MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies

A single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a significant reduction in M. tuberculosis infection-induced disease pathology measured using in vivo medical imaging, in gross pathology lesion counts and pathology scores recorded at necropsy, the frequency and severity of pulmonary granulomas and the frequency of recovery of viable M. tuberculosis from extrapulmonary tissues following challenge. The immune profiles induced following immunisation with MTBVAC reflect those identified in human clinical trials of MTBVAC. Evaluation of MTBVAC- and TB peptide-pool-specific T-cell cytokine production revealed a predominantly Th1 response from poly- (IFN-¿+TNF-a+IL2+) and multi-(IFN-¿+TNF-a+) functional CD4 T cells, while only low levels of Th22, Th17 and cytokine-producing CD8 T-cell populations were detected together with low-level, but significant, increases in CFP10-specific IFN-¿ secreting cells. In this report, we describe concordance between immune profiles measured in clinical trials and a macaque pre-clinical study demonstrating significantly improved outcome after M. tuberculosis challenge as evidence to support the continued development of MTBVAC as an effective prophylactic vaccine for TB vaccination campaigns

Actin-interacting and flagellar proteins in Leishmania spp.: Bioinformatics predictions to functional assignments in phagosome formation

Several motile processes are responsible for the movement of proteins into and within the flagellar membrane, but little is known about the process by which specific proteins (either actin-associated or not) are targeted to protozoan flagellar membranes. Actin is a major cytoskeleton protein, while polymerization and depolymerization of parasite actin and actin-interacting proteins (AIPs) during both processes of motility and host cell entry might be key events for successful infection. For a better understanding the eukaryotic flagellar dynamics, we have surveyed genomes, transcriptomes and proteomes of pathogenic Leishmania spp. to identify pertinent genes/proteins and to build in silico models to properly address their putative roles in trypanosomatid virulence. In a search for AIPs involved in flagellar activities, we applied computational biology and proteomic tools to infer from the biological meaning of coronins and Arp2/3, two important elements in phagosome formation after parasite phagocytosis by macrophages. Results presented here provide the first report of Leishmania coronin and Arp2/3 as flagellar proteins that also might be involved in phagosome formation through actin polymerization within the flagellar environment. This is an issue worthy of further in vitro examination that remains now as a direct, positive bioinformatics-derived inference to be presented

A comparison of predictive methods in extinction risk studies: contrasts and decision trees

Over the last two decades an increasing emphasis has been placed on the importance of controlling for phylogeny when examining cross-species data; so-called comparative methods. These methods are appropriate for testing hypotheses about correlations between evolutionary events in the history of a clade and adaptive responses to those changes. When this approach is applied to extinction risk, possible correlations between evolutionary changes in, for example, body size or habitat specialisation and some measure(s) of current threat status are examined. However, there may be a mismatch here between the results of such studies, and the real, pragmatic needs of species conservation. This kind of approach certainly adds to our knowledge of some fundamental processes, but it is more difficult to see how this can be applied to conservation decision-making. For more practical purposes a decision-tree approach can be extremely useful. This paper illustrates the use of a contrasts based analysis of extinction risk compared with a decision-tree analysis for Galliformes (Aves). While the contrasts analyses concur with some general macroecological trends found in other studies, the decision-tree models provide lists of species predicted to be more at risk than current assessments would suggest. We argue that in practical terms, decision tree models might be more useful than a macroecological linear model-based approach

Physical activity and the prevention of mental illness, dysfunction and cognitive deterioration

Describes the role of physical activity in the prevention of mental illness, dysfunction and cognitive deterioration