Selection of conserved epitopes from hepatitis C virus for pan-populational stimulation of T-cell responses

The hepatitis C virus (HCV) is able to persist as a chronic infection, which can lead to cirrhosis and liver cancer. There is evidence that clearance of HCV is linked to strong responses by CD8 cytotoxic T lymphocytes (CTLs), suggesting that eliciting CTL responses against HCV through an epitope-based vaccine could prove an effective means of immunization. However, HCV genomic plasticity as well as the polymorphisms of HLA I molecules restricting CD8 T-cell responses challenges the selection of epitopes for a widely protective vaccine. Here, we devised an approach to overcome these limitations. From available databases, we first collected a set of 245 HCV-specific CD8 T-cell epitopes, all known to be targeted in the course of a natural infection in humans. After a sequence variability analysis, we next identified 17 highly invariant epitopes. Subsequently, we predicted the epitope HLA I binding profiles that determine their potential presentation and recognition. Finally, using the relevant HLA I-genetic frequencies, we identified various epitope subsets encompassing 6 conserved HCV-specific CTL epitopes each predicted to elicit an effective T-cell response in any individual regardless of their HLA I background. We implemented this epitope selection approach for free public use at the EPISOPT web server

EPIPOX:immunoinformatic characterization of the shared T-cell epitome between variola virus and related pathogenic orthopoxviruses

Concerns that variola viruses might be used as bioweapons have renewed the interest in developing new and safer smallpox vaccines. Variola virus genomes are now widely available, allowing computational characterization of the entire T-cell epitome and the use of such information to develop safe and yet effective vaccines. To this end, we identified 124 proteins shared between various species of pathogenic orthopoxviruses including variola minor and major, monkeypox, cowpox, and vaccinia viruses, and we targeted them for T-cell epitope prediction. We recognized 8,106, and 8,483 unique class I and class II MHC-restricted T-cell epitopes that are shared by all mentioned orthopoxviruses. Subsequently, we developed an immunological resource, EPIPOX, upon the predicted T-cell epitome. EPIPOX is freely available online and it has been designed to facilitate reverse vaccinology. Thus, EPIPOX includes key epitope-focused protein annotations: time point expression, presence of leader and transmembrane signals, and known location on outer membrane structures of the infective viruses. These features can be used to select specific T-cell epitopes suitable for experimental validation restricted by single MHC alleles, as combinations thereof, or by MHC supertypes

On the Influence of VOCs on New Particle Growth in a Continental-Mediterranean Region

[Abstract] A field campaign has been performed in the Madrid region to study the VOC influence in the growth of new particles in ambient air. A number of instruments have been deployed to characterize the main pollutant gases and particle properties and composition. The measurements were performed simultaneously at three sites (rural, urban background and urban traffic influenced) in the period 1–17 July 2019. The sites: Tres Cantos (rural), CIEMAT (urban background) and Leganés (urban traffic) were located within the Madrid airshed. Particle size distributions, mass concentrations at fractions PM10, PM2.5 and PM1, black carbon, VOCs species and gaseous pollutants (NOx and O3) were obtained in the sites. Some supplementary measurements were obtained in at least one of the sites: meteorological parameters, non-refractory submicron aerosol species and vertical profiles of aerosol optical properties. It has been observed that the new particle formation (NPF) events, nucleation and subsequent growth, happened at a regional scale, although differently among the sites. In the rural site, fewer events than expected were observed because of the high temperatures that affected the BVOC emissions. In the urban background site, the highest number of events was reached. In this station, it is common to receive air masses from the nearby forest and from the urban area, producing a mix of conditions with high BVOC and AVOC concentrations. In the urban traffic site, several NPF cases appeared, being a site dominated by AVOCs. Among the BVOCs measured in the three stations, the most common were α-Pinene and Limonene. Among the AVOCs measured, aromatics and linear hydrocarbon compounds for C10 and above were found. The linear group was found to be predominant during the NPF event days in the urban background site. This work provides new insights about the aerosol-forming precursors and growth of new particles in the Madrid region.This research has been partially funded by the CRISOL Project (CGL2017-85344-R MINECO/AEI/FEDER, UE), OASIS project (PID2021-127885OB-I00 fund by MCIN/ AEI/10.13039/501100011033 and by 'ERDF A way of making Europe') and by the TIGAS-CM project (Madrid Regional Government Y2018/EMT-5177)Comunidad de Madrid; Y2018/EMT-517

Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small- cell lung cancer

Most patients with advanced non-small-cell lung cancer (NSCLC) fail to derive significant benefit from programmed cell death protein-1 (PD-1) axis blockade, and new biomarkers of response are needed. In this study, we aimed to discover and validate spatially resolved protein markers associated with sensitivity to PD-1 axis inhibition in NSCLC

Relationship between self-reported dietary intake and physical activity levels among adolescents: The HELENA study

Background Evidence suggests possible synergetic effects of multiple lifestyle behaviors on health risks like obesity and other health outcomes. Therefore it is important to investigate associations between dietary and physical activity behavior, the two most important lifestyle behaviors influencing our energy balance and body composition. The objective of the present study is to describe the relationship between energy, nutrient and food intake and the physical activity level among a large group of European adolescents. Methods The study comprised a total of 2176 adolescents (46.2% male) from ten European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study. Dietary intake and physical activity were assessed using validated 24-h dietary recalls and self-reported questionnaires respectively. Analyses of covariance (ANCOVA) were used to compare the energy and nutrient intake and the food consumption between groups of adolescents with different physical activity levels (1st to 3rd tertile). Results In both sexes no differences were found in energy intake between the levels of physical activity. The most active males showed a higher intake of polysaccharides, protein, water and vitamin C and a lower intake of saccharides compared to less active males. Females with the highest physical activity level consumed more polysaccharides compared to their least active peers. Male and female adolescents with the highest physical activity levels, consumed more fruit and milk products and less cheese compared to the least active adolescents. The most active males showed higher intakes of vegetables and meat, fish, eggs, meat substitutes and vegetarian products compared to the least active ones. The least active males reported the highest consumption of grain products and potatoes. Within the female group, significantly lower intakes of bread and cereal products and spreads were found for those reporting to spend most time in moderate to vigorous physical activity. The consumption of foods from the remaining food groups, did not differ between the physical activity levels in both sexes. Conclusion It can be concluded that dietary habits diverge between adolescents with different self-reported physical activity levels. For some food groups a difference in intake could be found, which were reflected in differences in some nutrient intakes. It can also be concluded that physically active adolescents are not always inclined to eat healthier diets than their less active peers.The HELENA study took place with the financial support of the European Community Sixth RTD Framework Programme (Contract FOOD-CT: 2005-007034). This work was also partially supported by the European Union, in the framework of the Public Health Programme (ALPHA project, Ref: 2006120), the Swedish Council for Working Life and Social Research (FAS), the Spanish Ministry of Education (EX-2007-1124, and EX-2008-0641), and the Spanish Ministry of Health, Maternal, Child Health and Development Network (number RD08/0072) (JPRL, LAM)

Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small- cell lung cancer

Most patients with advanced non-small-cell lung cancer (NSCLC) fail to derive significant benefit from programmed cell death protein-1 (PD-1) axis blockade, and new biomarkers of response are needed. In this study, we aimed to discover and validate spatially resolved protein markers associated with sensitivity to PD-1 axis inhibition in NSCLC