Current trends in research, development and production of prophylactic vaccines : Report of Vaccipharma 2015 Congress

On June 14-19, 2015, the IUPHAR Section of Immunopharmacology and the Cuban Society of Pharmacology, together with the Latin- American Association of Pharmacology (ALF), Finlay Vaccine Institute and other prestigious Cuban scientific institutions, organized the Congress VACCIPHARMA 2015 (3rd International Congress on Pharmacology of Vaccines), held as part of the First International Convention IMMUNOPHARMACOLOGY–VACCIPHARMA 2015 (Meliá Marina Varadero Hotel, in Varadero beach, Cuba) VACCIPHARMA 2015 was organised into two large Workshops, addressing topics related to the research, development, clinical evaluation, production and quality control of Therapeutic and Prophylactic Vaccines, respectively. At the same time the Workshop on Prophylactic Vaccines was integrated by several Symposiums, focused on meningococcal, pneumococcal, enteric, tuberculosis and pertussis vaccines. About 250 delegates, including 100 international researchers from 15 countries, attended this meeting. The Congress had a remarkable Opening Session, with a Key Lecture given by the outstanding scientist Professor Dr. Shiv Pillai (United States of America), who talked about the changing views in the field of the immunology of vaccination and the challenges ahead. The aim of this review is to give an overview of the main topics discussed in the Prophylactic Vaccines Workshop, not as a complete narration of the events, but to provide an update of the latest state of the art and methodologies being applied to prophylactic vaccines with an expert commentary on the invited speakers

Rationalising drug delivery using nanoparticles: a combined simulation and immunology study of GnRH adsorbed to silica nanoparticles

Silica nanoparticles (SiNPs) have been shown to have significant potential for drug delivery and as adjuvants for vaccines. We have simulated the adsorption of GnRH-I (gonadotrophin releasing hormone I) and a cysteine-tagged modification (cys-GnRH-I) to model silica surfaces, as well as its conjugation to the widely-used carrier protein bovine serum albumin (BSA). Our subsequent immunological studies revealed no significant antibody production was caused by the peptide-SiNP systems, indicating that the treatment was not effective. However, the testosterone response with the native peptide-SiNPs indicated a drug effect not found with cys-GnRH-I-SiNPs; this behaviour is explained by the specific orientation of the peptides at the silica surface found in the simulations. With the BSA systems, we found significant testosterone reduction, particularly for the BSA-native conjugates, and an antibody response that was notably higher with the SiNPs acting as an adjuvant; this behaviour again correlates well with the epitope presentation predicted by the simulations. The range of immunological and hormone response can therefore be interpreted and understood by the simulation results and the presentation of the peptides to solution, paving the way for the future rational design of drug delivery and vaccine systems guided by biomolecular simulation

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example

<p>Abstract</p> <p>Background</p> <p>Our aim was to determine the efficacy of a trivalent inactivated split virus influenza vaccine (TIV) against culture-confirmed influenza A and/or B in adults 18 to 64 years of age during the 2005/2006 season in the Czech Republic.</p> <p>Methods</p> <p>6203 subjects were randomized to receive TIV (N = 4137) or placebo (N = 2066). The sample size was based on an assumed attack rate of 4% which provided 90% power to reject the hypothesis that vaccine efficacy (VE) was ≥ 45%. Cases of influenza like illness (defined as fever (oral temperature ≥37.8°C) plus cough and/or sore throat) were identified both by active (biweekly phone contact) and passive (self reporting) surveillance and nasal and throat swabs were collected from subjects for viral culture.</p> <p>Results</p> <p>TIV was well tolerated and induced a good immune response. The 2005/2006 influenza season was exceptionally mild in the study area, as it was throughout Europe, and only 46 culture-confirmed cases were found in the study cohort (10 influenza A and 36 influenza B). Furthermore among the B isolates, 35 were identified as B/Hong Kong 330/2001-like (B/Victoria/2/87 lineage) which is antigenically unrelated to the vaccine B strain (B/Yamagata/16/88 lineage). The attack rate in the vaccine group (0.7%) was not statistically significantly different from the attack rate in the placebo group (0.9%).</p> <p>Conclusion</p> <p>Due to the atypical nature of the influenza season during this study we were unable to assess TIV efficacy. This experience illustrates the challenge of conducting a prospective influenza vaccine efficacy trial during a single season when influenza attack rates and drift in circulating strains or B virus lineage match can be difficult to estimate in advance.</p> <p>Trial Registration</p> <p>Clinical trial registery: NCT00197223.</p

Interaction of Hydrogen with Graphitic Surfaces, Clean and Doped with Metal Clusters

Producción CientíficaHydrogen is viewed as a possible alternative to the fossil fuels in transportation. The technology of fuel-cell engines is fully developed, and the outstanding remaining problem is the storage of hydrogen in the vehicle. Porous materials, in which hydrogen is adsorbed on the pore walls, and in particular nanoporous carbons, have been investigated as potential onboard containers. Furthermore, metallic nanoparticles embedded in porous carbons catalyze the dissociation of hydrogen in the anode of the fuel cells. For these reasons the interaction of hydrogen with the surfaces of carbon materials is a topic of high technological interest. Computational modeling and the density functional formalism (DFT) are helping in the task of discovering the basic mechanisms of the interaction of hydrogen with clean and doped carbon surfaces. Planar and curved graphene provide good models for the walls of porous carbons. We first review work on the interaction of molecular and atomic hydrogen with graphene and graphene nanoribbons, and next we address the effects due to the presence of metal clusters on the surface because of the evidence of their role in enhancing hydrogen storage.Ministerio de Economía, Industria y Competitividad (Grant MAT2014-54378-R

Combinations of Plant Water-Stress and Neonicotinoids Can Lead to Secondary Outbreaks of Banks Grass Mite (Oligonychus Pratensis Banks)

Spider mites, a cosmopolitan pest of agricultural and landscape plants, thrive under hot and dry conditions, which could become more frequent and extreme due to climate change. Recent work has shown that neonicotinoids, a widely used class of systemic insecticides that have come under scrutiny for non-target effects, can elevate spider mite populations. Both water-stress and neonicotinoids independently alter plant resistance against herbivores. Yet, the interaction between these two factors on spider mites is unclear, particularly for Banks grass mite (Oligonychus pratensis; BGM). We conducted a field study to examine the effects of water-stress (optimal irrigation = 100% estimated evapotranspiration (ET) replacement, water stress = 25% of the water provided to optimally irrigated plants) and neonicotinoid seed treatments (control, clothianidin, thiamethoxam) on resident mite populations in corn (Zea mays, hybrid KSC7112). Our field study was followed by a manipulative field cage study and a parallel greenhouse study, where we tested the effects of water-stress and neonicotinoids on BGM and plant responses. We found that water-stress and clothianidin consistently increased BGM densities, while thiamethoxam-treated plants only had this effect when plants were mature. Water-stress and BGM herbivory had a greater effect on plant defenses than neonicotinoids alone, and the combination of BGM herbivory with the two abiotic factors increased the concentration of total soluble proteins. These results suggest that spider mite outbreaks by combinations of changes in plant defenses and protein concentration are triggered by water-stress and neonicotinoids, but the severity of the infestations varies depending on the insecticide active ingredient

Antimicrobial activity against oral pathogens and immunomodulatory effects and toxicity of geopropolis produced by the stingless bee Melipona fasciculata Smith

<p>Abstract</p> <p>Background</p> <p>Native bees of the tribe Meliponini produce a distinct kind of propolis called geopropolis. Although many pharmacological activities of propolis have already been demonstrated, little is known about geopropolis, particularly regarding its antimicrobial activity against oral pathogens. The present study aimed at investigating the antimicrobial activity of <it>M. fasciculata </it>geopropolis against oral pathogens, its effects on <it>S. mutans </it>biofilms, and the chemical contents of the extracts. A gel prepared with a geopropolis extract was also analyzed for its activity on <it>S. mutans </it>and its immunotoxicological potential.</p> <p>Methods</p> <p>Antimicrobial activities of three hydroalcoholic extracts (HAEs) of geopropolis, and hexane and chloroform fractions of one extract, were evaluated using the agar diffusion method and the broth dilution technique. Ethanol (70%, v/v) and chlorhexidine (0.12%, w/w) were used as negative and positive controls, respectively. Total phenol and flavonoid concentrations were assayed by spectrophotometry. Immunotoxicity was evaluated in mice by topical application in the oral cavity followed by quantification of biochemical and immunological parameters, and macro-microscopic analysis of animal organs.</p> <p>Results</p> <p>Two extracts, HAE-2 and HAE-3, showed inhibition zones ranging from 9 to 13 mm in diameter for <it>S. mutans </it>and <it>C. albicans</it>, but presented no activity against <it>L</it>. <it>acidophilus</it>. The MBCs for HAE-2 and HAE-3 against <it>S. mutans </it>were 6.25 mg/mL and 12.5 mg/mL, respectively. HAE-2 was fractionated, and its chloroform fraction had an MBC of 14.57 mg/mL. HAE-2 also exhibited bactericidal effects on <it>S. mutans </it>biofilms after 3 h of treatment. Significant differences (p < 0.05) in total phenol and flavonoid concentrations were observed among the samples. Signs toxic effects were not observed after application of the geopropolis-based gel, but an increase in the production of IL-4 and IL-10, anti-inflammatory cytokines, was detected.</p> <p>Conclusions</p> <p>In summary, geopropolis produced by <it>M. fasciculata </it>can exert antimicrobial action against <it>S. mutans </it>and <it>C. albicans</it>, with significant inhibitory activity against <it>S. mutans </it>biofilms. The extract with the highest flavonoid concentration, HAE-2, presented the highest antimicrobial activity. In addition, a geopropolis-based gel is not toxic in an animal model and displays anti-inflammatory effect.</p

Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells

During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC