El impacto de los Ciberriesgos en la Gerencia de Riesgos Tradicional

Màster de Direcció d'Entitats Asseguradores i Financeres, Universitat de Barcelona, Facultat d'Economia i Empresa, Curs: 2016-2017, Tutor: Francesc Xavier Monràs VidiellaLa tecnología está transformando el día a día de la sociedad, tanto a nivel particular como a nivel industrial. En las organizaciones puede tener un impacto muy positivo en tanto en cuanto de mejora de productividad, pero puede traer nuevos riesgos. Es por ello que en la Gerencia de Riesgos se debería monitorizar los ciberataques, analizando en todo momento las posibilidades de transferencia de dicho riesgo (generalmente a una compañía aseguradora). En esta tesis se hace una introducción al concepto “Gerencia de Riesgos”, un análisis de lo que son los ciberriesgos y lo que ellos representan y cómo, la aparición de estos ciberataques, debe hacer evolucionar la Gerencia de Riesgos tradicional

Sow vaccination against virulent Glaesserella parasuis shapes the nasal microbiota of their offspring

Glaesserella parasuis is the etiological agent of Glässer's disease, a common pathology in the pork industry with higher prevalence in the postweaning period. Vaccination is one of the strategies to control this disease. Here, we investigated the effect that sow vaccination against virulent strains of G. parasuis had in the nasal microbiota of their offspring. Nasal swabs from fifteen days-old piglets from vaccinated (vs-P, n = 11) and unvaccinated sows (cs-P, n = 11) were obtained and DNA was extracted for 16S amplicon sequencing. Microbiota composition was different, with lower diversity in vs-P, and a strong clustering of the groups in beta diversity analysis. Among the 1509 sequences associated to either study group, all the sequences classified as G. parasuis (10 ASVs) had lower relative abundance in the vs-P group. A list of 32 inferred metabolic pathways were statistically different between groups. A distinctive structure of the two microbial networks was detected, with modules in the cs-P not conserved in the vs-P network. In conclusion, vaccination of the sows had a large effect in the microbiota composition of their offspring that went beyond the effect on the targeted pathogen. The mechanisms underneath these changes may include alteration of the microbiota network due to the elimination of the targeted pathogen and/or immunological changes

Influenza NG-34 T cell conserved epitope adjuvanted with CAF01 as a possible influenza vaccine candidate

Conserved epitopes are targets commonly researched to be part of universal vaccine candidates against influenza viruses (IV). These conserved epitopes need to be cross-protecting against distinct IV subtypes and to have a strong immunogenic potential. Nevertheless, subunit vaccines generally require a strong adjuvant to enhance their immunological effects. Herewith, we compare four different adjuvants differing in their immunological signatures that may enhance efficacy of a conserved hemagglutinin (HA)-epitope from IV, the NG-34, to define the most efficient combination of antigen/adjuvant to combat IV infections. Soluble NG-34 was mixed with adjuvants like aluminium hydroxide (AH) and AddaVax, known to induce Th2 and humoral responses; CAF01 which displays a biased Th1/Th17 profile and Diluvac Forte which augments the humoral response. Combinations were tested in different groups of mice which were subjected to immunological analyses. CAF01 + NG-34 induced a complete immune response with the highest IgG1, IgG2c titers and percentages of activated CD4 T cell promoting IFN-γ, IL-2 and TNF-α producing cells. Furthermore, in NG-34 stimulated mice splenocytes, cytokine levels of IFN-γ, IL-1β, IL-6, IL-10, IL-17 and TNF-α were also the highest in the CAF01 + NG-34 mouse group. This complete induced immune response covering the humoral and the cellular arms of the adaptive immunity promoted by CAF01 + NG-34 group suggests that CAF01 could be a good candidate as an adjuvant to combine with NG-34 for an efficacious vaccine against IV. However, more studies performed in IV hosts as well as studies with a challenge model are further required.info:eu-repo/semantics/publishedVersio

Heterogeneity of Moraxella isolates found in the nasal cavities of piglets

Background Previous studies have shown that the genus Moraxella is commonly present in the nasal microbiota of swine. Results In this study, 51 isolates of Moraxella were obtained from nasal swabs from 3 to 4 week old piglets, which represented 26 different fingerprintings by enterobacterial repetitive intergenic consensus (ERIC)-PCR. Whole 16S rRNA gene sequencing allowed the identification at species level of the Moraxella spp. isolates. The majority of the field strains were identified as Moraxella pluranimalium, but Moraxella porci was also detected. In addition, a cluster of 7 strains did not group with any described Moraxella species, probably representing a new species. Subsequent phenotypic characterization indicated that strains of Moraxella pluranimalium were mainly sensitive to serum complement, while the cluster representing the putative new species was highly resistant. Biofilm formation capacity was very variable among the Moraxella spp. isolates, while adherence to epithelial cell lines was similar among selected strains. Additionally, variability was also observed in the association of selected strains to porcine alveolar macrophages. Antimicrobial tests evidenced the existence of multidrug-resistance in the strains. Conclusions In summary, phenotypic characterization revealed heterogeneity among Moraxella strains from the nasal cavity of piglets. Strains with pathogenic potential were detected as well as those that may be commensal members of the nasal microbiota. However, the role of Moraxella in porcine diseases and health should be further evaluated.info:eu-repo/semantics/publishedVersio

Identification and Characterization of Swine Influenza Virus H1N1 Variants Generated in Vaccinated and Nonvaccinated, Challenged Pigs

Influenza viruses represent a continuous threat to both animal and human health. The 2009 H1N1 A influenza pandemic highlighted the importance of a swine host in the adaptation of influenza viruses to humans. Nowadays, one of the most extended strategies used to control swine influenza viruses (SIVs) is the trivalent vaccine application, whose formulation contains the most frequently circulating SIV subtypes H1N1, H1N2, and H3N2. These vaccines do not provide full protection against the virus, allowing its replication, evolution, and adaptation. To better understand the main mechanisms that shape viral evolution, here, the SIV intra-host diversity was analyzed in samples collected from both vaccinated and nonvaccinated animals challenged with the H1N1 influenza A virus. Twenty-eight whole SIV genomes were obtained by next-generation sequencing, and differences in nucleotide variants between groups were established. Substitutions were allocated along all influenza genetic segments, while the most relevant nonsynonymous substitutions were allocated in the NS1 protein on samples collected from vaccinated animals, suggesting that SIV is continuously evolving despite vaccine application. Moreover, new viral variants were found in both vaccinated and nonvaccinated pigs, showing relevant substitutions in the HA, NA, and NP proteins, which may increase viral fitness under field conditions.info:eu-repo/semantics/publishedVersio

Immune responses following neonatal vaccination with conserved F4 fragment of VtaA proteins from virulent Glaesserella parasuis adjuvanted with CAF®01 or CDA

Glaesserella parasuis is a Gram-negative bacterium that colonizes the upper airways of swine, capable of causing a systemic infection called Glässer’s disease. This disease is more frequent in young post-weaning piglets. Current treatments against G. parasuis infection are based on the use of antimicrobials or inactivated vaccines, which promote limited cross-protection against different serovars. For this reason, there is an interest in developing novel subunit vaccines with the capacity to confer effective protection against different virulent strains. Herein, we characterize the immunogenicity and the potential benefits of neonatal immunization with two different vaccine formulations based on the F4 polypeptide, a conserved immunogenic protein fragment from the virulence-associated trimeric autotransporters of virulent G. parasuis strains. With this purpose, we immunized two groups of piglets with F4 combined with cationic adjuvant CAF®01 or cyclic dinucleotide CDA. Piglets immunized with a commercial bacterin and non-immunized animals served as control groups. The vaccinated piglets received two doses of vaccine, at 14 days old and 21 days later. The immune response induced against the F4 polypeptide varied depending on the adjuvant used. Piglets vaccinated with the F4+CDA vaccine developed specific anti-F4 IgGs, biased towards the induction of IgG1 responses, whereas no anti-F4 IgGs were de novo induced after immunization with the CAF®01 vaccine. Piglets immunized with both formulations displayed balanced memory T-cell responses, evidenced upon in vitro re-stimulation of peripheral blood mononuclear cells with F4. Interestingly, pigs immunized with F4+CAF®01 controlled more efficiently a natural nasal colonization by a virulent serovar 4 G. parasuis that spontaneously occurred during the experimental procedure. According to the results, the immunogenicity and the protection afforded by F4 depend on the adjuvant used. F4 may represent a candidate to consider for a Glässer‘s disease vaccine and could contribute to a better understanding of the mechanisms involved in protection against virulent G. parasuis colonization.This study was financially supported by the European Project TRANSVAC2–730964–INFRAIA–2016-1 of the European Vaccine Initiative funded in turn by the European Commission under the Horizon 2020 Program. Sergi López-Serrano was funded by this Project. IRTA-CReSA is also supported by the Centres de Recerca de Catalunya (CERCA) Program from the Generalitat de Catalunya.info:eu-repo/semantics/publishedVersio

Alendronate and etidronate do not regulate interleukin 6 and 11 synthesis in normal human osteoblasts in culture

Bisphosphonates exert a potent inhibitory effect on bone resorption. Several studies have been performed, with contradictory results, to ascertain whether the effect of bisphosphonates on osteoclasts could be produced, at least in part, by modulation of the synthesis of resorption-promoting factors by osteoblasts. The aim of this study was to evaluate the effect of etidronate (10)4–10)9 M) and alendronate (10)7–10)12 M) on the production of IL-6 and IL-11 using human osteoblast cultures. Cytokines were quantified by ELISA, and mRNA expression was tested. Treatment with alendronate and etidronate had no effect on the synthesis of IL-6 or IL-11, and IL-6 and IL-11 mRNA levels. These results were obtained both in nonstimulated cultures and in cultures stimulated by means of TNF-a, IL-1b, and TNF-a+IL-1b, with or without FCS. In conclusion, a possible indirect osteoclast-mediated effect of alendronate and etidronate on bone resorption would not be exerted through reduction in osteoblastic synthesis of IL-6 and IL-11.Postprint (published version

Potential of Oral Nanoparticles Containing Cytokines as Intestinal Mucosal Immunostimulants in Pigs : A Pilot Study

Antibiotics are essential compounds to cope with bacterial infections. However, their inadequate and excessive use has triggered the rapid arising of antimicrobial-resistant bacteria. In this scenario, immunostimulants, which are molecules that boost the immune system, open up a new approach to face this problem, enhancing treatment efficacy and preventing infections by immune system response. Cytokines are central effector molecules of the immune system, and their recombinant production and administration in animals could be an interesting immune modulation strategy. The aim of this study was the development of a highly stable nanoparticle of porcine cytokines to achieve the immunostimulation of intestinal mucosa in piglets. The outcomes of the present study prove this approach is able to stimulate swine intestinal cells and macrophages in vitro and tends to modulate inflammatory responses in vivo, although further studies are required to definitively evaluate their potential in animals. Antimicrobial resistance is a global threat that is worryingly rising in the livestock sector. Among the proposed strategies, immunostimulant development appears an interesting approach to increase animal resilience at critical production points. The use of nanoparticles based on cytokine aggregates, called inclusion bodies (IBs), has been demonstrated as a new source of immunostimulants in aquaculture. Aiming to go a step further, the objective of this study was to produce cytokine nanoparticles using a food-grade microorganism and to test their applicability to stimulate intestinal mucosa in swine. Four cytokines (IL-1β, IL-6, IL-8, and TNF-α) involved in inflammatory response were produced recombinantly in Lactococcus lactis in the form of protein nanoparticles (IBs). They were able to stimulate inflammatory responses in a porcine enterocyte cell line (IPEC-J2) and alveolar macrophages, maintaining high stability at low pH and high temperature. In addition, an in vivo assay was conducted involving 20 piglets housed individually as a preliminary exploration of the potential effects of IL-1β nanoparticles in piglet intestinal mucosa after a 7 d oral administration. The treated animals tended to have greater levels of TNF-α in the blood, indicating that the tested dose of nanoparticles tended to generate an inflammatory response in the animals. Whether this response is sufficient to increase animal resilience needs further evaluation

Conserved HA-peptides expressed along with flagellin in Trichoplusia ni larvae protects chicken against intranasal H7N1 HPAIV challenge

The immunization of poultry where H5 and H7 influenza viruses (IVs) are endemic is one of the strategies to prevent unexpected zoonoses. Our group has been focused on conserved HA-epitopes as potential vaccine candidates to obtain multivalent immune responses against distinct IV subtypes. In this study, two conserved epitopes (NG-34 and CS-17) fused to flagellin were produced in a Baculovirus platform based on Trichoplusia ni larvae as living biofactories. Soluble extracts obtained from larvae expressing "flagellin-NG34/CS17 antigen" were used to immunize chickens and the efficacy of the vaccine was evaluated against a heterologous H7N1 HPAIV challenge in chickens. The flagellin-NG34/CS17 vaccine protected the vaccinated chickens and blocked viral shedding orally and cloacally. Furthermore, no apparent clinical signs were monitored in 10/12 vaccinated individuals. The mechanism of protection conferred is under investigation.info:eu-repo/semantics/publishedVersio

Genetic parameters and associated genomic regions for global immunocompetence and other health-related traits in pigs

The inclusion of health-related traits, or functionally associated genetic markers, in pig breeding programs could contribute to produce more robust and disease resistant animals. The aim of the present work was to study the genetic determinism and genomic regions associated to global immunocompetence and health in a Duroc pig population. For this purpose, a set of 30 health-related traits covering immune (mainly innate), haematological, and stress parameters were measured in 432 healthy Duroc piglets aged 8 weeks. Moderate to high heritabilities were obtained for most traits and significant genetic correlations among them were observed. A genome wide association study pointed out 31 significantly associated SNPs at whole-genome level, located in six chromosomal regions on pig chromosomes SSC4, SSC6, SSC17 and SSCX, for IgG, γδ T-cells, C-reactive protein, lymphocytes phagocytic capacity, total number of lymphocytes, mean corpuscular volume and mean corpuscular haemoglobin. A total of 16 promising functionally-related candidate genes, including CRP, NFATC2, PRDX1, SLA, ST3GAL1, and VPS4A, have been proposed to explain the variation of immune and haematological traits. Our results enhance the knowledge of the genetic control of traits related with immunity and support the possibility of applying effective selection programs to improve immunocompetence in pigs.info:eu-repo/semantics/publishedVersio