Immunology of Infectious Disease News Volume 7.32 | Aug 21 2019

TOP STORY

Nuclear hnRNPA2B1 Initiates and Amplifies the Innate Immune Response to DNA Viruses

Scientists report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) recognized pathogenic DNA and amplified interferon-α/β production. Upon DNA virus infection, nuclear-localized hnRNPA2B1 sensed viral DNA, homodimerizes, and was then demethylated at arginine-226 by the arginine demethylase JMJD6. [Science] Abstract

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Safety and Immunogenicity of the Chlamydia Vaccine Candidate CTH522 Adjuvanted with CAF01 Liposomes or Aluminium Hydroxide: A First-In-Human, Randomized, Double-Blind, Placebo-Controlled, Phase I Trial

The authors assessed the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime-boost immunization schedule. [Lancet Infect Dis] Abstract | Press Release

Mycobacterium tuberculosis Releases an Antacid that Remodels Phagosomes

During macrophage infection, a 1-tuberculosinyladenosine biosynthesis gene conferred marked phagosomal swelling and intraphagosomal inclusions, demonstrating an essential role in regulating the M. tuberculosis (Mtb) cellular microenvironment. Although macrophages killed intracellular bacteria through phagosome acidification, Mtb coated itself abundantly with antacid. [Nat Chem Biol] Abstract | Press Release

Repeated Semen Exposure Decreases Cervicovaginal SIVmac251 Infection in Rhesus Macaques

Repeated semen exposures result in lower CCR5 expression in circulating CD4⁺ T cells, as well as higher expression of Mx1 and FoxP3 in the cervicovaginal mucosa, and increased infiltration of CD4⁺ T cells. [Nat Commun] Full Article | Press Release

Expression of CD20 after Viral Reactivation Renders HIV-Reservoir Cells Susceptible to Rituximab

In lymph node samples from infected patients, CD20 was present in productively HIV-infected cells, and ex vivo viral infection selectively upregulated the expression of CD20 during early infection. In samples from patients on antiretroviral therapy this subpopulation was significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induced cell killing, which reduced the pool of HIV-expressing cells when combined with latency reversal agents. [Nat Commun] Full Article

Risk of Zika Microcephaly Correlates with Features of Maternal Antibodies

Scientists examined the serum antibody response to Zika virus (ZIKV) and other flaviviruses in Brazilian women giving birth during the 2015–2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers. [J Exp Med] Full Article | Press Release

Immunogenicity of RNA Replicons Encoding HIV Env Immunogens Designed for Self-Assembly into Nanoparticles

To evaluate the potential of lipid nanoparticle-formulated replicons for delivery of HIV immunogens, the authors designed and tested an alphavirus replicon expressing a self-assembling protein nanoparticle immunogen, the gp120 engineered outer domain (eOD-GT8)-60mer. The eOD-GT8 immunogen was a germline-targeting antigen designed to prime human B cells capable of evolving toward VRC01class broadly neutralizing antibodies. [Mol Ther] Abstract | Graphical Abstract

Attenuation of the Innate Immune Response against Viral Infection Due to ZNF598-Promoted Binding of FAT10 to RIG-I

Researchers showed that ZNF598 was a negative regulator of the RIG-I-mediated signaling pathway, and endogenous ZNF598 protein bound to RIG-I. ZNF598 ubiquitin ligase activity was dispensable for the suppression of RIG-I signaling. [Cell Rep] Full Article | Graphical Abstract

Neutrophils Express Pro- and Anti-Inflammatory Cytokines in Granulomas from Mycobacterium tuberculosis-Infected Cynomolgus Macaques

Scientists compared neutrophil and T-cell expression of the Th1 cytokines IFNγ and TNF, the Th2 cytokine IL-4, and regulatory cytokine IL-10 in M. tuberculosis-infected macaques to determine if neutrophil cytokine expression contributes to dysregulated immunity in tuberculosis. [Mucosal Immunol] Abstract

HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy

HIV-specific T cell responses were detectable by ex vivo IFN-γ ELISpot in persons living with HIV, despite median durable ART suppression of 5.0 years. No substantial association was detected between the summed HIV-specific T cell response and the size of the replication competent HIV reservoir. [Mol Ther Methods Clin Dev] Abstract | Full Article

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Interplay between Intrinsic and Innate Immunity during HIV Infection

The authors highlight recent knowledge of the interplay between restriction factors and immunity inducing antiviral defenses. Counteraction of this intrinsic and innate immunity by HIV viral proteins is also discussed. [Cells] Full Article

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IBBR Collaborates with Integrated BioTherapeutics to Advance a Novel Approach to Treating Infectious Disease

Institute for Bioscience and Biotechnology Research (IBBR) Fellow Dr. Daniel Nelson is working on an innovative approach to treating bacterial disease in collaboration with Dr. Rajan Adhikari, Assistant Director of Bacteriology at Integrated BioTherapeutics, and George Mason University’s Dr. Ramin Hakami. The group recently received a $3M Phase II STTR award from the National Institutes of Health that will fund advancement of their novel immunotherapeutic into non-human primates, as well as optimization of a cell line for biomanufacturing the drug. [Institute for Bioscience and Biotechnology Research] Press Release

CytoDyn Provides Update on Dose Escalating Trial with Leronlimab for HIV Monotherapy for a Potential Pivotal Trial

CytoDyn Inc. announced an update on its HIV dose escalating monotherapy trial. HIV patients received dosages of 350 mg, 525 mg, or 700 mg of leronlimab once a week with approximately 150 patients exhibiting sustained viral suppression at approximately one year of monotherapy. [CytoDyn Inc.] Press Release

Altimmune Announces $3.7 Million in Additional BARDA Funding to Advance NasoShield^™ Clinical Development

Altimmune, Inc. announced that the Biomedical Advanced Research and Development Authority (BARDA) is modifying its existing anthrax vaccine development contract with Altimmune by awarding an additional $3.7 million. [Altimmune, Inc.] Press Release

Eiger Announces FDA Breakthrough Therapy Designation for Peginterferon Lambda for Treatment of Hepatitis Delta Virus Infection

Eiger BioPharmaceuticals, Inc. announced that the FDA has granted Breakthrough Therapy Designation for peginterferon lambda (Lambda) for the treatment of hepatitis delta virus infection. Lambda is a well-characterized, late-stage, first-in-class, type III interferon that stimulates immune responses that are critical for the development of host protection during viral infections. [Eiger BioPharmaceuticals, Inc. (PR Newswire Association LLC.)] Press Release

Moderna Receives FDA Fast Track Designation for Zika Vaccine mRNA-1893

Moderna, Inc. announced that the FDA has granted Fast Track designation for its investigational Zika vaccine currently being evaluated in a Phase I study for the prevention of Zika virus infection in healthy adults. [Moderna, Inc.] Press Release

The Pfizer Foundation Invests in 20 Organizations Tackling Infectious Diseases and Antimicrobial Resistance

The Pfizer Foundation announced 20 grants to help non-governmental organizations, non-profits and social enterprises address critical health challenges related to infectious diseases, including the increasing threat of antimicrobial resistance, in some of the world’s most vulnerable communities. [The Pfizer Foundation] Press Release

NIH Awards $2.7M Grant to UTEP Biology Professor to Study AIDS-Associated Fungal Meningitis

The National Institutes of Health (NIH) recently awarded a $2.7 million grant to Luis R. Martinez, Ph.D., associate professor of biological sciences at The University of Texas at El Paso, to study a potentially life-threatening fungus and suggest possible treatments. [The University of Texas at El Paso] Press Release

AIDS Activists Say Gilead Put Profits over Patients — and Misled Congress about an HIV Pill

Last May, Gilead Sciences chief executive Daniel O’Day testified before Congress that a revised version of a best-selling HIV pill was a “brand new medicine” and that the company was “absolutely not” aware it was safer than an older version during the early stages of development. Yet a recently filed lawsuit offers details that purportedly contradict his remarks and, in the process, raises questions about the extent to which Gilead may have deliberately delayed bringing a new treatment to market in order to milk sales of an older, lucrative franchise. [STAT News] Editorial

Brazil’s Budget Cuts Threaten More Than 80,000 Science Scholarships

Brazil’s main science-funding agency will have to suspend more than 80,000 scholarships to postdoctoral researchers and graduate and undergraduate students starting in September unless it receives additional cash from the government. [Nature News] Editorial

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