Immunology of Infectious Disease News Volume 6.23 | Jun 13 2018

TOP STORY

Malaria: Cooperating Antibodies Enhance Immune Response

Researchers have discovered a previously unnoticed characteristic of antibodies against the malaria parasite: They can cooperate with each other, thus binding even stronger to the pathogens and improving the immune response. [Press release from The German Cancer Research Center discussing online prepublication in Science] Press Release | Full Article

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HIV-1 Gag Recruits PACSIN2 to Promote Virus Spreading

Scientists showed that the PPXY-type Rous sarcoma virus late assembly domain specifically recruits the BAR domain protein PACSIN2 into virus-like particles, in addition to the NEDD4-like ubiquitin ligase ITCH and ESCRT pathway components such as TSG101. Although PACSIN2 was not required for a single cycle of HIV-1 replication after infection with cell-free virus, HIV-1 spreading was nevertheless severely impaired in T cell lines and primary human peripheral blood mononuclear cells depleted of PACSIN2. [Proc Natl Acad Sci USA] Abstract

EcoHIV Infection of Mice Establishes Latent Viral Reservoirs in T Cells and Active Viral Reservoirs in Macrophages That Are Sufficient for Induction of Neurocognitive Impairment

Investigators showed that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on antiretroviral therapy including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-associated conditions including neurocognitive impairment. [PLoS Pathog] Full Article | Press Release

Scaffold Attachment Factor B Suppresses HIV-1 Infection of CD4⁺ Cells by Preventing Binding of RNA Polymerase II to HIV-1’s Long Terminal Repeat

Researchers identified an RNA-/DNA-binding protein, scaffold attachment factor B (SAFB1) as a host-cell factor that represses HIV-1 transcription. They found that SAFB1 bound to HIV-1 5′-long terminal repeat (LTR) and significantly repressed 5′-LTR-driven-viral transcription and HIV-1 infection of CD4⁺ T cells. [J Biol Chem] Abstract

Residual T Cell Activation and Skewed CD8⁺ T Cell Memory Differentiation despite Antiretroviral Therapy-Induced HIV Suppression

Scientists longitudinally assessed the influence of one year of antiretroviral therapy (ART) on the phenotype of T cells in HIV-infected African women, relative to matched HIV-uninfected women, using activation and differentiation markers. ART induced a substantial reduction in T cell activation, but remained higher than HIV-uninfected controls. [Clin Immunol] Abstract

Identification of Mycobacterial Ribosomal Proteins As Targets for CD4⁺ T Cells that Enhance Protective Immunity in Tuberculosis

A library of Mycobacterium tuberculosis (Mtb) ribosomal proteins and in silico predicted peptide libraries were used to screen CD4⁺ T cell responses in IKEPLUS immunized mice. This identified 24 out of 57 Mtb ribosomal proteins distributed over both large and small ribosome subunits as specific CD4⁺ T cell targets. [Infect Immun] Abstract

Low Levels of T Cell Exhaustion in Tuberculous Lung Granulomas

The authors characterized the expression of inhibitory receptors on T cells and functionality of these cells in TB lung granulomas. They then used these experimental data to calibrate and inform an agent-based computational model that captures environmental, cellular, and bacterial dynamics within granulomas in lungs during Mycobacterium tuberculosis infection. [Infect Immun] Abstract

Fibroblast-Stimulating Lipopeptide-1 As a Potential Mucosal Adjuvant Enhances Mucosal and Systemic Immune Responses to Enterovirus 71 Vaccine

Researchers observed more enterovirus 71 (EV71)-specific IgG and IgA-producing cells in treatments using EV71 formulated with fibroblast-stimulating lipopeptide-1 (FSL-1). T cell-proliferative responses and interferon-γ and interleukin-17 secretion were significantly increased when inactivated EV71 was formulated using FSL-1. [Vaccine] Abstract

Protection by Universal Influenza Vaccine Is Mediated by Memory CD4 T Cells

Investigators developed a novel universal vaccine which elicits robust T cell responses and protection against diverse influenza viruses in mouse and human models. Vaccine mediated protection was dependent on influenza-specific CD4⁺ T cells, whereby depletion of CD4⁺ T cells at either vaccination or challenge time points significantly reduced survival in mice. [Vaccine] Abstract

The p110δ Isoform of Phosphatidylinositol 3-Kinase Plays an Important Role in Host Defense against Chlamydial Lung Infection through Influencing CD4⁺ T Cell Function

The authors investigated the role of p110δ isoform of PI3Ks in host defense against chlamydial lung infection in a mouse model. They showed that mice which received CD4⁺ T cells from infected p110δD910A mice exhibited greater body weight loss and higher bacterial loads in the lung than those which received CD4⁺ T cells from WT mice following challenge infection. [Pathog Dis] Abstract

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Immunological Mechanisms of Human Resistance to Persistent Mycobacterium tuberculosis Infection

The authors discuss the epidemiological and genetic data that support the existence of resisters and propose criteria to optimally define and characterize the resister phenotype. They review recent insights into the immune mechanisms of M. tuberculosis clearance, including responses mediated by macrophages, T cells and B cells. [Nat Rev Immunol] Abstract

Harnessing Immune History to Combat Influenza Viruses

Researchers highlight the role of imprinting on the regulation of antibody responses induced by influenza viruses and explores potential vaccine strategies to harness imprinted antibody responses to increase protection against influenza. [Curr Opin Immunol] Abstract

Current Status of Zika Vaccine Development: Zika Vaccines Advance into Clinical Evaluation

In addition to clinical studies, substantial progress continues to be made in nonclinical development, particularly in terms of the ability of candidate vaccines to protect reproductive tissues, and the potential use of monoclonal antibodies for passive prophylaxis. [npj Vaccines] Full Article

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CytoDyn Announces Presentation of Positive Efficacy Results from Pivotal PRO140 Combination Therapy Trial in HIV

Results from a pivotal trial with PRO 140, a novel humanized CCR5 monoclonal antibody under development by CytoDyn Inc., support the value of its use in combination with antiretroviral treatment as a long-acting therapeutic for heavily treatment-experienced HIV-1 infected patients. Results from the one-week, single-dose, randomized, double-blind, placebo-controlled portion of the pivotal trial showing that PRO 140 met the primary efficacy endpoint were presented. [Press release from CytoDyn Inc. discussing research presented at the American Society for Microbiology (ASM) Microbe 2018 Meeting, Atlanta] Press Release

Translate Bio Collaborates with Sanofi to Develop mRNA Vaccines for Infectious Diseases

Translate Bio announced a multi-year research and development collaboration and exclusive licensing agreement with Sanofi Pasteur, the vaccines global business unit of Sanofi, to develop mRNA vaccines for up to five undisclosed infectious disease pathogens. [Translate Bio] Press Release

Themis Receives EMA PRIME Designation for Chikungunya Vaccine

Themis announced that the European Medicines Agency (EMA) has granted PRIority MEdicines (PRIME) designation to its most advanced program in development, a vaccine to prevent chikungunya fever. [Themis Bioscience GmbH (Business Wire, Inc.)] Press Release

Vical Reports Phase II Trial of HSV-2 Therapeutic Vaccine Did Not Meet Primary Endpoint

Vical Incorporated announced top-line results from a randomized, double-blind, placebo-controlled, Phase II clinical study of its therapeutic bivalent vaccine candidate for herpes simplex virus type 2 (HSV-2), the leading cause of recurrent genital herpes. The study did not meet its primary endpoint of annualized lesion recurrence rate calculated based on those genital recurrences that were both clinically- and virologically-confirmed during a minimum of nine months of surveillance. [Vical Incorporated] Press Release

China Introduces Sweeping Reforms to Crack Down on Academic Misconduct

China is getting tough on scientific misconduct. The country’s most powerful bodies, the Chinese Communist Party and the State Council, introduced a raft of reforms on 30 May aimed at improving integrity across the research spectrum, from funding and job applications to peer-review and publications. [Nature News] Editorial

More Restrictive U.S. Policy on Chinese Graduate Student Visas Raises Alarm

Reversing yet another policy of the previous administration, the U.S. Department of State began applying tougher restrictions on some Chinese graduate students. The new policy shortens from five years to one year the duration of visas for those planning to study aviation, robotics, and advanced manufacturing. [ScienceInsider] Editorial

Leading Salk Scientist Resigns after Allegations of Harassment

The prominent cancer biologist Inder Verma unconditionally resigned from the Salk Institute for Biological Studies in San Diego, California, June 6, and the research institute’s board of trustees voted unanimously to accept his resignation. [ScienceInsider] Editorial

Sexual Harassment Is Rife in the Sciences, Finds Landmark US Study

Sexual harassment is pervasive throughout academic science in the United States, driving talented researchers out of the field and harming others’ careers, finds a report from the US National Academies of Sciences, Engineering, and Medicine in Washington DC. The analysis concludes that policies to fight the problem are ineffective because they are set up to protect institutions, not victims — and that universities, funding agencies, scientific societies and other organizations must take stronger action. [Nature News] Editorial

North American Universities Increasingly Cancel Publisher Packages

Florida State University (FSU) will head into negotiations with the publisher Elsevier to see how it can resolve a pricing issue. Back in April, FSU announced that it would not renew a so-called “big deal” with Elsevier in 2019, due to its “high and ever-increasing cost,” and would instead subscribe to a subset of the most-needed journals. The university’s move represents the latest example of academic libraries walking away from these comprehensive and expensive subscriptions, which include all or most of a publisher’s catalog, and instead signing up for a la carte titles. [The Scientist] Editorial

NEW ComBio 2018
September 23-26, 2018
Sydney, Australia

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NEW PhD Scholarships – Systems Biology in Immunity and Infectious Diseases (Università degli Studi di Perugia)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Chair – Department of Microbiology, Immunology, and Tropical Medicine (The George Washington University School of Medicine and Health Sciences)

Chief Executive Officer – Vaccine and Infectious Disease Organization (Vaccine and Infectious Disease Organization)

Assistant Professor – Microbial Pathogenesis (University of Maryland School of Dentistry)

Senior Vice President – Vaccine Development and Viral Disease Programs (Infectious Disease Research Institute)

Postdoctoral Research Fellow – Immunity and Viral Infection (Fred Hutchinson Cancer Research Center)

Faculty Positions – Infectious Disease Research (Institut Pasteur of Shanghai)

Postdoctoral Research Fellow – B Cell Immunology and Vaccines (Fred Hutchinson Cancer Research Center)

Tenure-Track/Tenure-Eligible Investigator – Antiviral Therapies and Vaccines (National Institute of Allergy and Infectious Diseases)

Postdoctoral Training Opportunity – Infection and Immunity (Institut Pasteur of Shanghai – Chinese Academy of Sciences)

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