Volume 1.05 | Apr 17

Immunology of Infectious Disease News 1.05 April 17, 2013
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TOP STORY
TNF Dually Mediates Resistance and Susceptibility to Mycobacteria via Mitochondrial Reactive Oxygen Species
Using the zebrafish, researchers elucidated the pathways by which tumor necrosis factor (TNF) mediates tuberculosis pathogenesis. TNF excess induces mitochondrial reactive oxygen species (ROS) in infected macrophages through RIP1-RIP3-dependent pathways. While initially increasing macrophage microbicidal activity, ROS rapidly induced programmed necrosis (necroptosis) and released mycobacteria into the growth-permissive extracellular milieu. [Cell] Abstract | Graphical Abstract | Press Release

Isolate Mouse Cells In As Little As 15 Minutes

PUBLICATIONS (Ranked by impact factor of the journal)

Blockade of Chronic Type I Interferon Signaling to Control Persistent LCMV Infection
Type I interferons (IFN-I) are critical for antiviral immunity; however, chronic IFN-I signaling is associated with hyperimmune activation and disease progression in persistent infections. The authors demonstrated in mice that blockade of IFN-I signaling diminished chronic immune activation and immune suppression, restored lymphoid tissue architecture, and increased immune parameters associated with control of virus replication, ultimately facilitating clearance of the persistent infection. [Science] Abstract | Press Release

Persistent LCMV Infection Is Controlled by Blockade of Type I Interferon Signaling
Researchers demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. [Science] Abstract | Press Release

Comprehensive Analysis of Dengue Virus-Specific Responses Supports an HLA-Linked Protective Role for CD8+ T Cells
The role of CD8+ T cells in dengue virus infection and subsequent disease manifestations is not fully understood. According to the original antigenic sin theory, skewing of T-cell responses induced by primary infection with one serotype causes less effective response upon secondary infection with a different serotype, predisposing individuals to severe disease. A comprehensive analysis of CD8+ responses in the general population from the Sri Lankan hyperendemic area, involving the measurement of ex vivo IFNγ responses associated with more than 400 epitopes, challenges the original antigenic sin theory. [Proc Natl Acad Sci USA] Abstract | Press Release

The Immune Complex CTA1-DD/IgG Adjuvant Specifically Targets Connective Tissue Mast Cells through FcγRIIIA and Augments Anti-HPV Immunity after Nasal Immunization
Researchers previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, they extended these studies and demonstrated that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. [Mucosal Immunol] Abstract

Potentiating Functional Antigen-Specific CD8+ T Cell Immunity by a Novel PD1 Isoform-Based Fusion DNA Vaccine
Although upregulated programmed death-1 (PD1) in chronic infections (such as HIV-1 and tuberculosis) impedes T cell responses, blocking the PD1/PD-L pathway could functionally rescue the “exhausted” T cells. However, there exists a number of PD1 spliced variants with unknown biological function. Researchers identified a new isoform of human PD1 (Δ42PD1) that contains a 42-nucleotide in-frame deletion located at exon 2 domain found expressed in peripheral blood mononuclear cells. [Mol Ther] Abstract

Inhibition of Ondoleamine 2, 3- Dioxygenase (IDO) Enhances the T Cell Response to Influenza Virus Infection
The impact of IDO on the primary immune response to influenza virus infection was determined using the IDO inhibitor 1-methyl-D, L-tryptophan (1MT). C57BL/6 mice treated with 1MT and infected with A/HKx31 influenza virus had increased numbers of activated and functional CD4+, influenza-specific CD8+ T cells, and effector memory cells in the lung. Inhibition of IDO increased the Th1 response in CD4+ T cells as well as enhanced the Th17 response. [J Gen Virol] Abstract

HIV

Interleukin-7 Promotes HIV Persistence during Antiretroviral Therapy
By isolating large numbers of CD4+ T cells from HIV-infected subjects, researchers demonstrated that IL-7 enhances viral production in productively infected cells but does not disrupt viral latency in latently infected cells isolated from subjects who received antiretroviral therapy for years. [Blood] Abstract

The Immunologic Effects of Maraviroc Intensification in Treated HIV-Infected Individuals with Incomplete CD4+ T cell Recovery: A Randomized Trial
Researchers randomized 45 HIV-infected subjects with CD4 counts less than 350 cells/mm3 and plasma HIV RNA levels less than 48 copies/ml on antiretroviral therapy (ART) to add maraviroc vs. placebo to their existing regimen for 24 weeks followed by 12 weeks on ART alone. Compared to placebo-treated subjects, maraviroc-treated subjects unexpectedly experienced a greater median increase in %CD38+HLA-DR+ peripheral blood CD8+ T cells at week 24, and less of a decline in activated CD4+T cells. [Blood] Abstract

SHIV Antigen Immunization Alters Patterns of Immune Responses to SHIV/Malaria Co-Infection and Protects against Life-Threatening SHIV-Related Malaria

Overlapping endemicity of HIV and malaria suggests that HIV/malaria co-infection frequently complicates acute and chronic HIV infection. Scientists showed that vaccination of macaques with recombinant(r) Listeria ΔactA prfA* expressing SHIV gag and env elicited Gag and Env-specific T-cell responses, and protected against life-threatening SHIV-related malaria after SHIV/P. fragile co-infection. [J Infect Dis] Abstract

Low-Level Viremia Is Associated with Non-B Subtypes in Patients Infected with HIV with Virological Success following HAART Introduction
This prospective study aimed to determine factors associated with detection of very low-level viremia in patients infected with HIV-1 with virological success following HAART introduction. Fifty-seven patients, mostly treated with a protease inhibitor-based regimen, were included and followed for 2 years. [J Med Virol] Abstract

A Truncated Plasmid-Encoded HIV-1 Reverse Transcriptase Displays Strong Immunogenicity

Besides being an important target in the antiretroviral therapy against the human immunodeficiency virus type 1 (HIV-1), the HIV-1 reverse transcriptase (RT) enzyme has potential as a vaccine antigen. Researchers explored the ability of plasmid-encoded RT to induce cell-mediated immune responses. The strategy for increasing the immunogenicity of the protein was to delete non- or low-immunogenic parts in order to focus the immune responses to known immunogenic regions. [Viral Immunol] Abstract

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REVIEWS

Mapping the Crossroads of Immune Activation and Cellular Stress Response Pathways
The innate immune cell network detects specific microbes and damages to cell integrity in order to coordinate and polarize the immune response against invading pathogens. In recent years, a cross-talk between microbial-sensing pathways and endoplasmic reticulum (ER) homeostasis has been discovered and have attracted the attention of many researchers from the inflammation field. The authors discuss how the innate immune and ER-signaling pathways intersect. [EMBO J] Abstract

Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load
This review examines and discusses differences of the cell-mediated immune responses between HIV+ individuals with disease progression and elite controllers. [Front Immunol] Abstract

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

SCIENCE NEWS
IDRI and Medicago Report Positive Results for Phase I Clinical Trial for an H5N1 Vaccine
IDRI (Infectious Disease Research Institute) and Medicago Inc. reported positive interim results from a Phase I clinical trial for an H5N1 Avian Influenza VLP vaccine candidate (“H5N1 vaccine”). The H5N1 vaccine was found to be safe and well-tolerated and induced a solid immune response exceeding the three Committee for Medicinal Products for Human Use immunogenicity criteria for licensure of influenza vaccines. [Press release from the Infectious Disease Research Institute discussing research presented at the World Vaccine Congress, Washington] Press Release
 
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INDUSTRY NEWS

An Update on EpiVax’ H7N9 “FastVax” Progress
EpiVax scientists are currently in discussions with groups in China, Canada and the US about producing an H7N9 vaccine. They highlight a few key points about the current progress of EpiVax’ FastVax vaccine design. [EpiVax, Inc.] Press Release

World Demand for Infection Prevention Products to Reach $130 Billion in 2017
The upgrading and enforcement of patient and staff safety standards in health care facilities, coupled with an expanding volume of hospital, surgical, and outpatient procedures, will promote overall gains. China, the United States, India, Russia, Japan, Germany, France, Italy, Brazil, and the United Kingdom will comprise the 10 largest national markets, combining to account for nearly two-thirds of global demand in 2017. [PR Newswire Association LLC] Press Release

Benitec Selects University of California, San Diego as a Site for Phase I/II Clinical Trial of TT-034 in Patients with Hepatitis C Infections
RNAi-based therapeutics company Benitec Biopharma Limited announced the selection of the University of California, San Diego, Health Sciences as the second site for its upcoming phase I/II first-in-man trial for TT-034 in Hepatitis C infections. Benitec previously announced the selection of Duke Clinical Research Unit as the other site. [Benitec Biopharma, Ltd.] Press Release

Benitec’s Hep C Program Moves Closer to Clinic with RAC Application
Benitec Biopharma, which is developing innovative therapeutics based on its gene-silencing technology, DNA-directed RNA interference, announced that it has moved closer to clinical trials for TT-034, a first-in-class treatment of chronic hepatitis C virus. [Benitec Biopharma, Ltd.] Press Release

POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS

NEW IDWeek 2013
October 2-6, 2013
San Francisco, United States

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

JOB OPPORTUNITIES

Postdoctoral Fellow – Immunology (California Institute for Biomedical Research)

Postdoctoral Fellow (Columbia Initiative for Systems Biology / Columbia University)

Postdoctoral Fellows (Louisiana State University (LSU))

Postdoctoral Position – Immunology and Vaccinology (Université de Liège)

Postdoctoral Position – Immunology (New York University)

Postdoctoral Scientist (National Institute for Medical Research, Medical Research Council)

Director – Basic Sciences Program (National Institute of Allergy and Infectious Disease/National Institutes of Health)

Postdoctoral Position – Synthetic Biology, RNAi & Gene Therapy (University of Heidelberg Medical School)


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