Immunology of Infectious Disease News Volume 5.23 | Jun 14 2017

TOP STORY

Vaccine Priming Is Restricted to Draining Lymph Nodes and Controlled by Adjuvant-Mediated Antigen Uptake

The authors introduce a model to delineate the steps of how adjuvant-driven innate immune activation leads to priming of vaccine responses using Rhesus macaques. Fluorescently labeled HIV-1 envelope glycoprotein (Env) was administered together with the conventional aluminum salt (alum) adjuvant. This was compared to Env given with alum with preabsorbed Toll-like receptor 7 ligand or the emulsion MF59 because they showed superiority over alum for qualitatively and quantitatively improved vaccine responses. [Sci Transl Med] Abstract

(Ranked by impact factor of the journal)

Different Populations of CD11b⁺ Dendritic Cells Drive Th2 Responses in the Small Intestine and Colon

The authors showed that intestinal T-helper 2 (Th2) responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient dendritic cells (DCs). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, was sufficient to prime S. mansoni-specific Th2 responses. [Nat Commun] Full Article

Aberrant Plasma IL-7 and Soluble IL-7 Receptor Levels Indicate Impaired T-Cell Response to IL-7 in Human Tuberculosis

Scientists investigated the role of interleukin-7 (IL-7)/IL-7 receptor (IL-7R) on T-cell immunity in human tuberculosis. Tuberculosis patients had lower levels of mIL-7R in T cells caused by post-transcriptional mechanisms. Functional in vitro tests indicated diminished IL-7-induced STAT5 phosphorylation and impaired IL-7-promoted cytokine release of Mycobacterium tuberculosis-specific CD4⁺ T cells from tuberculosis patients. [PLoS Pathog] Full Article

NLRP3 Inflammasome Pathway Has a Critical Role in the Host Immunity against Clinically Relevant Acinetobacter baumannii Pulmonary Infection

Using a sublethal mouse pneumonia model, investigators demonstrated that an extensively drug-resistant clinical isolate of A. baumannii exhibits reduced/delayed early pulmonary neutrophil recruitment, higher lung persistence, and, most importantly, elicits enhanced interleukin-1β (IL-1β)/IL-18 production and lung damage through NLRP3 inflammasome, in comparison with A. baumannii-type strain. [Mucosal Immunol] Abstract

Anti-Bovine Programmed Death-1 Rat–Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle

Anti-bovine programmed death-1 (PD-1) rat–bovine chimeric monoclonal antibody 5D2 (Boch5D2) was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus. Purified Boch5D2 was capable of detecting bovine PD-1 molecules expressed on cell membranes in flow cytometric analysis. [Front Immunol] Full Article | Press Release

Epitope Mapping and Kinetics of CD4 T Cell Immunity to Pneumonia Virus of Mice in the C57BL/6 Strain

Researchers set out to map H2-IA^b-restricted epitopes along the pneumonia virus of mice (PVM) proteome. By means of in silico prediction and subsequent functional validation, they were able to identify a MHCII-restricted CD4 T cell epitope, corresponding to amino acids 37–47 in the PVM matrix protein. [Sci Rep] Full Article

HIV

Pentavalent HIV-1 Vaccine Protects against Simian-Human Immunodeficiency Virus Challenge

The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Scientists designed an ALVAC/pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 motifs in the immunogen to elicit a broader antibody response and enhance protection. [Nat Commun] Full Article

Identification of IL-27/IL-27RA as a Critical Immune Axis for In Vivo HIV Control

Investigators sought to determine whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray able to measure >600 plasma proteins involved in cell-to-cell communication was used to measure plasma protein profiles in 96 HIV-infected, treatment-naïve individuals with high or low viral loads. [J Virol] Abstract | Full Article

HIV-1 Epitope Variability Is Associated with T Cell Receptor Repertoire Instability and Breadth

Scientists investigated the clonal repertoire of 29 CD8⁺ T lymphocyte responses against 23 HIV-1 epitopes longitudinally in nine chronically infected untreated subjects with plasma viremia <3000 RNA copies/ml over 17 to 179 weeks. The composition of T cell receptors targeting each epitope varied considerably in stability over time, although clonal stability was not significantly time-dependent within this interval. [J Virol] Abstract

Decline in CD4 T Lymphocytes with Monotherapy Bridging Strategy for Non-Adherent Adolescents Living with HIV Infection: Results of the IMPAACT P1094 Randomized Trial

Participants with documented nonadherence, M184V mutation, CD4⁺ T cell count ≥100 cells/mm³ and virologic failure were enrolled and randomized to continue failing combination antiretroviral therapy (cART) vs. switch to 3TC/ FTC monotherapy (3TC/FTC). Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4⁺ count of ≥30%. [PLoS One] Full Article

Subscribe to our sister publications: Human Immunology News & Immune Regulation News.

Fungal Dysbiosis: Immunity and Interactions at Mucosal Barriers

Researchers summarize specific mycobiota patterns that are associated with fungal dysbiosis, and discuss how mucosal immunity has evolved to distinguish fungal infections from dysbiosis and how it responds to these different conditions. [Nat Rev Immunol] Abstract

Variant Surface Antigens of Plasmodium falciparum and Their Roles in Severe Malaria

The authors discuss the multigene families of surface variant polypeptides and highlight their roles in causing severe malaria. [Nat Rev Microbiol] Abstract

Citrobacter rodentium: A Model Enteropathogen for Understanding the Interplay of Innate and Adaptive Components of Type 3 Immunity

Scientists discuss type 3 immunity in the context of C. rodentium infection and discuss recent publications that use the model to understand how the innate and adaptive components of immunity intersect to mediate host protection against enteric pathogens and maintain homeostasis with the microbiota. [Mucosal Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immunology of infectious disease research field.

GSK and MMV Announce Positive Headline Phase III Results Showing Single-Dose Tafenoquine Reduces Risk of Relapse in Patients with Plasmodium vivax Malaria

GSK and Medicines for Malaria Venture announced positive results from two Phase III studies of tafenoquine, an investigational 8-aminoquinoline, for the prevention of relapse of P. vivax malaria. [Press release from GlaxoSmithKline plc. discussing research presented at the 2017 International Conference on Plasmodium vivax Research (ICPVR), Manaus] Press Release

Pimodivir Alone or in Combination with Oseltamivir Demonstrated a Significant Reduction in Viral Load in Adults with Influenza A

Janssen Pharmaceuticals, Inc. announced results from the Phase IIb Topaz Trial which demonstrated that treatment with pimodivir significantly decreased viral load over seven days versus placebo, in adult patients with acute, uncomplicated seasonal influenza A. Patients treated with pimodivir and oseltamivir demonstrated a significantly lower viral load compared with those who received pimodivir alone at the same dose. [Press release from Janssen Pharmaceuticals, Inc. discussing research presented at the 2017 International Society for Influenza and Respiratory Diseases Antiviral Group (ISIRV-AVG) Conference, Shanghai] Press Release

GeoVax Presents Data on Novel Zika Vaccine

GeoVax Labs, Inc. presented research showing that a single dose of its Zika vaccine gave 100% protection in mice challenged with a lethal dose of Zika virus (ZIKV). This is the first report of i) a Zika vaccine based on the ZIKV NS1 protein, and ii) single-dose protection against ZIKV using an immunocompetent lethal mouse challenge model. [Press release from GeoVax Labs, Inc. discussing research presented at the 2017 American Society for Microbiology (ASM) Microbe Conference, New Orleans] Press Release

NovaDigm Therapeutics Awarded $6 Million by U.S. Department of Defense to Conduct a Phase IIa Staphylococcus aureus Vaccine Trial

NovaDigm Therapeutics announced awards totaling $6 million from the U.S. Department of Defense to conduct a clinical study of NDV-3A in military personnel at high risk for skin and soft tissue infections due to S. aureus, including methicillin-resistant S. aureus. [NovaDigm Therapeutics] Press Release

NIAID-Sponsored Trial of Experimental Chikungunya Vaccine Begins

A clinical trial of an experimental vaccine to prevent infection with chikungunya virus is enrolling healthy adult volunteers at three sites in the United States. The Phase I/II trial, which is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is being conducted at several NIAID-funded Vaccine and Treatment Evaluation Units. [National Institutes of Health] Press Release

NIH Funds NYC Center for AIDS Research

The National Institutes of Health (NIH) has awarded researchers at Albert Einstein College of Medicine, the Rockefeller University, and the City University of New York Graduate School of Public Health and Health Policy, a $7.5 million grant for the Center for AIDS Research focused on preventing HIV transmission and ending the AIDS epidemic. [Albert Einstein College of Medicine] Press Release

UMD Awarded $6 Million NIH Grant for Structure-Based Design of a Hepatitis C Vaccine

The University of Maryland (UMD)’s Institute for Bioscience and Biotechnology Research has been awarded a $6-million grant entitled, “Structure-Based Vaccine Design for Hepatitis C Virus,” to develop a novel prophylactic vaccine to prevent hepatitis C virus infection. The grant is funded by the National Institutes of Health (NIH) and the research will take place over a five-year period. [University of Maryland] Press Release

Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide for HIV Treatment

Gilead Sciences, Inc. announced that it has submitted a New Drug Application to the U.S. Food and Drug Administration 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. [Gilead Sciences, Inc.] Press Release

Basilea Announces License Agreement with Pfizer for Antifungal Cresemba^® (Isavuconazole) for Europe, Russia, Turkey and Israel

Basilea Pharmaceutica Ltd. announced that Basilea Pharmaceutica International Ltd. has entered into a license agreement with Pfizer Inc. for Basilea’s marketed antifungal Cresemba for the treatment of life-threatening invasive mold infections. Pfizer will have the right to manufacture isavuconazole and to exclusively commercialize the drug in Europe (excluding the Nordics), Russia, Turkey and Israel. [Basilea Pharmaceutica Ltd.] Press Release

ABIVAX to Receive €390,000 from Bpifrance for the Development of Its Ebola Hyperimmune Candidate

ABIVAX announced that Bpifrance and Région Occitanie/Pyrénées-Méditerranée have agreed to provide a loan of €390,000 to the company for the development of a cocktail of polyclonal antibodies against the Ebola virus. [ABIVAX] Press Release

CureVac Extends Global Intellectual Property Estate for Prophylactic mRNA Vaccines

CureVac AG announced it has been granted important patents claiming the use of mRNA-based prophylactic vaccines, significantly adding to the company’s intellectual property (IP) position for its RNActive^® Prophylactic Vaccine technology. The IP includes patents granted in the USA and Europe covering mRNA vaccines against respiratory syncytial virus, as well as patents regarding the vaccination of elderly and newborns/infants with mRNA vaccines. [CureVac AG] Press Release

Empty Rhetoric over Data Sharing Slows Science

Government agencies lack the funds to build platforms for data sharing and resist taking responsibility for such infrastructure. They may hope that universities will host data, but the development of institutional repositories is patchy, and to rely on them is effectively to discourage common data standards and curation. [Nature News] Editorial

Can Fake Names Tease Out NIH Reviewer Bias?

When the label “white male” is attached to a research grant application, do peer reviewers give it a better score? That’s the question psychologist Patricia Devine of the University of Wisconsin in Madison has spent the past four years, and more than $1 million from the National Institutes of Health (NIH) in Bethesda, Maryland, trying to answer with an unusual experiment. [ScienceInsider] Editorial

NEW Keystone Symposia: Lymphocytes and Their Roles in Cancer
February 11-15, 2018
Keystone, Colorado, United States

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

NEW Research Associate – HIV Immunology (University College London)

NEW Postdoctoral Scientist – HIV-1 and Malaria Vaccine Research (Center for Infectious Disease Research)

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

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)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Immunology of Infectious Disease News? Click here to submit!

Comments or suggestions? Submit your feedback here.