLR3, TLR7, and TLR9. [Cell Mol Immunol] Full Article

Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections

Ten combinations of PreS1 and/or chronic hepatitis D virus (HBD) antigen sequences were evaluated for induction of PreS1 and/or HBV- and HDV- specific T cells in vitro and in vivo. Neutralization of HBV by PreS1-specific murine and rabbit antibodies was evaluated in cell culture, and rabbit anti-PreS1 were tested for neutralization of HBV in mice repopulated with human hepatocytes. [J Infect Dis] Full Article

Chromatin Maturation of the HIV-1 Provirus in Primary Resting CD4⁺ T Cells

Investigators characterized proviral transcription and chromatin development in cultures of resting primary CD4⁺ T-cells for four months after ex vivo HIV-1 infection. As heterochromatin gradually stabilized, the provirus became less accessible with reduced activation potential. [PLoS Pathog] Full Article

Cell-Mediated Immune Response and Protective Efficacy of Porcine Reproductive and Respiratory Syndrome Virus Modified-Live Vaccines Against Co-Challenge with PRRSV-1 and PRRSV-2

70, porcine reproductive and respiratory syndrome virus (PRRSV)-free, three-week old, pigs were allocated into seven groups. Six groups were intramuscularly vaccinated with modified live vaccines (MLV), including Porcilis, Amervac, Fostera, Ingelvac PRRS MLV and Ingelvac PRRS ATP, and Prime Pac PRRS. Unvaccinated pigs were left as control. Lymphocyte proliferative response, IL-10 and IFN-γ production were determined. [Sci Rep] Full Article

GABA Potentiate the Immunoregulatory Effects of Lactobacillus brevis BGZLS10-17 via ATG5-Dependent Autophagy In Vitro

Researchers investigated the immunological effects of live bacteria-free supernatant collected from GABA-producing L. brevis BGZLS10-17 on Concanavalin A-stimulated mesenteric lymph node cells (MLNC), an in vitro model of activated immune cells. They showed that GABA containing and GABA-free supernatant of Lactobacillus brevis BGZLS10-17 had strong immunoregulatory effects on MLNC. [Sci Rep] Full Article

A New Class of Broadly Neutralizing Antibodies That Target the Glycan Loop of Zika Virus Envelope Protein

The authors isolated five Zika virus (ZIKV) neutralizing monoclonal antibodies from E80-immunized mice. These five mAbs specifically bound and neutralized Asian-lineage ZIKV strains. Epitope mapping revealed that all of the five mAbs recognized a novel linear epitope located on the glycan loop of E protein domain I. [Cell Discov] Full Article

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Rethinking Mucosal Antibody Responses: IgM, IgG and IgD Join IgA

The authors discuss how mucosal IgA responses occur in an increasingly complex humoral defence network that also encompasses IgM, IgG and IgD. Aside from integrating the protective functions of IgA, these hitherto neglected mucosal antibodies may strengthen the communication between mucosal and systemic immune compartments. [Nat Rev Immunol] Abstract

Skin Interface, a Key Player for Borrelia Multiplication and Persistence in Lyme Borreliosis

Numerous in vitro studies have been conducted to better understand the role of specific skin cells and tick saliva in host defense, vector feeding, and pathogen transmission. Investigators present the achievements in this field as well as the gaps that impede comprehensive knowledge of the disease pathophysiology and the development of efficient diagnostic tools and vaccines in humans. [Trends Parasitol] Abstract

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Alkahest Initiates a Phase II Clinical Trial of AKST4290 in Parkinson’s Disease with Funding from the Michael J. Fox Foundation

Alkahest, Inc. announced the dosing of the first patient in a Phase II clinical trial of AKST4290, an orally administered CCR3 inhibitor, for treatment of Parkinson’s disease. The trial, AKST4290-211, is funded in part by The Michael J. Fox Foundation for Parkinson’s Research and will evaluate the effect of AKST4290 on motor function and activities of daily living in patients with Parkinson’s disease. [Alkahest, Inc (GlobeNewswire, Inc.)] Press Release

Insmed Announces Positive Top-Line Results from Phase II WILLOW Study of INS1007 in Patients with Non-Cystic Fibrosis Bronchiectasis

Insmed Incorporated announced positive top-line results from its global, randomized, double-blind placebo-controlled Phase II WILLOW study evaluating the efficacy, safety, and pharmacokinetics of INS1007 administered once daily in adults with non-cystic fibrosis bronchiectasis. [Insmed, Inc.] Press Release

SQZ Biotech Announces First Patient Dosed in Phase I Trial of SQZ-PBMC-HPV for HPV⁺ Tumors

SQZ Biotechnologies (SQZ) announced that the first patient in its Phase I clinical trial of SQZ-PBMC-HPV has received their first dose. SQZ-PBMC-HPV is an autologous cell therapy candidate comprised of SQZ-engineered antigen presenting cells designed to induce CD8 T cell responses against HPV16. [SQZ Biotechnologies] Press Release

‘This Beast Is Moving Very Fast.’ Will the New Coronavirus Be Contained-or Go Pandemic?

Two months after 2019-nCoV emerged—and with well over 20,000 cases and 427 deaths as of 4 February—mathematical modelers have been racing to predict where the virus will move next, how big a toll it might ultimately take, and whether isolating patients and limiting travel will slow it. But to make confident predictions, they need to know much more about how easily the virus spreads, how sick it makes people, and whether infected people with no symptoms can still infect others. [ScienceInsider] Editorial

Ex-Emory Scientist with Ties to China Charged with Fraud

A former Emory University neuroscientist has been charged with defrauding the US government by taking a salary from a Chinese institution while also being paid through research grants from the National Institutes of Health. The charges against Li Xiao-Jiang were filed on 21 November 2019 in US district court in Atlanta and were first reported by NBC News. [ScienceInsider] Editorial

NEW Exosomes in Human Infectious Diseases Conference
March 5-8, 2020
Nassau, Bahamas

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NEW Postdoctoral Fellow – Innate Immune Response to Mycobacterium tuberculosis (The Francis Crick Institute)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Pathogen/Host Cell Interactions (University Hospital of Müenster)

Postdoctoral Researcher – Microtubules in Viral Infection (Northwestern Feinberg School of Medicine)

Postdoctoral Researcher – HIV Antiretroviral Therapy (Karolinska Institutet)

Postdoctoral Researcher – Infection and Aging Biology (Karolinska Institutet)

Postdoctoral Fellow – HIV (Massachusetts General Hospital)

Postdoctoral Fellow – Vaccine Research (University of Rhode Island)

Postdoctoral Scientist – Tuberculosis Research (Texas Biomedical Research Institute)

Research Associate – Immunology (University Hospital of Muenster)

Postdoctoral Fellow – Immunology (Harvard T.H. Chan School of Public Health)

Postdoctoral Fellowship – Infectious Disease (Brigham and Women’s Hospital)

Postdoctoral Research Fellow – HIV (Fred Hutchinson Cancer Research Center)

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