Immunology of Infectious Disease News Volume 4.45 | Nov 16 2016

TOP STORY

Local Cellular and Cytokine Cues in the Spleen Regulate In Situ T Cell Receptor Affinity, Function, and Fate of CD8⁺ T Cells

During the contraction phase of an acute infection with lymphocytic choriomeningitis virus, the authors found that virus-specific CD8⁺ T cells within the splenic red pulp had higher two-dimensional effective affinity than those within the white pulp. [Immunity] Abstract | Graphical Abstract

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CD301b⁺ Dendritic Cells Stimulate Tissue-Resident Memory CD8⁺ T Cells to Protect against Genital HSV-2

Scientists report that tissue-resident memory CD8⁺ T (CD8 T_RM) cells established by ‘prime and pull’ method confer protection against genital HSV-2 infection, and that IFN-γ produced by CD8 T_RM cells is required for this protection. [Nat Commun] Full Article

Trypanosoma brucei Metabolite Indolepyruvate Decreases HIF-1α and Glycolysis in Macrophages as a Mechanism of Innate Immune Evasion

The reduction in HIF-1α levels by indolepyruvate, following LPS or trypanosome activation, resulted in a decrease in production of the proinflammatory cytokine IL-1β. [Proc Natl Acad Sci USA] Abstract

Non-Neutralizing Antibodies Induced by Seasonal Influenza Vaccine Prevent, Not Exacerbate A(H1N1)pdm09 Disease

The authors investigated if prior immunization with trivalent influenza vaccine (TIV) enhanced disease upon A(H1N1)pdm09 infection in mice. They found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. [Sci Rep] Full Article

The Host Genetic Background Defines Diverse Immune-Reactivity and Susceptibility to Chronic Pseudomonas aeruginosa Respiratory Infection

Scientists investigated the cellular events involved in resistance and susceptibility to P. aeruginosa chronic infection using genetically distinct inbred mouse strains. As for patients, different murine genotypes revealed variable susceptibility to infection. [Sci Rep] Full Article

In Vivo Protection against ZIKV Infection and Pathogenesis through Passive Antibody Transfer and Active Immunization with a prMEnv DNA Vaccine

Researchers generated and evaluated the in vivo efficacy of a novel, synthetic, DNA vaccine targeting the pre-membrane+envelope proteins (prME) of Zika virus (ZIKV). Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunized with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery. [npj Vaccines] Full Article

HIV

Subset- and Antigen-Specific Effects of Treg on CD8⁺ T Cell Responses in Chronic HIV Infection

Researchers investigated regulatory CD4⁺CD25^highFoxP3⁺ T cells (Treg)–mediated effects on CD8 responses in chronic HIV infection. As compared to Treg from HIV negative controls, they showed that Treg from HIV infected patients (Treg/HIV⁺) did not significantly inhibit polyclonal autologous CD8⁺ T cell function indicating either a defect in the suppressive capacity of Treg/HIV⁺ or a lack of sensitivity of effector T cells in HIV infection. [PLoS Pathog] Full Article

HLA-G⁺ HIV-1-Specific CD8 T Cells Are Associated with HIV-1 Immune Control

Scientists assessed the frequency and function of HIV-1-specific HLA-G⁺ CD8 T cells in HIV-1 controllers and progressors. [AIDS] Abstract

Modulation of Innate and Adaptive Cellular Immunity Relevant to HIV-1 Vaccine Design by Seminal Plasma

The authors investigated the effects of seminal plasma on immune responses considered important for prophylactic HIV-1 vaccine development, namely innate and adaptive cellular immunity mediated by NK cells and T-cells, respectively. [AIDS] Abstract

Blood-CSF Barrier and Compartmentalization of CNS Cellular Immune Response in HIV Infection

HIV infection is persistent in the CNS, to evaluate the compartmentalization of the CNS immune response to HIV, scientists compared soluble markers of cellular immunity in the blood and CSF among HIV⁻ and HIV⁺, as well as among HIV participants with or without CSF pleocytosis. [J Neuroimmunol] Abstract

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Promise and Problems Associated with the Use of Recombinant AAV for the Delivery of Anti-HIV Antibodies

The authors highlight the promise of recombinant adeno-associated virus (AAV)-mediated antibody delivery for the prevention or treatment of HIV infection in humans, but they also discuss the obstacles that will need to be understood and solved in order for the promise of this approach to be realized. [Mol Ther Methods Clin Dev] Full Article

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Merck Announces Findings for Investigational Triple-Combination Chronic Hepatitis C Therapy Showing High Rates of Sustained Virologic Response in People with Genotypes 1, 2 or 3 Infection

Merck announced the presentation of results from three Phase II clinical trials evaluating MK-3682B, the company’s investigational all-oral, triple-combination regimen for the treatment of chronic hepatitis C infection. [Press release from Merck & Co., Inc. discussing research presented at The Liver Meeting^® 2016, Boston] Press Release

Transgene Presents Preclinical Results of TG1050, an HBV-Targeted Immunotherapy

Transgene presented a poster on TG1050 preclinical results. TG1050 is a therapeutic vaccine for the treatment of chronic hepatitis B. [Press release from Transgene discussing research presented at The Liver Meeting^® 2016, Boston] Press Release

Replicor Discloses Late Breaking HBV and Follow-Up HBV / HDV Clinical Data

Replicor Inc. presented its preliminary interim analysis from its latest REP 401 clinical trial. [Press release from Replicor Inc. discussing research presented at The Liver Meeting^® 2016, Boston] Press Release

European CHMP Adopts Positive Opinion for Gilead’s Vemlidy^® (Tenofovir Alafenamide, TAF) for the Treatment of Chronic Hepatitis B Virus Infection

Gilead Sciences, Inc. announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency, has adopted a positive opinion on the company’s Marketing Authorization Application for Vemlidy^® 25 mg, an investigational, once-daily tablet for the treatment of chronic hepatitis B virus infection in adults and adolescents. [Gilead Sciences, Inc.] Press Release

Enanta Announces Eight Weeks of Treatment with AbbVie’s Investigational, Pan-Genotypic Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved High SVR Rates Across All Major Genotypes of Chronic Hepatitis C

Enanta Pharmaceuticals, Inc. announced that AbbVie has published high SVR12 rates across all major chronic hepatitis C virus genotypes with 8 weeks of treatment with its investigational, pan-genotypic regimen consisting of glecaprevir/pibrentasvir. [Enanta Pharmaceuticals, Inc.] Press Release

Integrated BioTherapeutics, Inc. Announces Licensing Agreement with Emergent BioSolutions for Development of Equine Immunoglobulin Therapeutics for Filovirus Infections

Integrated BioTherapeutics announced that it has entered into an exclusive worldwide license agreement with Emergent BioSolutions Inc. whereby Emergent will gain exclusive rights to use IBT’s proprietary vaccine antigens and know-how in a joint research, development, and manufacturing collaboration focused on an equine-based hyperimmunoglobulin for the treatment of hemorrhagic fever caused by Filoviruses. [Integrated BioTherapeutics, Inc. (PR Newswire Association LLC.)] Press Release

In Bold New Step, Dutch Science Academy Holds Women-Only Elections

In order to reduce its perpetual gender imbalance—87% of its 556 members are men—the Royal Netherlands Academy of Arts and Sciences seeks to recruit ten new members in 2017 and six more in 2018, all with two X chromosomes. [ScienceInsider] Editorial

How Self-Appointed Guardians of “Sound Science” Tip the Scales toward Industry

At a time when public mistrust of science runs high, and non-experts are hard-pressed to separate fact from industry-sponsored spin, Sense About Science, a charity based in London with an affiliate in New York, presents itself as a trustworthy arbiter. The organization purports to help the misinformed public sift through alarmist claims about public health and the environment by directing journalists, policymakers, and others to vetted sources who can explain the evidence behind debates about controversial products like e-cigarettes and flame retardants. [The Intercept] Editorial

CRISPR Gene-Editing Tested in a Person for the First Time

A Chinese group has become the first to inject a person with cells that contain genes edited using the revolutionary CRISPR–Cas9 technique. A team led by oncologist Lu You at Sichuan University in Chengdu delivered the modified cells into a patient with aggressive lung cancer as part of a clinical trial at the West China Hospital, also in Chengdu. The move by Chinese scientists could spark a biomedical duel between China and the United States. [Nature News] Editorial

Rwanda Feels the Pinch as Donors Slash Health Aid

Rwanda has made major public-health strides since the country’s genocide against the Tutsi people ended in June 1994, but declines in foreign aid now threaten that progress. Donors such as the US President’s Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, Tuberculosis and Malaria have reduced assistance to Rwanda by 40% over the past three years, jeopardizing advances in a country seen as a development success story. [Nature News] Editorial

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