Immunology of Infectious Disease News Volume 5.22 | Jun 7 2017

TOP STORY

New Library of HIV Mutants Could Inform Vaccine Design

Researchers describe their library of mutant HIVs, its creation, and how they used it to show that a certain type of HIV vaccine, designed to elicit the immune molecules known as broadly neutralizing antibodies, could be on the right track. [Press release from the Fred Hutchinson Cancer Research Center discussing online prepublication in Cell Host & Microbe] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

DNA Vaccination Protects Mice against Zika Virus-Induced Damage to the Testes

Investigators report that administration of a synthetic DNA vaccine encoding Zika virus (ZIKV) pre-membrane and envelope completely protected mice against ZIKV-associated damage to the testes and sperm and prevented viral persistence in the testes following challenge with a contemporary strain of ZIKV. [Nat Commun] Full Article

Fibroblast-Adapted Human CMV Vaccines Elicit Predominantly Conventional CD8 T Cell Responses in Humans

Researchers describe the CD8 T cell responses of human subjects vaccinated with two fibroblast-adapted human cytomegalovirus (CMV) vaccines. Most responses were identified as conventional classically MHC I restricted, and they found no evidence for MHC II or HLA-E restriction. [J Exp Med] Abstract

IL17A Augments Autophagy in Mycobacterium tuberculosis-Infected Monocytes from Patients with Active Tuberculosis in Association with the Severity of the Disease

The authors investigated the role of IFNG and IL17A during autophagy in monocytes infected with M. tuberculosis (Mt)H37Rv or the mutant MtΔRD1. They showed that IL17A and IFNG expression in lymphocytes from tuberculosis patients correlates with disease severity. [Autophagy] Abstract

IRE1α Promotes Viral Infection by Conferring Resistance to Apoptosis

Scientists found that X-box binding protein 1 (Xbp1)-deficient mouse embryonic fibroblasts and macrophages had impaired antiviral resistance. However, this was not because of a defect in type I interferon responses but rather an inability of Xbp1-deficient cells to undergo viral-induced apoptosis. The ability to undergo apoptosis limited infection in wild-type cells. [Sci Signal] Abstract

Antibodies against a β-Glucan-Protein Complex of Candida albicans and Its Potential as Indicator of Protective Immunity in Candidemic Patients

Sera from candidemic and non-candidemic subjects were examined for antibodies against the cell wall β1,3- and β1,6-glucans, as well as the β-glucan-associated protein MP65 of Candida species. Although antibodies against each of the components were detected in all subjects, candidemic patients had lower antibody titers against β1,3-glucan, but higher antibody titers against β1,6-glucan and MP65, than non-candidemic subjects. [Sci Rep] Full Article

An Avian Influenza H7 DNA Priming Vaccine Is Safe and Immunogenic in a Randomized Phase I Clinical Trial

Scientists report the safety and immunogenicity of a H7 DNA-H7N9 monovalent inactivated vaccine prime-boost regimen. The novel H7 DNA vaccine was safe, well-tolerated, and immunogenic when boosted with H7N9 monovalent inactivated vaccine, while priming for higher HAI and neutralizing antibody titers than H7N9 monovalent inactivated vaccine alone. [npj Vaccines] Full Article

Resident Memory CD8⁺ T Cells in the Upper Respiratory Tract Prevent Pulmonary Influenza Virus Infection

Nasal epithelial tissue of the upper respiratory tract is the first site of contact by inhaled pathogens such as influenza virus. The authors showed that this region is key to limiting viral spread to the lower respiratory tract and associated disease pathology. Immunization of the upper respiratory tract lead to the formation of local tissue-resident memory CD8⁺ T cells. [Sci Immunol] Abstract

HIV

A Critical Role for Monocytes/Macrophages in the Rapid Progression to AIDS in Pediatric SIV-Infected Rhesus Macaques

Researchers sought to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. They observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. [J Virol] Abstract

Epigenetic Metabolite Acetate Inhibits Class I/II Histone Deacetylases, Promotes Histone Acetylation and Increases HIV-1 Integration in CD4⁺ T Cells

Scientists investigated the effect of acetate, the most concentrated short-chain fatty acid in the gut and bloodstream, on the susceptibility of primary human CD4⁺ T cells to HIV-1 infection. They report that HIV-1 replication was increased in CD3/CD28-costimulated CD4⁺ T cells upon acetate treatment. [J Virol] Abstract

HIV-1 Decreases Nrf2/ARE Activity and Phagocytic Function in Alveolar Macrophages

The authors hypothesized that nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master transcription factor that activates the antioxidant response element (ARE) and regulates antioxidant defenses, has an important role in alveolar macrophage (AMs) immune dysfunction in individuals with HIV infections. Treating HIV-1–infected human monocyte-derived macrophages or AMs from HIV-1 transgenic rats with sulforaphane significantly improved their phagocytic function. [J Leukoc Biol] Abstract

BCL6 Represses Antiviral Resistance in Follicular T Helper Cells

Investigators showed that murine and human follicular Th (Tfh) cells have diminished constitutive expression of IFN-stimulated genes inclusive of antiviral resistance factor MX dynamin-like GTPase 2 and IFN-induced transmembrane 3 compared with non-Tfh cells. A lower antiviral resistance in Tfh was consistent with a higher susceptibility to retroviral infections. [J Leukoc Biol] Abstract

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T Cell Immunity and Zika Virus Vaccine Development

The authors summarize the key discoveries in the area of flavivirus T cell immunity and postulate on how these findings can inform Zika virus vaccine strategies for inducing protective immunity. [Trends Immunol] Abstract

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Georgia State Researcher Receives $7.7 Million Federal Grant to Study West Nile and Zika Viruses

A Georgia State University researcher, in collaboration with researchers at the University of Pennsylvania and Florida State University, has received a five-year, $7.7 million federal grant to study the consequences of West Nile and Zika virus infections on the human central nervous system. [Georgia State University] Press Release

AbCellera Announces an Antibody Discovery Program in Influenza Vaccine Research

AbCellera announced a project with Sanofi Pasteur to apply its human antibody discovery and immune profiling technology for the research and development of next-generation influenza vaccines. [AbCellera Biologics Inc.] Press Release

ViiV Healthcare Submits Regulatory Applications for the First HIV Maintenance Regimen Comprising Only Two Medicines

GSK and ViiV Healthcare announced regulatory submissions to the European Medicines Agency and US Food and Drug Administration for a single-tablet, two-drug regimen of dolutegravir and rilpivirine for the maintenance treatment of HIV-1 infection. [ViiV Healthcare UK Limited] Press Release

Trump Retains Collins as NIH Director

President Donald Trump announced that he is keeping Francis Collins as director of the National Institutes of Health (NIH). Collins, who was appointed by former President Barack Obama in 2009, was asked to stay on temporarily after the election. The decision comes despite a recent call from some conservative members of Congress to fire Collins because he supports embryonic stem cell research. Collins has said he would return to full-time research if Trump asked him to step down. [ScienceInsider] Editorial

Romania’s Science Reforms Prompt Boycott

Researchers in Romania are stepping up protests against controversial government science reforms. Hundreds of scientists at leading research institutions say they will refuse to sit on national panels that assess and award grants, after the Romanian researchers’ association Ad Astra called for the boycott. But not all scientists in the country support the move. [Nature News] Editorial

Puerto Rico Declares Its Outbreak of Zika Virus Is Over

Puerto Rico declared its Zika epidemic over, saying transmission of the virus on the island has fallen to relatively low levels. In a statement, the territorial government said there have been only about ten cases of Zika reported in every four-week period since mid-April, down from more than 8,000 cases in four-week periods at the same time last year. [STAT News] Editorial

Congo Health Minister Says Ebola Outbreak under Control

Congo’s health minister says there have been no new confirmed cases of Ebola and the outbreak has been controlled. [The Washington Post] Editorial

NEW 2^nd International Conference and Expo on Vaccines and Vaccination
November 20-21, 2017
Dubai, United Arab Emirates

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

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

Postdoctoral Fellow – HIV Molecular Biology/Immunology (University of California, San Francisco)

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)

Assistant or Associate Member – Microbiome (Fred Hutchinson Cancer Research Center)

Junior Research Group Leader – Infection Biology (Julius-Maximilians Universitat Wurzburg)

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