Development and Validation of an Epitope Prediction Tool for Swine (PigMatrix) Based on the Pocket Profile Method

Background: T cell epitope prediction tools and associated vaccine design algorithms have accelerated the development of vaccines for humans. Predictive tools for swine and other food animals are not as well developed, primarily because the data required to develop the tools are lacking. Here, we overcome a lack of T cell epitope data to construct swine epitope predictors by systematically leveraging available human information. Applying the “pocket profile method”, we use sequence and structural similarities in the binding pockets of human and swine major histocompatibility complex proteins to infer Swine Leukocyte Antigen (SLA) peptide binding preferences. We developed epitope-prediction matrices (PigMatrices), for three SLA class I alleles (SLA-1*0401, 2*0401 and 3*0401) and one class II allele (SLA-DRB1*0201), based on the binding preferences of the best-matched Human Leukocyte Antigen (HLA) pocket for each SLA pocket. The contact residues involved in the binding pockets were defined for class I based on crystal structures of either SLA (SLA-specific contacts, Ssc) or HLA supertype alleles (HLA contacts, Hc); for class II, only Hc was possible. Different substitution matrices were evaluated (PAM and BLOSUM) for scoring pocket similarity and identifying the best human match. The accuracy of the PigMatrices was compared to available online swine epitope prediction tools such as PickPocket and NetMHCpan. Results: PigMatrices that used Ssc to define the pocket sequences and PAM30 to score pocket similarity demonstrated the best predictive performance and were able to accurately separate binders from random peptides. For SLA-1*0401 and 2*0401, PigMatrix achieved area under the receiver operating characteristic curves (AUC) of 0.78 and 0.73, respectively, which were equivalent or better than PickPocket (0.76 and 0.54) and NetMHCpan version 2.4 (0.41 and 0.51) and version 2.8 (0.72 and 0.71). In addition, we developed the first predictive SLA class II matrix, obtaining an AUC of 0.73 for existing SLA-DRB1*0201 epitopes. Notably, PigMatrix achieved this level of predictive power without training on SLA binding data. Conclusions: Overall, the pocket profile method combined with binding preferences from HLA binding data shows significant promise for developing T cell epitope prediction tools for pigs. When combined with existing vaccine design algorithms, PigMatrix will be useful for developing genome-derived vaccines for a range of pig pathogens for which no effective vaccines currently exist (e.g. porcine reproductive and respiratory syndrome, influenza and porcine epidemic diarrhea)

Genome Degradation in Brucella ovis Corresponds with Narrowing of Its Host Range and Tissue Tropism

Brucella ovis is a veterinary pathogen associated with epididymitis in sheep. Despite its genetic similarity to the zoonotic pathogens B. abortus, B. melitensis and B. suis, B. ovis does not cause zoonotic disease. Genomic analysis of the type strain ATCC25840 revealed a high percentage of pseudogenes and increased numbers of transposable elements compared to the zoonotic Brucella species, suggesting that genome degradation has occurred concomitant with narrowing of the host range of B. ovis. The absence of genomic island 2, encoding functions required for lipopolysaccharide biosynthesis, as well as inactivation of genes encoding urease, nutrient uptake and utilization, and outer membrane proteins may be factors contributing to the avirulence of B. ovis for humans. A 26.5 kb region of B. ovis ATCC25840 Chromosome II was absent from all the sequenced human pathogenic Brucella genomes, but was present in all of 17 B. ovis isolates tested and in three B. ceti isolates, suggesting that this DNA region may be of use for differentiating B. ovis from other Brucella spp. This is the first genomic analysis of a non-zoonotic Brucella species. The results suggest that inactivation of genes involved in nutrient acquisition and utilization, cell envelope structure and urease may have played a role in narrowing of the tissue tropism and host range of B. ovis

Marine Biodiversity in the Caribbean: Regional Estimates and Distribution Patterns

This paper provides an analysis of the distribution patterns of marine biodiversity and summarizes the major activities of the Census of Marine Life program in the Caribbean region. The coastal Caribbean region is a large marine ecosystem (LME) characterized by coral reefs, mangroves, and seagrasses, but including other environments, such as sandy beaches and rocky shores. These tropical ecosystems incorporate a high diversity of associated flora and fauna, and the nations that border the Caribbean collectively encompass a major global marine biodiversity hot spot. We analyze the state of knowledge of marine biodiversity based on the geographic distribution of georeferenced species records and regional taxonomic lists. A total of 12,046 marine species are reported in this paper for the Caribbean region. These include representatives from 31 animal phyla, two plant phyla, one group of Chromista, and three groups of Protoctista. Sampling effort has been greatest in shallow, nearshore waters, where there is relatively good coverage of species records; offshore and deep environments have been less studied. Additionally, we found that the currently accepted classification of marine ecoregions of the Caribbean did not apply for the benthic distributions of five relatively well known taxonomic groups. Coastal species richness tends to concentrate along the Antillean arc (Cuba to the southernmost Antilles) and the northern coast of South America (Venezuela – Colombia), while no pattern can be observed in the deep sea with the available data. Several factors make it impossible to determine the extent to which these distribution patterns accurately reflect the true situation for marine biodiversity in general: (1) highly localized concentrations of collecting effort and a lack of collecting in many areas and ecosystems, (2) high variability among collecting methods, (3) limited taxonomic expertise for many groups, and (4) differing levels of activity in the study of different taxa

The role of Streptococcus pneumoniae in community-acquired pneumonia among adults in Europe:a meta-analysis

<p>The primary objective of this meta-analysis was to estimate the prevalence of adult community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae in Europe, adjusted for possible independent covariates. Two reviewers conducted a systematic literature search using PubMed on English-language articles that involved human subjects with CAP during the period from January 1990 to November 2011 across European countries. A mixed-effects meta-regression model was developed and populated with 24,410 patients obtained from 77 articles that met the inclusion criteria. The model showed that the observed prevalence of S. pneumoniae in CAP significantly varies between European regions, even after adjusting for explanatory covariates, including patient characteristics, diagnostic tests, antibiotic resistance, and health-care setting. The probability of detecting S. pneumoniae was substantially higher in studies that performed more frequently a diagnostic polymerase chain reaction assay compared to all the other diagnostic tests included. Furthermore, S. pneumoniae was more likely to be confirmed as the cause of a CAP in studies with intensive care unit patients as compared to those with hospital- or community-treated patients. This study provides estimates of the average observed prevalence of S. pneumoniae, which could be used for projecting the health and economic benefits of pneumococcal immunization.</p>