Volume 1.34 | Nov 6

Immunology of Infectious Disease News 1.34 November 6, 2013
Immunology of Infectious Disease News
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Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys
Investigators showed that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viremia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian-human immunodeficiency virus SHIV-SF162P3. [ Nature] Abstract | Press Release
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Natural Regulatory T Cells Inhibit Production of Cytotoxic Molecules in CD8+ T Cells during Low-Level Friend Retrovirus Infection
Researchers previously showed that the level of Friend retrovirus replication determines the cytotoxic pathway for the control of viral infection. In low-level infection only the Fas pathway is active, whereas cytotoxic molecules are not produced. Here, they elucidated the role of CD4+ regulatory T cells in suppressing the exocytosis pathway during an asymptomatic low-level infection. [Retrovirology] Full Article

Mucosal Pre-Exposure to Th17-Inducing Adjuvants Exacerbates Pathology after Influenza Infection
The authors tested the hypothesis that mucosal pre-exposure to Th17-inducing adjuvants can promote disease exacerbation upon subsequent infection with influenza virus. Mice mucosally pre-exposed to Th17-inducing adjuvants, such as type II heat-labile enterotoxin or cholera toxin, resulted in increased morbidity and exacerbated lung inflammation upon subsequent infection with influenza virus. [Am J Pathol] Abstract

Mycobacterium avium Biofilm Attenuates Human Mononuclear Phagocyte Function by Triggering Hyper-Stimulation and Apoptosis during Early Infection
The reasoning behind how Mycobacterium avium subsp. hominissuis (MAH) biofilm is allowed to establish and persist without being cleared by the innate immune system is currently unknown. To identify the mechanism responsible for this, investigators developed an in vitro model using THP-1 human mononuclear phagocytes co-cultured with established MAH biofilm and surveyed various aspects of the interaction including phagocyte stimulation and response, bacterial killing, and apoptosis. [Infect Immun] Abstract

Human Immune Responses to Plasmodium falciparum Infection: Molecular Evidence for a Suboptimal THalphabeta and TH17 Bias Over Ideal and Effective Traditional TH1 Immune Response
Using microarray analysis, this study showed up-regulation of toll-like receptors 1, 2, 4, 7, 8, NF-kappaB, TNF, p38-MAPK, and MHC molecules in human peripheral blood mononuclear cells following infection with Plasmodium falciparum. The results showed that in early malaria, selected immune response-related genes were up-regulated including alpha beta and gamma interferon-related genes, as well as genes of IL-15, CD36, chemokines, TRAIL and IgG Fc receptors. [Malar J] Abstract | Press Release


Antibody-Mediated Immunotherapy of Macaques Chronically Infected with SHIV Suppresses Viremia
A new generation of anti-HIV-1 monoclonal antibodies, possessing extraordinary potency and breadth of neutralizing activity, has recently been isolated from infected individuals. Here researchers examined two of the new antibodies, directed to the CD4-binding site and the V3 region, for their ability to block infection and suppress viremia in macaques infected with the R5 tropic simian-human immunodeficiency virus (SHIV)-AD8, which emulates many of the pathogenic and immunogenic properties of HIV-1 during infections of rhesus macaques. [Nature] Abstract | Press Release

IFI16 Senses DNA Forms of the Lentiviral Replication Cycle and Controls HIV-1 Replication
Using ssDNAs derived from HIV-1 proviral DNA, researchers report that this DNA form potently induces the expression of IFNs in primary human macrophages. This response was stimulated by stem regions in the DNA structure and was dependent on IFN-inducible protein 16 (IFI16), which bound immunostimulatory DNA directly and activated the stimulator of IFN genes -TANK-binding kinase 1 – IFN regulatory factors 3/7 pathway. [Proc Natl Acad Sci USA] Abstract | Press Release

MCPIP1 Restricts HIV Infection and Is Rapidly Degraded in Activated CD4+ T Cells
Scientists showed that the previously reported immune regulator monocyte chemotactic protein-induced protein 1 (MCPIP1) restricts HIV-1 production in CD4+ T cells. While the ectopic expression of MCPIP1 in cell lines abolished the production of HIV-1, silencing of MCPIP1 enhanced HIV-1 production. [Proc Natl Acad Sci USA] Abstract

Evidence for Innate Immune System Activation in HIV-1 Infected Elite Controllers
Soluble biomarkers were measured in cryopreserved plasma by ELISA and electrochemilluminescence-based assays from 68 Elite Controllers, 68 ART-treated patients with suppressed viremia and 35 HIV- participants. Cryopreserved PBMC were used to assess monocyte phenotype and function and interferon-inducible gene expression. [J Infect Dis] Abstract
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Escaping the Immune System: How the Malaria Parasite Makes Vaccine Development a Challenge
An inadequate understanding of natural immunity, host-parasite interactions, and a lack of reliable immune correlates of protection that could predict vaccine efficacy in the field have hindered development of a vaccine. With data from Phase III trials indicating that the leading malaria vaccine candidate, RTS,S, has limited efficacy, it is necessary to reconsider approaches to the development of a vaccine capable of inducing long-lived protection. [Trends Parasitol] Abstract

Tightly Regulated Migratory Subversion of Immune Cells Promotes the Dissemination of Toxoplasma gondii
The authors review the emerging knowledge on how the obligate intracellular protozoan, Toxoplasma gondii orchestrates the subversion of leukocytes to achieve systemic dissemination and reach peripheral organs where pathology manifests. [Int J Parasitol] Abstract

Role of Innate Immunity against Human Papillomavirus (HPV) Infections and Effect of Adjuvants in Promoting Specific Immune Response
This review focuses on HPV immune evasion mechanisms and on the proposed response of the innate immune system, suggesting a role for the surrounding pro-inflammatory microenvironment and the natural killer (NK) and (NK) T cells in the clearance of HPV infections. [Viruses-Basel] Abstract | Full Article

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Boehringer Ingelheim’s Interferon-Free Hepatitis C Treatment Portfolio Strengthened by Promising Phase II Data
Interim data showed that all patients who reached their 4-week post-treatment follow-up have undetectable levels of hepatitis C virus after completing a 12-week regimen of faldaprevir, deleobuvir, PPI-668 and ribavirin. [Press release from Boehringer Ingelheim GmbH discussing research presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Washington] Press Release

Gilead Announces Phase III Results for an All-Oral, Sofosbuvir-Based Regimen for the Treatment of Hepatitis C in Patients Co-Infected With HIV
Gilead Sciences, Inc. announced results from a Phase III study, PHOTON-1, evaluating the investigational once-daily nucleotide analogue sofosbuvir for the treatment of chronic hepatitis C virus (HCV) infection among patients co-infected with HIV. [Press release from Gilead Sciences, Inc. discussing research presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Washington] Press Release

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PDL BioPharma Provides $70 Million in Financing to Durata Therapeutics
PDL BioPharma, Inc. announced that it closed a financing transaction with Durata Therapeutics, Inc., a pharmaceutical company focused on the development and commercialization of novel therapeutics for patients with infectious diseases and acute illnesses. Under the credit agreement, PDL will provide Durata with up to $70 million of debt financing with a five year term and will receive interest on the principal amount outstanding and a security interest in substantially all of Durata’s assets. [PDL BioPharma, Inc.]
Press Release

CytoDyn Inc. Completes $14.5 Million Private Equity Offering
CytoDyn Inc., a biotechnology company focused on the development of new therapies for combating infection with immune deficiency viruses, announced the completion of its equity capital raise for a total of $14.5 million through a private offering. The proceeds from the offering will be used to fund current operating expenses in order to continue the development of the Company’s primary drug candidate PRO 140 which is believed to be one of the leading monoclonal antibodies for the treatment of HIV. [CytoDyn Inc.]
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