Immunology of Infectious Disease News Volume 1.04 | Apr 10 2013

PUBLICATIONS (Ranked by impact factor of the journal)

MHC II Tetramers Visualize Human CD4⁺ T Cell Responses to Epstein-Barr Virus Infection and Demonstrate Atypical Kinetics of the Nuclear Antigen EBNA1 Response
Virus-specific CD4⁺ T cells are key orchestrators of host responses to viral infection yet, compared with their CD8⁺ T cell counterparts, remain poorly characterized at the single cell level. Researchers used nine MHC II-epitope peptide tetramers to visualize human CD4⁺ T cell responses to Epstein-Barr virus, the causative agent of infectious mononucleosis, a disease associated with large virus-specific CD8⁺ T cell responses. [J Exp Med] Abstract

IL-27 Receptor Signaling Regulates CD4⁺ T Cell Chemotactic Responses during Infection
Using Plasmodium berghei NK65 as a model of a systemic, proinflammatory infection, investigators demonstrated that IL-27R signaling represses chemotaxis of infection-derived splenic CD4⁺ T cells in response to the CCR5 ligands, CCL4 and CCL5. Consistent with these observations, CCR5 was expressed on significantly higher frequencies of splenic CD4⁺ T cells from malaria-infected, IL-27R-deficient mice than from infected wild-type mice. [J Immunol] Abstract

TcVac3 Induced Control of Trypanosoma cruzi Infection and Chronic Myocarditis in Mice
The authors characterized the immune responses elicited by a DNA-prime/MVA-boost vaccine (TcVac3) constituted of antigenic candidates (TcG2 and TcG4), shown to be recognized by B and T cell responses in Trypanosoma cruzi (Tc) infected multiple hosts. C57BL/6 mice immunized with TcVac3 elicited a strong antigen-specific, high-avidity, trypanolytic antibody response (IgG2b>IgG1); and a robust antigen- and Tc-specific CD8⁺T cell response with type-1 cytokine (IFN-γ⁺TNF-a>IL-4⁺IL-10) and cytolytic effector (CD8⁺CD107a⁺IFN-γ⁺Perforin⁺) phenotype. [PLoS One] Full Article | Press Release

The Role of Innate versus Adaptive Immune Responses in a Mouse Model of O’Nyong-Nyong Virus Infection
O’nyong-nyong virus (ONNV), an alphavirus closely related to chikungunya virus (CHIKV), has caused three major epidemics in Africa since 1959. The ONNV and CHIKV produce similar syndromes with fever, rash, and debilitating arthralgia. To determine the roles of the innate and adaptive immune responses, the authors infected different knockout mice with two strains of ONNV. [Am J Trop Med Hyg] Abstract

The Anti-Idiotypic Antibody 1F7 Stimulates Monocyte Interleukin-10 Production and Induces Endotoxin Tolerance
Researchers report that induction of antibodies expressing the 1F7 idiotype by chronic pathogens may facilitate IL-10 production and progression to chronic infection. Direct effects of IL-10 from human monocytes stimulated by 1F7-like antibodies, followed by monocyte transition to an alternatively activated phenotype illustrated by endotoxin tolerance, are two complementary features favoring a tolerogenic or non-responsive immunological environment. [J Inflamm (Lond)] Abstract

HIV

Influence of HLA-C Expression Level on HIV Control
The authors characterized the differential cell surface expression levels of all common leukocyte antigen C (HLA-C) allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. [Science] Abstract

Correlates of T-Cell Mediated Viral Control and Phenotype of CD8+ T-Cells in HIV-2, a Naturally Contained Human Retroviral Infection
While a significant proportion of HIV-2-infected individuals are asymptomatic and maintain undetectable viral loads (controllers), 15-20% progress to AIDS and are predicted by detectable viraemia. Researchers performed a detailed study of HIV-2-specific cellular responses in a unique community cohort in Guinea-Bissau followed for over two decades. T-cell responses were compared between controllers and viraemic subjects using overlapping peptides, MHC class I tetramers and multi-parameter flow cytometry. [Blood] Abstract

Association of Functional Impairment with Inflammation and Immune Activation in HIV-1-Infected Adults on Effective Antiretroviral Therapy
The relationships of inflammation, immune activation and immune senescence markers with functional impairment in aging HIV-1-infected persons are unknown. The authors report that functional impairment during successful antiretroviral therapy was associated with higher CD8+ T cell activation and interleukin-6 levels. [J Infect Dis] Abstract

Role of CD8⁺ T Cells in Triggering Reversal Reaction in HIV/Leprosy Patients
Researchers observed that ex vivo PBMCs of both reversal reaction (RR) and RR/HIV patients presented increased percentages of activated CD4⁺T cells when compared with the HC group. The frequency of CD8⁺CD38⁺ cells increased in the PBMCs of RR / HIV but not in RR patients when compared with the HC group. [Immunology] Abstract

Synthetic Immunotherapy Induces HIV Virus Specific Th1 Cytotoxic Response and Death of an HIV-1 Infected Human Cell Line through Classic Complement Activation
The authors describe the development of a novel synthetic immunotherapy (HIV-v) composed of four multi-epitope polypeptides targeting conserved regions in the Nef, Rev, Vif and Vpr viral proteins. Immunogenicity and cytotoxicity of HIV-v are discussed. [Virol J] Abstract | Full Article

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Mucosal Immunity in Human and Simian Immunodeficiency Lentivirus Infections
This review discusses overwhelming evidence that indicates that distinct pathological phenomenon occurs within the gastrointestinal tract of progressively simian immunodeficiency virus-infected Asian macaques and HIV-infected humans compared with other anatomical sites. [Mucosal Immunol] Abstract

How Malaria Modulates Memory: Activation and Dysregulation of B Cells in Plasmodium Infection
The authors integrate recent findings on the effect of Plasmodium falciparum on B cells and the association of parasite exposure with altered B cell proportions, such as the expansion of atypical memory B cells. [Trends Parasitol] Abstract

Persistent Bacterial Infections, Antibiotic Tolerance, and the Oxidative Stress Response
This review highlights the clinical significance of persistent infections and discusses different in vitro models used to investigate the altered physiology of bacteria during persistent infections. The authors specifically focus on recent work establishing increased protection against oxidative stress as a key element of the altered physiologic state across different in vitro models and pathogens. [Virulence] Abstract

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

Inovio Pharmaceuticals & U.S. Army Receive $3.5 Million Biodefense Grant to Further Develop Mass Vaccination Device
Inovio Pharmaceuticals, Inc. has been selected to receive a $3.5 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) to advance the development of its next generation DNA vaccine delivery device capable of simultaneously administering multiple synthetic vaccines via skin surface electroporation. [Inovio Pharmaceuticals, Inc.] Press Release

Pitt Team Gets $5 Million National Institutes of Health Grant to Make Vaccine Component That Stimulates TB-Fighting T-Cells
Researchers at the University of Pittsburgh School of Medicine have received a $5 million federal grant to develop a vaccine ingredient that can generate the type of immune response needed to protect against tuberculosis (TB) infection. [UPMC/University of Pittsburgh Schools of the Health Sciences] Press Release

Tetragenetics Receives Phase II Grand Challenges Explorations Funding
Tetragenetics announced that it has received Phase II funding through Grand Challenges Explorations, an initiative created by the Bill & Melinda Gates Foundation that enables individuals worldwide to test bold ideas to address persistent health and development challenges. Dr. Ted Clark will continue to pursue an innovative global health research project, titled “A Highly Potent Delivery System for Malaria Vaccine Antigens”. [Tetragenetics, Inc.] Press Release

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)

NEW HIV Drug Therapy in the Americas
June 13-15, 2013
Sao Paulo, Brazil

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

Director – Vaccine Research Center (National Institute of Allergy and Infectious Diseases)

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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