Immunology of Infectious Disease News Volume 6.16 | Apr 25 2018

TOP STORY

New Method Allows Scientists to Study How HIV Persists

In a step toward unlocking a cure, scientists in Michel C. Nussenzweig’s laboratory have developed a new strategy to study the cells that host these reservoirs of latent virus: a highly specialized type of immune cell that is exceedingly rare in the blood, making it difficult to identify and isolate. [Press release from The Rockefeller University discussing online prepublication in Nature Medicine] Press Release | Abstract

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An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus

Scientists isolated human antibodies recognizing the Epstein-Barr virus (EBV) fusion machinery (gH/gL and gB) from rare memory B cells. One anti-gH/gL antibody, AMMO1, potently neutralized infection of B cells and epithelial cells, the two major cell types targeted by EBV. [Immunity] Abstract | Press Release

c-Maf Controls Immune Responses by Regulating Disease-Specific Gene Networks and Repressing IL-2 in CD4⁺ T Cells

Researchers found that c-Maf regulated IL-10 production in CD4⁺ T cells in disease models involving the T_H1 subset of helper T cells (malaria), T_H2 cells (allergy) and T_H17 cells (autoimmunity) in vivo. Although mice with c-Maf deficiency targeted to T cells showed greater pathology in T_H1 and T_H2 responses, T_H17 cell-mediated pathology was reduced in this context, with an accompanying decrease in T_H17 cells and increase in Foxp3⁺ regulatory T cells. [Nat Immunol] Abstract | Press Release

CD32 Is Expressed on Cells with Transcriptionally Active HIV but Does Not Enrich for HIV DNA in Resting T Cells

The authors determined whether CD32 expression marks HIV latently or transcriptionally active infected CD4⁺ T cells. Using peripheral blood and lymphoid tissue of antiretroviral therapy-treated HIV⁺ or SIV⁺ subjects, they found that most of the circulating memory CD32⁺ CD4⁺ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a T_H2 phenotype as defined by CXCR3, CCR4, and CCR6. [Sci Transl Med] Abstract | Press Release

Suppression of Costimulation by Human Cytomegalovirus Promotes Evasion of Cellular Immune Defenses

Researchers describe a virally encoded gene that inhibits CD58 surface expression. Blocking studies with antagonistic anti-CD58 mAb and an human cytomegalovirus (HCMV) UL148 deletion mutant with restored CD58 expression demonstrated that the CD2/CD58 axis was essential for the recognition of HCMV-infected targets by CD8⁺ HCMV-specific cytotoxic T lymphocytes. [Proc Natl Acad Sci USA] Abstract

Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells

Scientists demonstrated that the cell membrane-permeable HIV Tat proteins enhance activation-induced deaminase-mediated somatic hypermutation of antibody V regions through their modulation of the endogenous polymerase II transcriptional process. [mBio] Full Article

Amino Acid Substitutions within HLA-B*27-Restricted T Cell Epitopes Prevent Recognition by Hepatitis Delta Virus-Specific CD8⁺ T Cells

Molecular modeling of HLA-B*27 complexes with the L-HDAg epitope and its potential viral escape mutations indicates that the structural and electrostatic properties of the bound peptides differ considerably at the T-cell receptor interface, which provides a possible molecular explanation for the escape mechanism. This viral escape from the HLA-B*27-restricted CD8 T-cell response correlates to chronic outcome of hepatitis D infection. [J Virol] Abstract

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue Following Influenza Infection

Using a mouse model of influenza infection in conjunction with intravascular labeling in vivo, the cell surface phenotype, epitope specificity, and functional potential of the endogenous polyclonal CD4 T cell response was examined by tracking nine independent CD4 T cell epitope specificities. [J Virol] Abstract

Effects of Pre-Existing Orthopoxvirus-Specific Immunity on the Performance of Modified Vaccinia Virus Ankara-Based Influenza Vaccines

Orthopoxvirus-specific pre-existing immunity reduced the induction of antigen-specific antibodies under specific conditions and completely prevented induction of antigen-specific T cell responses by recombinant modified vaccinia virus Ankara-based vaccination. [Sci Rep] Full Article

Immunological Responses following Administration of a Genotype 1a/1b/2/3a Quadrivalent HCV VLP Vaccine

Researchers produced a quadrivalent genotype 1a/1b/2a/3a hepatitis C virus (HCV) viral-like particle (VLP) vaccine to produce broader immune responses. They showed that this quadrivalent vaccine produces antibody and neutralizing antibody responses together with strong T and B cell responses in vaccinated mice. [Sci Rep] Full Article

Therapeutic Conserved Elements (CE) DNA Vaccine Induces Strong T-Cell Responses against Highly Conserved Viral Sequences during Simian-Human Immunodeficiency Virus Infection

The authors investigated a novel, epidermally administered DNA vaccine expressing SIV capsid homologues of highly CE of the HIV proteome in macaques experiencing chronic but controlled SHIV infection. They assessed the ability to boost or induce de novo T-cell responses against the conserved but immunologically subdominant CE epitopes. [Hum Vaccin Immunother] Full Article

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HIV Vaccination: A Roadmap among Advancements and Concerns

Researchers provide a brief overview of different HIV-1 vaccine approaches and discuss the current understanding of the cellular and humoral correlates of HIV-1 immunity. [Int J Mol Sci] Full Article

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STEMCELL Technologies Announces $45 Million Government Funding for Advanced Manufacturing Facility

STEMCELL Technologies announced a $45 million joint funding agreement between the Governments of Canada and British Columbia to help the company build a state-of-the-art advanced manufacturing facility. The funding agreement will accelerate the Vancouver company’s rapidly scaling business of providing cutting-edge reagents and tools to support life science researchers around the world working in the cell therapy and regenerative medicine fields. [STEMCELL Technologies Inc.] Press Release

UofL Receives $11.2 Million Grant to Support Microorganism and Disease Research

To further understand associations linking the microbiome – bacteria, yeasts, fungi, viruses and protozoans – with inflammation and disease, The University of Louisville (UofL) has received an $11.2 million federal grant over five years to establish an interdisciplinary research program. [The University of Louisville] Press Release

UB Receives $1.1 Million to Improve Study of Zika, Dengue, HIV, Hepatitis and Other Viruses in Jamaica

The University at Buffalo (UB) has received a $1.1 million award from the National Institutes of Health Fogarty International Center to lead the training of 15 scientists from Jamaica and the Caribbean in viral infection research. [University at Buffalo] Press Release

VBI Vaccines Announces Completion of Enrollment in PROTECT Phase III Clinical Study for Sci-B-Vac^® Hepatitis B Vaccine

VBI Vaccines Inc. announced the completion of enrollment with the last patient receiving the first dose in the ongoing PROTECT Phase III study of Sci-B-Vac^®, the company’s third-generation hepatitis B vaccine. [VBI Vaccines Inc.] Press Release

PaxVax Announces the Initiation of Phase IIb Trial for Its Chikungunya Vaccine

PaxVax announced the enrollment of the first patient in its Phase IIb dose-finding trial of the chikungunya virus-like particle vaccine, building upon a Phase IIa study by the National Institutes of Health with 400 subjects. [PaxVax, Inc.] Press Release

Wistar Team Receives Prestigious Award from National Clinical Research Forum for DNA-Based Zika Research

The Wistar Institute and partners at the Perelman School of Medicine at the University of Pennsylvania, Inovio Pharmaceuticals, and GeneOne Life Science were recognized among the Top 10 Clinical Research Achievement Awards by the Clinical Research Forum for their ground-breaking Phase I DNA-based Zika vaccine research – the first trial of a Zika vaccine in humans, which proved safe and effective. [The Wistar Institute of Anatomy and Biology] Press Release

A New Dengue Vaccine Should Only Be Used in People Who Were Previously Infected, WHO Says

The World Health Organization (WHO) in Geneva, Switzerland, put the brakes on implementation of the world’s first dengue vaccine when it recommended it only be used in people who have previously been infected with the disease—a move that will shrink the potential market for the vaccine’s producer, Sanofi Pasteur. [ScienceInsider] Editorial

U.K. Commits to EU Trial Rules Post-Brexit as CRUK Hails ‘Fantastic News’

The U.K. government said it will endeavor to keep pace with the European Union’s impending changes in clinical trial procedures, bringing some solace to those wondering how the two will stay aligned after Brexit starts in earnest next March. [Questex LLC.] Editorial

Rent Increase Hits Europe’s Drug Regulator before Brexit Move

With less than a year to go before the European Medicines Agency must leave its London headquarters because of Brexit, the agency is facing an unexpected rent increase that could cut into its budget for approving new medicines and overseeing clinical trials. [Nature News] Editorial

Columbia University Graduate Students Go on Strike

Administration officials contend that research and teaching assistants are students, not workers, and want to take the matter to federal court. [The Scientist] Editorial

NEW Keystone Symposia: Tuberculosis: Mechanisms, Pathogenesis and Treatment
January 17-21, 2019
Banff, Alberta, Canada

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NEW Postdoctoral Position – Host-Pathogen Interactions (Sanford Burnham Prebys Medical Discovery Insitute)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow/Junior Scientist – Pathogen Genomics (Fudan University)

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

Postdoctoral Research Scientist – HIV Vaccine Design (Simon Fraser University)

Postdoctoral Position – Influenza Vaccine Research and Design (Simon Fraser University)

Postdoctoral Associate – Infectious Disease (Research Foundation for SUNY)

Director of Biomarkers & Assays – Infectious Diseases Research (Moderna Therapeutics)

Postdoctoral Position – Zika Virus (London School of Hygiene & Tropical Medicine)

Research Associate – Vaccine Research (University of Bristol)

Senior Research Associate – Infectious Disease (Moderna Therapeutics)

Assistant/Associate Professor – Virology (Saint Louis University)

Associate Senior Lecurer – Tissue Repair in Infectious Diseases (Lund University)

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

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