Immunology of Infectious Disease News Volume 5.28 | Jul 19 2017

TOP STORY

Mouse Models of Acute and Chronic Hepacivirus Infection

Scientists showed that a hepatitis C virus-related hepacivirus discovered in Norway rats could establish high-titer hepatotropic infections in laboratory mice with immunological features resembling those seen in human viral hepatitis. Immune-compromised mice developed persistent infection, immune-competent mice cleared the virus within three to five weeks. [Science] Abstract | Press Release

(Ranked by impact factor of the journal)

SNP-Mediated Disruption of CTCF Binding at the IFITM3 Promoter Is Associated with Risk of Severe Influenza in Humans

The authors found evidence of a new association of rs34481144 with severe influenza in three influenza-infected cohorts characterized by different levels of influenza illness severity. They determined a role for rs34481144 as an expression quantitative trait locus for IFITM3, with the risk allele associated with lower mRNA expression. [Nat Med] Abstract | Press Release

The Fc Domain of Immunoglobulin Is Sufficient to Bridge NK Cells with Virally Infected Cells

Investigators showed that the Fc domain of IgG alone mediates the recognition and clearance of herpes simplex virus (HSV1)-infected cells. NK cells utilized the Fc domain of bound IgG to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc domain of IgG but at a site distinct from CD16a. [Immunity] Abstract

Preferential Induction of Cross-Group Influenza a Hemagglutinin Stem–Specific Memory B Cells after H7N9 Immunization in Humans

To better understand the elicitation of hemagglutinin (HA) stem–targeted B cells to group 1 and group 2 influenza subtypes, researchers compared the memory B cell response to group 2 H7N9 and group 1 H5N1 vaccines in humans. Immunoglobulin repertoire analysis of HA-specific B cells indicated that the H7N9 and H5N1 vaccines induced genetically similar cross-group HA stem–binding B cells, albeit at a much higher frequency upon H7N9 vaccination. [Sci Immunol] Full Article | Press Release

Identification and Pathological Characterization of Persistent Asymptomatic Ebola Virus Infection in Rhesus Monkeys

Scientists detected persistent Ebola virus (EBOV) replication coinciding with systematic inflammatory responses in otherwise asymptomatic rhesus monkeys that had survived infection in the absence of or after treatment with candidate medical countermeasures. They identified CD68⁺ cells as the cryptic EBOV reservoir cells in the vitreous humor and its immediately adjacent tissue, in the tubular lumina of the epididymides, and in foci of histiocytic inflammation in the brain, but not in organs typically affected during acute infection [Nat Microbiol] Abstract | Press Release

HIV

Interval Dosing with the HDAC Inhibitor Vorinostat Effectively Reverses HIV Latency

Researchers measured resting CD4⁺ T cell–associated HIV RNA ex vivo and in vivo following a single exposure to vorinostat (VOR), and then in vivo after a pair of doses separated by 48 or 72 hours, and finally following a series of 10 doses given at 72-hour intervals. Serial VOR exposures separated by 72 hours most often resulted in an increase in cell-associated HIV RNA within circulating resting CD4⁺ T cells. [J Clin Invest] Full Article

Fusion Stage of HIV-1 Entry Depends on Virus-Induced Cell Surface Exposure of Phosphatidylserine

The authors report that formation of the pre-fusion envelope glycoprotein-CD4-coreceptor complexes triggers non-apoptotic cell surface exposure of the membrane lipid phosphatidylserine. [Cell Host Microbe] Abstract | Press Release | Graphical Abstract

Negative Modulation of Suppressive HIV-Specific Regulatory T Cells by IL-2 Adjuvanted Therapeutic Vaccine

Investigators revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. HIV-specific Tregs were inversely correlated with IFN-γ producing specific-effectors and positively correlated with viral load, revealing their undesired presence during chronic infection. [PLoS Pathog] Full Article

Increased, Durable B-Cell and ADCC Responses Associated with T-Helper Responses to HIV-1 Envelope in Macaques Vaccinated with gp140 Occluded at the CD4 Receptor Binding Site

Scientists hypothesized that HIV-1 envelope engagement of the CD4 receptor on T-helper cells may result in anergic effects on T-cell recruitment and consequently a lack of strong robust and durable B-memory responses. To test this hypothesis they occluded the CD4 binding site of gp140 by stable cross-linking with a 3kD CD4 miniprotein mimetic serving to block ligation of gp140 on CD4⁺ T-cells while preserving CD4 inducible neutralizing and epitopes targeted by antibody dependent cellular cytotoxic (ADCC) effector responses. [J Virol] Abstract

HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses Associated with Elite Control of HIV

HIV Env- and non-Env-specific antibody-dependent cellular cytotoxicity may contribute to protection from progressive HIV infection but the evidence is limited. Researchers recruited 22 elite controllers (ECs) and matched them with 44 viremic subjects. ECs had higher levels of HIV Env-specific antibodies capable of binding FcγRIIIa, activating NK cells and mediating Granzyme B activity compared to viremic subjects. [J Virol] Abstract

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Improving Vaccine Trials in Infectious Disease Emergencies

Focusing on studies of vaccine efficacy and effectiveness in emergencies, the authors highlight three needs: for formal randomized trials—even in most emergencies; for individually randomized trials—even in many emergencies; and for six areas of innovation in trial methodology. [Science] Abstract

Opportunities and Challenges in Modeling Emerging Infectious Diseases

Mathematical models of emergent pathogens allow forecasts of case numbers, investigation of transmission mechanisms, and evaluation of control options. Yet, there are numerous limitations and pitfalls to their use, often driven by data scarcity. Growing availability of data on pathogen genetics and human ecology, coupled with computational and methodological innovations, is amplifying the power of models to inform the public health response to emergence events. [Science] Abstract

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ABL Awarded NIH Contract for HIV Vaccine Development Worth up to $318 Million

ABL, Inc. announced it has been awarded the recompetition of the contract for Preclinical Development Support by the Division of AIDS within the National Institute of Allergy and Infectious Disease of the National Institutes of Health. The contract will run for a total of seven years with a maximum funding level of $318 million. [ABL, Inc.] Press Release

European Medicines Agency Validates Gilead’s Marketing Application for Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide for Treatment of HIV

Gilead Sciences, Inc. announced that the company’s Marketing Authorization Application for an investigational, once-daily single tablet regimen containing bictegravir, a novel investigational integrase strand transfer inhibitor, and emtricitabine/tenofovir alafenamide for the treatment of HIV-1 infection in adults has been fully validated and is now under evaluation by the European Medicines Agency. [Gilead Sciences, Inc.] Press Release

U.S. Food and Drug Administration Approves Gilead’s Vosevi™ (Sofosbuvir/Velpatasvir/Voxilaprevir) for Re-Treatment of Adults with Chronic Hepatitis C Virus

Gilead Sciences, Inc. announced that the U.S. FDA has approved Vosevi™ tablets, a single-tablet regimen for the re-treatment of chronic hepatitis C virus infection in adults with genotype one, two, three, four, five or six previously treated with an NS5A inhibitor-containing regimen, or with genotype 1a or 3 previously treated with a sofosbuvir-containing regimen without an NS5A inhibitor. [Gilead Sciences, Inc.] Press Release

Can We Beat Influenza?

Currently, only two influenza A viruses and two influenza B clades are circulating and causing disease in humans, but 16 additional subtypes of influenza A viruses are circulating in nature. Of the latter, six occasionally infect humans, providing an ever-looming pandemic threat. However, there is still a lack of fundamental knowledge to predict if and when a particular viral subtype will acquire pandemic ability. [Science] Editorial

Vaccines Promoted as Key to Stamping out Drug-Resistant Microbes

The battle against drug-resistant superbugs has neglected a key weapon, scientists say: using vaccines to quell the spread of resistance. As drug-resistant infections sweep across the globe, public-health organizations have focused mainly on developing new antimicrobial treatments and cutting the overuse of existing ones, to prevent resistant strains emerging. [Nature News] Editorial

Relatively Few NIH Grantees Get Lion’s Share of Agency’s Funding

The rich have been getting richer in the biomedical research enterprise, and the system favors those who are already doing pretty well, according to a new analysis of National Institutes of Health (NIH) grant recipients. [ScienceInsider] Editorial

Two Female Scientists Sue Salk Institute, Alleging Discrimination at ‘Old Boys Club’

Two senior female scientists are suing their employer, the prestigious Salk Institute for Biological Studies, alleging pervasive, long-standing gender discrimination. In the pair of lawsuits, filed in California Superior Court in San Diego, plaintiffs Vicki Lundblad and Katherine Jones seek unspecified compensation for an array of harms. [ScienceInsider] Editorial

NEW Keystone Symposia: Antibodies as Drugs: Translating Molecules into Treatments
February 25-March 1, 2018
Whistler, British Columbia, Canada

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NEW Postdoctoral Research Fellow – Quantitative Infectious Disease Methods (Fred Hutchinson Cancer Research Center)

NEW Full Faculty Member – Immunology (Fred Hutchinson Cancer Research Center)

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

NEW Research Fellow – HIV/AIDS Research (Dana-Farber Cancer Institute)

Infectious Disease Outcomes Epidemiologist/Transfusion Safety Research (University of California San Francisco)

Assistant/Associate Professor – Disease-Specific Immunology/Vaccinology (Brown University)

Postdoctoral Position – Cell Biology and Innate Immunity (Molecular Infection Medicine Sweden)

Postdoctoral Position – Infectious Diseases Pathogenesis (Massachusetts General Hospital & Harvard Medical School)

Lab Aide – Infectious Disease Sciences Program (Fred Hutchinson Cancer Research Center)

Staff Clinician Position – Laboratory of Clinical Infectious Diseases (National Institute of Allergy and Infectious Diseases)

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