Oral re-vaccination of Eurasian wild boar with Mycobacterium bovis BCG yields a strong protective response against challenge with a field strain

Background: Field vaccination trials with Mycobacterium bovis BCG, an attenuated mutant of M. bovis, are ongoing in Spain, where the Eurasian wild boar (Sus scrofa) is regarded as the main driver of animal tuberculosis (TB). The oral baiting strategy consists in deploying vaccine baits twice each summer, in order to gain access to a high proportion of wild boar piglets. The aim of this study was to assess the response of wild boar to re-vaccination with BCG and to subsequent challenge with an M. bovis field strain.Results: BCG re-vaccinated wild boar showed reductions of 75.8% in lesion score and 66.9% in culture score, as compared to unvaccinated controls. Only one of nine vaccinated wild boar had a culture-confirmed lung infection, as compared to seven of eight controls. Serum antibody levels were highly variable and did not differ significantly between BCG re-vaccinated wild boar and controls. Gamma IFN levels differed significantly between BCG re-vaccinated wild boar and controls. The mRNA levels for IL-1b, C3 and MUT were significantly higher in vaccinated wild boar when compared to controls after vaccination and decreased after mycobacterial challenge.Conclusions: Oral re-vaccination of wild boar with BCG yields a strong protective response against challenge with a field strain. Moreover, re-vaccination of wild boar with BCG is not counterproductive. These findings are relevant given that re-vaccination is likely to happen under real (field) conditions.Peer reviewedVeterinary Pathobiolog

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Red deer in Iberia: Molecular ecological studies in a southern refugium and inferences on European postglacial colonization history.

The red deer (Cervus elaphus) is a widespread wild ungulate in Europe that has suffered strong anthropogenic impacts over their distribution during the last centuries, but also at the present time, due its economic importance as a game species. Here we focus on the evolutionary history of the red deer in Iberia, one of the three main southern refugial areas for temperate species in Europe, and addressed the hypothesis of a cryptic refugia at higher latitudes during the Last Glacial Maximum (LGM). A total of 911 individuals were sampled, genotyped for 34 microsatellites specifically developed for red deer and sequenced for a fragment of 670 bp of the mitochondrial (mtDNA) D-loop. The results were combined with published mtDNA sequences, and integrated with species distribution models and historical European paleo-distribution data, in order to further examine the alternative glacial refugial models and the influence of cryptic refugia on European postglacial colonization history. Clear genetic differentiation between Iberian and European contemporary populations was observed at nuclear and mtDNA levels, despite the mtDNA haplotypes central to the phylogenetic network are present across western Europe (including Iberia) suggesting a panmictic population in the past. Species distribution models, fossil records and genetic data support a timing of divergence between Iberian and European populations that overlap with the LGM. A notable population structure was also found within the Iberian Peninsula, although several populations displayed high levels of admixture as a consequence of recent red deer translocations. Five D-loop sub-lineages were found in Iberia that belong to the Western European mtDNA lineage, while there were four main clusters based on analysis of nuclear markers. Regarding glacial refugial models, our findings provide detailed support for the hypothesis that red deer may have persisted in cryptic northern refugia in western Europe during the LGM, most likely in southern France, southern Ireland, or in a region between them (continental shelf), and these regions were the source of individuals during the European re-colonization. This evidence heightens the importance of conserving the high mitochondrial and nuclear diversity currently observed in Iberian populations

Analysis of the apparent nuclear modification in peripheral Pb–Pb collisions at 5.02 TeV

International audienceCharged-particle spectra at midrapidity are measured in Pb–Pb collisions at the centre-of-mass energy per nucleon–nucleon pair sNN=5.02 TeV and presented in centrality classes ranging from most central (0–5%) to most peripheral (95–100%) collisions. Possible medium effects are quantified using the nuclear modification factor ( RAA ) by comparing the measured spectra with those from proton–proton collisions, scaled by the number of independent nucleon–nucleon collisions obtained from a Glauber model. At large transverse momenta ( 8<pT<20GeV/c ), the average RAA is found to increase from about 0.15 in 0–5% central to a maximum value of about 0.8 in 75–85% peripheral collisions, beyond which it falls off strongly to below 0.2 for the most peripheral collisions. Furthermore, RAA initially exhibits a positive slope as a function of pT in the 8–20 GeV/c interval, while for collisions beyond the 80% class the slope is negative. To reduce uncertainties related to event selection and normalization, we also provide the ratio of RAA in adjacent centrality intervals. Our results in peripheral collisions are consistent with a PYTHIA-based model without nuclear modification, demonstrating that biases caused by the event selection and collision geometry can lead to the apparent suppression in peripheral collisions. This explains the unintuitive observation that RAA is below unity in peripheral Pb–Pb, but equal to unity in minimum-bias p–Pb collisions despite similar charged-particle multiplicities