A U.S. Government-Coordinated Effort to Leverage Non-Human Primate Data to Facilitate Ebolavirus Vaccine Development.

A United States Government (USG) interagency group, the Filovirus Animal Non-Clinical Group (FANG), has been established to support the development of biodefense medical countermeasures (MCMs). As both vaccines and therapeutics are licensed using "non-traditional pathways", such as the U.S.

Immunology of protection from Ebola virus infection.

A December 2014 meeting reviewed Ebola virus immunology relevant to vaccine development, including Ebola prevention, immunity, assay standardization, and regulatory considerations. Vaccinated humans appear to achieve immune responses comparable in magnitude with those associated with protection in nonhuman primates, suggesting that immunological data could be used to demonstrate vaccine efficacy.

Current biodefense vaccine programs and challenges.

The Defense Threat Reduction Agency's Joint Science and Technology Office manages the Chemical and Biological Defense Program's Science and Technology portfolio. The Joint Science and Technology Office's mission is to invest in transformational ideas, innovative people and actionable technology development for Chemical and Biological Defense solutions, with the primary goal to deliver Science and Technology products and capabilities to the warfighter and civilian population that outpace the threat. This commentary focuses on one thrust area within this mission: the Vaccine program of the Joint Science and Technology Office's Translational Medical Division.

DM, but not cathepsin L, is required to control an aerosol infection with Mycobacterium tuberculosis.

Antigen presentation by class II MHC molecules in the uninfected host is a multi-step process involving key functions provided by specific cathepsins (Cat) and the peptide editor DM. Herein, we examined the requirement for each of these components in mice to control a low-dose aerosol infection with Mycobacterium tuberculosis (MTB). Mice lacking Cat B, -L, or -S were similar to wild-type in their ability to control the growth and dissemination of MTB.

Cathepsin L maturation and activity is impaired in macrophages harboring M. avium and M. tuberculosis.

Mycobacterium tuberculosis-infected macrophages demonstrate diminished capacity to present antigens via class II MHC molecules. Since successful class II MHC-restricted antigen presentation relies on the actions of endocytic proteases, we asked whether the activities of cathepsins (Cat) B, S and L-three major lysosomal cysteine proteases-are modulated in macrophages infected with pathogenic Mycobacterium spp. Infection of murine bone marrow-derived macrophages with either Mycobacterium avium or M.

Evidenced-based factors in readmission of patients with heart failure.

The purpose of this project was to organize the variables associated with the hospital readmission of patients with heart failure (HF) into a usable framework to inform clinical practice and facilitate administrative decision making. An integrated, systematic review of the literature was used as the research approach. A content analysis of the sample (31 research reports from the years 1986-2004) yielded multiple factors associated with the hospital readmission of HF patients.

Transplant data: sources, collection, and caveats.

By examining the sources, quality and organization of transplant data available, as well as making observations about data reporting patterns and accuracy, we hope to improve understanding of existing results, help researchers with study design and stimulate new exploratory initiatives. The primary data source, collected by the OPTN, has benefited from extensive recent technological advances. Transplant professionals now report patient and donor data more easily, quickly, and accurately, improving data timeliness and precision.

Class II MHC peptide loading by the professionals.

The loading of class II MHC molecules with antigenic peptides is largely confined to the endocytic vesicles of specialized antigen-presenting cells (APCs), such as B cells, macrophages and dendritic cells. At first glance, the pathway utilized by each of these professional APCs to generate class II-peptide complexes on their surface appears to be indistinguishable. All three types of APC rely on the chaperone Ii for correct class II assembly and transport to the endocytic pathway, they all depend on the action of specific cysteine proteases to remove Ii from the class II-Ii complex, and they all utilize the class II-like molecule DM to facilitate peptide loading.

Zwitterionic polysaccharides stimulate T cells by MHC class II-dependent interactions.

Polysaccharides of pathogenic extracellular bacteria commonly have negatively charged groups or no charged groups at all. These molecules have been considered classic T cell-independent Ags that do not elicit cell-mediated immune responses in mice. However, bacterial polysaccharides with a zwitterionic charge motif (ZPSs), such as the capsular polysaccharides of many strains of Bacteroides fragilis, Staphylococcus aureus, and Streptococcus pneumoniae type 1 elicit potent CD4(+) T cell responses in vivo and in vitro.

Proteolysis and antigen presentation by MHC class II molecules.

Proteolysis is the primary mechanism used by all cells not only to dispose of unwanted proteins but also to regulate protein function and maintain cellular homeostasis. Proteases that reside in the endocytic pathway are the principal actors of terminal protein degradation. The proteases contained in the endocytic pathway are classified into four major groups based on the active-site amino acid used by the enzyme to hydrolyze amide bonds of proteins: cysteine, aspartyl, serine, and metalloproteases.