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Sample records for ps vaccine based

  1. A comparative evaluation of a novel vaccine in APP/PS1 mouse models of Alzheimer's disease.

    Science.gov (United States)

    Carrera, Iván; Etcheverría, Ignacio; Fernández-Novoa, Lucía; Lombardi, Valter Ruggero Maria; Lakshmana, Madepalli Krishnappa; Cacabelos, Ramón; Vigo, Carmen

    2015-01-01

    Immunization against amyloid-beta-peptide (Aβ) has been widely investigated as a potential immunotherapeutic approach for Alzheimer's disease (AD). With the aim of developing an active immunogenic vaccine without need of coadjuvant modification for human trials and therefore avoiding such side effects, we designed the Aβ 1-42 vaccine (EB101), delivered in a liposomal matrix, that based on our previous studies significantly prevents and reverses the AD neuropathology, clearing Aβ plaques while markedly reducing neuronal degeneration, behavioral deficits, and minimizing neuroinflammation in APP/PS1 transgenic mice. Here, the efficacy of our immunogenic vaccine EB101 was compared with the original immunization vaccine cocktail Aβ 42 + CFA/IFA (Freund's adjuvant), in order to characterize the effect of sphingosine-1-phosphate (S1P) in the immunotherapeutic response. Quantitative analysis of amyloid burden showed a notable decrease in the neuroinflammation reaction against Aβ plaques when S1P was compared with other treatments, suggesting that S1P plays a key role as a neuroprotective agent. Moreover, EB101 immunized mice presented a protective immunogenic reaction resulting in the increase of Aβ-specific antibody response and decrease of reactive glia in the affected brain areas, leading to a Th2 immunological reaction.

  2. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, M; Met, Ö; Svane, I M

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... to transiently affect in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  3. MER5101, a novel Aβ1-15:DT conjugate vaccine, generates a robust anti-Aβ antibody response and attenuates Aβ pathology and cognitive deficits in APPswe/PS1ΔE9 transgenic mice.

    Science.gov (United States)

    Liu, Bin; Frost, Jeffrey L; Sun, Jing; Fu, Hongjun; Grimes, Stephen; Blackburn, Peter; Lemere, Cynthia A

    2013-04-17

    Active amyloid-β (Aβ) immunotherapy is under investigation to prevent or treat early Alzheimer's disease (AD). In 2002, a Phase II clinical trial (AN1792) was halted due to meningoencephalitis in ∼6% of the AD patients, possibly caused by a T-cell-mediated immunological response. Thus, generating a vaccine that safely generates high anti-Aβ antibody levels in the elderly is required. In this study, MER5101, a novel conjugate of Aβ1-15 peptide (a B-cell epitope fragment) conjugated to an immunogenic carrier protein, diphtheria toxoid (DT), and formulated in a nanoparticular emulsion-based adjuvant, was administered to 10-month-old APPswe/PS1ΔE9 transgenic (Tg) and wild-type (Wt) mice. High anti-Aβ antibody levels were observed in both vaccinated APPswe/PS1ΔE9 Tg and Wt mice. Antibody isotypes were mainly IgG1 and IgG2b, suggesting a Th2-biased response. Restimulation of splenocytes with the Aβ1-15:DT conjugate resulted in a strong proliferative response, whereas proliferation was absent after restimulation with Aβ1-15 or Aβ1-40/42 peptides, indicating a cellular immune response against DT while avoiding an Aβ-specific T-cell response. Moreover, significant reductions in cerebral Aβ plaque burden, accompanied by attenuated microglial activation and increased synaptic density, were observed in MER5101-vaccinated APPswe/PS1ΔE9 Tg mice compared with Tg adjuvant controls. Last, MER5101-immunized APPswe/PS1ΔE9 Tg mice showed improvement of cognitive deficits in both contextual fear conditioning and the Morris water maze. Our novel, highly immunogenic Aβ conjugate vaccine, MER5101, shows promise for improving Aβ vaccine safety and efficacy and therefore, may be useful for preventing and/or treating early AD.

  4. Introduction and Rollout of a New Group A Meningococcal Conjugate Vaccine (PsA-TT) in African Meningitis Belt Countries, 2010–2014

    Science.gov (United States)

    Djingarey, Mamoudou H.; Diomandé, Fabien V. K.; Barry, Rodrigue; Kandolo, Denis; Shirehwa, Florence; Lingani, Clement; Novak, Ryan T.; Tevi-Benissan, Carol; Perea, William; Preziosi, Marie-Pierre; LaForce, F. Marc

    2015-01-01

    Background. A group A meningococcal conjugate vaccine (PsA-TT) was developed specifically for the African “meningitis belt” and was prequalified by the World Health Organization (WHO) in June 2010. The vaccine was first used widely in Burkina Faso, Mali, and Niger in December 2010 with great success. The remaining 23 meningitis belt countries wished to use this new vaccine. Methods. With the help of African countries, WHO developed a prioritization scheme and used or adapted existing immunization guidelines to mount PsA-TT vaccination campaigns. Vaccine requirements were harmonized with the Serum Institute of India, Ltd. Results. Burkina Faso was the first country to fully immunize its 1- to 29-year-old population in December 2010. Over the next 4 years, vaccine coverage was extended to 217 million Africans living in 15 meningitis belt countries. Conclusions. The new group A meningococcal conjugate vaccine was well received, with country coverage rates ranging from 85% to 95%. The rollout proceeded smoothly because countries at highest risk were immunized first while attention was paid to geographic contiguity to maximize herd protection. Community participation was exemplary. PMID:26553672

  5. Likelihood-based methods for evaluating principal surrogacy in augmented vaccine trials.

    Science.gov (United States)

    Liu, Wei; Zhang, Bo; Zhang, Hui; Zhang, Zhiwei

    2017-04-01

    There is growing interest in assessing immune biomarkers, which are quick to measure and potentially predictive of long-term efficacy, as surrogate endpoints in randomized, placebo-controlled vaccine trials. This can be done under a principal stratification approach, with principal strata defined using a subject's potential immune responses to vaccine and placebo (the latter may be assumed to be zero). In this context, principal surrogacy refers to the extent to which vaccine efficacy varies across principal strata. Because a placebo recipient's potential immune response to vaccine is unobserved in a standard vaccine trial, augmented vaccine trials have been proposed to produce the information needed to evaluate principal surrogacy. This article reviews existing methods based on an estimated likelihood and a pseudo-score (PS) and proposes two new methods based on a semiparametric likelihood (SL) and a pseudo-likelihood (PL), for analyzing augmented vaccine trials. Unlike the PS method, the SL method does not require a model for missingness, which can be advantageous when immune response data are missing by happenstance. The SL method is shown to be asymptotically efficient, and it performs similarly to the PS and PL methods in simulation experiments. The PL method appears to have a computational advantage over the PS and SL methods.

  6. Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study [corrected].

    Science.gov (United States)

    Daugla, D M; Gami, J P; Gamougam, K; Naibei, N; Mbainadji, L; Narbé, M; Toralta, J; Kodbesse, B; Ngadoua, C; Coldiron, M E; Fermon, F; Page, A-L; Djingarey, M H; Hugonnet, S; Harrison, O B; Rebbetts, L S; Tekletsion, Y; Watkins, E R; Hill, D; Caugant, D A; Chandramohan, D; Hassan-King, M; Manigart, O; Nascimento, M; Woukeu, A; Trotter, C; Stuart, J M; Maiden, McJ; Greenwood, B M

    2014-01-04

    A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA-TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and 4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. Roughly 1·8 million individuals aged 1-29 years received one dose of PsA-TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100,000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100,000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (pvaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2-4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001). PSA-TT was highly

  7. A fit-based frequency programme for the PS

    CERN Document Server

    Hancock, S

    2007-01-01

    Since the probes in the PS reference magnet that generate the so-called B-train are fairly short, they cannot register any change in magnetic length due to saturation. Hence the idea to derive the effective dipole magnetic field seen by the beam from measurements of revolution frequency and mean radial position over an entire cycle, to fit a saturation law, and to use the result to make a new frequency programme. Although far from new, the idea has never been implemented due to the tacit assumption that any imperfections in the existing frequency programme are taken care of by the action of the servo loops of the various beam controls. More recently, the delivery of ions at low energy from LEIR has called into question the accuracy the raw frequency programme and the idea has been revisited in a brief parasitic MD.

  8. Immunocytochemical Characterization of Alzheimer Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-β Vaccine

    Directory of Open Access Journals (Sweden)

    Iván Carrera

    2013-01-01

    Full Text Available APP/PS1 double-transgenic mouse models of Alzheimer’s disease (AD, which overexpress mutated forms of the gene for human amyloid precursor protein (APP and presenilin 1 (PS1, have provided robust neuropathological hallmarks of AD-like pattern at early ages. This study characterizes immunocytochemical patterns of AD mouse brain as a model for human AD treated with the EB101 vaccine. In this novel vaccine, a new approach has been taken to circumvent past failures by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol. Our findings showed that administration of amyloid-β1−42 (Aβ and sphingosine-1-phosphate emulsified in liposome complex (EB101 to APP/PS1 mice before onset of Aβ deposition (7 weeks of age and/or at an older age (35 weeks of age is effective in halting the progression and clearing the AD-like neuropathological hallmarks. Passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus in the brain of treated mice was notably reduced. These results demonstrate that immunization with EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.

  9. Probability-of-Superiority SEM (PS-SEM—Detecting Probability-Based Multivariate Relationships in Behavioral Research

    Directory of Open Access Journals (Sweden)

    Johnson Ching-Hong Li

    2018-06-01

    Full Text Available In behavioral research, exploring bivariate relationships between variables X and Y based on the concept of probability-of-superiority (PS has received increasing attention. Unlike the conventional, linear-based bivariate relationship (e.g., Pearson's correlation, PS defines that X and Y can be related based on their likelihood—e.g., a student who is above mean in SAT has 63% likelihood of achieving an above-mean college GPA. Despite its increasing attention, the concept of PS is restricted to a simple bivariate scenario (X-Y pair, which hinders the development and application of PS in popular multivariate modeling such as structural equation modeling (SEM. Therefore, this study addresses an empirical-based simulation study that explores the potential of detecting PS-based relationship in SEM, called PS-SEM. The simulation results showed that the proposed PS-SEM method can detect and identify PS-based when data follow PS-based relationships, thereby providing a useful method for researchers to explore PS-based SEM in their studies. Conclusions, implications, and future directions based on the findings are also discussed.

  10. Rational design of gene-based vaccines.

    Science.gov (United States)

    Barouch, Dan H

    2006-01-01

    Vaccine development has traditionally been an empirical discipline. Classical vaccine strategies include the development of attenuated organisms, whole killed organisms, and protein subunits, followed by empirical optimization and iterative improvements. While these strategies have been remarkably successful for a wide variety of viruses and bacteria, these approaches have proven more limited for pathogens that require cellular immune responses for their control. In this review, current strategies to develop and optimize gene-based vaccines are described, with an emphasis on novel approaches to improve plasmid DNA vaccines and recombinant adenovirus vector-based vaccines. Copyright 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. Nanoporous polymeric nanofibers based on selectively etched PS-b-PDMS block copolymers.

    Science.gov (United States)

    Demirel, Gokcen B; Buyukserin, Fatih; Morris, Michael A; Demirel, Gokhan

    2012-01-01

    One-dimensional nanoporous polymeric nanofibers have been fabricated within an anodic aluminum oxide (AAO) membrane by a facile approach based on selective etching of poly(dimethylsiloxane) (PDMS) domains in polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS) block copolymers that had been formed within the AAO template. It was observed that prior to etching, the well-ordered PS-b-PDMS nanofibers are solid and do not have any porosity. The postetched PS nanofibers, on the other hand, had a highly porous structure having about 20-50 nm pore size. The nanoporous polymeric fibers were also employed as a drug carrier for the native, continuous, and pulsatile drug release using Rhodamine B (RB) as a model drug. These studies showed that enhanced drug release and tunable drug dosage can be achieved by using ultrasound irradiation. © 2011 American Chemical Society

  12. Beam test results of a 16 ps timing system based on ultra-fast silicon detectors

    Energy Technology Data Exchange (ETDEWEB)

    Cartiglia, N., E-mail: cartiglia@to.infn.it [INFN, Torino (Italy); Staiano, A.; Sola, V. [INFN, Torino (Italy); Arcidiacono, R. [INFN, Torino (Italy); Università del Piemonte Orientale (Italy); Cirio, R.; Cenna, F.; Ferrero, M.; Monaco, V.; Mulargia, R.; Obertino, M.; Ravera, F.; Sacchi, R. [INFN, Torino (Italy); Università di Torino, Torino (Italy); Bellora, A.; Durando, S. [Università di Torino, Torino (Italy); Mandurrino, M. [Politecnico di Torino, Torino (Italy); Minafra, N. [University of Kansas, KS (United States); Fadeyev, V.; Freeman, P.; Galloway, Z.; Gkougkousis, E. [SCIPP, University of California Santa Cruz, CA 95064 (United States); and others

    2017-04-01

    In this paper we report on the timing resolution obtained in a beam test with pions of 180 GeV/c momentum at CERN for the first production of 45 µm thick Ultra-Fast Silicon Detectors (UFSD). UFSD are based on the Low-Gain Avalanche Detector (LGAD) design, employing n-on-p silicon sensors with internal charge multiplication due to the presence of a thin, low-resistivity diffusion layer below the junction. The UFSD used in this test had a pad area of 1.7 mm{sup 2}. The gain was measured to vary between 5 and 70 depending on the sensor bias voltage. The experimental setup included three UFSD and a fast trigger consisting of a quartz bar readout by a SiPM. The timing resolution was determined by doing Gaussian fits to the time-of-flight of the particles between one or more UFSD and the trigger counter. For a single UFSD the resolution was measured to be 34 ps for a bias voltage of 200 V, and 27 ps for a bias voltage of 230 V. For the combination of 3 UFSD the timing resolution was 20 ps for a bias voltage of 200 V, and 16 ps for a bias voltage of 230 V.

  13. 7YSZ coating prepared by PS-PVD based on heterogeneous nucleation

    Directory of Open Access Journals (Sweden)

    Ziqian DENG

    2018-04-01

    Full Text Available Plasma spray-physical vapor deposition (PS-PVD as a novel coating process based on low-pressure plasma spray (LPPS has been significantly used for thermal barrier coatings (TBCs. A coating can be deposited from liquid splats, nano-sized clusters, and the vapor phase forming different structured coatings, which shows obvious advantages in contrast to conventional technologies like atmospheric plasma spray (APS and electron beam-physical vapor deposition (EB-PVD. In addition, it can be used to produce thin, dense, and porous ceramic coatings for special applications because of its special characteristics, such as high power, very low pressure, etc. These provide new opportunities to obtain different advanced microstructures, thus to meet the growing requirements of modern functional coatings. In this work, focusing on exploiting the potential of gas-phase deposition from PS-PVD, a series of 7YSZ coating experiments with various process conditions was performed in order to better understand the deposition process in PS-PVD, where coatings were deposited on different substrates including graphite and zirconia. Meanwhile, various substrate temperatures were investigated for the same substrate. As a result, a deposition mechanism of heterogeneous nucleation has been presented showing that surface energy is an important influencing factor for coating structures. Besides, undercooling of the interface between substrate and vapor phase plays an important role in coating structures. Keywords: 7YSZ, Deposition mechanism, Heterogeneous nucleation, PS-PVD, TBC

  14. Typhoid fever vaccination strategies.

    Science.gov (United States)

    Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

    2015-06-19

    Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by

  15. Adolescent Attitudes toward Influenza Vaccination and Vaccine Uptake in a School-Based Influenza Vaccination Intervention: A Mediation Analysis

    Science.gov (United States)

    Painter, Julia E.; Sales, Jessica M.; Pazol, Karen; Wingood, Gina M.; Windle, Michael; Orenstein, Walter A.; DiClemente, Ralph J.

    2011-01-01

    Background: School-based vaccination programs may provide an effective strategy to immunize adolescents against influenza. This study examined whether adolescent attitudes toward influenza vaccination mediated the relationship between receipt of a school-based influenza vaccination intervention and vaccine uptake. Methods: Participants were…

  16. Algae-based oral recombinant vaccines

    Science.gov (United States)

    Specht, Elizabeth A.; Mayfield, Stephen P.

    2014-01-01

    Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for “molecular pharming” in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae could be poised to become the next candidate in recombinant subunit vaccine production, as they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and systemic immune reactivity. PMID:24596570

  17. Algae-based oral recombinant vaccines

    Directory of Open Access Journals (Sweden)

    Elizabeth A Specht

    2014-02-01

    Full Text Available Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for molecular pharming in food crops has waned in the last decade due to difficulty in developing transgenic crop plants and concerns of contaminating the food supply. Microalgae are poised to become the next candidate in recombinant subunit vaccine production, and they present several advantages over terrestrial crop plant-based platforms including scalable and contained growth, rapid transformation, easily obtained stable cell lines, and consistent transgene expression levels. Algae have been shown to accumulate and properly fold several vaccine antigens, and efforts are underway to create recombinant algal fusion proteins that can enhance antigenicity for effective orally-delivered vaccines. These approaches have the potential to revolutionize the way subunit vaccines are made and delivered – from costly parenteral administration of purified protein, to an inexpensive oral algae tablet with effective mucosal and system immune reactivity.

  18. Multichannel FPGA based MVT system for high precision time (20 ps RMS) and charge measurement

    Science.gov (United States)

    Pałka, M.; Strzempek, P.; Korcyl, G.; Bednarski, T.; Niedźwiecki, Sz.; Białas, P.; Czerwiński, E.; Dulski, K.; Gajos, A.; Głowacz, B.; Gorgol, M.; Jasińska, B.; Kamińska, D.; Kajetanowicz, M.; Kowalski, P.; Kozik, T.; Krzemień, W.; Kubicz, E.; Mohhamed, M.; Raczyński, L.; Rudy, Z.; Rundel, O.; Salabura, P.; Sharma, N. G.; Silarski, M.; Smyrski, J.; Strzelecki, A.; Wieczorek, A.; Wiślicki, W.; Zieliński, M.; Zgardzińska, B.; Moskal, P.

    2017-08-01

    In this article it is presented an FPGA based Multi-Voltage Threshold (MVT) system which allows of sampling fast signals (1-2 ns rising and falling edge) in both voltage and time domain. It is possible to achieve a precision of time measurement of 20 ps RMS and reconstruct charge of signals, using a simple approach, with deviation from real value smaller than 10%. Utilization of the differential inputs of an FPGA chip as comparators together with an implementation of a TDC inside an FPGA allowed us to achieve a compact multi-channel system characterized by low power consumption and low production costs. This paper describes realization and functioning of the system comprising 192-channel TDC board and a four mezzanine cards which split incoming signals and discriminate them. The boards have been used to validate a newly developed Time-of-Flight Positron Emission Tomography system based on plastic scintillators. The achieved full system time resolution of σ(TOF) ≈ 68 ps is by factor of two better with respect to the current TOF-PET systems.

  19. A 2.9 ps equivalent resolution interpolating time counter based on multiple independent coding lines

    International Nuclear Information System (INIS)

    Szplet, R; Jachna, Z; Kwiatkowski, P; Rozyc, K

    2013-01-01

    We present the design, operation and test results of a time counter that has an equivalent resolution of 2.9 ps, a measurement uncertainty at the level of 6 ps, and a measurement range of 10 s. The time counter has been implemented in a general-purpose reprogrammable device Spartan-6 (Xilinx). To obtain both high precision and wide measurement range the counting of periods of a reference clock is combined with a two-stage interpolation within a single period of the clock signal. The interpolation involves a four-phase clock in the first interpolation stage (FIS) and an equivalent coding line (ECL) in the second interpolation stage (SIS). The ECL is created as a compound of independent discrete time coding lines (TCL). The number of TCLs used to create the virtual ECL has an effect on its resolution. We tested ECLs made from up to 16 TCLs, but the idea may be extended to a larger number of lines. In the presented time counter the coarse resolution of the counting method equal to 2 ns (period of the 500 MHz reference clock) is firstly improved fourfold in the FIS and next even more than 400 times in the SIS. The proposed solution allows us to overcome the technological limitation in achievable resolution and improve the precision of conversion of integrated interpolators based on tapped delay lines. (paper)

  20. Vaccination of carp against SVCV with an oral DNA vaccine or an insect cells-based subunit vaccine.

    Science.gov (United States)

    Embregts, C W E; Rigaudeau, D; Tacchi, L; Pijlman, G P; Kampers, L; Veselý, T; Pokorová, D; Boudinot, P; Wiegertjes, G F; Forlenza, M

    2018-03-19

    We recently reported on a successful vaccine for carp against SVCV based on the intramuscular injection of a DNA plasmid encoding the SVCV glycoprotein (SVCV-G). This shows that the intramuscular (i.m.) route of vaccination is suitable to trigger protective responses against SVCV, and that the SVCV G-protein is a suitable vaccine antigen. Yet, despite the general success of DNA vaccines, especially against fish rhabdoviruses, their practical implementation still faces legislative as well as consumer's acceptance concerns. Furthermore, the i.m. route of plasmid administration is not easily combined with most of the current vaccination regimes largely based on intraperitoneal or immersion vaccination. For this reason, in the current study we evaluated possible alternatives to a DNA-based i.m. injectable vaccine using the SVCV-G protein as the vaccine antigen. To this end, we tested two parallel approaches: the first based on the optimization of an alginate encapsulation method for oral delivery of DNA and protein antigens; the second based on the baculovirus recombinant expression of transmembrane SVCV-G protein in insect cells, administered as whole-cell subunit vaccine through the oral and injection route. In addition, in the case of the oral DNA vaccine, we also investigated the potential benefits of the mucosal adjuvants Escherichia coli lymphotoxin subunit B (LTB). Despite the use of various vaccine types, doses, regimes, and administration routes, no protection was observed, contrary to the full protection obtained with our reference i.m. DNA vaccine. The limited protection observed under the various conditions used in this study, the nature of the host, of the pathogen, the type of vaccine and encapsulation method, will therefore be discussed in details to provide an outlook for future vaccination strategies against SVCV. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Active immunization with the peptide epitope vaccine Aβ3-10-KLH induces a Th2-polarized anti-Aβ antibody response and decreases amyloid plaques in APP/PS1 transgenic mice.

    Science.gov (United States)

    Ding, Li; Meng, Yuan; Zhang, Hui-Yi; Yin, Wen-Chao; Yan, Yi; Cao, Yun-Peng

    2016-11-10

    Active amyloid-β (Aβ) immunotherapy is effective in preventing Aβ deposition, facilitating plaque clearance, and improving cognitive functions in mouse models of Alzheimer's disease (AD). Developing a safe and effective AD vaccine requires a delicate balance between inducing adequate humoral immune responses and avoiding T cell-mediated autoimmune responses. In this study, we designed 2 peptide epitope vaccines, Aβ3-10-KLH and 5Aβ3-10, prepared respectively by coupling Aβ3-10 to the immunogenic carrier protein keyhole limpet hemocyanin (KLH) or by joining 5 Aβ3-10 epitopes linearly in tandem. Young APP/PS1 mice were immunized subcutaneously with Aβ3-10-KLH or 5Aβ3-10 mixed with Freund's adjuvant, and the immunopotencies of these Aβ3-10 peptide vaccines were tested. Aβ3-10-KLH elicited a robust Th2-polarized anti-Aβ antibody response and inhibited Aβ deposition in APP/PS1 mice. However, 5Aβ3-10 did not induce an effective humoral immune response. These results indicated that Aβ3-10-KLH may be a safe and efficient vaccine for AD and that conjugating the antigen to a carrier protein may be more effective than linking multiple peptide antigens in tandem in applications for antibody production and vaccine preparation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Economic benefit evaluation for renewable energy transmitted by HVDC based on production simulation (PS) and analytic hierarchy process(AHP)

    Science.gov (United States)

    Zhang, Jinfang; Zheng, Kuan; Liu, Jun; Huang, Xinting

    2018-02-01

    In order to support North and West China’s RE (RE) development and enhance accommodation in reasonable high level, HVDC’s traditional operation curves need some change to follow the output characteristic of RE, which helps to shrink curtailment electricity and curtailment ratio of RE. In this paper, an economic benefit analysis method based on production simulation (PS) and Analytic hierarchy process (AHP) has been proposed. PS is the basic tool to analyze chosen power system operation situation, and AHP method could give a suitable comparison result among many candidate schemes. Based on four different transmission curve combinations, related economic benefit has been evaluated by PS and AHP. The results and related index have shown the efficiency of suggested method, and finally it has been validated that HVDC operation curve in following RE output mode could have benefit in decreasing RE curtailment level and improving economic operation.

  3. Replacing PS controls front end minicomputers by VME based 32-bit processors

    International Nuclear Information System (INIS)

    Gagnaire, A.; Metz Noblat, N. de; Serre, Ch.; Sicard, Cl.H.

    1992-01-01

    The PS controls have started the first phase of system rejuvenation, targeted towards the LEP Preinjector Controls. The main impact of this phase is in the architectural change, as both the front-end minicomputers and the CAMAC embedded microprocessors are replaced by microprocessor based VME crates called Device Stub Controllers (DSC). This paper discusses the different steps planned for this first phase, i.e: (1) implementing the basic set of CERN Accelerator common facilities for DSCs (error handling, system surveillance, remote boot and network access); (2) porting the equipment access software layer; (3) applying the Real-time tasks to the LynxOS operating system and I/O architecture, conforming to the real-time constraints for control and acquisition; (4) defining the number and contents of the different DSC needed, according to geographical and cpu-load constraints; (5) providing the general services outside the DSC crates (file servers, data-base services); (6) emulating the current Console programs onto the new workstations. (author)

  4. School-based influenza vaccination: parents' perspectives.

    Directory of Open Access Journals (Sweden)

    Candace Lind

    Full Text Available School-age children are important drivers of annual influenza epidemics yet influenza vaccination coverage of this population is low despite universal publicly funded influenza vaccination in Alberta, Canada. Immunizing children at school may potentially increase vaccine uptake. As parents are a key stakeholder group for such a program, it is important to consider their concerns.We explored parents' perspectives on the acceptability of adding an annual influenza immunization to the immunization program that is currently delivered in Alberta schools, and obtained suggestions for structuring such a program.Forty-eight parents of children aged 5-18 years participated in 9 focus groups. Participants lived in urban areas of the Alberta Health Services Calgary Zone.Three major themes emerged: Advantages of school-based influenza vaccination (SBIV, Disadvantages of SBIV, and Implications for program design & delivery. Advantages were perceived to occur for different populations: children (e.g. emotional support, families (e.g. convenience, the community (e.g. benefits for school and multicultural communities, the health sector (e.g. reductions in costs due to burden of illness and to society at large (e.g. indirect conduit of information about health services, building structure for pandemic preparedness, building healthy lifestyles. Disadvantages, however, might also occur for children (e.g. older children less likely to be immunized, families (e.g. communication challenges, perceived loss of parental control over information, choices and decisions and the education sector (loss of instructional time. Nine second-level themes emerged within the major theme of Implications for program design & delivery: program goals/objectives, consent process, stakeholder consultation, age-appropriate program, education, communication, logistics, immunizing agent, and clinic process.Parents perceived advantages and disadvantages to delivering annual seasonal

  5. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Directory of Open Access Journals (Sweden)

    Samantha Sayers

    2012-01-01

    Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

  6. Vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.

    Science.gov (United States)

    Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

    2012-01-01

    Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.

  7. PsOr1, a potential target for RNA interference-based pest management.

    Science.gov (United States)

    Zhao, Y Y; Liu, F; Yang, G; You, M S

    2011-02-01

    Insect pests cause billions of dollars in agricultural losses, and attempts to kill them have resulted in growing threats from insecticide resistance, dietary pesticide pollution and environmental destruction. New approaches to control refractory insect pests are therefore needed. The host-plant preferences of insect pests rely on olfaction and are mediated via a seven transmembrane-domain odorant receptor (Or) family. The present study reports the cloning and characterization of PsOr1, the first candidate member of the Or gene family from Phyllotreta striolata, a devastating beetle pest that causes damage worldwide. PsOr1 is remarkably well conserved with respect to other insect orthologues, including DmOr83b from Drosophila melanogaster. These insect orthologues form an essential non-conventional Or sub-family and may play an important and generalized role in insect olfaction. We designed double-stranded (ds) RNA directly against the PsOr1 gene and exploited RNA interference (RNAi) to control P. striolata. The chemotactic behavioural measurements showed that adult beetles were unable to sense the attractant or repellent odour stimulus after microinjection of dsRNA against PsOr1. Reverse Transcription (RT)-PCR analysis showed specific down-regulation of mRNA transcript levels for this gene. Furthermore, host-plant preference experiments confirmed that silencing PsOr1 by RNAi treatment impaired the host-plant preferences of P. striolata for cruciferous vegetables. These results demonstrate that this insect control approach of using RNAi to target PsOr1 and its orthologues might be effective in blocking host-plant-seeking behaviours in diverse insect pests. The results also support the theory that this unique receptor type plays an essential general role in insect olfaction. © 2010 Fujian Agriculture and Forestry University. Insect Molecular Biology © 2010 The Royal Entomological Society.

  8. PS-FW: A Hybrid Algorithm Based on Particle Swarm and Fireworks for Global Optimization

    Science.gov (United States)

    Chen, Shuangqing; Wei, Lixin; Guan, Bing

    2018-01-01

    Particle swarm optimization (PSO) and fireworks algorithm (FWA) are two recently developed optimization methods which have been applied in various areas due to their simplicity and efficiency. However, when being applied to high-dimensional optimization problems, PSO algorithm may be trapped in the local optima owing to the lack of powerful global exploration capability, and fireworks algorithm is difficult to converge in some cases because of its relatively low local exploitation efficiency for noncore fireworks. In this paper, a hybrid algorithm called PS-FW is presented, in which the modified operators of FWA are embedded into the solving process of PSO. In the iteration process, the abandonment and supplement mechanism is adopted to balance the exploration and exploitation ability of PS-FW, and the modified explosion operator and the novel mutation operator are proposed to speed up the global convergence and to avoid prematurity. To verify the performance of the proposed PS-FW algorithm, 22 high-dimensional benchmark functions have been employed, and it is compared with PSO, FWA, stdPSO, CPSO, CLPSO, FIPS, Frankenstein, and ALWPSO algorithms. Results show that the PS-FW algorithm is an efficient, robust, and fast converging optimization method for solving global optimization problems. PMID:29675036

  9. Ontology-based Brucella vaccine literature indexing and systematic analysis of gene-vaccine association network

    Science.gov (United States)

    2011-01-01

    Background Vaccine literature indexing is poorly performed in PubMed due to limited hierarchy of Medical Subject Headings (MeSH) annotation in the vaccine field. Vaccine Ontology (VO) is a community-based biomedical ontology that represents various vaccines and their relations. SciMiner is an in-house literature mining system that supports literature indexing and gene name tagging. We hypothesize that application of VO in SciMiner will aid vaccine literature indexing and mining of vaccine-gene interaction networks. As a test case, we have examined vaccines for Brucella, the causative agent of brucellosis in humans and animals. Results The VO-based SciMiner (VO-SciMiner) was developed to incorporate a total of 67 Brucella vaccine terms. A set of rules for term expansion of VO terms were learned from training data, consisting of 90 biomedical articles related to Brucella vaccine terms. VO-SciMiner demonstrated high recall (91%) and precision (99%) from testing a separate set of 100 manually selected biomedical articles. VO-SciMiner indexing exhibited superior performance in retrieving Brucella vaccine-related papers over that obtained with MeSH-based PubMed literature search. For example, a VO-SciMiner search of "live attenuated Brucella vaccine" returned 922 hits as of April 20, 2011, while a PubMed search of the same query resulted in only 74 hits. Using the abstracts of 14,947 Brucella-related papers, VO-SciMiner identified 140 Brucella genes associated with Brucella vaccines. These genes included known protective antigens, virulence factors, and genes closely related to Brucella vaccines. These VO-interacting Brucella genes were significantly over-represented in biological functional categories, including metabolite transport and metabolism, replication and repair, cell wall biogenesis, intracellular trafficking and secretion, posttranslational modification, and chaperones. Furthermore, a comprehensive interaction network of Brucella vaccines and genes were

  10. A thermostable messenger RNA based vaccine against rabies.

    Science.gov (United States)

    Stitz, Lothar; Vogel, Annette; Schnee, Margit; Voss, Daniel; Rauch, Susanne; Mutzke, Thorsten; Ketterer, Thomas; Kramps, Thomas; Petsch, Benjamin

    2017-12-01

    Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine from -80°C to up to +70°C for several months did not impact the protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection. Moreover, storing the vaccine at oscillating temperatures between +4° and +56°C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine's immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine.

  11. Establishing a CoPs-based innovation ecosystem to enhance competence - the case of CGN in China

    DEFF Research Database (Denmark)

    Chen, Jian; Lui, Xielin; Hu, Yimei

    2016-01-01

    This research investigated how an innovation system is created, and how technology, value and capability evolve at different stages of an innovation ecosystem. Based on an exploratory and process-oriented case study onof the innovation ecosystem strategy of a nuclear power giant- China General...... Nuclear Power Group (CGN, formerly known as China Guangdong Nuclear Power Group) for the period 1987-2014, this paper presents an integrative framework to explicate the micro-foundation of the formation mechanism of an innovation ecosystem for complex product system (CoPs) characterized by interdependency...

  12. Animal vaccines based on orally presented yeast recombinants.

    Science.gov (United States)

    Shin, Min-Kyoung; Yoo, Han Sang

    2013-09-13

    In veterinary vaccinology, the oral route of administration is an attractive alternative compared to the commonly used parenteral route. Yeasts have a number of properties that make them potential live delivery systems for oral vaccination purposes such as their high expression levels, their GRAS status, adjuvant properties, and post-translational modification possibilities. Consequently, yeasts have been employed for the expression of heterologous genes and for the production of therapeutic proteins. Yeast-based vaccines are reviewed with regard to their ability to express and produce antigens from pathogens for veterinary use. Many of these vaccines have been shown to elicit protective immune responses following oral immunization in animals. Ultimately, yeast-based oral vaccines may offer a potential opportunity for the development of novel ideal vaccines in veterinary medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Hybrid titanium dioxide/PS-b-PEO block copolymer nanocomposites based on sol-gel synthesis

    International Nuclear Information System (INIS)

    Gutierrez, J; Tercjak, A; Garcia, I; Peponi, L; Mondragon, I

    2008-01-01

    The poly(styrene)-b-poly(ethylene oxide) (SEO) amphiphilic block copolymer, with two different molecular weights, has been used as a structure directing agent for generating nanocomposites of TiO 2 /SEO via the sol-gel process. SEO amphiphilic block copolymers are designed with a hydrophilic PEO-block which can interact with inorganic molecules, as well as a hydrophobic PS-block which builds the matrix. The addition of different amounts of sol-gel provokes strong variations in the self-assembled morphology of TiO 2 /SEO nanocomposites with respect to the neat block copolymer. As confirmed by atomic force microscopy (AFM), TiO 2 /PEO-block micelles get closer, forming well-ordered spherical domains, in which TiO 2 nanoparticles constitute the core surrounded by a corona of PEO-blocks. Moreover, for 20 vol% sol-gel the generated morphology changes to a hexagonally ordered structure for both block copolymers. The cylindrical structure of these nanocomposites has been confirmed by the two-dimensional Fourier transform power spectrum of the corresponding AFM height images. Affinity between titanium dioxide precursor and PEO-block of SEO allows us to generate hybrid inorganic/organic nanocomposites, which retain the optical properties of TiO 2 , as evaluated by UV-vis spectroscopy

  14. The European Regulatory Environment of RNA-Based Vaccines.

    Science.gov (United States)

    Hinz, Thomas; Kallen, Kajo; Britten, Cedrik M; Flamion, Bruno; Granzer, Ulrich; Hoos, Axel; Huber, Christoph; Khleif, Samir; Kreiter, Sebastian; Rammensee, Hans-Georg; Sahin, Ugur; Singh-Jasuja, Harpreet; Türeci, Özlem; Kalinke, Ulrich

    2017-01-01

    A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients. In the EU no regulatory guidelines presently exist that specifically address mRNA-based vaccines. The existing regulatory framework, however, clearly defines that mRNA-based vaccines in most cases have to be centrally approved. Interestingly, depending on whether RNA-based vaccines are directed against tumors or infectious disease, they are formally considered gene therapy products or not, respectively. Besides an overview on the current clinical use of mRNA vaccines in various therapeutic areas a detailed discussion of the current regulatory situation is provided and regulatory perspectives are discussed.

  15. Chikungunya Virus Vaccines: Viral Vector-Based Approaches.

    Science.gov (United States)

    Ramsauer, Katrin; Tangy, Frédéric

    2016-12-15

    In 2013, a major chikungunya virus (CHIKV) epidemic reached the Americas. In the past 2 years, >1.7 million people have been infected. In light of the current epidemic, with millions of people in North and South America at risk, efforts to rapidly develop effective vaccines have increased. Here, we focus on CHIKV vaccines that use viral-vector technologies. This group of vaccine candidates shares an ability to potently induce humoral and cellular immune responses by use of highly attenuated and safe vaccine backbones. So far, well-described vectors such as modified vaccinia virus Ankara, complex adenovirus, vesicular stomatitis virus, alphavirus-based chimeras, and measles vaccine Schwarz strain (MV/Schw) have been described as potential vaccines. We summarize here the recent data on these experimental vaccines, with a focus on the preclinical and clinical activities on the MV/Schw-based candidate, which is the first CHIKV-vectored vaccine that has completed a clinical trial. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  16. Prospects of HA-Based Universal Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Anwar M. Hashem

    2015-01-01

    Full Text Available Current influenza vaccines afford substantial protection in humans by inducing strain-specific neutralizing antibodies (Abs. Most of these Abs target highly variable immunodominant epitopes in the globular domain of the viral hemagglutinin (HA. Therefore, current vaccines may not be able to induce heterosubtypic immunity against the divergent influenza subtypes. The identification of broadly neutralizing Abs (BnAbs against influenza HA using recent technological advancements in antibody libraries, hybridoma, and isolation of single Ab-secreting plasma cells has increased the interest in developing a universal influenza vaccine as it could provide life-long protection. While these BnAbs can serve as a source for passive immunotherapy, their identification represents an important step towards the design of such a universal vaccine. This review describes the recent advances and approaches used in the development of universal influenza vaccine based on highly conserved HA regions identified by BnAbs.

  17. RNA-Based Vaccines in Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Megan A. McNamara

    2015-01-01

    Full Text Available RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.

  18. School-based human papillomavirus vaccination: An opportunity to ...

    African Journals Online (AJOL)

    School-based human papillomavirus vaccination: An opportunity to increase knowledge about cervical cancer and improve uptake of ... Poor knowledge about cervical cancer plays a role in limiting screening uptake. HPV ... Article Metrics.

  19. Chimeric L2-Based Virus-Like Particle (VLP Vaccines Targeting Cutaneous Human Papillomaviruses (HPV.

    Directory of Open Access Journals (Sweden)

    Bettina Huber

    Full Text Available Common cutaneous human papillomavirus (HPV types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas, but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa 17-36 on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross- protected against beta HPV5/20/24/38/96/16 (but not type 76, while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target

  20. Particle-based vaccines for HIV-1 infection.

    Science.gov (United States)

    Young, Kelly R; Ross, Ted M

    2003-06-01

    The use of live-attenuated viruses as vaccines has been successful for the control of viral infections. However, the development of an effective vaccine against the human immunodeficiency virus (HIV) has proven to be a challenge. HIV infects cells of the immune system and results in a severe immunodeficiency. In addition, the ability of the virus to adapt to immune pressure and the ability to reside in an integrated form in host cells present hurdles for vaccinologists to overcome. A particle-based vaccine strategy has promise for eliciting high titer, long-lived, immune responses to a diverse number of viral epitopes from different HIV antigens. Live-attenuated viruses are effective at generating both cellular and humoral immunity, however, a live-attenuated vaccine for HIV is problematic. The possibility of a live-attenuated vaccine to revert to a pathogenic form or recombine with a wild-type or defective virus in an infected individual is a drawback to this approach. Therefore, these vaccines are currently only being tested in non-human primate models. Live-attenuated vaccines are effective in stimulating immunity, however challenged animals rarely clear viral infection and the degree of attenuation directly correlates with the protection of animals from disease. Another particle-based vaccine approach for HIV involves the use of virus-like particles (VLPs). VLPs mimic the viral particle without causing an immunodeficiency disease. HIV-like particles (HIV-LP) are defined as self-assembling, non-replicating, nonpathogenic, genomeless particles that are similar in size and conformation to intact virions. A variety of VLPs for both HIV and SIV are currently in pre-clinical and clinical trials. This review focuses on the current knowledge regarding the immunogenicity and safety of particle-based vaccine strategies for HIV-1.

  1. Development of an epitope-based HIV-1 vaccine strategy from HIV-1 lipopeptide to dendritic-based vaccines.

    Science.gov (United States)

    Surenaud, Mathieu; Lacabaratz, Christine; Zurawski, Gérard; Lévy, Yves; Lelièvre, Jean-Daniel

    2017-10-01

    Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells. But to date, no vaccine candidate has proven to significantly alter the natural history of an individual with HIV-1 infection. Areas covered: For over 25 years, the ANRS (France Recherche Nord&Sud Sida-HIV hépatites) has been committed to an original program combining basic science and clinical research developing an epitope-based vaccine strategy to induce a multiepitopic cellular response against HIV-1. This review describes the evolution of concepts, based on strategies using HIV-1 lipopeptides towards the use of dendritic cell (DC) manipulation. Expert commentary: Understanding the crucial role of DCs in immune responses allowed moving from the non-specific administration of HIV-1 sequences with lipopeptides to DC-based vaccines. These DC-targeting strategies should improve HIV-1 vaccine efficacy.

  2. Wall-Current-Monitor based Ghost and Satellite Bunch Detection in the CERN PS and the LHC Accelerators

    CERN Document Server

    Steinhagen, R J; Belleman, J; Bohl, T; Damerau, H

    2012-01-01

    While most LHC detectors and instrumentation systems are optimised for a nominal bunch spacing of 25 ns, the LHC RF cavities themselves operate at the 10th harmonic of the maximum bunch frequency. Due to the beam production scheme and transfers in the injector chain, part of the nominally ‘empty’ RF buckets may contain particles, referred to as ghost or satellite bunches. These populations must be accurately quantified for high-precision experiments, luminosity calibration and control of parasitic particle encounters at the four LHC interaction points. This contribution summarises the wall-current-monitor based ghost and satellite bunch measurements in CERN’s PS and LHC accelerators. Instrumentation set-up, post-processing and achieved performance are discussed.

  3. Viral vector-based influenza vaccines

    Science.gov (United States)

    de Vries, Rory D.; Rimmelzwaan, Guus F.

    2016-01-01

    ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

  4. A history of adolescent school based vaccination in Australia.

    Science.gov (United States)

    Ward, Kirsten; Quinn, Helen; Menzies, Robert; McIntyre, Peter

    2013-06-30

    As adolescents have become an increasingly prominent target group for vaccination, school-based vaccination has emerged as an efficient and effective method of delivering nationally recommended vaccines to this often hard to reach group. School-based delivery of vaccines has occurred in Australia for over 80 years and has demonstrated advantages over primary care delivery for this part of the population. In the last decade school-based vaccination programs have become routine practice across all Australian states and territories. Using existing records and the recollection of experts we have compiled a history of school-based vaccination in Australia, primarily focusing on adolescents. This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.

  5. Efficient Vaccine Distribution Based on a Hybrid Compartmental Model.

    Directory of Open Access Journals (Sweden)

    Zhiwen Yu

    Full Text Available To effectively and efficiently reduce the morbidity and mortality that may be caused by outbreaks of emerging infectious diseases, it is very important for public health agencies to make informed decisions for controlling the spread of the disease. Such decisions must incorporate various kinds of intervention strategies, such as vaccinations, school closures and border restrictions. Recently, researchers have paid increased attention to searching for effective vaccine distribution strategies for reducing the effects of pandemic outbreaks when resources are limited. Most of the existing research work has been focused on how to design an effective age-structured epidemic model and to select a suitable vaccine distribution strategy to prevent the propagation of an infectious virus. Models that evaluate age structure effects are common, but models that additionally evaluate geographical effects are less common. In this paper, we propose a new SEIR (susceptible-exposed-infectious šC recovered model, named the hybrid SEIR-V model (HSEIR-V, which considers not only the dynamics of infection prevalence in several age-specific host populations, but also seeks to characterize the dynamics by which a virus spreads in various geographic districts. Several vaccination strategies such as different kinds of vaccine coverage, different vaccine releasing times and different vaccine deployment methods are incorporated into the HSEIR-V compartmental model. We also design four hybrid vaccination distribution strategies (based on population size, contact pattern matrix, infection rate and infectious risk for controlling the spread of viral infections. Based on data from the 2009-2010 H1N1 influenza epidemic, we evaluate the effectiveness of our proposed HSEIR-V model and study the effects of different types of human behaviour in responding to epidemics.

  6. [VACCINES].

    Science.gov (United States)

    Bellver Capella, Vincente

    2015-10-01

    Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.

  7. Multiturn Extraction Based on Trapping in Stable Islands at CERN PS: Recent Measurement Advances

    CERN Multimedia

    Cappi, R; Giovannozzi, Massimo; Martini, M; Métral, Elias; Müller, A S; Sakumi, A; Steerenberg, R

    2004-01-01

    Recently a novel approach to perform multi-turn extraction was proposed based on beam splitting in the transverse phase space by means of trapping inside stable islands. During the year 2002, preliminary measurements at the CERN Proton Synchrotron with a low-intensity, singlebunch, proton beam, confirmed the possibility of generating various beamlets starting from a single Gaussian beam. The experimental campaign continued also during the year 2003 to assess a number of key issues, such as the feasibility of trapping with high-intensity beam and capture efficiency. The experimental results are presented and discussed in detail in this paper.

  8. Studies on semiconductors based on InP with sub-ps response times; Untersuchungen an auf InP basierenden Halbleitern mit sub-ps Responsezeiten

    Energy Technology Data Exchange (ETDEWEB)

    Biermann, K.

    2007-06-28

    The present work describes investigation of new material concepts accomplished using molecular-beam-epitaxy (MBE) growth for application in ultra-fast photonic components. Nominally undoped and Be doped GaInAs/AlInAs multiple-quantumwell structures (MQW) were grown by MBE at growth temperatures down to 100 C (LT-MBE) on semi-insulating InP substrates. Crystalline, electric and optical properties of as-grown and annealed structures were investigated. Energy states near the conduction band of GaInAs determine the electrical and optical properties of LT-MQWs. The dynamics of charge carrier relaxation was studied by means of pump and probe experiments. Measurements of the differential transmission when excited by an additional cw laser and measurements utilizing two closely sequenced pump pulses support the capability of Be doped as-grown (annealed) LT GaInAs/AlInAs MQW structures for use in optical switches at switching frequencies in the 1 Tbit/s (250 Gbit/s) range. The voltage-induced change of interband transmission of InP based quantumcascade-lasers (QCL) during pulsed mode operation was analyzed by means of 8 band k.p calculations. The impacts of varying charge carrier distributions and of electrically heated samples can be neglected compared to the dominating effect of the electrical field on the interband transmission. The impact of MBE growth parameters on the interface quality of AlAsSb/ GaInAs heterostructures were determined by means of Hall measurements, temperature- and intensity-dependent PL measurements and spectral measurements of the interband- and intersubband-absorption. The impact of In segregation and Sb diffusion on the intersubband absorption was analyzed on the basis of bandstructure calculations. Intersubband transitions at wavelengths of about 1.8 {mu}m (1.55 {mu}m) were successfully achieved in MQW (coupled QW) structures. (orig.)

  9. Immune complex-based vaccine for pig protection against parvovirus.

    Science.gov (United States)

    Roić, B; Cajavec, S; Ergotić, N; Lipej, Z; Madić, J; Lojkić, M; Pokrić, B

    2006-02-01

    generated by the IC containing the allogeneic antibodies were higher than that generated by the ICs containing the xenogeneic pig antibodies. It was similar to that generated by two-times higher content of the virus material administered by a commercially available vaccine. The IC-based vaccines belong to non-replicating, subunit vaccines, which are both ecologically convenient and the safest vaccines of all.

  10. Vaxvec: The first web-based recombinant vaccine vector database and its data analysis

    Science.gov (United States)

    Deng, Shunzhou; Martin, Carly; Patil, Rasika; Zhu, Felix; Zhao, Bin; Xiang, Zuoshuang; He, Yongqun

    2015-01-01

    A recombinant vector vaccine uses an attenuated virus, bacterium, or parasite as the carrier to express a heterologous antigen(s). Many recombinant vaccine vectors and related vaccines have been developed and extensively investigated. To compare and better understand recombinant vectors and vaccines, we have generated Vaxvec (http://www.violinet.org/vaxvec), the first web-based database that stores various recombinant vaccine vectors and those experimentally verified vaccines that use these vectors. Vaxvec has now included 59 vaccine vectors that have been used in 196 recombinant vector vaccines against 66 pathogens and cancers. These vectors are classified to 41 viral vectors, 15 bacterial vectors, 1 parasitic vector, and 1 fungal vector. The most commonly used viral vaccine vectors are double-stranded DNA viruses, including herpesviruses, adenoviruses, and poxviruses. For example, Vaxvec includes 63 poxvirus-based recombinant vaccines for over 20 pathogens and cancers. Vaxvec collects 30 recombinant vector influenza vaccines that use 17 recombinant vectors and were experimentally tested in 7 animal models. In addition, over 60 protective antigens used in recombinant vector vaccines are annotated and analyzed. User-friendly web-interfaces are available for querying various data in Vaxvec. To support data exchange, the information of vaccine vectors, vaccines, and related information is stored in the Vaccine Ontology (VO). Vaxvec is a timely and vital source of vaccine vector database and facilitates efficient vaccine vector research and development. PMID:26403370

  11. Measuring Surface Deformation in Glacier Retreated Areas Based on Ps-Insar - Geladandong Glacier as a Case Study

    Science.gov (United States)

    Mohamadi, B.; Balz, T.

    2018-04-01

    Glaciers are retreating in many parts of the world as a result of global warming. Many researchers consider Qinghai-Tibetan Plateau as a reference for climate change by measuring glaciers retreat on the plateau. This retreat resulted in some topographic changes in retreated areas, and in some cases can lead to geohazards as landslides, and rock avalanches, which is known in glacier retreated areas as paraglacial slope failure (PSF). In this study, Geladandong biggest and main glacier mass was selected to estimate surface deformation on its glacier retreated areas and define potential future PSF based on PS-InSAR technique. 56 ascending and 49 descending images were used to fulfill this aim. Geladandong glacier retreated areas were defined based on the maximum extent of the glacier in the little ice age. Results revealed a general uplift in the glacier retreated areas with velocity less than 5mm/year. Obvious surface motion was revealed in seven parts surround glacier retreated areas with high relative velocity reached ±60mm/year in some parts. Four parts were considered as PSF potential motion, and two of them showed potential damage for the main road in the study area in case of rock avalanche into recent glacier lakes that could result in glacier lake outburst flooding heading directly to the road. Finally, further analysis and field investigations are needed to define the main reasons for different types of deformation and estimate future risks of these types of surface motion in the Qinghai-Tibetan Plateau.

  12. Studies on semiconductors based on InP with sub-ps response times

    International Nuclear Information System (INIS)

    Biermann, K.

    2007-01-01

    The present work describes investigation of new material concepts accomplished using molecular-beam-epitaxy (MBE) growth for application in ultra-fast photonic components. Nominally undoped and Be doped GaInAs/AlInAs multiple-quantumwell structures (MQW) were grown by MBE at growth temperatures down to 100 C (LT-MBE) on semi-insulating InP substrates. Crystalline, electric and optical properties of as-grown and annealed structures were investigated. Energy states near the conduction band of GaInAs determine the electrical and optical properties of LT-MQWs. The dynamics of charge carrier relaxation was studied by means of pump and probe experiments. Measurements of the differential transmission when excited by an additional cw laser and measurements utilizing two closely sequenced pump pulses support the capability of Be doped as-grown (annealed) LT GaInAs/AlInAs MQW structures for use in optical switches at switching frequencies in the 1 Tbit/s (250 Gbit/s) range. The voltage-induced change of interband transmission of InP based quantumcascade-lasers (QCL) during pulsed mode operation was analyzed by means of 8 band k.p calculations. The impacts of varying charge carrier distributions and of electrically heated samples can be neglected compared to the dominating effect of the electrical field on the interband transmission. The impact of MBE growth parameters on the interface quality of AlAsSb/ GaInAs heterostructures were determined by means of Hall measurements, temperature- and intensity-dependent PL measurements and spectral measurements of the interband- and intersubband-absorption. The impact of In segregation and Sb diffusion on the intersubband absorption was analyzed on the basis of bandstructure calculations. Intersubband transitions at wavelengths of about 1.8 μm (1.55 μm) were successfully achieved in MQW (coupled QW) structures. (orig.)

  13. School-Based Influenza Vaccination: Health and Economic Impact of Maine's 2009 Influenza Vaccination Program.

    Science.gov (United States)

    Basurto-Dávila, Ricardo; Meltzer, Martin I; Mills, Dora A; Beeler Asay, Garrett R; Cho, Bo-Hyun; Graitcer, Samuel B; Dube, Nancy L; Thompson, Mark G; Patel, Suchita A; Peasah, Samuel K; Ferdinands, Jill M; Gargiullo, Paul; Messonnier, Mark; Shay, David K

    2017-12-01

    To estimate the societal economic and health impacts of Maine's school-based influenza vaccination (SIV) program during the 2009 A(H1N1) influenza pandemic. Primary and secondary data covering the 2008-09 and 2009-10 influenza seasons. We estimated weekly monovalent influenza vaccine uptake in Maine and 15 other states, using difference-in-difference-in-differences analysis to assess the program's impact on immunization among six age groups. We also developed a health and economic Markov microsimulation model and conducted Monte Carlo sensitivity analysis. We used national survey data to estimate the impact of the SIV program on vaccine coverage. We used primary data and published studies to develop the microsimulation model. The program was associated with higher immunization among children and lower immunization among adults aged 18-49 years and 65 and older. The program prevented 4,600 influenza infections and generated $4.9 million in net economic benefits. Cost savings from lower adult vaccination accounted for 54 percent of the economic gain. Economic benefits were positive in 98 percent of Monte Carlo simulations. SIV may be a cost-beneficial approach to increase immunization during pandemics, but programs should be designed to prevent lower immunization among nontargeted groups. © Health Research and Educational Trust.

  14. Trial watch: Naked and vectored DNA-based anticancer vaccines.

    Science.gov (United States)

    Bloy, Norma; Buqué, Aitziber; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-05-01

    One type of anticancer vaccine relies on the administration of DNA constructs encoding one or multiple tumor-associated antigens (TAAs). The ultimate objective of these preparations, which can be naked or vectored by non-pathogenic viruses, bacteria or yeast cells, is to drive the synthesis of TAAs in the context of an immunostimulatory milieu, resulting in the (re-)elicitation of a tumor-targeting immune response. In spite of encouraging preclinical results, the clinical efficacy of DNA-based vaccines employed as standalone immunotherapeutic interventions in cancer patients appears to be limited. Thus, efforts are currently being devoted to the development of combinatorial regimens that allow DNA-based anticancer vaccines to elicit clinically relevant immune responses. Here, we discuss recent advances in the preclinical and clinical development of this therapeutic paradigm.

  15. Effect of School-based Human Papillomavirus (HPV) Vaccination on ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    assessed girls' knowledge of cervical cancer and HPV vaccine, and their acceptance of future vaccination of ... studies involve parents and young adults. The ... vaccine was delivered during the routine Child ... and attitudes about the vaccine.

  16. Updates on the web-based VIOLIN vaccine database and analysis system.

    Science.gov (United States)

    He, Yongqun; Racz, Rebecca; Sayers, Samantha; Lin, Yu; Todd, Thomas; Hur, Junguk; Li, Xinna; Patel, Mukti; Zhao, Boyang; Chung, Monica; Ostrow, Joseph; Sylora, Andrew; Dungarani, Priya; Ulysse, Guerlain; Kochhar, Kanika; Vidri, Boris; Strait, Kelsey; Jourdian, George W; Xiang, Zuoshuang

    2014-01-01

    The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, >10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 'virmugens', a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.

  17. Ontology-Based Vaccine Adverse Event Representation and Analysis.

    Science.gov (United States)

    Xie, Jiangan; He, Yongqun

    2017-01-01

    Vaccine is the one of the greatest inventions of modern medicine that has contributed most to the relief of human misery and the exciting increase in life expectancy. In 1796, an English country physician, Edward Jenner, discovered that inoculating mankind with cowpox can protect them from smallpox (Riedel S, Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center) 18(1):21, 2005). Based on the vaccination worldwide, we finally succeeded in the eradication of smallpox in 1977 (Henderson, Vaccine 29:D7-D9, 2011). Other disabling and lethal diseases, like poliomyelitis and measles, are targeted for eradication (Bonanni, Vaccine 17:S120-S125, 1999).Although vaccine development and administration are tremendously successful and cost-effective practices to human health, no vaccine is 100% safe for everyone because each person reacts to vaccinations differently given different genetic background and health conditions. Although all licensed vaccines are generally safe for the majority of people, vaccinees may still suffer adverse events (AEs) in reaction to various vaccines, some of which can be serious or even fatal (Haber et al., Drug Saf 32(4):309-323, 2009). Hence, the double-edged sword of vaccination remains a concern.To support integrative AE data collection and analysis, it is critical to adopt an AE normalization strategy. In the past decades, different controlled terminologies, including the Medical Dictionary for Regulatory Activities (MedDRA) (Brown EG, Wood L, Wood S, et al., Drug Saf 20(2):109-117, 1999), the Common Terminology Criteria for Adverse Events (CTCAE) (NCI, The Common Terminology Criteria for Adverse Events (CTCAE). Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html . Access on 7 Oct 2015), and the World Health Organization (WHO) Adverse Reactions Terminology (WHO-ART) (WHO, The WHO Adverse Reaction Terminology - WHO-ART. Available from: https://www.umc-products.com/graphics/28010.pdf

  18. In vivo quantitative whole-brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel-based and atlas-based methods

    International Nuclear Information System (INIS)

    Qin, Yuan-Yuan; Li, Mu-Wei; Oishi, Kenichi; Zhang, Shun; Zhang, Yan; Zhao, Ling-Yun; Zhu, Wen-Zhen; Lei, Hao

    2013-01-01

    Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model. VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy. Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p 0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen. This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the feasibility of applying whole-brain analysis methods to the investigation of an AD mouse model. (orig.)

  19. Current advances in the generation of human iPS cells: implications in cell-based regenerative medicine.

    Science.gov (United States)

    Revilla, Ana; González, Clara; Iriondo, Amaia; Fernández, Bárbara; Prieto, Cristina; Marín, Carlos; Liste, Isabel

    2016-11-01

    Over the last few years, the generation of induced pluripotent stem cells (iPSCs) from human somatic cells has proved to be one of the most potentially useful discoveries in regenerative medicine. iPSCs are becoming an invaluable tool to study the pathology of different diseases and for drug screening. However, several limitations still affect the possibility of applying iPS cell-based technology in therapeutic prospects. Most strategies for iPSCs generation are based on gene delivery via retroviral or lentiviral vectors, which integrate into the host's cell genome, causing a remarkable risk of insertional mutagenesis and oncogenic transformation. To avoid such risks, significant advances have been made with non-integrative reprogramming strategies. On the other hand, although many different kinds of somatic cells have been employed to generate iPSCs, there is still no consensus about the ideal type of cell to be reprogrammed. In this review we present the recent advances in the generation of human iPSCs, discussing their advantages and limitations in terms of safety and efficiency. We also present a selection of somatic cell sources, considering their capability to be reprogrammed and tissue accessibility. From a translational medicine perspective, these two topics will provide evidence to elucidate the most suitable combination of reprogramming strategy and cell source to be applied in each human iPSC-based therapy. The wide variety of diseases this technology could treat opens a hopeful future for regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  20. In vivo quantitative whole-brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel-based and atlas-based methods

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Yuan-Yuan [Huazhong University of Science and Technology, Department of Radiology, Tongji Hospital, Tongji Medical College, Wuhan (China); The Johns Hopkins University School of Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Li, Mu-Wei; Oishi, Kenichi [The Johns Hopkins University School of Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Zhang, Shun; Zhang, Yan; Zhao, Ling-Yun; Zhu, Wen-Zhen [Huazhong University of Science and Technology, Department of Radiology, Tongji Hospital, Tongji Medical College, Wuhan (China); Lei, Hao [Chinese Academy of Sciences, Wuhan Center for Magnetic Resonance, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Wuhan (China)

    2013-08-15

    Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model. VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy. Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p < 0.05, corrected). The average kappa value between manual and atlas-based structure delineation was approximately 0.8, and there was no significant difference between APP/PS1 and WT mice (p > 0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen. This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the

  1. A potential disruptive technology in vaccine development: gene-based vaccines and their application to infectious diseases.

    Science.gov (United States)

    Kaslow, David C

    2004-10-01

    Vaccine development requires an amalgamation of disparate disciplines and has unique economic and regulatory drivers. Non-viral gene-based delivery systems, such as formulated plasmid DNA, are new and potentially disruptive technologies capable of providing 'cheaper, simpler, and more convenient-to-use' vaccines. Typically and somewhat ironically, disruptive technologies have poorer product performance, at least in the near-term, compared with the existing conventional technologies. Because successful product development requires that the product's performance must meet or exceed the efficacy threshold for a desired application, the appropriate selection of the initial product applications for a disruptive technology is critical for its successful evolution. In this regard, the near-term successes of gene-based vaccines will likely be for protection against bacterial toxins and acute viral and bacterial infections. Recent breakthroughs, however, herald increasing rather than languishing performance improvements in the efficacy of gene-based vaccines. Whether gene-based vaccines ultimately succeed in eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria and tuberculosis, for which the conventional vaccine technologies have failed, remains to be determined. A success against any one of the persistent intracellular pathogens would be sufficient proof that gene-based vaccines represent a disruptive technology against which future vaccine technologies will be measured.

  2. MEASURING SURFACE DEFORMATION IN GLACIER RETREATED AREAS BASED ON PS-INSAR – GELADANDONG GLACIER AS A CASE STUDY

    Directory of Open Access Journals (Sweden)

    B. Mohamadi

    2018-04-01

    Full Text Available Glaciers are retreating in many parts of the world as a result of global warming. Many researchers consider Qinghai-Tibetan Plateau as a reference for climate change by measuring glaciers retreat on the plateau. This retreat resulted in some topographic changes in retreated areas, and in some cases can lead to geohazards as landslides, and rock avalanches, which is known in glacier retreated areas as paraglacial slope failure (PSF. In this study, Geladandong biggest and main glacier mass was selected to estimate surface deformation on its glacier retreated areas and define potential future PSF based on PS-InSAR technique. 56 ascending and 49 descending images were used to fulfill this aim. Geladandong glacier retreated areas were defined based on the maximum extent of the glacier in the little ice age. Results revealed a general uplift in the glacier retreated areas with velocity less than 5mm/year. Obvious surface motion was revealed in seven parts surround glacier retreated areas with high relative velocity reached ±60mm/year in some parts. Four parts were considered as PSF potential motion, and two of them showed potential damage for the main road in the study area in case of rock avalanche into recent glacier lakes that could result in glacier lake outburst flooding heading directly to the road. Finally, further analysis and field investigations are needed to define the main reasons for different types of deformation and estimate future risks of these types of surface motion in the Qinghai-Tibetan Plateau.

  3. Are Clade Specific HIV Vaccines a Necessity? An Analysis Based on Mathematical Models

    Directory of Open Access Journals (Sweden)

    Dobromir Dimitrov

    2015-12-01

    Full Text Available As HIV-1 envelope immune responses are critical to vaccine related protection, most candidate HIV vaccines entering efficacy trials are based upon a clade specific design. This need for clade specific vaccine prototypes markedly reduces the implementation of potentially effective HIV vaccines. We utilized a mathematical model to determine the effectiveness of immediate roll-out of a non-clade matched vaccine with reduced efficacy compared to constructing clade specific vaccines, which would take considerable time to manufacture and test in safety and efficacy trials. We simulated the HIV epidemic in San Francisco (SF and South Africa (SA and projected effectiveness of three vaccination strategies: i immediate intervention with a 20–40% vaccine efficacy (VE non-matched vaccine, ii delayed intervention by developing a 50% VE clade-specific vaccine, and iii immediate intervention with a non-matched vaccine replaced by a clade-specific vaccine when developed. Immediate vaccination with a non-clade matched vaccine, even with reduced efficacy, would prevent thousands of new infections in SF and millions in SA over 30 years. Vaccination with 50% VE delayed for five years needs six and 12 years in SA to break-even with immediate 20 and 30% VE vaccination, respectively, while not able to surpass the impact of immediate 40% VE vaccination over 30 years. Replacing a 30% VE with a 50% VE vaccine after 5 years reduces the HIV acquisition by 5% compared to delayed vaccination. The immediate use of an HIV vaccine with reduced VE in high risk communities appears desirable over a short time line but higher VE should be the pursued to achieve strong long-term impact. Our analysis illustrates the importance of developing surrogate markers (correlates of protection to allow bridging types of immunogenicity studies to support more rapid assessment of clade specific vaccines.

  4. Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

    Science.gov (United States)

    Oyarzún, Patricio; Kobe, Bostjan

    2016-03-03

    Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

  5. Oral Modeling of an Adenovirus-Based Quadrivalent Influenza Vaccine in Ferrets and Mice.

    Science.gov (United States)

    Scallan, Ciaran D; Lindbloom, Jonathan D; Tucker, Sean N

    2016-06-01

    Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required. In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets. We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine. The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines. Vaxart, Inc.

  6. Parameter optimization toward optimal microneedle-based dermal vaccination.

    Science.gov (United States)

    van der Maaden, Koen; Varypataki, Eleni Maria; Yu, Huixin; Romeijn, Stefan; Jiskoot, Wim; Bouwstra, Joke

    2014-11-20

    Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles. Microneedles are used to deliver a drug into the skin in a minimally-invasive and potentially pain free manner. Besides, the skin is a potent immune organ that is highly suitable for vaccination. However, there are several factors that influence the penetration ability of the skin by microneedles and the immune responses upon microneedle-based immunization. In this study we assessed several different microneedle arrays for their ability to penetrate ex vivo human skin by using trypan blue and (fluorescently or radioactively labeled) ovalbumin. Next, these different microneedles and several factors, including the dose of ovalbumin, the effect of using an impact-insertion applicator, skin location of microneedle application, and the area of microneedle application, were tested in vivo in mice. The penetration ability and the dose of ovalbumin that is delivered into the skin were shown to be dependent on the use of an applicator and on the microneedle geometry and size of the array. Besides microneedle penetration, the above described factors influenced the immune responses upon microneedle-based vaccination in vivo. It was shown that the ovalbumin-specific antibody responses upon microneedle-based vaccination could be increased up to 12-fold when an impact-insertion applicator was used, up to 8-fold when microneedles were applied over a larger surface area, and up to 36-fold dependent on the location of microneedle application. Therefore, these influencing factors should be considered to optimize microneedle-based dermal immunization technologies. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. A microprocessor-based system for continuous monitoring of radiation levels around the CERN PS and PSB accelerators

    Science.gov (United States)

    Agoritsas, V.; Beck, F.; Benincasa, G. P.; Bovigny, J. P.

    1986-06-01

    This paper describes a new beam loss monitor system which has been installed in the PS and PSB machines, replacing an earlier system. The new system is controlled by a microprocessor which can operate independently of the accelerator control system, though setting up and central display are usually done remotely, using the standard control system facilities.

  8. Microprocessor-based system for continuous monitoring of radiation levels around the CERN PS and PSB accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Agoritsas, V.; Beck, F.; Benincasa, G.P.; Bovigny, J.P.

    1986-06-01

    This paper describes a new beam loss monitor system which has been installed in the PS and PSB machines, replacing an earlier system. The new system is controlled by a microprocessor which can operate independently of the accelerator control system, though setting up and central display are usually done remotely, using the standard control system facilities.

  9. An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

    Directory of Open Access Journals (Sweden)

    Aiala Salvador

    2011-01-01

    Full Text Available The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity.

  10. PS Booster - Festive colloquium

    CERN Multimedia

    2012-01-01

    A festive colloquium will be held to celebrate the 40th anniversary of the PS Booster on Friday, 28 September at 2 p.m. in the CERN council chamber. The meeting will be open to everybody. Read more on the PS Booster in the CERN Bulletin and in the CERN Courier.

  11. Novel Vaccine Against Mycoplasma Hyosynoviae: The Immunogenic Effect of Iscom-Based Vaccines in Swine

    DEFF Research Database (Denmark)

    Lauritsen, Klara Tølbøll; Vinther Heydenreich, Annette; Riber, Ulla

    Arthritis in swine is frequently caused by Mycoplasma hyosynoviae (Mhs). For the development of an effective vaccine we investigated the immunogenic effect of three vaccine preparations with the ISCOM adjuvant Posintro™ from Nordic Vaccine. A: formalin fixed whole-cells Mhs (300 µg/dose) mixed...... with Posintro, B: Deoxycholate extracted lipoproteins from Mhs organisms (DOC-antigen, 300 μg/dose) in Posintro and C: DOC-antigen (50 μg/dose) in Posintro. Each vaccine-group contained three pigs. Vaccinations (i.m.) were performed at 12 and 15 weeks of age. The development of specific IgG and secretion...... of IFNγ were measured. Three weeks after the second vaccination, pigs were euthanised and autopsied. Vaccine B induced a high level of specific serum IgG in all pigs a week after boost. Vaccine C gave a variable response after boost, with two pigs seroconverting, while no response was seen by vaccine A...

  12. Tipping the Proteome with Gene-Based Vaccines: Weighing in on the Role of Nano materials

    International Nuclear Information System (INIS)

    Flores, K.J.; Craig, M.; Smith, J.J.; DeLong, R.K.; Wanekaya, A.; Dong, L.

    2012-01-01

    Since the first generation of DNA vaccines was introduced in 1988, remarkable improvements have been made to improve their efficacy and immunogenicity. Although human clinical trials have shown that delivery of DNA vaccines is well tolerated and safe, the potency of these vaccines in humans is somewhat less than optimal. The development of a gene-based vaccine that was effective enough to be approved for clinical use in humans would be one of, if not the most important, advance in vaccines to date. This paper highlights the literature relating to gene-based vaccines, specifically DNA vaccines, and suggests possible approaches to boost their performance. In addition, we explore the idea that combining RNA and nano materials may hold the key to successful gene-based vaccines for prevention and treatment of disease

  13. School-based human papillomavirus vaccination: An opportunity to ...

    African Journals Online (AJOL)

    cational drive to improve knowledge and screening of mothers can be successful ... invited to sign consent and assent for the girl child to be vaccinated, and all mothers were .... view of the positive attitudes towards vaccines in general, vaccine.

  14. Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG-ps) in patients receiving palliative chemotherapy for gastroesophageal cancer.

    Science.gov (United States)

    Crumley, Andrew B C; Stuart, Robert C; McKernan, Margaret; McDonald, Alexander C; McMillan, Donald C

    2008-08-01

    The aim of the present study was to compare an inflammation-based prognostic score (Glasgow Prognostic Score, GPS) with performance status (ECOG-ps) in patients receiving platinum-based chemotherapy for palliation of gastroesophageal cancer. Sixty-five patients presenting with gastroesophageal carcinoma to the Royal Infirmary, Glasgow between January 1999 and December 2005 and who received palliative chemotherapy or chemo-radiotherapy were studied. ECOG-ps, C-reactive protein, and albumin were recorded at diagnosis. Patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (L) were allocated a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS of 1 and patients with a normal C-reactive protein and albumin were allocated a score of 0. Toxicity was recorded using the Common Toxicity Criteria. The minimum follow up was 14 months. During the follow-up period, 59 (91%) of the patients died. On univariate and multivariate survival analysis, only the GPS (hazard ratios 1.65, 95% CI 1.10-2.47, P GPS of 0, those patients with a GPS of 1 or 2 required more frequent chemotherapy dose reduction (P GPS, appears to be superior to the subjective assessment of performance status (ECOG-ps) in predicting the response to platinum-based chemotherapy in patients with advanced gastroesophageal cancer.

  15. Strengthening vaccination policies in Latin America: an evidence-based approach.

    Science.gov (United States)

    Tapia-Conyer, Roberto; Betancourt-Cravioto, Miguel; Saucedo-Martínez, Rodrigo; Motta-Murguía, Lourdes; Gallardo-Rincón, Héctor

    2013-08-20

    Despite many successes in the region, Latin American vaccination policies have significant shortcomings, and further work is needed to maintain progress and prepare for the introduction of newly available vaccines. In order to address the challenges facing Latin America, the Commission for the Future of Vaccines in Latin America (COFVAL) has made recommendations for strengthening evidence-based policy-making and reducing regional inequalities in immunisation. We have conducted a comprehensive literature review to assess the feasibility of these recommendations. Standardisation of performance indicators for disease burden, vaccine coverage, epidemiological surveillance and national health resourcing can ensure comparability of the data used to assess vaccination programmes, allowing deeper analysis of how best to provide services. Regional vaccination reference schemes, as used in Europe, can be used to develop best practice models for vaccine introduction and scheduling. Successful models exist for the continuous training of vaccination providers and decision-makers, with a new Latin American diploma aiming to contribute to the successful implementation of vaccination programmes. Permanent, independent vaccine advisory committees, based on the US Advisory Committee on Immunization Practices (ACIP), could facilitate the uptake of new vaccines and support evidence-based decision-making in the administration of national immunisation programmes. Innovative financing mechanisms for the purchase of new vaccines, such as advance market commitments and cost front-loading, have shown potential for improving vaccine coverage. A common regulatory framework for vaccine approval is needed to accelerate delivery and pool human, technological and scientific resources in the region. Finally, public-private partnerships between industry, government, academia and non-profit sectors could provide new investment to stimulate vaccine development in the region, reducing prices in the

  16. Experimental demonstration of wavelength conversion between ps-pulses based on cascaded sum- and difference frequency generation (SFG+DFG) in LiNbO3 waveguides

    Science.gov (United States)

    Wang, Jian; Sun, Junqiang; Lou, Chuanhong; Sun, Qizhen

    2005-09-01

    All-optical wavelength conversion between ps-pulses based on cascaded sum- and difference frequency generation (SFG+DFG) is proposed and experimentally demonstrated in periodically poled LiNbO3 (PPLN) waveguides. The signal pulse with 40-GHz repetition rate and 1.57- ps pulse width is adopted. The converted idler wavelength can be tuned from 1527.4 to 1540.5nm as the signal wavelength is varied from 1561.9 to 1548.4nm. No obvious changes of the pulse shape and width, also no chirp are observed in the converted idler pulse. The results imply that single-to-multiple channel wavelength conversions can be achieved by appropriately tuning the two pump wavelengths.

  17. A population-based evaluation of a publicly funded, school-based HPV vaccine program in British Columbia, Canada: parental factors associated with HPV vaccine receipt.

    Science.gov (United States)

    Ogilvie, Gina; Anderson, Maureen; Marra, Fawziah; McNeil, Shelly; Pielak, Karen; Dawar, Meena; McIvor, Marilyn; Ehlen, Thomas; Dobson, Simon; Money, Deborah; Patrick, David M; Naus, Monika

    2010-05-04

    Information on factors that influence parental decisions for actual human papillomavirus (HPV) vaccine receipt in publicly funded, school-based HPV vaccine programs for girls is limited. We report on the level of uptake of the first dose of the HPV vaccine, and determine parental factors associated with receipt of the HPV vaccine, in a publicly funded school-based HPV vaccine program in British Columbia, Canada. All parents of girls enrolled in grade 6 during the academic year of September 2008-June 2009 in the province of British Columbia were eligible to participate. Eligible households identified through the provincial public health information system were randomly selected and those who consented completed a validated survey exploring factors associated with HPV vaccine uptake. Bivariate and multivariate analyses were conducted to calculate adjusted odds ratios to identify the factors that were associated with parents' decision to vaccinate their daughter(s) against HPV. 2,025 parents agreed to complete the survey, and 65.1% (95% confidence interval [CI] 63.1-67.1) of parents in the survey reported that their daughters received the first dose of the HPV vaccine. In the same school-based vaccine program, 88.4% (95% CI 87.1-89.7) consented to the hepatitis B vaccine, and 86.5% (95% CI 85.1-87.9) consented to the meningococcal C vaccine. The main reasons for having a daughter receive the HPV vaccine were the effectiveness of the vaccine (47.9%), advice from a physician (8.7%), and concerns about daughter's health (8.4%). The main reasons for not having a daughter receive the HPV vaccine were concerns about HPV vaccine safety (29.2%), preference to wait until the daughter is older (15.6%), and not enough information to make an informed decision (12.6%). In multivariate analysis, overall attitudes to vaccines, the impact of the HPV vaccine on sexual practices, and childhood vaccine history were predictive of parents having a daughter receive the HPV vaccine in a

  18. A population-based evaluation of a publicly funded, school-based HPV vaccine program in British Columbia, Canada: parental factors associated with HPV vaccine receipt.

    Directory of Open Access Journals (Sweden)

    Gina Ogilvie

    2010-05-01

    Full Text Available BACKGROUND: Information on factors that influence parental decisions for actual human papillomavirus (HPV vaccine receipt in publicly funded, school-based HPV vaccine programs for girls is limited. We report on the level of uptake of the first dose of the HPV vaccine, and determine parental factors associated with receipt of the HPV vaccine, in a publicly funded school-based HPV vaccine program in British Columbia, Canada. METHODS AND FINDINGS: All parents of girls enrolled in grade 6 during the academic year of September 2008-June 2009 in the province of British Columbia were eligible to participate. Eligible households identified through the provincial public health information system were randomly selected and those who consented completed a validated survey exploring factors associated with HPV vaccine uptake. Bivariate and multivariate analyses were conducted to calculate adjusted odds ratios to identify the factors that were associated with parents' decision to vaccinate their daughter(s against HPV. 2,025 parents agreed to complete the survey, and 65.1% (95% confidence interval [CI] 63.1-67.1 of parents in the survey reported that their daughters received the first dose of the HPV vaccine. In the same school-based vaccine program, 88.4% (95% CI 87.1-89.7 consented to the hepatitis B vaccine, and 86.5% (95% CI 85.1-87.9 consented to the meningococcal C vaccine. The main reasons for having a daughter receive the HPV vaccine were the effectiveness of the vaccine (47.9%, advice from a physician (8.7%, and concerns about daughter's health (8.4%. The main reasons for not having a daughter receive the HPV vaccine were concerns about HPV vaccine safety (29.2%, preference to wait until the daughter is older (15.6%, and not enough information to make an informed decision (12.6%. In multivariate analysis, overall attitudes to vaccines, the impact of the HPV vaccine on sexual practices, and childhood vaccine history were predictive of parents having

  19. Increased immunogenicity of recombinant Ad35-based malaria vaccine through formulation with aluminium phosphate adjuvant

    NARCIS (Netherlands)

    Ophorst, Olga J. A. E.; Radosevic, Katarina; Klap, Jaco M.; Sijtsma, Jeroen; Gillissen, Gert; Mintardjo, Ratna; van Ooij, Mark J. M.; Holterman, Lennart; Companjen, Arjen; Goudsmit, Jaap; Havenga, Menzo J. E.

    2007-01-01

    Previously, we have shown the potency of recombinant Adenovirus serotype 35 viral vaccines (rAd35) to induce strong immune response against the circumsporozoite protein (CS) of the plasmodium parasite. To further optimize immunogenicity of Ad35-based malaria vaccines we formulated rAd35.CS vaccine

  20. Learning from Successful School-based Vaccination Clinics during 2009 pH1N1

    Science.gov (United States)

    Klaiman, Tamar; O'Connell, Katherine; Stoto, Michael A.

    2014-01-01

    Background: The 2009 H1N1 vaccination campaign was the largest in US history. State health departments received vaccines from the federal government and sent them to local health departments (LHDs) who were responsible for getting vaccines to the public. Many LHD's used school-based clinics to ensure children were the first to receive limited…

  1. Last PS magnet refurbished

    CERN Multimedia

    2009-01-01

    PS Magnet Refurbishment Programme Completed. The 51st and final refurbished magnet was transported to the PS on Tuesday 3 February. The repair and consolidation work on the PS started back in 2003 when two magnets and a busbar connection were found to be faulty during routine high-voltage tests. The cause of the fault was a combination of age and radiation on electrical insulation. After further investigation the decision was taken to overhaul half of the PS’s 100 magnets to reduce the risk of a similar fault. As from 20 February the PS ring will start a five-week test programme to be ready for operation at the end of March.

  2. Evaluation of near-surface attenuation of S-waves based on PS logging and vertical array seismic observation

    International Nuclear Information System (INIS)

    Kobayashi, Genyu

    2014-01-01

    As a result of the lessons learned from the experience of Kashiwazaki-Kariwa NPP due to the 2007 Niigata Chuetsu Oki Earthquake, it has become clear that a rational method of near-surface attenuation characteristics covering a depth range from engineering bedrock to seismic bedrock urgently needs to be established. JNES performed PS logging and vertical array seismic ground motion observation at a soil ground site (SODB 1. site), sedimentary rock site, and an igneous rock site (SODB 2. site), and proposed an evaluation method of attenuation characteristics (site characteristics) for the deep underground. (author)

  3. Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation.

    Science.gov (United States)

    Renukaradhya, Gourapura J; Narasimhan, Balaji; Mallapragada, Surya K

    2015-12-10

    Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers - 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, is discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Utilization of APPswe/PS1dE9 Transgenic Mice in Research of Alzheimer's Disease: Focus on Gene Therapy and Cell-Based Therapy Applications

    Directory of Open Access Journals (Sweden)

    Tarja Malm

    2011-01-01

    Full Text Available One of the most extensively used transgenic mouse model of Alzheimer’s disease (AD is APPswe/PS1dE9 mice, which over express the Swedish mutation of APP together with PS1 deleted in exon 9. These mice show increase in parenchymal Aβ load with Aβ plaques starting from the age of four months, glial activation, and deficits in cognitive functions at the age of 6 months demonstrated by radial arm water maze and 12-13 months seen with Morris Water Maze test. As gene transfer technology allows the delivery of DNA into target cells to achieve the expression of a protective or therapeutic protein, and stem cell transplantation may create an environment supporting neuronal functions and clearing Aβ plaques, these therapeutic approaches alone or in combination represent potential therapeutic strategies that need to be tested in relevant animal models before testing in clinics. Here we review the current utilization of APPswe/PS1dE9 mice in testing gene transfer and cell transplantation aimed at improving the protection of the neurons against Aβ toxicity and also reducing the brain levels of Aβ. Both gene therapy and cell based therapy may be feasible therapeutic approaches for human AD.

  5. Pre-vaccination care-seeking in females reporting severe adverse reactions to HPV vaccine. A registry based case-control study

    DEFF Research Database (Denmark)

    Mølbak, Kåre; Hansen, Niels Dalum; Valentiner-Branth, Palle

    2016-01-01

    to the DMA of suspected severe adverse reactions.We selected controls without reports of adverse reactions from the Danish vaccination registry and matched by year of vaccination, age of vaccination, and municipality, and obtained from the Danish National Patient Registry and The National Health Insurance...... vaccination programme has declined. The aim of the present study was to determine health care-seeking prior to the first HPV vaccination among females who suspected adverse reactions to HPV vaccine. Methods In this registry-based case-control study, we included as cases vaccinated females with reports...... Service Register the history of health care usage two years prior to the first vaccine. We analysed the data by logistic regression while adjusting for the matching variables. Results The study included 316 cases who received first HPV vaccine between 2006 and 2014. Age range of cases was 11 to 52 years...

  6. Vaccination rates among the general adult population and high-risk groups in the United States.

    Directory of Open Access Journals (Sweden)

    Kathy Annunziata

    Full Text Available BACKGROUND: In order to adequately assess the effectiveness of vaccination in helping to control vaccine-preventable infectious disease, it is important to identify the adherence and uptake of risk-based recommendations. METHODS: The current project includes data from five consecutive datasets of the National Health and Wellness Survey (NHWS: 2007 through 2011. The NHWS is an annual, Internet-based health questionnaire, administered to a nationwide sample of adults (aged 18 or older which included items on vaccination history as well as high-risk group status. Vaccination rates and characteristics of vaccinees were reported descriptively. Logistic regressions were conducted to predict vaccination behavior from sociodemographics and risk-related variables. RESULTS: The influenza vaccination rate for all adults 18 years and older has increased significantly from 28.0% to 36.2% from 2007 to 2011 (ps<.05. Compared with those not at high risk (25.1%, all high-risk groups were vaccinated at a higher rate, from 36.8% (pregnant women to 69.7% (those with renal/kidney disease; however, considerable variability among high-risk groups was observed. Vaccination rates among high-risk groups for other vaccines varied considerably though all were below 50%, with the exception of immunocompromised respondents (57.5% for the hepatitis B vaccine and 52.5% for the pneumococcal vaccine and the elderly (50.4% for the pneumococcal. Multiple risk factors were associated with increased rate of vaccination for most vaccines. Significant racial/ethnic differences with influenza, hepatitis, and herpes zoster vaccination rates were also observed (ps<.05. CONCLUSIONS: Rates of influenza vaccination have increased over time. Rates varied by high-risk status, demographics, and vaccine. There was a pattern of modest vaccination rate increases for individuals with multiple risk factors. However, there were relatively low rates of vaccination for most risk-based recommendations

  7. Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

    Science.gov (United States)

    Golden, Joseph W; Josleyn, Matthew; Mucker, Eric M; Hung, Chien-Fu; Loudon, Peter T; Wu, T C; Hooper, Jay W

    2012-01-01

    Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA). We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

  8. Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Joseph W Golden

    Full Text Available Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA. We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV nonhuman primate (NHP challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

  9. Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus.

    Directory of Open Access Journals (Sweden)

    Chad E Mire

    Full Text Available Ebola virus (EBOV causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (NHPs. Currently, there are no licensed vaccines or therapeutics for human use. Recombinant vesicular stomatitis virus (rVSV-based vaccine vectors, which encode an EBOV glycoprotein in place of the VSV glycoprotein, have shown 100% efficacy against homologous Sudan ebolavirus (SEBOV or Zaire ebolavirus (ZEBOV challenge in NHPs. In addition, a single injection of a blend of three rVSV vectors completely protected NHPs against challenge with SEBOV, ZEBOV, the former Côte d'Ivoire ebolavirus, and Marburg virus. However, recent studies suggest that complete protection against the newly discovered Bundibugyo ebolavirus (BEBOV using several different heterologous filovirus vaccines is more difficult and presents a new challenge. As BEBOV caused nearly 50% mortality in a recent outbreak any filovirus vaccine advanced for human use must be able to protect against this new species. Here, we evaluated several different strategies against BEBOV using rVSV-based vaccines. Groups of cynomolgus macaques were vaccinated with a single injection of a homologous BEBOV vaccine, a single injection of a blended heterologous vaccine (SEBOV/ZEBOV, or a prime-boost using heterologous SEBOV and ZEBOV vectors. Animals were challenged with BEBOV 29-36 days after initial vaccination. Macaques vaccinated with the homologous BEBOV vaccine or the prime-boost showed no overt signs of illness and survived challenge. In contrast, animals vaccinated with the heterologous blended vaccine and unvaccinated control animals developed severe clinical symptoms consistent with BEBOV infection with 2 of 3 animals in each group succumbing. These data show that complete protection against BEBOV will likely require incorporation of BEBOV glycoprotein into the vaccine or employment of a prime-boost regimen. Fortunately, our results demonstrate that heterologous rVSV-based filovirus vaccine

  10. Parents' decision-making regarding vaccinating their children against influenza: A web-based survey.

    Science.gov (United States)

    Flood, Emuella M; Rousculp, Matthew D; Ryan, Kellie J; Beusterien, Kathleen M; Divino, Victoria M; Toback, Seth L; Sasané, Medha; Block, Stan L; Hall, Matthew C; Mahadevia, Parthiv J

    2010-08-01

    Despite the recommendation from the Centers for Disease Control and Prevention that children between the ages of 6 months and 18 years be vaccinated against influenza annually, vaccination rates remain suboptimal. This study was conducted to explore factors that influence parents' decisions regarding influenza vaccination for children aged 2 to 12 years, to quantify the relative importance of these factors, to identify an appropriate theoretical model for illustrating the relationships among these factors, and to characterize parents by their likelihood of vaccinating their children against influenza. A quantitative Web-based survey was administered to a sample of parents from an online panel representative of the US population. Parents were stratified based on self-reported rates of their personal influenza vaccination (every year, sometimes, or never) and the age of their child (2-4 years or 5-12 years). The results were examined by parents' likelihood of vaccinating their child in the next year (high, medium, or low). Participants were asked to rank their agreement with statements representing various beliefs and perceptions about influenza and influenza vaccine on a scale from 1 = strongly agree to 5 = strongly disagree. Parents who indicated that they vaccinate their child every year were asked to select the drivers of their decision to vaccinate; parents who indicated that they never vaccinate their child were asked to select the barriers affecting their decision not to vaccinate; and parents who responded that they sometimes vaccinate their child were asked to select both the drivers and barriers affecting their decision. Participants were then asked to rank the importance of each driver or barrier on a scale from 1 = a little important to 5 = extremely important. Mean agreement ratings were calculated for parents' beliefs and perceptions about influenza and influenza vaccine and were compared across likelihood subgroups. Mean importance ratings of the

  11. The Evolution of the Meningitis Vaccine Project.

    Science.gov (United States)

    Tiffay, Kathleen; Jodar, Luis; Kieny, Marie-Paule; Socquet, Muriel; LaForce, F Marc

    2015-11-15

    In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a "virtual vaccine company," and over the next decade managed a network of public-private and public-public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. The development, through a public-private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  12. Can dendritic cells improve whole cancer cell vaccines based on immunogenically killed cancer cells?

    Science.gov (United States)

    Cicchelero, Laetitia; Denies, Sofie; Devriendt, Bert; de Rooster, Hilde; Sanders, Niek N

    2015-01-01

    Immunogenic cell death (ICD) offers interesting opportunities in cancer cell (CC) vaccine manufacture, as it increases the immunogenicity of the dead CC. Furthermore, fusion of CCs with dendritic cells (DCs) is considered a superior method for generating whole CC vaccines. Therefore, in this work, we determined in naive mice whether immunogenically killed CCs per se (CC vaccine) elicit an antitumoral immune response different from the response observed when immunogenically killed CCs are associated with DCs through fusion (fusion vaccine) or through co-incubation (co-incubation vaccine). After tumor inoculation, the type of immune response in the prophylactically vaccinated mice differed between the groups. In more detail, fusion vaccines elicited a humoral anticancer response, whereas the co-incubation and CC vaccine mainly induced a cellular response. Despite these differences, all three approaches offered a prophylactic protection against tumor development in the murine mammary carcinoma model. In summary, it can be concluded that whole CC vaccines based on immunogenically killed CCs may not necessarily require association with DCs to elicit a protective anticancer immune response. If this finding can be endorsed in other cancer models, the manufacture of CC vaccines would greatly benefit from this new insight, as production of DC-based vaccines is laborious, time-consuming and expensive. PMID:26587315

  13. From non school-based, co-payment to school-based, free Human Papillomavirus vaccination in Flanders (Belgium): A retrospective cohort study describing vaccination coverage, age-specific coverage and socio-economic inequalities

    OpenAIRE

    Lefevere, Eva; Theeten, Heidi; Hens, Niel; De Smet, Frank; Top, Geert; Van Damme, Pierre

    2015-01-01

    School-based, free HPV vaccination for girls in the first year of secondary school was introduced in Flanders (Belgium) in 2010. Before that, non school-based, co-payment vaccination for girls aged 12-18 was in place. We compared vaccination coverage, age-specific coverage and socio-economic inequalities in coverage -3 important parameters contributing to the effectiveness of the vaccination programs - under both vaccination systems. We used retrospective administrative data from different so...

  14. Efficacy, Safety, and Interactions of a Live Infectious Bursal Disease Virus Vaccine for Chickens Based on Strain IBD V877.

    Science.gov (United States)

    Geerligs, Harm J; Ons, Ellen; Boelm, Gert Jan; Vancraeynest, Dieter

    2015-03-01

    Infectious bursal disease (IBD) is a highly contagious disease in young chickens which can result in high morbidity and mortality and also in great economic losses. The main target for the virus is the lymphoid tissue with a special predilection for the bursa of Fabricius. Several vaccines are available to control the disease. Intermediate plus vaccines are used in chickens with high maternal antibody titers which face high infection pressure. An example of an intermediate plus vaccine is a live vaccine based on IBD strain V877. The results of an efficacy study in commercial broilers with different levels of maternally derived antibodies (MDA) showed that the V877-based IBD vaccine can break through maternal antibody titers of higher than 1100 as determined by an IBD ELISA. The safety of the vaccine was demonstrated in a study in which specific-pathogen-free (SPF) chickens were vaccinated with a tenfold dose of the vaccine strain and a tenfold dose of the vaccine strain after five back passages in SPF chickens. The vaccine virus caused lesions, as could be expected for an intermediate plus vaccine, but the scores were not much higher than the maximal scores allowed for mild IBD vaccines in the European Pharmacopoeia, and reversion to virulence was absent. In studies in SPF chickens, there were no negative impacts by the IBD V877 vaccine on the efficacy of a live QX-like IB vaccine and a live Newcastle disease La Sota vaccine in vaccination challenge studies, although the IBD vaccine had a negative effect on the antibody response generated by the QX-like IB vaccine. It is concluded that the IBD V877 vaccine has the capacity to break through high levels of MDA, has a satisfactory safety profile, and interactions with other live vaccines are limited. In order to limit bursal lesions after vaccination it is recommended to confirm the presence of MDA before vaccinating with the V877 vaccine.

  15. Print News Coverage of School-Based HPV Vaccine Mandate

    Science.gov (United States)

    Casciotti, Dana; Smith, Katherine C.; Andon, Lindsay; Vernick, Jon; Tsui, Amy; Klassen, Ann C.

    2015-01-01

    BACKGROUND In 2007, legislation was proposed in 24 states and the District of Columbia for school-based HPV vaccine mandates, and mandates were enacted in Texas, Virginia, and the District of Columbia. Media coverage of these events was extensive, and media messages both reflected and contributed to controversy surrounding these legislative activities. Messages communicated through the media are an important influence on adolescent and parent understanding of school-based vaccine mandates. METHODS We conducted structured text analysis of newspaper coverage, including quantitative analysis of 169 articles published in mandate jurisdictions from 2005-2009, and qualitative analysis of 63 articles from 2007. Our structured analysis identified topics, key stakeholders and sources, tone, and the presence of conflict. Qualitative thematic analysis identified key messages and issues. RESULTS Media coverage was often incomplete, providing little context about cervical cancer or screening. Skepticism and autonomy concerns were common. Messages reflected conflict and distrust of government activities, which could negatively impact this and other youth-focused public health initiatives. CONCLUSIONS If school health professionals are aware of the potential issues raised in media coverage of school-based health mandates, they will be more able to convey appropriate health education messages, and promote informed decision-making by parents and students. PMID:25099421

  16. Rotavirus vaccines

    Directory of Open Access Journals (Sweden)

    Kang G

    2006-01-01

    Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.

  17. Nanostructured silicate substituted calcium phosphate (NanoSiCaPs) nanoparticles — Efficient calcium phosphate based non-viral gene delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Shekhar, Sudhanshu [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Center for Complex Engineered Multifunctional Materials, University of Pittsburgh, Pittsburgh, PA 15261 (United States); McGowan Institute of Regenerative Medicine, University of Pittsburgh, PA 15261 (United States); Roy, Abhijit; Hong, Daeho [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Kumta, Prashant N., E-mail: pkumta@pitt.edu [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Center for Complex Engineered Multifunctional Materials, University of Pittsburgh, Pittsburgh, PA 15261 (United States); McGowan Institute of Regenerative Medicine, University of Pittsburgh, PA 15261 (United States)

    2016-12-01

    Nanostructured ceramic particles, particularly, nanoparticles of calcium phosphate (CaP) remain an attractive option among the various types of non-viral gene delivery vectors studied because of their safety, biocompatibility, biodegradability, and ease of handling as well as their adsorptive capacity for DNA. We have accordingly developed an enhanced version of nanostructured calcium phosphates (NanoCaPs), by substituting known amounts of silicate for phosphate in the hydroxyapatite (HA) lattice (NanoSiCaPs). Results indicate that in addition to the excellent transfection levels exhibited by un-substituted NanoCaPs alone in vitro, an additional 20–50% increase in transfection is observed for NanoCaPs containing 8.3–50 mol% silicate aptly called NanoSiCaPs, owing to its rapid dissolution properties enabling nanoparticles escaping the lysosomal degradation. However, high silicate substitution (> 50 mol%) resulted in a drastic decline in transfection as the synthesized NanoCaPs deviated far from the characteristic hydroxyapatite phase formed as evidenced by the materials characterization results. - Highlights: • Successful demonstration of nanostructured NanoSiCaPs formation • Demonstration of superior transfection of NanoSiCaPs contrasted to NanoCaPs • Silicate substitution leads to smaller aggregates of nanoparticle complexes. • Enhanced dissolution of NanoSiCaPs demonstrated • Faster NanoSiCaPs dissolution leads to escape of pDNA from lysosomal degradation.

  18. PS Control Room

    CERN Multimedia

    CERN PhotoLab

    1963-01-01

    The good old PS Control Room, all manual. For each parameter, a knob or a button to control it; for each, a light or meter or oscilloscope to monitor it; carefully written pages serve as the data bank; phones and intercom for communication. D.Dekkers is at the microphone, M.Valvini sits in front.

  19. PS auxiliary magnet

    CERN Multimedia

    CERN PhotoLab

    1974-01-01

    Units of the PS auxiliary magnet system. The picture shows how the new dipoles, used for vertical and horizontal high-energy beam manipulation, are split for installation and removal so that it is not necessary to break the accelerator vacuum. On the right, adjacent to the sector valve and the windings of the main magnet, is an octupole of the set.

  20. In silico-based vaccine design against Ebola virus glycoprotein

    Directory of Open Access Journals (Sweden)

    Dash R

    2017-03-01

    Full Text Available Raju Dash,1 Rasel Das,2 Md Junaid,3 Md Forhad Chowdhury Akash,4 Ashekul Islam,5 SM Zahid Hosen1 1Molecular Modeling and Drug Design Laboratory (MMDDL, Pharmacology Research Division, Bangladesh Council of Scientific and Industrial Research (BCSIR, Chittagong, Bangladesh; 2Nanotechnology and Catalysis Research Center, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh; 4Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh; 5Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong, Bangladesh Abstract: Ebola virus (EBOV is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154–162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV. Keywords: Ebola virus, epitope, glycoprotein, vaccine design

  1. Artificial intelligence systems based on texture descriptors for vaccine development.

    Science.gov (United States)

    Nanni, Loris; Brahnam, Sheryl; Lumini, Alessandra

    2011-02-01

    The aim of this work is to analyze and compare several feature extraction methods for peptide classification that are based on the calculation of texture descriptors starting from a matrix representation of the peptide. This texture-based representation of the peptide is then used to train a support vector machine classifier. In our experiments, the best results are obtained using local binary patterns variants and the discrete cosine transform with selected coefficients. These results are better than those previously reported that employed texture descriptors for peptide representation. In addition, we perform experiments that combine standard approaches based on amino acid sequence. The experimental section reports several tests performed on a vaccine dataset for the prediction of peptides that bind human leukocyte antigens and on a human immunodeficiency virus (HIV-1). Experimental results confirm the usefulness of our novel descriptors. The matlab implementation of our approaches is available at http://bias.csr.unibo.it/nanni/TexturePeptide.zip.

  2. Chemotherapy and quality of life in NSCLC PS 2 patients

    DEFF Research Database (Denmark)

    Helbekkmo, Nina; Strøm, Hans H; Sundstrøm, Stein H

    2009-01-01

    , fatigue, dyspnea, sleeping problems and appetite loss in comparison to the PS 0/1 group. CONCLUSIONS: PS 2 NSCLC patients seem to achieve valuable HRQOL benefits from platinum-based combination therapy. Prospective clinical studies with predefined HRQOL outcomes in PS 2 patients are needed to confirm...

  3. Active SMS-based influenza vaccine safety surveillance in Australian children.

    Science.gov (United States)

    Pillsbury, Alexis; Quinn, Helen; Cashman, Patrick; Leeb, Alan; Macartney, Kristine

    2017-12-18

    Australia's novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration. Parent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia's National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles. 7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p safety profile between brands. Active participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has particular utility in monitoring the safety of influenza vaccines, given that they may vary in composition annually. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Vaccination-challenge studies with a Port Chalmers/73 (H3N2)-based swine influenza virus vaccine: Reflections on vaccine strain updates and on the vaccine potency test.

    Science.gov (United States)

    De Vleeschauwer, Annebel; Qiu, Yu; Van Reeth, Kristien

    2015-05-11

    The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu(®) and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0-7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998-2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test

  5. Gene-based vaccine development for improving animal production in developing countries. Possibilities and constraints

    International Nuclear Information System (INIS)

    Egerton, J.R.

    2005-01-01

    For vaccine production, recombinant antigens must be protective. Identifying protective antigens or candidate antigens is an essential precursor to vaccine development. Even when a protective antigen has been identified, cloning of its gene does not lead directly to vaccine development. The fimbrial protein of Dichelobacter nodosus, the agent of foot-rot in ruminants, was known to be protective. Recombinant vaccines against this infection are ineffective if expressed protein subunits are not assembled as mature fimbriae. Antigenic competition between different, but closely related, recombinant antigens limited the use of multivalent vaccines based on this technology. Recombinant antigens may need adjuvants to enhance response. DNA vaccines, potentiated with genes for different cytokines, may replace the need for aggressive adjuvants, and especially where cellular immunity is essential for protection. The expression of antigens from animal pathogens in plants and the demonstration of some immunity to a disease like rinderpest after ingestion of these, suggests an alternative approach to vaccination by injection. Research on disease pathogenesis and the identification of candidate antigens is specific to the disease agent. The definition of expression systems and the formulation of a vaccine for each disease must be followed by research to establish safety and efficacy. Where vaccines are based on unique gene sequences, the intellectual property is likely to be protected by patent. Organizations, licensed to produce recombinant vaccines, expect to recover their costs and to make a profit. The consequence is that genetically-derived vaccines are expensive. The capacity of vaccines to help animal owners of poorer countries depends not only on quality and cost but also on the veterinary infrastructure where they are used. Ensuring the existence of an effective animal health infrastructure in developing countries is as great a challenge for the developed world as

  6. New Kids on the Block: RNA-Based Influenza Virus Vaccines.

    Science.gov (United States)

    Scorza, Francesco Berlanda; Pardi, Norbert

    2018-04-01

    RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.

  7. Investigating Stakeholder Attitudes and Opinions on School-Based Human Papillomavirus Vaccination Programs

    Science.gov (United States)

    Nodulman, Jessica A.; Starling, Randall; Kong, Alberta S.; Buller, David B.; Wheeler, Cosette M.; Woodall, W. Gill

    2015-01-01

    Background: In several countries worldwide, school-based human papillomavirus (HPV) vaccination programs have been successful; however, little research has explored US stakeholders' acceptance toward school-based HPV vaccination programs. Methods: A total of 13 focus groups and 12 key informant interviews (N?=?117; 85% females; 66% racial/ethnic…

  8. Childhood vaccine refusal and hesitancy intentions in Croatia: insights from a population-based study.

    Science.gov (United States)

    Repalust, Anja; Šević, Sandra; Rihtar, Stanko; Štulhofer, Aleksandar

    2017-10-01

    Considering that programmatic data suggest a recent rise in vaccine refusal in Croatia, this study, first of its kind in Southeast Europe, aimed to estimate the prevalence, and sociodemographic, and sociocultural determinants of childhood vaccine refusal and hesitancy (CVRH) intentions among Croatian adults. Multi-stage stratified population-based survey included 1000 individuals aged 18-88 years (M age  = 47.7, SD = 17.8), of whom 51.7% were women. The outcome, a categorical indicator, distinguished among individuals who would approve vaccinating their children (vaccine accepting), those who would approve some but not all vaccines (vaccine hesitant), and those who would refuse vaccination (vaccine refusing). A sizeable minority of participants was characterized by childhood vaccine refusal (10.6%) and hesitancy intentions (19.5%). In a multivariate assessment controlling for parenthood, the odds of vaccine hesitancy were significantly increased by a younger age (AOR = 1.96-3.03, p Croatia. Following the social contagion model, future research should move beyond individual-level approach and take into account social interaction and social network effects.

  9. The PS booster

    CERN Multimedia

    CERN PhotoLab

    1972-01-01

    The PS booster which accelerates protons from the linac at an energy of 50 MeV to an energy of 800 MeV before injecting them into the main magnet ring of the synchrotron. The booster consists of four superposed rings. In the photograph can be seen the input beam line from the linac and the output beam lines, where beams from the four booster levels have been combined into two beams before final recombination.

  10. Clarification of vaccines: An overview of filter based technology trends and best practices.

    Science.gov (United States)

    Besnard, Lise; Fabre, Virginie; Fettig, Michael; Gousseinov, Elina; Kawakami, Yasuhiro; Laroudie, Nicolas; Scanlan, Claire; Pattnaik, Priyabrata

    2016-01-01

    Vaccines are derived from a variety of sources including tissue extracts, bacterial cells, virus particles, recombinant mammalian, yeast and insect cell produced proteins and nucleic acids. The most common method of vaccine production is based on an initial fermentation process followed by purification. Production of vaccines is a complex process involving many different steps and processes. Selection of the appropriate purification method is critical to achieving desired purity of the final product. Clarification of vaccines is a critical step that strongly impacts product recovery and subsequent downstream purification. There are several technologies that can be applied for vaccine clarification. Selection of a harvesting method and equipment depends on the type of cells, product being harvested, and properties of the process fluids. These techniques include membrane filtration (microfiltration, tangential-flow filtration), centrifugation, and depth filtration (normal flow filtration). Historically vaccine harvest clarification was usually achieved by centrifugation followed by depth filtration. Recently membrane based technologies have gained prominence in vaccine clarification. The increasing use of single-use technologies in upstream processes necessitated a shift in harvest strategies. This review offers a comprehensive view on different membrane based technologies and their application in vaccine clarification, outlines the challenges involved and presents the current state of best practices in the clarification of vaccines. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. An Adenoviral Vector Based Vaccine for Rhodococcus equi.

    Directory of Open Access Journals (Sweden)

    Carla Giles

    Full Text Available Rhodococcus equi is a respiratory pathogen which primarily infects foals and is endemic on farms around the world with 50% mortality and 80% morbidity in affected foals. Unless detected early and treated appropriately the disease can be fatal. Currently, there is no vaccine available to prevent this disease. For decades researchers have endeavoured to develop an effective vaccine to no avail. In this study a novel human adenoviral vector vaccine for R. equi was developed and tested in the mouse model. This vaccine generated a strong antibody and cytokine response and clearance of R. equi was demonstrated following challenge. These results show that this vaccine could potentially be developed further for use as a vaccine to prevent R. equi disease in foals.

  12. Prophylactic effect of a therapeutic vaccine against TB based on fragments of Mycobacterium tuberculosis.

    Science.gov (United States)

    Vilaplana, Cristina; Gil, Olga; Cáceres, Neus; Pinto, Sergio; Díaz, Jorge; Cardona, Pere-Joan

    2011-01-01

    The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis.

  13. Making evidence-based selections of influenza vaccines

    OpenAIRE

    Childress, Billy-Clyde; Montney, Joshua D; Albro, Elise A

    2014-01-01

    Years ago, intramuscular influenza vaccines were the only option for those who wanted to arm themselves against the flu. Today there are alternatives, including intradermal injections and intranasal sprays. In order to select the right influenza vaccine for their patients, pharmacists, and other healthcare professionals must have a basic understanding of the immune system. Influenza vaccines elicit different levels of immune response involving innate and adaptive immunity, which are critical ...

  14. Effect of School-based Human Papillomavirus (HPV) Vaccination on ...

    African Journals Online (AJOL)

    ... de comportement des pairs positifs. Des obstacles majeurs à l'acceptation du vaccin ont été: les rumeurs et les idées fausses au sujet des effets secondaires possibles, information inadéquate perçue sur le vaccin, et la peur des effets secondaires. Mots clés: adolescentes; connaissances; acceptabilité; vaccin; Ouganda ...

  15. Development of Cytomegalovirus-Based Vaccines Against Melanoma

    Science.gov (United States)

    2016-10-01

    Efficacy will be examined in mice by vaccination at 7, 14, and 21 days after tumor induction through monitoring tumor incidence, size, survival...intradermal B16 solid tumor model. Mice were inoculated with B16F10 and 3 days later were vaccinated with MCMVgp100KGP. For one experiment, mice were...We are now comparing the efficacy of this new vaccine to other single epitope virus vectors. Q6. can you please also clarify the AIMS of the SPARK

  16. Gamma Transition Jump for PS2

    CERN Document Server

    Bartmann, W; Métral, E; Möhl, D; Peggs, S

    2008-01-01

    The PS2, which is proposed as a replacement for the existing ~50-year old PS accelerator, is presently considered to be a normal conducting synchrotron with an injection kinetic energy of 4 GeV and a maximum energy of 50 GeV. One of the possible lattices (FODO option) foresees crossing of transition energy near 10 GeV. Since the phase-slip-factor $\\eta$ becomes very small near transition energy, many intensity dependent effects can take place in both longitudinal and transverse planes. The aim of the present paper is on the one hand to scale the gamma transition jump, used since 1973 in the PS, to the projected PS2 and on the other hand based on these results the analysis of the implementation and feasibility of a gamma transition jump scheme in a conventional FODO lattice.

  17. Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

    Directory of Open Access Journals (Sweden)

    Yoshikazu Nakayama

    2015-03-01

    Full Text Available Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region.

  18. Acute disseminated encephalomyelitis onset: evaluation based on vaccine adverse events reporting systems.

    Directory of Open Access Journals (Sweden)

    Paolo Pellegrino

    Full Text Available OBJECTIVE: To evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM by considering data from different pharmacovigilance surveillance systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS database and the EudraVigilance post-authorisation module (EVPM were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed. RESULTS: We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40±21.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines. CONCLUSIONS: This study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely not [corrected] due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reaction.

  19. Making evidence-based selections of influenza vaccines.

    Science.gov (United States)

    Childress, Billy-Clyde; Montney, Joshua D; Albro, Elise A

    2014-01-01

    Years ago, intramuscular influenza vaccines were the only option for those who wanted to arm themselves against the flu. Today there are alternatives, including intradermal injections and intranasal sprays. In order to select the right influenza vaccine for their patients, pharmacists, and other healthcare professionals must have a basic understanding of the immune system. Influenza vaccines elicit different levels of immune response involving innate and adaptive immunity, which are critical to fighting infection. For the 2013-2014 flu season, there were 13 different formulations of influenza vaccines on the market with vast differences in indications, contraindications, and effectiveness. The CDC does not recommend one vaccine over another, but recommends that all patients be vaccinated against the flu. Preventing the spread of influenza is no simple task; however, the most recent evidence on influenza vaccines and sufficient knowledge of the immune system will allow pharmacists and other healthcare providers to better advocate for vaccines, determine which are most appropriate, and ensure their proper administration.

  20. Cell culture based production of avian influenza vaccines

    NARCIS (Netherlands)

    Wielink, van R.

    2012-01-01

    Vaccination of poultry can be used as a tool to control outbreaks of avian influenza, including that of highly pathogenic H5 and H7 strains. Influenza vaccines are traditionally produced in embryonated chicken eggs. Continuous cell lines have been suggested as an alternative substrate to produce

  1. HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

    Science.gov (United States)

    Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

    2015-12-01

    The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

    Science.gov (United States)

    Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

    2017-11-02

    Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

  3. At PS170 (APPLE)

    CERN Multimedia

    CERN PhotoLab

    1983-01-01

    APPLE stands for Antiproton-Proton to Pair of LEptons (an acronym of the ancestor experiment PAPLEP), the PS170 experiment setup at LEAR to study e+e-pair production in antiproton-proton annihilation by Padova-(CEN) Saclay- Torino Collaboration. It consisted of a liquid hydrogen target surrounded by several layers of proportional chambers in the vertical field of a C-magnet (this photo), a gas Cerenkov counter, wire chambers, hodoscopes, and an electromagnetic calorimeter (see photo 8302539X, 8302540X). See also photo 8301539X for the setup assembly at an early stage.

  4. Vaccines based on the cell surface carbohydrates of pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Jones Christopher

    2005-01-01

    Full Text Available Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development. This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

  5. Designing Peptide-Based HIV Vaccine for Chinese

    Science.gov (United States)

    Fan, Xiaojuan

    2014-01-01

    CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV-specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese. PMID:25136573

  6. Recent advances in recombinant protein-based malaria vaccines

    DEFF Research Database (Denmark)

    Draper, Simon J; Angov, Evelina; Horii, Toshihiro

    2015-01-01

    Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito...... vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard......, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite...

  7. Antigenic specificity of a monovalent versus polyvalent MOMP based Chlamydia pecorum vaccine in koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Kollipara, Avinash; Wan, Charles; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

    2013-02-06

    Chlamydia continues to be a major pathogen of koalas. The bacterium is associated with ocular, respiratory and urogenital tract infections and a vaccine is considered the best option to limit the decline of mainland koala populations. Over the last 20 years, efforts to develop a chlamydial vaccine in humans have focussed on the use of the chlamydial major outer membrane protein (MOMP). Potential problems with the use of MOMP-based vaccines relate to the wide range of genetic diversity in its four variable domains. In the present study, we evaluated the immune response of koalas vaccinated with a MOMP-based C. pecorum vaccine formulated with genetically and serologically diverse MOMPs. Animals immunised with individual MOMPs developed strong antibody and lymphocyte proliferation responses to both homologous as well as heterologous MOMP proteins. Importantly, we also showed that vaccine induced antibodies which effectively neutralised various heterologous strains of koala C. pecorum in an in vitro assay. Finally, we also demonstrated that the immune responses in monovalent as well as polyvalent MOMP vaccine groups were able to recognise whole chlamydial elementary bodies, illustrating the feasibility of developing an effective MOMP based C. pecorum vaccine that could protect against a range of strains. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  8. Zika virus-like particle (VLP) based vaccine

    Science.gov (United States)

    Boigard, Hélène; Alimova, Alexandra; Martin, George R.; Katz, Al; Gottlieb, Paul

    2017-01-01

    The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development. PMID:28481898

  9. Simultaneous catalytic degradation of 2,4-D and MCPA herbicides using sulfate radical-based heterogeneous oxidation over persulfate activated by natural hematite (α-Fe2O3/PS)

    Science.gov (United States)

    Kermani, Majid; Mohammadi, Farzad; Kakavandi, Babak; Esrafili, Ali; Rostamifasih, Zeinab

    2018-06-01

    Herein, a sulfate radical (SO4rad -)-based oxidation process was utilized for simultaneous degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) herbicides using mesoporous hematite-based natural semi-conductor minerals (HM-NSMs) as efficient activators of persulfate (PS). The features of the catalyst were characterized using field emission scanning electron microscopy (FESEM); Brunauer, Emmett and Teller (BET) analysis; X-ray diffraction (XRD); and energy-dispersive X-ray spectroscopy (EDS). The effect of some operational parameters, including solution pH, catalyst loading, PS dosage and temperature, on the performance system of PS/HM-NSMs was examined. A plausible oxidation mechanism for degradation of both pollutants was also proposed. Increasing the removal efficiency of herbicides follows the order of PS/HM-NSM > HM-NSM > PS. In all experiments, the 2,4-D removal rates were slightly lower than those for MCPA, indicating that 2,4-D has a more recalcitrant nature than MCPA. Under optimized conditions, degradation rates of 68.1% and 74.5% were achieved for 2,4-D and MCPA, respectively, during a 120-min reaction. HM-NSM displays a highly synergistic effect on the degradation of herbicides in the presence of PS. The trapping experiments demonstrated that both OHrad and SO4rad - radicals contribute significantly during the degradation of 2,4-D and MCPA and that sulfate radicals were the dominant species. A mineralization degree of 36% was obtained under optimum conditions. In conclusion, the coupling of PS and HM-NSM is a promising and effective technique to degrade organic matter for the treatment of herbicide-contaminated waters and wastewaters under real conditions.

  10. Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

    Science.gov (United States)

    Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

    2015-02-01

    Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination.

  11. Beyond iPS!

    Directory of Open Access Journals (Sweden)

    Editorial

    2012-01-01

    Full Text Available It’s undoubtedly a jubilant moment for scientists and clinicians working in the stem cell arena as Prof. Gurdon and Prof. Shinya Yamanaka have been chosen for the Nobel Prize in Physiology & Medicine this year. The mystery of cell biology is something unfathomable and probably the work of this duo as well as the other scientists, who have put their hands on in- vitro de-differentiation have opened our eyes to a new window or a new paradigm in cell biology. The iPS invention has brought a lot of hope in terms of potential direct benefits to treat several diseases, which have no definite options at the moment. But, we envisage that several spin-offs could come out of this invention and one very significant spin-off finding recently witnessed is the finding by Prof. Masaharu Seno and his team of researchers at the Okayama University, Japan (Chen L, et al. 2012, PLoS ONE 7(4:e33544.doi:10.1371/journal.pone.0033544. According to Prof. Seno, mouse iPS cells (miPS when cultured in the conditioned medium derived from cancer cell lines, differentiate into cancer stem cells (CSCs. While differentiating into CSCs, they do retain the potential to develop endothelial progenitor cells. Several questions arise here: 1.Are these miPS derived CSCs really pluripotent, even if the terminal differentiation destined to specific phenotypes? 2.Shouldn’t the Cancer Stem Cells be termed as cancer progenitor cells, as till date they are considered to be producing only cancer cells but not pluripotent to yield other types of normal tissues? The spin-offs could be infinite as the process of differentiation and de-differentiation happening due to trillions of signals and pathways, most still remaining not-so-well understood. A special mention should be made to Prof. Shinya Yamanaka as he has several sterling qualities to be a role-model for budding scientists. Apart from his passion for science, which made him shift his career from orthopedics to a cell biologist, his

  12. Implementation of a national school-based Human Papillomavirus (HPV) vaccine campaign in Fiji: knowledge, vaccine acceptability and information needs of parents.

    Science.gov (United States)

    La Vincente, S F; Mielnik, D; Jenkins, K; Bingwor, F; Volavola, L; Marshall, H; Druavesi, P; Russell, F M; Lokuge, K; Mulholland, E K

    2015-12-18

    In 2008 Fiji implemented a nationwide Human Papillomavirus (HPV) vaccine campaign targeting all girls aged 9-12 years through the existing school-based immunisation program. Parents of vaccine-eligible girls were asked to provide written consent for vaccination. The purpose of this study was to describe parents' knowledge, experiences and satisfaction with the campaign, the extent to which information needs for vaccine decision-making were met, and what factors were associated with vaccine consent. Following vaccine introduction, a cross-sectional telephone survey was conducted with parents of vaccine-eligible girls from randomly selected schools, stratified by educational district. Factors related to vaccine consent were explored using Generalised Estimating Equations. There were 560 vaccine-eligible girls attending the participating 19 schools at the time of the campaign. Among these, 313 parents could be contacted, with 293 agreeing to participate (93.6%). Almost 80% of participants reported having consented to HPV vaccination (230/293, 78.5%). Reported knowledge of cervical cancer and HPV prior to the campaign was very low. Most respondents reported that they were satisfied with their access to information to make an informed decision about HPV vaccination (196/293, 66.9%). and this was very strongly associated with provision of consent. Despite their young age, the vaccine-eligible girls were often involved in the discussion and decision-making. Most consenting parents were satisfied with the campaign and their decision to vaccinate, with almost 90% indicating they would consent to future HPV vaccination. However, negative media reports about the vaccine campaign created confusion and concern. Local health staff were cited as a trusted source of information to guide decision-making. Just over half of the participants who withheld consent cited vaccine safety fears as the primary reason (23/44, 52.3%). This is the first reported experience of HPV introduction

  13. Low prevalence of vaccine-type HPV infections in young women following the implementation of a school-based and catch-up vaccination in Quebec, Canada.

    Science.gov (United States)

    Goggin, P; Sauvageau, C; Gilca, V; Defay, F; Lambert, G; Mathieu-C, S; Guenoun, J; Comète, E; Coutlée, F

    2018-01-02

    In Quebec, Canada, a school-based HPV vaccination for girls has been offered since 2008. The vaccine used in the program targets HPV16/18, responsible for ∼70% of cervical cancers and HPV6/11, responsible for the majority of anogenital warts. The objective of this study was to assess the prevalence of HPV in vaccinated and unvaccinated women. Women aged 17-29 years were eligible to participate. Participants' age, vaccination status and diverse risk factors were assessed by a computer-assisted questionnaire. Biological specimens were obtained by self-sampling. HPV genotyping was performed by Linear Array. A total of 2,118 women were recruited. 2,042 completed the questionnaire and 1,937 provided a vaginal sample. Vaccination coverage varied from 83.5% in women aged 17-19 to 19.1% in those aged 23-29. The overall prevalence of HPV in sexually active women was 39.4% (95%CI: 37.0-41.7) and 56.7% of infected women had multiple type infections. The prevalence of vaccine HPV types varied by age and vaccination status except for women aged 23-29 for whom similar results were observed. Vaccine HPV types were detected in 0.3%, 1.4% and 10.5% of vaccinated women aged 17-19, 20-23, and 23-29 (pHPV16 or HPV18 were detected in 10 women having received at least one dose of vaccine. Nine of these women were already sexually active at the time of vaccination. Infections with HPV types included in the vaccine are rare in women aged less than 23 years and are virtually absent in those who received at least one dose of vaccine before sexual debut.

  14. Impact of a website based educational program for increasing vaccination coverage among adolescents.

    Science.gov (United States)

    Esposito, Susanna; Bianchini, Sonia; Tagliabue, Claudia; Umbrello, Giulia; Madini, Barbara; Di Pietro, Giada; Principi, Nicola

    2018-04-03

    Data regarding the use of technology to improve adolescent knowledge on vaccines are scarce. The main aim of this study was to evaluate whether different web-based educational programmes for adolescents might increase their vaccination coverage. Overall, 917 unvaccinated adolescents (389 males, 42.4%; mean age ± standard deviation, 14.0 ± 2.2 years) were randomized 1:1:1 into the following groups: no intervention (n = 334), website educational program only (n = 281), or website plus face to face lesson (n = 302) groups. The use of the website plus the lesson significantly increased the overall knowledge of various aspects of vaccine-preventable disease and reduced the fear of vaccines (p education of adolescents while considering all of the vaccines recommended for this age group. Our results demonstrate the possibility of increasing vaccination coverage by using a website based educational program with tailored information. However, to be most effective, this program should be supplemented with face-to-face discussions of vaccines at school and at home. Thus, specific education should also include teachers and parents so that they will be prepared to discuss with adolescents what is true and false in the vaccination field.

  15. Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Fischer, Anders; Myschetzky, Peter S

    2008-01-01

    Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based...... with this DC-based cancer vaccine was safe and non-toxic. Stable disease was found in 24% (4/17) of the patients. The quality of life remained for most categories high and stable throughout the study period.......Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based......-testis antigens. Vaccines were biweekly administered intradermally with a total of 10 vaccines per patient. CT scans were performed and responses were graded according to the RECIST criteria. Quality of life was monitored with the SF-36 questionnaire. Toxicity and adverse events were graded according...

  16. Mechanism of action of mRNA-based vaccines.

    Science.gov (United States)

    Iavarone, Carlo; O'hagan, Derek T; Yu, Dong; Delahaye, Nicolas F; Ulmer, Jeffrey B

    2017-09-01

    The present review summarizes the growing body of work defining the mechanisms of action of this exciting new vaccine technology that should allow rational approaches in the design of next generation mRNA vaccines. Areas covered: Bio-distribution of mRNA, localization of antigen production, role of the innate immunity, priming of the adaptive immune response, route of administration and effects of mRNA delivery systems. Expert commentary: In the last few years, the development of RNA vaccines had a fast growth, the rising number of proof will enable rational approaches to improving the effectiveness and safety of this modern class of medicine.

  17. Plasma thermal performance of a dual-process PVD/PS tungsten coating on carbon-based panels for nuclear fusion application

    International Nuclear Information System (INIS)

    Kim, Hyunmyung; Lee, Ho Jung; Kim, Sung Hwan; Jang, Changheui

    2016-01-01

    Highlights: • Plasma thermal performance of a dual-process PVD/PS W coating was evaluated. • Steady-state heat fluxes of 1–3 MW/m 2 were applied to the W coated specimens. • Less micro-pores and grain growth were observed for the dual-process coating. • Loss of coating thickness was observed for the simple PS W coating. • Dual-process PVD/PS W coating was resistant to erosion due to the surface PVD layer. - Abstract: Various tungsten (W) coating techniques have been used for the application of plasma facing material in nuclear fusion devices, which resulted in limited success. In this study, a dual-process W coating structure was developed on a graphite substrate to improve the thermal performance of the coating structure. The dual-process coating structure consisted of a thin (∼7 μm) multilayer W/Mo physical vapor deposition (PVD) coating layer deposited on top of the relatively thick (∼160 μm) plasma spray (PS) W coating on a graphite substrate panel. Then the coated sample was exposed to plasma heat flux of 1–3 MW/m 2 for 300 s. With addition of a thin surface PVD coating layer, the microstructure change in underlying PS W coating was substantially reduced compared to the simple PS W coating structure. The thickness of overall coating structure was maintained for the dual-process PVD/PS coated samples after the thermal loading tests, while a significant reduction in thickness due to surface erosion was observed for the simple PS W coated samples. The improvement in surface erosion resistance in the dual-process coating structure was discussed in view of the characteristics of PVD and PS coating layers.

  18. Plasma thermal performance of a dual-process PVD/PS tungsten coating on carbon-based panels for nuclear fusion application

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyunmyung; Lee, Ho Jung; Kim, Sung Hwan; Jang, Changheui, E-mail: chjang@kaist.ac.kr

    2016-11-01

    Highlights: • Plasma thermal performance of a dual-process PVD/PS W coating was evaluated. • Steady-state heat fluxes of 1–3 MW/m{sup 2} were applied to the W coated specimens. • Less micro-pores and grain growth were observed for the dual-process coating. • Loss of coating thickness was observed for the simple PS W coating. • Dual-process PVD/PS W coating was resistant to erosion due to the surface PVD layer. - Abstract: Various tungsten (W) coating techniques have been used for the application of plasma facing material in nuclear fusion devices, which resulted in limited success. In this study, a dual-process W coating structure was developed on a graphite substrate to improve the thermal performance of the coating structure. The dual-process coating structure consisted of a thin (∼7 μm) multilayer W/Mo physical vapor deposition (PVD) coating layer deposited on top of the relatively thick (∼160 μm) plasma spray (PS) W coating on a graphite substrate panel. Then the coated sample was exposed to plasma heat flux of 1–3 MW/m{sup 2} for 300 s. With addition of a thin surface PVD coating layer, the microstructure change in underlying PS W coating was substantially reduced compared to the simple PS W coating structure. The thickness of overall coating structure was maintained for the dual-process PVD/PS coated samples after the thermal loading tests, while a significant reduction in thickness due to surface erosion was observed for the simple PS W coated samples. The improvement in surface erosion resistance in the dual-process coating structure was discussed in view of the characteristics of PVD and PS coating layers.

  19. Pre-Vaccination Care-Seeking in Females Reporting Severe Adverse Reactions to HPV Vaccine. A Registry Based Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Kåre Mølbak

    Full Text Available Since 2013 the number of suspected adverse reactions to the quadrivalent human papillomavirus (HPV vaccine reported to the Danish Medicines Agency (DMA has increased. Due to the resulting public concerns about vaccine safety, the coverage of HPV vaccinations in the childhood vaccination programme has declined. The aim of the present study was to determine health care-seeking prior to the first HPV vaccination among females who suspected adverse reactions to HPV vaccine.In this registry-based case-control study, we included as cases vaccinated females with reports to the DMA of suspected severe adverse reactions. We selected controls without reports of adverse reactions from the Danish vaccination registry and matched by year of vaccination, age of vaccination, and municipality, and obtained from the Danish National Patient Registry and The National Health Insurance Service Register the history of health care usage two years prior to the first vaccine. We analysed the data by logistic regression while adjusting for the matching variables.The study included 316 cases who received first HPV vaccine between 2006 and 2014. Age range of cases was 11 to 52 years, with a peak at 12 years, corresponding to the recommended age at vaccination, and another peak at 19 to 28 years, corresponding to a catch-up programme targeting young women. Compared with 163,910 controls, cases had increased care-seeking in the two years before receiving the first HPV vaccine. A multivariable model showed higher use of telephone/email consultations (OR 1.9; 95% CI 1.2-3.2, physiotherapy (OR 2.1; 95% CI 1.6-2.8 and psychologist/psychiatrist (OR 1.9; 95% CI 1.3-2.7. Cases were more likely to have a diagnosis in the ICD-10 chapters of diseases of the digestive system (OR 1.6; 95% CI 1.0-2.4, of the musculoskeletal system (OR 1.6; 95% CI 1.1-2.2, symptoms or signs not classified elsewhere (OR 1.8; 95% CI 1.3-2.5 as well as injuries (OR 1.5; 95% CI 1.2-1.9.Before receiving the

  20. PS Booster Orbit Correction

    CERN Document Server

    Chanel, M; Rumolo, G; Tomás, R; CERN. Geneva. AB Department

    2008-01-01

    At the end of the 2007 run, orbit measurements were carried out in the 4 rings of the PS Booster (PSB) for different working points and beam energies. The aim of these measurements was to provide the necessary input data for a PSB realignment campaign during the 2007/2008 shutdown. Currently, only very few corrector magnets can be operated reliably in the PSB; therefore the orbit correction has to be achieved by displacing (horizontally and vertically) and/or tilting some of the defocusing quadrupoles (QDs). In this report we first describe the orbit measurements, followed by a detailed explanation of the orbit correction strategy. Results and conclusions are presented in the last section.

  1. PS proton source

    CERN Multimedia

    1959-01-01

    The first proton source used at CERN's Proton Synchrotron (PS) which started operation in 1959. This is CERN's oldest accelerator still functioning today (2018). It is part of the accelerator chain that supplies proton beams to the Large Hadron Collider. The source is a Thonemann type. In order to extract and accelerate the protons at high energy, a high frequency electrical field is used (140Mhz). The field is transmitted by a coil around a discharge tube in order to maintain the gas hydrogen in an ionised state. An electrical field pulse, in the order of 15kV, is then applied via an impulse transformer between anode and cathode of the discharge tube. The electrons and protons of the plasma formed in the ionised gas in the tube, are then separated. Currents in the order of 200mA during 100 microseconds have benn obtained with this type of source.

  2. 'It's a logistical nightmare!' Recommendations for optimising human papillomavirus school-based vaccination experience.

    Science.gov (United States)

    Robbins, Spring Chenoa Cooper; Bernard, Diana; McCaffery, Kirsten; Skinner, S Rachel

    2010-09-01

    To date, no published studies examine procedural factors of the school-based human papillomavirus (HPV) vaccination program from the perspective of those involved. This study examines the factors that were perceived to impact optimal vaccination experience. Schools across Sydney were selected to reflect a range of vaccination coverage at the school level and different school types to ensure a range of experiences. Semi-structured focus groups were conducted with girls; and one-on-one interviews were undertaken with parents, teachers and nurses until saturation of data in all emergent themes was reached. Focus groups and interviews explored participants' experiences in school-based HPV vaccination. Transcripts were analysed, letting themes emerge. Themes related to participants' experience of the organisational, logistical and procedural aspects of the vaccination program and their perceptions of an optimal process were organised into two categories: (1) preparation for the vaccination program and (2) vaccination day strategies. In (1), themes emerged regarding commitment to the process from those involved, planning time and space for vaccinations, communication within and between agencies, and flexibility. In (2), themes included vaccinating the most anxious girls first, facilitating peer support, use of distraction techniques, minimising waiting time girls, and support staff. A range of views exists on what constitutes an optimal school-based program. Several findings were identified that should be considered in the development of guidelines for implementing school-based programs. Future research should evaluate how different approaches to acquiring parental consent, and the use of anxiety and fear reduction strategies impact experience and uptake in the school-based setting.

  3. Overcoming the knowledge-behavior gap: The effect of evidence-based HPV vaccination leaflets on understanding, intention, and actual vaccination decision.

    Science.gov (United States)

    Wegwarth, O; Kurzenhäuser-Carstens, S; Gigerenzer, G

    2014-03-10

    Informed decision making requires transparent and evidence-based (=balanced) information on the potential benefit and harms of medical preventions. An analysis of German HPV vaccination leaflets revealed, however, that none met the standards of balanced risk communication. We surveyed a sample of 225 girl-parent pairs in a before-after design on the effects of balanced and unbalanced risk communication on participants' knowledge about cervical cancer and the HPV vaccination, their perceived risk, their intention to have the vaccine, and their actual vaccination decision. The balanced leaflet increased the number of participants who were correctly informed about cervical cancer and the HPV vaccine by 33 to 66 absolute percentage points. In contrast, the unbalanced leaflet decreased the number of participants who were correctly informed about these facts by 0 to 18 absolute percentage points. Whereas the actual uptake of the HPV vaccination 14 months after the initial study did not differ between the two groups (22% balanced leaflet vs. 23% unbalanced leaflet; p=.93, r=.01), the originally stated intention to have the vaccine reliably predicted the actual vaccination decision for the balanced leaflet group only (concordance between intention and actual uptake: 97% in the balanced leaflet group, rs=.92, p=.00; 60% in the unbalanced leaflet group, rs=.37, p=.08). In contrast to a unbalanced leaflet, a balanced leaflet increased people's knowledge of the HPV vaccination, improved perceived risk judgments, and led to an actual vaccination uptake, which first was robustly predicted by people's intention and second did not differ from the uptake in the unbalanced leaflet group. These findings suggest that balanced reporting about HPV vaccination increases informed decisions about whether to be vaccinated and does not undermine actual uptake. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Using Dynamic Transmission Modeling to Determine Vaccination Coverage Rate Based on 5-Year Economic Burden of Infectious Disease: An Example of Pneumococcal Vaccine.

    Science.gov (United States)

    Wen, Yu-Wen; Wu, Hsin; Chang, Chee-Jen

    2015-05-01

    Vaccination can reduce the incidence and mortality of an infectious disease and thus increase the years of life and productivity for the entire society. But when determining the vaccination coverage rate, its economic burden is usually not taken into account. This article aimed to use a dynamic transmission modeling (DTM), which is based on a susceptible-infectious-recovered model and is a system of differential equations, to find the optimal vaccination coverage rate based on the economic burden of an infectious disease. Vaccination for pneumococcal diseases was used as an example to demonstrate the main purpose. 23-Valent pneumococcal polysaccharide vaccines (PPV23) and 13-valent pneumococcal conjugate vaccines (PCV13) have shown their cost-effectiveness in elderly and children, respectively. Scenarios analysis of PPV23 to elderly aged 65+ years and of PCV13 to children aged 0 to 4 years was applied to assess the optimal vaccination coverage rate based on the 5-year economic burden. Model parameters were derived from Taiwan's National Health Insurance Research Database, government data, and published literature. Various vaccination coverage rates, the vaccine efficacy, and all epidemiologic parameters were substituted into DTM, and all differential equations were solved in R Statistical Software. If the coverage rate of PPV23 for the elderly and of PCV13 for the children both reach 50%, the economic burden due to pneumococcal disease will be acceptable. This article provided an alternative perspective from the economic burden of diseases to obtain a vaccination coverage rate using the DTM. This will provide valuable information for vaccination policy decision makers. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  5. Parents' views of including young boys in the Swedish national school-based HPV vaccination programme: a qualitative study.

    Science.gov (United States)

    Gottvall, Maria; Stenhammar, Christina; Grandahl, Maria

    2017-02-28

    To explore parents' views of extending the human papillomavirus (HPV) vaccination programme to also include boys. Explorative qualitative design using individual, face-to-face, interviews and inductive thematic analysis. 11 strategically chosen municipalities in central Sweden. Parents (n=42) who were offered HPV vaccination for their 11-12 years old daughter in the national school-based vaccination programme. The key themes were: equality from a public health perspective and perception of risk for disease . Parents expressed low knowledge and awareness about the health benefits of male HPV vaccination, and they perceived low risk for boys to get HPV. Some parents could not see any reason for vaccinating boys. However, many parents preferred gender-neutral vaccination, and some of the parents who had not accepted HPV vaccination for their daughter expressed that they would be willing to accept vaccination for their son, if it was offered. It was evident that there was both trust and distrust in authorities' decision to only vaccinate girls. Parents expressed a preference for increased sexual and reproductive health promotion such as more information about condom use. Some parents shared that it was more important to vaccinate girls than boys since they believed girls face a higher risk of deadly diseases associated with HPV, but some also believed girls might be more vulnerable to side effects of the vaccine. A vaccine offered only to girls may cause parents to be hesitant to vaccinate, while also including boys in the national vaccination programme might improve parents' trust in the vaccine. More information about the health benefits of HPV vaccination for males is necessary to increase HPV vaccination among boys. This may eventually lead to increased HPV vaccine coverage among both girls and boys. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Controlling chitosan-based encapsulation for protein and vaccine delivery

    Science.gov (United States)

    Koppolu, Bhanu prasanth; Smith, Sean G.; Ravindranathan, Sruthi; Jayanthi, Srinivas; Kumar, Thallapuranam K.S.; Zaharoff, David A.

    2014-01-01

    Chitosan-based nano/microencapsulation is under increasing investigation for the delivery of drugs, biologics and vaccines. Despite widespread interest, the literature lacks a defined methodology to control chitosan particle size and drug/protein release kinetics. In this study, the effects of precipitation-coacervation formulation parameters on chitosan particle size, protein encapsulation efficiency and protein release were investigated. Chitosan particle sizes, which ranged from 300 nm to 3 μm, were influenced by chitosan concentration, chitosan molecular weight and addition rate of precipitant salt. The composition of precipitant salt played a significant role in particle formation with upper Hofmeister series salts containing strongly hydrated anions yielding particles with a low polydispersity index (PDI) while weaker anions resulted in aggregated particles with high PDIs. Sonication power had minimal effect on mean particle size, however, it significantly reduced polydispersity. Protein loading efficiencies in chitosan nano/microparticles, which ranged from 14.3% to 99.2%, was inversely related to the hydration strength of precipitant salts, protein molecular weight and directly related to the concentration and molecular weight of chitosan. Protein release rates increased with particle size and were generally inversely related to protein molecular weight. This study demonstrates that chitosan nano/microparticles with high protein loading efficiencies can be engineered with well-defined sizes and controllable release kinetics through manipulation of specific formulation parameters. PMID:24560459

  7. Symmetry of dipositronium Ps2

    International Nuclear Information System (INIS)

    Schrader, D.M.

    2004-01-01

    We work out the complete symmetry and spin problem for diatomic positronium Ps 2 for the ground and singly excited states of zero orbital angular momentum. The general form of the wave function for each state is given, with due regard to charge conjugation parity. Annihilation rates are discussed, and correlations to dissociation products are deduced. We indicate how the approach is extensible to larger aggregates: i.e., PsPs n , n>2

  8. Content of web-based continuing medical education about HPV vaccination.

    Science.gov (United States)

    Kornides, Melanie L; Garrell, Jacob M; Gilkey, Melissa B

    2017-08-16

    Addressing low HPV vaccination coverage will require U.S. health care providers to improve their recommendation practices and vaccine delivery systems. Because readily available continuing medical education (CME) could be an important tool for supporting providers in this process, we sought to assess the content of web-based CME activities related to HPV vaccination. We conducted a content analysis of web-based CME activities about HPV vaccination available to U.S. primary care providers in May-September 2016. Using search engines, educational clearinghouses, and our professional networks, we identified 15 activities eligible for study inclusion. Through a process of open coding, we identified 45 commonly occurring messages in the CME activities, which we organized into five topic areas: delivering recommendations for HPV vaccination, addressing common parent concerns, implementing office-based strategies to increase HPV vaccination coverage, HPV epidemiology, and guidelines for HPV vaccine administration and safety. Using a standardized abstraction form, two coders then independently assessed which of the 45 messages each CME activity included. CME activities varied in the amount of content they delivered, with inclusion of the 45 messages ranging from 17% to 86%. Across activities, the most commonly included messages were related to guidelines for HPV vaccine administration and safety. For example, all activities (100%) specified that routine administration is recommended for ages 11 and 12. Most activities (73%) also noted that provider recommendations are highly influential. Fewer activities modeled examples of effective recommendations (47%), gave specific approaches to addressing common parent concerns (47%), or included guidance on office-based strategies to increase coverage (40%). Given that many existing CME activities lack substantive content on how to change provider practice, future activities should focus on the practical application of interpersonal

  9. Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis.

    Science.gov (United States)

    Kelso, Joel K; Halder, Nilimesh; Milne, George J

    2013-02-11

    A critical issue in planning pandemic influenza mitigation strategies is the delay between the arrival of the pandemic in a community and the availability of an effective vaccine. The likely scenario, born out in the 2009 pandemic, is that a newly emerged influenza pandemic will have spread to most parts of the world before a vaccine matched to the pandemic strain is produced. For a severe pandemic, additional rapidly activated intervention measures will be required if high mortality rates are to be avoided. A simulation modelling study was conducted to examine the effectiveness and cost effectiveness of plausible combinations of social distancing, antiviral and vaccination interventions, assuming a delay of 6-months between arrival of an influenza pandemic and first availability of a vaccine. Three different pandemic scenarios were examined; mild, moderate and extreme, based on estimates of transmissibility and pathogenicity of the 2009, 1957 and 1918 influenza pandemics respectively. A range of different durations of social distancing were examined, and the sensitivity of the results to variation in the vaccination delay, ranging from 2 to 6 months, was analysed. Vaccination-only strategies were not cost effective for any pandemic scenario, saving few lives and incurring substantial vaccination costs. Vaccination coupled with long duration social distancing, antiviral treatment and antiviral prophylaxis was cost effective for moderate pandemics and extreme pandemics, where it saved lives while simultaneously reducing the total pandemic cost. Combined social distancing and antiviral interventions without vaccination were significantly less effective, since without vaccination a resurgence in case numbers occurred as soon as social distancing interventions were relaxed. When social distancing interventions were continued until at least the start of the vaccination campaign, attack rates and total costs were significantly lower, and increased rates of vaccination

  10. Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

    Science.gov (United States)

    Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  11. Association of prior HPV vaccination with reduced preterm birth: A population based study.

    Science.gov (United States)

    Lawton, Beverley; Howe, Anna S; Turner, Nikki; Filoche, Sara; Slatter, Tania; Devenish, Celia; Hung, Noelyn Anne

    2018-01-02

    Emerging evidence suggests that HPV infection is associated with negative pregnancy outcomes such as preterm birth (PTB), and pre-eclampsia. We aimed to determine if prior HPV vaccination reduced adverse pregnancy outcomes. A New Zealand population-based retrospective study linking first pregnancy outcome data (2008-2014 n = 35,646) with prior quadrivalent HPV vaccination status. Primary outcomes were likelihood (odds ratios, ORs) of PTB, pre-eclampsia, and stillbirth. Exposure groups were based on HPV vaccination. Adjusted ORs were calculated for each outcome, controlling for mother's age at delivery, ethnicity, socioeconomic status, health board region at time of delivery, and body mass index and smoking status at time of registration with maternity care provider. Mother's mean age at delivery was 19 (SD 2.1) years. Of 34,994 the pregnancies included in the final study analyses 62.3% of women were unvaccinated, 11.0% vaccinated with one or two doses and 27.7% vaccinated with three doses prior to pregnancy. PTB (OR: 0.87; CI 0.78, 0.96)) was significantly lower for women who previously received the HPV vaccine. A dose response effect was found with each successive dose received decreasing the likelihood of PTB. No associations between the vaccinated and unvaccinated groups were shown for pre-eclampsia or stillbirth. Prior receipt of the quadrivalent HPV vaccine was associated with a significant reduction in PTB (13%); suggesting that HPV vaccination may be effective in reducing PTB. The potential global public health impact is considerable and there is urgency to undertake further research to replicate and explore these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Development of Antibody-Based Vaccines Targeting the Tumor Vasculature.

    Science.gov (United States)

    Zhuang, Xiaodong; Bicknell, Roy

    2016-01-01

    A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.

  13. Recent Advances in Vaccines Against Leishmania Based on Patent Applications.

    Science.gov (United States)

    Thomaz-Soccol, Vanete; Ferreira da Costa, Eduardo Scopel; Karp, Susan Grace; Junior Letti, Luiz Alberto; Soccol, Flavia Thomaz; Soccol, Carlos Ricardo

    2018-01-01

    Leishmaniasis is caused by parasites of the genus Leishmania, and represents a group of chronic diseases with an epidemiological and clinical diversity. The disease is endemic in tropical regions, being found in 98 countries, affecting around 12 million people, with an estimated increase of 1.5 million per year. The present review aims to analyze recent and most important patents regarding development of vaccines to improve immunization against leishmaniasis. For this purpose, the Web of Science - Derwent Innovations Index was consulted. There is also a short description of the licensed vaccines already on the market for commercialization, and a critical opinion on future developments. The data herein presented comprises national and international filings, thus considering the patent's country of origin, and can be used an indicator of a country's technological development regarding a specific field. Several types of vaccines against Leishmania were studied. The main classes comprise: vaccines using live cells (virulent or attenuated); dead cells; containing recombinant protein; using DNA of the parasite. United States (74 patents) leads the ranking of patent applications for vaccines against Leishmania, followed by Brazil (36 patents), which is an endemic region of leishmaniasis with 20,000 human cases of cutaneous leishmaniasis and over 3,000 cases of visceral form. This review showed that there is still a lot of space for development regarding the creation of a feasible, effective vaccine against leishmaniasis. The scientific community appears to be taking steps in the right direction, though. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Rotavirus vaccination and herd immunity: an evidence-based review

    Directory of Open Access Journals (Sweden)

    Seybolt LM

    2012-06-01

    Full Text Available Lorna M Seybolt, Rodolfo E BéguéDepartment of Pediatrics, Division of Infectious Diseases, Louisiana State University Health Sciences Center, New Orleans, LA, USAAbstract: Until recently, rotavirus was the most common cause of diarrhea in infants and young children with over 100 million cases and 400,000 deaths every year worldwide. Yet, its epidemiology is changing rapidly with the introduction of two rotavirus vaccines in the mid 2000s. Both vaccines were shown to be highly efficacious in prelicensure studies to reduce severe rotavirus disease; the efficacy being more pronounced in high- and middle-income countries than in low-income countries. Herd immunity – the indirect protection of unimmunized individuals as a result of others being immunized – was not expected to be a benefit of rotavirus vaccination programs since the vaccines were thought to reduce severe disease but not to decrease virus transmission significantly. Postlicensure studies, however, have suggested that this assumption may need reassessment. Studies in a variety of settings have shown evidence of greater than expected declines in rotavirus disease. While these studies were not designed specifically to detect herd immunity – and few failed to detect this phenomenon – the consistency of the evidence is compelling. These studies are reviewed and described here. While further work is needed, clarifying the presence of herd immunity is not just an academic exercise but an important issue for rotavirus control, especially in lower income countries where the incidence of the disease is highest and the direct protection of the vaccines is lower.Keywords: rotavirus, vaccine, herd immunity, efficacy

  15. Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

    Science.gov (United States)

    Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  16. SPS and PS Experiments Committee

    CERN Multimedia

    CERN. Geneva

    2004-01-01

    OPEN SESSION: 09:00 Status report of NA58 / COMPASS: A. Magnon 09:40 Status report of PS212 / DIRAC: L. Tausher 10:10 PS212 / DIRAC Addendum: L. Nemenov CLOSED SESSION on Tuesday, 27 April 2004 after the open session, Main Building, 6th floor conference room

  17. Bacterial superglue enables easy development of efficient virus-like particle based vaccines

    DEFF Research Database (Denmark)

    Thrane, Susan; Janitzek, Christoph M; Matondo, Sungwa

    2016-01-01

    BACKGROUND: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches...... for VLP-based antigen display require labor-intensive trial-and-error optimization, and often fail to generate dense antigen display. Here we utilize the split-intein (SpyTag/SpyCatcher) conjugation system to generate stable isopeptide bound antigen-VLP complexes by simply mixing of the antigen and VLP......). CONCLUSIONS: The spy-VLP system constitutes a versatile and rapid method to develop highly immunogenic VLP-based vaccines. Our data provide proof-of-concept for the technology's ability to present complex vaccine antigens to the immune system and elicit robust functional antibody responses as well...

  18. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    DEFF Research Database (Denmark)

    Schmidt, Signe Tandrup; Foged, Camilla; Korsholm, Karen Smith

    2016-01-01

    be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode......The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens...... of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR expression profile of the target APCs. Here, we review state-of-the-art formulation approaches employed for the inclusion of immunostimulators and subunit...

  19. Virus like particle-based vaccines against emerging infectious disease viruses.

    Science.gov (United States)

    Liu, Jinliang; Dai, Shiyu; Wang, Manli; Hu, Zhihong; Wang, Hualin; Deng, Fei

    2016-08-01

    Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.

  20. Antitumour responses induced by a cell-based Reovirus vaccine in murine lung and melanoma models

    International Nuclear Information System (INIS)

    Campion, Ciorsdan A.; Soden, Declan; Forde, Patrick F.

    2016-01-01

    The ever increasing knowledge in the areas of cell biology, the immune system and the mechanisms of cancer are allowing a new phase of immunotherapy to develop. The aim of cancer vaccination is to activate the host immune system and some success has been observed particularly in the use of the BCG vaccine for bladder cancer as an immunostimulant. Reovirus, an orphan virus, has proven itself as an oncolytic virus in vitro and in vivo. Over 80 % of tumour cell lines have been found to be susceptible to Reovirus infection and it is currently in phase III clinical trials. It has been shown to induce immune responses to tumours with very low toxicities. In this study, Reovirus was examined in two main approaches in vivo, in mice, using the melanoma B16F10 and Lewis Lung Carcinoma (LLC) models. Initially, mice were treated intratumourally (IT) with Reovirus and the immune responses determined by cytokine analysis. Mice were also vaccinated using a cell-based Reovirus vaccine and subsequently exposed to a tumourigenic dose of cells (B16F10 or LLC). Using the same cell-based Reovirus vaccine, established tumours were treated and subsequent immune responses and virus retrieval investigated. Upregulation of several cytokines was observed following treatment and replication-competent virus was also retrieved from treated tumours. Varying levels of cytokine upregulation were observed and no replication-competent virus was retrieved in vaccine-treated mice. Prolongation of survival and delayed tumour growth were observed in all models and an immune response to Reovirus, either using Reovirus alone or a cell-based vaccine was also observed in all mice. This study provides evidence of immune response to tumours using a cell-based Reovirus vaccine in both tumour models investigated, B16F10 and LLC, cytokine induction was observed with prolongation of survival in almost all cases which may suggest a new method for using Reovirus in the clinic

  1. Plant-based anti-HIV-1 strategies: vaccine molecules and antiviral approaches.

    Science.gov (United States)

    Scotti, Nunzia; Buonaguro, Luigi; Tornesello, Maria Lina; Cardi, Teodoro; Buonaguro, Franco Maria

    2010-08-01

    The introduction of highly active antiretroviral therapy has drastically changed HIV infection from an acute, very deadly, to a chronic, long-lasting, mild disease. However, this requires continuous care management, which is difficult to implement worldwide, especially in developing countries. Sky-rocketing costs of HIV-positive subjects and the limited success of preventive recommendations mean that a vaccine is urgently needed, which could be the only effective strategy for the real control of the AIDS pandemic. To be effective, vaccination will need to be accessible, affordable and directed against multiple antigens. Plant-based vaccines, which are easy to produce and administer, and require no cold chain for their heat stability are, in principle, suited to such a strategy. More recently, it has been shown that even highly immunogenic, enveloped plant-based vaccines can be produced at a competitive and more efficient rate than conventional strategies. The high variability of HIV epitopes and the need to stimulate both humoral neutralizing antibodies and cellular immunity suggest the importance of using the plant system: it offers a wide range of possible strategies, from single-epitope to multicomponent vaccines, modulators of the immune response (adjuvants) and preventive molecules (microbicides), either alone or in association with plant-derived monoclonal antibodies, besides the potential use of the latter as therapeutic agents. Furthermore, plant-based anti-HIV strategies can be administered not only parenterally but also by the more convenient and safer oral route, which is a more suitable approach for possible mass vaccination.

  2. Liposome-based synthetic long peptide vaccines for cancer immunotherapy

    NARCIS (Netherlands)

    Varypataki, E.M.

    2016-01-01

    Synthetic long peptides (SLP) derived from cancer-associated antigens hold great promise as well-defined antigens for cancer immunotherapy. Clinical studies showed that SLP vaccines have functional potency when applied to pre-malignant stage patients, but need to be improved for use as a therapeutic

  3. Genetically engineered dendritic cell-based cancer vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2001-01-01

    Roč. 18, č. 3 (2001), s. 475-478 ISSN 1019-6439 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.330, year: 2001

  4. Genetically modified dendritic cell-based cancer vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2001-01-01

    Roč. 47, č. 5 (2001), s. 153-155 ISSN 0015-5500 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

  5. Universal or Specific? A Modeling-Based Comparison of Broad-Spectrum Influenza Vaccines against Conventional, Strain-Matched Vaccines.

    Directory of Open Access Journals (Sweden)

    Rahul Subramanian

    2016-12-01

    Full Text Available Despite the availability of vaccines, influenza remains a major public health challenge. A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population to cause a pandemic every few decades. Current vaccines have to be updated continually to keep up to date with this antigenic change, but emerging 'universal' vaccines-targeting more conserved components of the influenza virus-offer the potential to act across all influenza A strains and subtypes. Influenza vaccination programmes around the world are steadily increasing in their population coverage. In future, how might intensive, routine immunization with novel vaccines compare against similar mass programmes utilizing conventional vaccines? Specifically, how might novel and conventional vaccines compare, in terms of cumulative incidence and rates of antigenic evolution of seasonal influenza? What are their potential implications for the impact of pandemic emergence? Here we present a new mathematical model, capturing both transmission dynamics and antigenic evolution of influenza in a simple framework, to explore these questions. We find that, even when matched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccines could allow the increased spread of a novel pandemic strain. Conversely, universal vaccines could mitigate both seasonal and pandemic spread. However, where it is not possible to maintain annual, intensive vaccination coverage, the duration and breadth of immunity raised by universal vaccines are critical determinants of their performance relative to conventional vaccines. In future, conventional and novel vaccines are likely to play complementary roles in

  6. Correlates of Protection for M Protein-Based Vaccines against Group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Shu Ki Tsoi

    2015-01-01

    Full Text Available Group A streptococcus (GAS is known to cause a broad spectrum of illness, from pharyngitis and impetigo, to autoimmune sequelae such as rheumatic heart disease, and invasive diseases. It is a significant cause of infectious disease morbidity and mortality worldwide, but no efficacious vaccine is currently available. Progress in GAS vaccine development has been hindered by a number of obstacles, including a lack of standardization in immunoassays and the need to define human correlates of protection. In this review, we have examined the current immunoassays used in both GAS and other organisms, and explored the various challenges in their implementation in order to propose potential future directions to identify a correlate of protection and facilitate the development of M protein-based vaccines, which are currently the main GAS vaccine candidates.

  7. Correlates of Protection for M Protein-Based Vaccines against Group A Streptococcus

    Science.gov (United States)

    Smeesters, Pierre R.; Frost, Hannah R. C.; Steer, Andrew C.

    2015-01-01

    Group A streptococcus (GAS) is known to cause a broad spectrum of illness, from pharyngitis and impetigo, to autoimmune sequelae such as rheumatic heart disease, and invasive diseases. It is a significant cause of infectious disease morbidity and mortality worldwide, but no efficacious vaccine is currently available. Progress in GAS vaccine development has been hindered by a number of obstacles, including a lack of standardization in immunoassays and the need to define human correlates of protection. In this review, we have examined the current immunoassays used in both GAS and other organisms, and explored the various challenges in their implementation in order to propose potential future directions to identify a correlate of protection and facilitate the development of M protein-based vaccines, which are currently the main GAS vaccine candidates. PMID:26101780

  8. Ontology-based literature mining of E. coli vaccine-associated gene interaction networks.

    Science.gov (United States)

    Hur, Junguk; Özgür, Arzucan; He, Yongqun

    2017-03-14

    Pathogenic Escherichia coli infections cause various diseases in humans and many animal species. However, with extensive E. coli vaccine research, we are still unable to fully protect ourselves against E. coli infections. To more rational development of effective and safe E. coli vaccine, it is important to better understand E. coli vaccine-associated gene interaction networks. In this study, we first extended the Vaccine Ontology (VO) to semantically represent various E. coli vaccines and genes used in the vaccine development. We also normalized E. coli gene names compiled from the annotations of various E. coli strains using a pan-genome-based annotation strategy. The Interaction Network Ontology (INO) includes a hierarchy of various interaction-related keywords useful for literature mining. Using VO, INO, and normalized E. coli gene names, we applied an ontology-based SciMiner literature mining strategy to mine all PubMed abstracts and retrieve E. coli vaccine-associated E. coli gene interactions. Four centrality metrics (i.e., degree, eigenvector, closeness, and betweenness) were calculated for identifying highly ranked genes and interaction types. Using vaccine-related PubMed abstracts, our study identified 11,350 sentences that contain 88 unique INO interactions types and 1,781 unique E. coli genes. Each sentence contained at least one interaction type and two unique E. coli genes. An E. coli gene interaction network of genes and INO interaction types was created. From this big network, a sub-network consisting of 5 E. coli vaccine genes, including carA, carB, fimH, fepA, and vat, and 62 other E. coli genes, and 25 INO interaction types was identified. While many interaction types represent direct interactions between two indicated genes, our study has also shown that many of these retrieved interaction types are indirect in that the two genes participated in the specified interaction process in a required but indirect process. Our centrality analysis of

  9. Impact of Targeted Tuberculosis Vaccination Among a Mining Population in South Africa: A Model-Based Study.

    Science.gov (United States)

    Shrestha, Sourya; Chihota, Violet; White, Richard G; Grant, Alison D; Churchyard, Gavin J; Dowdy, David W

    2017-12-15

    Optimizing the use of new tools, such as vaccines, may play a crucial role in reaching global targets for tuberculosis (TB) control. Some of the most promising candidate vaccines target adults, although high-coverage mass vaccinations may be logistically more challenging among this population than among children. Vaccine-delivery strategies that target high-risk groups or settings might yield proportionally greater impact than do those that target the general population. We developed an individual-based TB transmission model representing a hypothetical population consisting of people who worked in South African gold mines or lived in associated labor-sending communities. We simulated the implementation of a postinfection adult vaccine with 60% efficacy and a mean effect duration of 10 years. We then compared the impact of a mine-targeted vaccination strategy, in which miners were vaccinated while in the mines, with that of a community-targeted strategy, in which random individuals within the labor-sending communities were vaccinated. Mine-targeted vaccination averted an estimated 0.37 TB cases per vaccine dose compared with 0.25 for community-targeted vaccination, for a relative efficacy of 1.46 (95% range, 1.13-1.91). The added benefit of mine-targeted vaccination primarily reflected the disproportionate demographic burden of TB among the population of adult males as a whole. As novel vaccines for TB are developed, venue-based vaccine delivery that targets high-risk demographic groups may improve both vaccine feasibility and the impact on transmission. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    Directory of Open Access Journals (Sweden)

    Signe Tandrup Schmidt

    2016-03-01

    Full Text Available The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

  11. Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV Based Delivery System.

    Directory of Open Access Journals (Sweden)

    Sukalyani Banik

    Full Text Available Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA, chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100 doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

  12. Evaluation of an ompA-based phage-mediated DNA vaccine against Chlamydia abortus in piglets.

    Science.gov (United States)

    Ou, Changbo; Tian, Deyu; Ling, Yong; Pan, Qing; He, Qing; Eko, Francis O; He, Cheng

    2013-08-01

    Chlamydia abortus (C. abortus) is an obligate intracellular pathogen that causes abortion in pigs and poses a zoonotic risk in pregnant women. Although attenuated and inactivated vaccines are available, they do not provide complete protection in animals underlining the need to develop new vaccines. In this study, we tested the hypothesis that intramuscular immunization with an ompA-based phage-mediated DNA chlamydial vaccine candidate will induce significant antigen-specific cellular and humoral immune responses. Thus, groups of piglets (five per group) were immunized intramuscularly with the phage-MOMP vaccine (λ-MOMP) or a commercial live-attenuated vaccine (1B vaccine) or a GFP-expressing phage (λ-GFP) or phosphate buffered saline (PBS) (control) and antigen-specific cell-mediated and humoral immune responses were evaluated. By day 63 post-immunization, the λ-MOMP vaccine elicited significantly higher (Pabortus. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Design and implementation of a children vaccination reminder system based on short message service

    Directory of Open Access Journals (Sweden)

    Marjan Ghazisaeedi

    2016-09-01

    Full Text Available Background: Most problems related to quality of care and patient safety are related to human negligence. One of the causes of these problems is forgetting to do something. This problem can be avoided with information technology in many cases. Some forgotten are very important. Among these is failure to comply with vaccination schedule by parents that can result in inappropriate outcomes. In this study, we developed and evaluated a SMS reminder system for regular and timely vaccination of children. Methods: In this developmental-applied research, firstly, a child vaccination reminder system was designed and implemented to help parents reduce the forgetfulness. This system based on the child's vaccination history and the date of birth, offer time and type of future vaccines. Then the parents of 27 children, that their vaccination was between 22 June and 21 August 2015, referred to Children's Medical Center, were sent text messages by using this system. We evaluated the accuracy of the system logic by using some scenarios. In addition, we evaluated parents' satisfaction with the system using a questionnaire. Results: In all cases but one, the system proposed the type and date of future children vaccines correctly. All the parents who have received text messages had good perception and satisfaction on the majority of questions (total mean score of 4.15 out of 5. Most parents (4.92 out of 5 stated that using the system to remind their visit for child immunization was helpful and willing to offer the system to their friends and other families. Conclusion: Using the short message system is beneficial for parents to remind their children’s vaccination time and increases their satisfaction. So, it can be considered as an important and essential tool in providing healthcare services. SMS is an easy, cheap and effective way to improve the quality of care services.

  14. Using magnetic resonance imaging to evaluate dendritic cell-based vaccination.

    Directory of Open Access Journals (Sweden)

    Peter M Ferguson

    Full Text Available Cancer immunotherapy with antigen-loaded dendritic cell-based vaccines can induce clinical responses in some patients, but further optimization is required to unlock the full potential of this strategy in the clinic. Optimization is dependent on being able to monitor the cellular events that take place once the dendritic cells have been injected in vivo, and to establish whether antigen-specific immune responses to the tumour have been induced. Here we describe the use of magnetic resonance imaging (MRI as a simple, non-invasive approach to evaluate vaccine success. By loading the dendritic cells with highly magnetic iron nanoparticles it is possible to assess whether the injected cells drain to the lymph nodes. It is also possible to establish whether an antigen-specific response is initiated by assessing migration of successive rounds of antigen-loaded dendritic cells; in the face of a successfully primed cytotoxic response, the bulk of antigen-loaded cells are eradicated on-route to the node, whereas cells without antigen can reach the node unchecked. It is also possible to verify the induction of a vaccine-induced response by simply monitoring increases in draining lymph node size as a consequence of vaccine-induced lymphocyte trapping, which is an antigen-specific response that becomes more pronounced with repeated vaccination. Overall, these MRI techniques can provide useful early feedback on vaccination strategies, and could also be used in decision making to select responders from non-responders early in therapy.

  15. Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines.

    Science.gov (United States)

    Bobbala, Sharan; Tamboli, Viral; McDowell, Arlene; Mitra, Ashim K; Hook, Sarah

    2016-01-01

    The need for multiple vaccinations to enhance the immunogenicity of subunit vaccines may be reduced by delivering the vaccine over an extended period of time. Here, we report two novel injectable pentablock copolymer based thermoresponsive hydrogels made of polyethyleneglycol-polycaprolactone-polylactide-polycaprolactone-polyethyleneglycol (PEG-PCL-PLA-PCL-PEG) with varying ratios of polycaprolactone (PCL) and polylactide (PLA), as single shot sustained release vaccines. Pentablock copolymer hydrogels were loaded with vaccine-encapsulated poly lactic-co-glycolic acid nanoparticles (PLGA-NP) or with the soluble vaccine components. Incorporation of PLGA-NP into the thermoresponsive hydrogels increased the complex viscosity of the gels, lowered the gelation temperature, and minimized the burst release of antigen and adjuvants. The two pentablock hydrogels stimulated both cellular and humoral responses. The addition of PLGA-NP to the hydrogels sustained immune responses for up to 49 days. The polymer with a higher ratio of PCL to PLA formed a more rigid gel, induced stronger immune responses, and stimulated effective anti-tumor responses in a prophylactic melanoma tumor model.

  16. Dendritic cell-based vaccination in cancer: therapeutic implications emerging from murine models

    Directory of Open Access Journals (Sweden)

    Soledad eMac Keon

    2015-05-01

    Full Text Available Dendritic cells (DCs play a pivotal role in the orchestration of immune responses, and are thus key targets in cancer vaccine design. Since the 2010 FDA approval of the first cancer DC-based vaccine (Sipuleucel T there has been a surge of interest in exploiting these cells as a therapeutic option for the treatment of tumors of diverse origin. In spite of the encouraging results obtained in the clinic, many elements of DC-based vaccination strategies need to be optimized. In this context, the use of experimental cancer models can help direct efforts towards an effective vaccine design. This paper reviews recent findings in murine models regarding the antitumoral mechanisms of DC-based vaccination, covering issues related to antigen sources, the use of adjuvants and maturing agents, and the role of DC subsets and their interaction in the initiation of antitumoral immune responses. The summary of such diverse aspects will highlight advantages and drawbacks in the use of murine models, and contribute to the design of successful DC-based translational approaches for cancer treatment.

  17. Vaccination: Developing and implementing a competency-based-curriculum at the Medical Faculty of LMU Munich

    Directory of Open Access Journals (Sweden)

    Vogel, B.

    2016-02-01

    Full Text Available Background: In Germany medical students should gain proficiency and specific skills in the vaccination field. Especially important is the efficient communication of scientific results about vaccinations to the community, in order to give professional counseling with a complete overview about therapeutic options.Aim of the project: The aim of this project is to set up a vaccination-related curriculum in the Medical Faculty at the Ludwig-Maximilians-University in Munich. The structure of the curriculum is based on the National catalogue for competency-based learning objectives in the field of vaccination (Nationaler Kompetenzbasierter Lernzielekatalog Medizin NKLM. Through this curriculum, the students will not only acquire the classical educational skills concerning vaccination in theory and practice, but they will also learn how to become independent in the decision-making process and counseling. Moreover, the students will become aware of consequences of action related to this specific topic.Methods: According to defined guidelines, an analysis was performed on courses, which are currently offered by the university. A separate analysis of the NKLM was carried out. Both analyses identified the active courses related to the topic of vaccination as well as the NKLM learning objectives. The match between the topics taught in current courses and the NKLM learning objectives identified gaps concerning the teaching of specific content. Courses were modified in order to implement the missing NKLM learning objectives.Results: These analyses identified 24 vaccination-related courses, which are currently taught at the University. Meanwhile, 35 learning objectives on vaccination were identified in the NKLM catalogue. Four of which were identified as not yet part of the teaching program. In summary, this interdisciplinary work enabled the development of a new vaccination-related curriculum, including 35 learning objectives, which are now implemented in

  18. Analysis of hepatitis B vaccination behavior and vaccination willingness among migrant workers from rural China based on protection motivation theory.

    Science.gov (United States)

    Liu, Rugang; Li, Youwei; Wangen, Knut R; Maitland, Elizabeth; Nicholas, Stephen; Wang, Jian

    2016-05-03

    With China's accelerating urbanization, migrant workers comprise up to 40% of the urban population of China's largest cities. More mobile than non-migrant urban dwellers, migrants are more likely to contract and spread hepatitis B (HB) than non-migrants. Due to the mandatory system of household registration (hukou), migrants are less likely to be covered by national HB immunization programs and also to have more limited access to public health services where they work than non-migrants. Migrants form a significant sub-group in all Chinese cities posing unique public policy vaccination challenges. Using protection motivation theory (PMT), we developed and measured HB cognitive variables and analyze the factors affecting HB vaccination behavior and willingness to vaccinate by migrant workers. We propose public policy interventions to increase HB vaccination rates of migrant workers. We developed a questionnaire to collect information on the HB vaccination characteristics of 1684 respondents from 6 provinces and Beijing. Exploratory factor analysis was used to create PMT variables and a binary logistic regression model was used to analyze the factors affecting migrant workers' HB vaccination behavior and willingness to vaccinate. Vulnerability and response-efficacy were significant PMT cognition factors determining HB vaccination behavior. The HB vaccination rate for migrants decreased with increasing age and was smaller for the primary education than the high education group. The vaccination rate of the medical insurance group was significantly greater than the non-insured group, and the vaccination probability was significantly higher for the self-rated good health compared to the self-rated poor health group. Geographical birth location mattered: the vaccination rate for Beijing city and Ningxia province migrants were higher than for Hebei province and the vaccination rate was lower for migrants born far from health facilities compared to those located middle

  19. Oxide-Based Composite Electrolytes Using Na3Zr2Si2PO12/Na3PS4 Interfacial Ion Transfer.

    Science.gov (United States)

    Noi, Kousuke; Nagata, Yuka; Hakari, Takashi; Suzuki, Kenji; Yubuchi, So; Ito, Yusuke; Sakuda, Atsushi; Hayashi, Akitoshi; Tatsumisago, Masahiro

    2018-05-31

    All-solid-state sodium batteries using Na 3 Zr 2 Si 2 PO 12 (NASICON) solid electrolytes are promising candidates for safe and low-cost advanced rechargeable battery systems. Although NASICON electrolytes have intrinsically high sodium-ion conductivities, their high sintering temperatures interfere with the immediate development of high-performance batteries. In this work, sintering-free NASICON-based composites with Na 3 PS 4 (NPS) glass ceramics were prepared to combine the high grain-bulk conductivity of NASICON and the interfacial formation ability of NPS. Before the composite preparation, the NASICON/NPS interfacial resistance was investigated by modeling the interface between the NASICON sintered ceramic and the NPS glass thin film. The interfacial ion-transfer resistance was very small above room temperature; the area-specific resistances at 25 and 100 °C were 15.8 and 0.40 Ω cm 2 , respectively. On the basis of this smooth ion transfer, NASICON-rich (70-90 wt %) NASICON-NPS composite powders were prepared by ball-milling fine powders of each component. The composite powders were well-densified by pressing at room temperature. Scanning electron microscopy observation showed highly dispersed sub-micrometer NASICON grains in a dense NPS matrix to form closed interfaces between the oxide and sulfide solid electrolytes. The composite green (unfired) compacts with 70 and 80 wt % NASICON exhibited high total conductivities at 100 °C of 1.1 × 10 -3 and 6.8 × 10 -4 S cm -1 , respectively. An all-solid-state Na 15 Sn 4 /TiS 2 cell was constructed using the 70 wt % NASICON composite electrolyte by the uniaxial pressing of the powder materials, and its discharge properties were evaluated at 100 °C. The cell showed the reversible capacities of about 120 mAh g -1 under the current density of 640 μA cm -2 . The prepared oxide-based composite electrolytes were thus successfully applied in all-solid-state sodium rechargeable batteries without sintering.

  20. Asymmetric PS-block-(PS-co-PB)-block-PS block copolymers: morphology formation and deformation behaviour

    International Nuclear Information System (INIS)

    Adhikari, Rameshwar; Huy, Trinh An; Buschnakowski, Matthias; Michler, Goerg H; Knoll, Konrad

    2004-01-01

    Morphology formation and deformation behaviour of asymmetric styrene/butadiene triblock copolymers (total polystyrene (PS) content ∼70%) consisting of PS outer blocks held apart by a styrene-co-butadiene random copolymer block (PS-co-PB) each were investigated. The techniques used were differential scanning calorimetry, transmission electron microscopy, uniaxial tensile testing and Fourier-transform infrared spectroscopy. A significant shift of the phase behaviour relative to that of a neat symmetric triblock copolymer was observed, which can be attributed to the asymmetric architecture and the presence of PS-co-PB as a soft block. The mechanical properties and the microdeformation phenomena were mainly controlled by the nature of their solid-state morphology. Independent of morphology type, the soft phase was found to deform to a significantly higher degree of orientation when compared with the hard phase

  1. Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management.

    Directory of Open Access Journals (Sweden)

    Gergana Galabova

    Full Text Available Low Density Lipoprotein (LDL hypercholesterolemia, and its associated cardiovascular diseases, are some of the leading causes of death worldwide. The ability of proprotein convertase subtilisin/kexin 9 (PCSK9 to modulate circulating LDL cholesterol (LDLc concentrations made it a very attractive target for LDLc management. To date, the most advanced approaches for PCSK9 inhibition are monoclonal antibody (mAb therapies. Although shown to lower LDLc significantly, mAbs face functional limitations because of their relatively short in vivo half-lives necessitating frequent administration. Here, we evaluated the long-term efficacy and safety of PCSK9-specific active vaccines in different preclinical models.PCSK9 peptide-based vaccines were successfully selected by our proprietary technology. To test their efficacy, wild-type (wt mice, Ldlr+/- mice, and rats were immunized with highly immunogenic vaccine candidates. Vaccines induced generation of high-affine PCSK9-specific antibodies in all species. Group mean total cholesterol (TC concentration was reduced by up to 30%, and LDLc up to 50% in treated animals. Moreover, the PCSK9 vaccine-induced humoral immune response persisted for up to one year in mice, and reduced cholesterol levels significantly throughout the study. Finally, the vaccines were well tolerated in all species tested.Peptide-based anti-PCSK9 vaccines induce the generation of antibodies that are persistent, high-affine, and functional for up to one year. They are powerful and safe tools for long-term LDLc management, and thus may represent a novel therapeutic approach for the prevention and/or treatment of LDL hypercholesterolemia-related cardiovascular diseases in humans.

  2. Immunogenicity of a DNA-launched replicon-based canine parvovirus DNA vaccine expressing VP2 antigen in dogs.

    Science.gov (United States)

    Dahiya, Shyam S; Saini, Mohini; Kumar, Pankaj; Gupta, Praveen K

    2012-10-01

    A replicon-based DNA vaccine encoding VP2 gene of canine parvovirus (CPV) was developed by cloning CPV-VP2 gene into a replicon-based DNA vaccine vector (pAlpha). The characteristics of a replicon-based DNA vaccine like, self-amplification of transcripts and induction of apoptosis were analyzed in transfected mammalian cells. When the pAlpha-CPV-VP2 was injected intradermal as DNA-launched replicon-based DNA vaccine in dogs, it induced CPV-specific humoral and cell mediated immune responses. The virus neutralization antibody and lymphocyte proliferative responses were higher than conventional CPV DNA vaccine and commercial CPV vaccine. These results indicated that DNA-launched replicon-based CPV DNA vaccine was effective in inducing both CPV-specific humoral and cellular immune responses and can be considered as effective alternative to conventional CPV DNA vaccine and commercial CPV vaccine. Crown Copyright © 2012. Published by Elsevier India Pvt Ltd. All rights reserved.

  3. Peptide-based subunit vaccine against hookworm infection.

    Directory of Open Access Journals (Sweden)

    Mariusz Skwarczynski

    Full Text Available Hookworms infect more people than HIV and malaria combined, predominantly in third world countries. Treatment of infection with chemotherapy can have limited efficacy and re-infections after treatment are common. Heavy infection often leads to debilitating diseases. All these factors suggest an urgent need for development of vaccine. In an attempt to develop a vaccine targeting the major human hookworm, Necator americanus, a B-cell peptide epitope was chosen from the apical enzyme in the hemoglobin digestion cascade, the aspartic protease Na-APR-1. The A(291Y alpha helical epitope is known to induce neutralizing antibodies that inhibit the enzymatic activity of Na-APR-1, thus reducing the capacity for hookworms to digest hemoglobin and obtain nutrients. A(291Y was engineered such that it was flanked on both termini by a coil-promoting sequence to maintain native conformation, and subsequently incorporated into a Lipid Core Peptide (LCP self-adjuvanting system. While A(291Y alone or the chimeric epitope with or without Freund's adjuvants induced negligible IgG responses, the LCP construct incorporating the chimeric peptide induced a strong IgG response in mice. Antibodies produced were able to bind to and completely inhibit the enzymatic activity of Na-APR-1. The results presented show that the new chimeric LCP construct can induce effective enzyme-neutralising antibodies in mice, without the help of any additional toxic adjuvants. This approach offers promise for the development of vaccines against helminth parasites of humans and their livestock and companion animals.

  4. Nuclear Magnetic Resonance: new applications in the quantification and assessment of polysaccharide-based vaccine intermediates

    International Nuclear Information System (INIS)

    Garrido, Raine; Velez, Herman; Verez, Vicente

    2013-01-01

    Nuclear Magnetic Resonance has become the choice for structural studies, identity assays and simultaneous quantification of active pharmaceutical ingredient of different polysaccharide-based vaccine. In the last two decades, the application of quantitative Nuclear Magnetic Resonance had an increasing impact to support several quantification necessities. The technique involves experiments with several modified parameters in order to obtain spectra with quantifiable signals. The present review is supported by some recent relevant reports and it discusses several applications of NMR in carbohydrate-based vaccines. Moreover, it emphasizes and describes several parameters and applications of quantitative Nuclear Magnetic Resonance

  5. Bone marrow dendritic cell-based anticancer vaccines

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Mendoza, Luis; Reiniš, Milan; Vonka, V.; Šmahel, M.; Němečková, Š.; Jandlová, Táňa; Bubeník, Jan

    2001-01-01

    Roč. 495, - (2001), s. 355-358 ISSN 0065-2598 R&D Projects: GA MZd NC5526; GA ČR GA312/98/0826; GA ČR GA312/99/0542; GA ČR GA301/00/0114; GA ČR GA301/01/0985; GA AV ČR IAA7052002 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV16 * dendritic cell s * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.513, year: 2000

  6. Relationship between dimensions of Brand Equity and 4Ps of Marketing Mix - Place, Product, Promotion, & Price: Coca Cola - Consumer Based Qualitative Survey

    OpenAIRE

    Arab, Nazanin

    2018-01-01

    The relationship between dimensions of brand equity (brand association, brand awareness, perceived quality, and customer's loyalty) and 4Ps of marketing mix (product, place, price, and promotion) are examined in this paper. Cross sectional research design while following inductive approach I have explore the relationship between research variables from consumer's perspective. Total 129 participants took part in this survey. Respondents were identified and approached through convenience sa...

  7. Immunological consequences of using three different clinical/laboratory techniques of emulsifying peptide-based vaccines in incomplete Freund's adjuvant

    Directory of Open Access Journals (Sweden)

    Kast W Martin

    2006-10-01

    Full Text Available Abstract Incomplete Freund's adjuvant (IFA serves as a carrier for water-in-oil emulsion (W/O vaccines. The stability of such emulsions greatly affects vaccine safety and efficacy since continued presence of antigen depots at lymphoid organs releasing low-level antigens is known to stimulate a potent immune response and high-level systemic release of antigens can lead to tolerance. W/O emulsions for the purpose of clinical and laboratory peptide-based vaccinations have been prepared using the techniques of syringe extrusion, vortex or high-speed homogenization. There is no consensus in the field over which technique would be best to use and no immunological data are available that compare the three techniques. In this study, we compared the immune responses induced by a peptide-based vaccine prepared using vortex, syringe-extrusion and homogenization. The vaccination led to tumor rejection by mice vaccinated with the peptide-based vaccine prepared using all three techniques. The immunological data from the in vivo cytotoxicity assay showed a trend for lower responses and a higher variability and greater range in the immune responses induced by a vaccine that was emulsified by the vortex or homogenizer techniques as compared to the syringe-extrusion technique. There were statistically significant lower numbers of IFNγ-secreting cells induced when the mice were vaccinated with a peptide-based vaccine emulsion prepared using the vortex compared to the syringe-extrusion technique. At a suboptimal vaccine dose, the mice vaccinated with a peptide-based vaccine emulsion prepared using the vortex technique had the largest tumors compared to the syringe-extrusion or the homogenizer technique. In the setting of a busy pharmacy that prepares peptide-based vaccine emulsions for clinical studies, the vortex technique can still be used but we urge investigators to take special care in their choice of mixing vessels for the vortex technique as that can

  8. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan; Claesson, Mogens; Nielsen, Hans

    2009-01-01

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...

  9. Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection.

    Science.gov (United States)

    Kwon, Ji-Sun; Yoon, Jungsoon; Kim, Yeon-Jung; Kang, Kyuho; Woo, Sunje; Jung, Dea-Im; Song, Man Ki; Kim, Eun-Ha; Kwon, Hyeok-Il; Choi, Young Ki; Kim, Jihye; Lee, Jeewon; Yoon, Yeup; Shin, Eui-Cheol; Youn, Jin-Won

    2014-08-01

    Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell-based vaccine, but the narrow breadth of T-cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T-cell immunodominance hierarchy in humans in an experimental setting, influenza-primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN-γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T-cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD50 challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP366 epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV-NP + PA showed improved protection. Taken together, a vaccinia-based influenza vaccine expressing conserved internal proteins improved the breadth of influenza-specific T-cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Recombinant allergy vaccines based on allergen-derived B cell epitopes.

    Science.gov (United States)

    Valenta, Rudolf; Campana, Raffaela; Niederberger, Verena

    2017-09-01

    Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensitivity disease. It affects more than 25% of the population. In IgE-sensitized subjects, allergen encounter can causes a variety of symptoms ranging from hayfever (allergic rhinoconjunctivitis) to asthma, skin inflammation, food allergy and severe life-threatening anaphylactic shock. Allergen-specific immunotherapy (AIT) is based on vaccination with the disease-causing allergens. AIT is an extremely effective, causative and disease-modifying treatment. However, administration of natural allergens can cause severe side effects and the quality of natural allergen extracts limits its application. Research in the field of molecular allergen characterization has allowed deciphering the molecular structures of the disease-causing allergens and it has become possible to engineer novel molecular allergy vaccines which precisely target the mechanisms of the allergic immune response and even appear suitable for prophylactic allergy vaccination. Here we discuss recombinant allergy vaccines which are based on allergen-derived B cell epitopes regarding their molecular and immunological properties and review the results obtained in clinical studies with this new type of allergy vaccines. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  11. [PERSPECTIVES OF DEVELOPMENT OF LIVE RECOMBINANT ANTHRAX VACCINES BASED ON OPPORTUNISTIC AND APATHOGENIC MICROORGANISMS].

    Science.gov (United States)

    Popova, P Yu; Mikshis, N I

    2016-01-01

    Live genetic engineering anthrax vaccines on the platform of avirulent and probiotic micro-organisms are a safe and adequate alternative to preparations based on attenuated Bacillus anthracis strains. Mucosal application results in a direct contact of the vaccine preparations with mucous membranes in those organs arid tissues of the macro-organisms, that are exposed to the pathogen in the first place, resulting in a development of local and systemic immune response. Live recombinant anthrax vaccines could be used both separately as well as in a prime-boost immunization scheme. The review focuses on immunogenic and protective properties of experimental live genetic engineering prearations, created based on members of geni of Salmonella, Lactobacillus and adenoviruses.

  12. An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

    Science.gov (United States)

    Fox, Christopher B; Haensler, Jean

    2013-07-01

    With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

  13. CORRELAÇÃO ENTRE PUBLICAÇÕES CIENTÍFICAS E PATENTES COM CÉLULAS-TRONCO PLURIPOTENTE INDUZIDAS (iPS: BASES PARA UMA PROSPECÇÃO TECNOLÓGICA

    Directory of Open Access Journals (Sweden)

    Maria Acelina Carvalho

    2014-12-01

    Full Text Available A reprogramação de células somáticas para uma célula pluripotente indiferenciada, com características de uma célula-tronco embrionária (CTE, é um dos avanços promissores no campo da biologia celular na última década. O objetivo desse trabalho foi reunir informações como base de uma prospecção tecnológica prévia sobre o tema células-tronco pluripotente induzidas (iPS e verificar se existe correlação entre o número de publicações científicas e número de patentes na referida área. Foram pesquisadas patentes depositadas no EPO, USPTO e INPI e publicações científicas na base de dados Web of Science com a finalidade de realizar a correlação entre a quantidade de publicações científicas e o número de patentes depositados por ano e por países .A Organização Mundial de Propriedade Intelectual (WO seguida dos Estados Unidos e China detém os maiores números de patentes depositadas envolvendo iPS. Observa-se que as patentes envolvendo iPS aparecem a partir de 2007 com uma única patente japonesa registrada no INPI. Os EUA lidera o número de publicações científicas sobre iPS com 1.679 publicações na base de dados Web of Science.

  14. Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Thomas W Geisbert

    2008-11-01

    Full Text Available Ebola virus (EBOV is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVDeltaG/ZEBOVGP in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV. All six animals showed no evidence of illness associated with the VSVDeltaG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.

  15. Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine.

    Science.gov (United States)

    Richardson, Jason S; Yao, Michel K; Tran, Kaylie N; Croyle, Maria A; Strong, James E; Feldmann, Heinz; Kobinger, Gary P

    2009-01-01

    The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP). Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the previous generation adenovirus-based Ebola vaccine. Understanding and improving the

  16. Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine.

    Directory of Open Access Journals (Sweden)

    Jason S Richardson

    Full Text Available BACKGROUND: The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP. The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. METHODOLOGY/PRINCIPAL FINDINGS: Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP. Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. CONCLUSIONS/SIGNIFICANCE: We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the

  17. Immunogenicity and protective efficacy of Semliki forest virus replicon-based DNA vaccines encoding goatpox virus structural proteins

    International Nuclear Information System (INIS)

    Zheng Min; Jin Ningyi; Liu Qi; Huo Xiaowei; Li Yang; Hu Bo; Ma Haili; Zhu Zhanbo; Cong Yanzhao; Li Xiao; Jin Minglan; Zhu Guangze

    2009-01-01

    Goatpox, caused by goatpox virus (GTPV), is an acute feverish and contagious disease in goats often associated with high morbidity and high mortality. To resolve potential safety risks and vaccination side effects of existing live attenuated goatpox vaccine (AV41), two Semliki forest virus (SFV) replicon-based bicistronic expression DNA vaccines (pCSm-AAL and pCSm-BAA) which encode GTPV structural proteins corresponding to the Vaccinia virus proteins A27, L1, A33, and B5, respectively, were constructed. Then, theirs ability to induce humoral and cellular response in mice and goats, and protect goats against virulent virus challenge were evaluated. The results showed that, vaccination with pCSm-AAL and pCSm-BAA in combination could elicit strong humoral and cellular responses in mice and goats, provide partial protection against viral challenge in goats, and reduce disease symptoms. Additionally, priming vaccination with the above-mentioned DNA vaccines could significantly reduce the goats' side reactions from boosting vaccinations with current live vaccine (AV41), which include skin lesions at the inoculation site and fevers. Data obtained in this study could not only facilitate improvement of the current goatpox vaccination strategy, but also provide valuable guidance to suitable candidates for evaluation and development of orthopoxvirus vaccines.

  18. From non school-based, co-payment to school-based, free Human Papillomavirus vaccination in Flanders (Belgium): a retrospective cohort study describing vaccination coverage, age-specific coverage and socio-economic inequalities.

    Science.gov (United States)

    Lefevere, Eva; Theeten, Heidi; Hens, Niel; De Smet, Frank; Top, Geert; Van Damme, Pierre

    2015-09-22

    School-based, free HPV vaccination for girls in the first year of secondary school was introduced in Flanders (Belgium) in 2010. Before that, non school-based, co-payment vaccination for girls aged 12-18 was in place. We compared vaccination coverage, age-specific coverage and socio-economic inequalities in coverage - 3 important parameters contributing to the effectiveness of the vaccination programs - under both vaccination systems. We used retrospective administrative data from different sources. Our sample consisted of all female members of the National Alliance of Christian Mutualities born in 1995, 1996, 1998 or 1999 (N=66,664). For each vaccination system we described the cumulative proportion HPV vaccination initiation and completion over time. We used life table analysis to calculate age-specific rates of HPV vaccination initiation and completion. Analyses were done separately for higher income and low income groups. Under non school-based, co-payment vaccination the proportions HPV vaccination initiation and completion slowly rose over time. By age 17, the proportion HPV vaccination initiation/completion was 0.75 (95% CI 0.74-076)/0.66 (95% CI 0.65-0.67). The median age at vaccination initiation/completion was 14.4 years (95% CI 14.4-14.5)/15.4 years (95% CI 15.3-15.4). Socio-economic inequalities in coverage widened over time and with age. Under school-based, free vaccination rates of HPV vaccination initiation were substantially higher. By age 14,the proportion HPV vaccination initiation/completion was 0.90 (95% CI 0.90-0.90)/0.87 (95% CI 0.87-0.88). The median age at vaccination initiation/completion was 12.7 years (95% CI 12.7-12.7)/13.3 years (95% CI 13.3-13.3). Socio-economic inequalities in coverage and in age-specific coverage were substantially smaller. Copyright © 2015. Published by Elsevier Ltd.

  19. TUMOUR VACCINE

    NARCIS (Netherlands)

    Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

    1999-01-01

    The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

  20. Characterization and standardization of Sabin based inactivated polio vaccine: proposal for a new antigen unit for inactivated polio vaccines.

    Science.gov (United States)

    Westdijk, Janny; Brugmans, Debbie; Martin, Javier; van't Oever, Aart; Bakker, Wilfried A M; Levels, Lonneke; Kersten, Gideon

    2011-04-18

    GMP-batches of Sabin-IPV were characterized for their antigenic and immunogenic properties. Antigenic fingerprints of Sabin-IPV reveal that the D-antigen unit is not a fixed amount of antigen but depends on antibody and assay type. Instead of the D-antigen unit we propose standardization of IPV based on a combination of protein amount for dose and D-antigenicity for quality of the vaccine. Although Sabin-IPV type 2 is less immunogenic than regular wild type IPV type 2, the immunogenicity (virus neutralizing titers) per microgram antigen for Sabin-IPV type 2 is in the same order as for wild type serotypes 1 and 3. The latter observations are in line with data from human trials. This suggests that a higher dose of Sabin-IPV type 2 to compensate for the lower rat immunogenicity may not be necessary. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Pre-Clinical Efficacy and Safety of Experimental Vaccines Based on Non-Replicating Vaccinia Vectors against Yellow Fever

    Science.gov (United States)

    Schäfer, Birgit; Holzer, Georg W.; Joachimsthaler, Alexandra; Coulibaly, Sogue; Schwendinger, Michael; Crowe, Brian A.; Kreil, Thomas R.; Barrett, P. Noel; Falkner, Falko G.

    2011-01-01

    Background Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. Methodology/Principal Findings A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 105 TCID50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. Conclusions/Significance The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice. PMID:21931732

  2. Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.

    Directory of Open Access Journals (Sweden)

    Birgit Schäfer

    Full Text Available BACKGROUND: Currently existing yellow fever (YF vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D. Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. METHODOLOGY/PRINCIPAL FINDINGS: A gene encoding the precursor of the membrane and envelope (prME protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5 TCID(50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. CONCLUSIONS/SIGNIFICANCE: The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

  3. A school-based human papillomavirus vaccination program in barretos, Brazil: final results of a demonstrative study.

    Directory of Open Access Journals (Sweden)

    José Humberto Tavares Guerreiro Fregnani

    Full Text Available The implementation of a public HPV vaccination program in several developing countries, especially in Latin America, is a great challenge for health care specialists.To evaluate the uptake and the three-dose completion rates of a school-based HPV vaccination program in Barretos (Brazil.THE STUDY INCLUDED GIRLS WHO WERE ENROLLED IN PUBLIC AND PRIVATE SCHOOLS AND WHO REGULARLY ATTENDED THE SIXTH AND SEVENTH GRADES OF ELEMENTARY SCHOOL (MEAN AGE: 11.9 years. A meeting with the parents or guardians occurred approximately one week before the vaccination in order to explain the project and clarify the doubts. The quadrivalent vaccine was administered using the same schedule as in the product package (0-2-6 months. The school visits for regular vaccination occurred on previously scheduled dates. The vaccine was also made available at Barretos Cancer Hospital for the girls who could not be vaccinated on the day when the team visited the school.Among the potential candidates for vaccination (n = 1,574, the parents or guardians of 1,513 girls (96.1% responded to the invitation to participate in the study. A total of 1,389 parents or guardians agreed to participate in the program (acceptance rate = 91.8%. The main reason for refusing to participate in the vaccination program was fear of adverse events. The vaccine uptake rates for the first, second, and third doses were 87.5%, 86.3% and 85.0%, respectively. The three-dose completion rate was 97.2%.This demonstrative study achieved high rates of vaccination uptake and completion of three vaccine doses in children 10-16 years old from Brazil. The feasibility and success of an HPV vaccination program for adolescents in a developing country may depend on the integration between the public health and schooling systems.

  4. Muc1 based breast cancer vaccines: role of post translational modifications

    International Nuclear Information System (INIS)

    Begum, M.; Khurshid, R.; Nagra, S.A.

    2008-01-01

    Vaccine development is one of the most promising fields in cancer research. After autologous transplantation, due to low tumour burden, patients are more likely to respond immunologically to a cancer vaccine. MUC1 with its adhesive and anti adhesive functions, immunostimulatory and immunosuppressive activities, is therefore a good candidate for breast cancer vaccine. A structure-based insight into the immunogenicity of natural MUC1 glyco forms, of its sub-domains, motifs and post translational modification like glycosylation and myriostoylation may aid the design of tumour vaccines. Primary sequences of human MUC1 were retrieved from the SWISSPROT data bank. Protein pattern search: The primary sequence of Human MUC1 was searched at PROSITE (a dictionary of protein sites and patterns) database. Our study observes that post-translational modifications play an important role in presenting MUC1 as a candidate for breast cancer vaccine. It is found that the phosphorylation and glycosylation of important functional motifs of MUC1 may take part in the production of cytokines that may provide immunization. (author)

  5. Using Community Engagement to Develop a Web-Based Intervention for Latinos about the HPV Vaccine.

    Science.gov (United States)

    Maertens, Julie A; Jimenez-Zambrano, Andrea M; Albright, Karen; Dempsey, Amanda F

    2017-04-01

    Human papillomavirus (HPV) infection is pervasive among sexually active women and men, and Hispanic women are at particularly high risk as they have higher rates of invasive cervical cancer compared to other racial or ethnic groups in the United States. There is a need for interventions to increase HPV vaccination among this high-risk population. This study investigated how to modify a previously developed web-based intervention that provided individually tailored information about HPV to improve its use among the Latino population. A community-oriented modification approach incorporated feedback from a community advisory committee, and focus groups among the Latino population, to modify the intervention. Several themes emerged including a need for basic information about HPV and HPV vaccination, changes to make the intervention appear less clinical, and incorporation of information addressing barriers specific to the Latino community. This work was done in preparation for a randomized trial to assess the impact of this modified intervention on HPV vaccination attitudes and uptake among Latino young adults and parents of adolescents. If effective, our intervention could be a resource for reducing HPV vaccination concerns, improving immunization rates, and educating Latinos about HPV and the HPV vaccine outside of the time boundaries of the traditional clinical encounter.

  6. Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shigetaka Shimodaira

    2015-12-01

    Full Text Available Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1 class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1–2 × 107 DCs with 1–2 KE of OK-432 (streptococcal preparation in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT assays. WT1 expression with human leukocyte antigen (HLA-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.

  7. Toolbox for non-intrusive structural and functional analysis of recombinant VLP based vaccines: a case study with hepatitis B vaccine.

    Directory of Open Access Journals (Sweden)

    Anke M Mulder

    Full Text Available BACKGROUND: Fundamental to vaccine development, manufacturing consistency, and product stability is an understanding of the vaccine structure-activity relationship. With the virus-like particle (VLP approach for recombinant vaccines gaining popularity, there is growing demand for tools that define their key characteristics. We assessed a suite of non-intrusive VLP epitope structure and function characterization tools by application to the Hepatitis B surface antigen (rHBsAg VLP-based vaccine. METHODOLOGY: The epitope-specific immune reactivity of rHBsAg epitopes to a given monoclonal antibody was monitored by surface plasmon resonance (SPR and quantitatively analyzed on rHBsAg VLPs in-solution or bound to adjuvant with a competitive enzyme-linked immunosorbent assay (ELISA. The structure of recombinant rHBsAg particles was examined by cryo transmission electron microscopy (cryoTEM and in-solution atomic force microscopy (AFM. PRINCIPAL FINDINGS: SPR and competitive ELISA determined relative antigenicity in solution, in real time, with rapid turn-around, and without the need of dissolving the particulate aluminum based adjuvant. These methods demonstrated the nature of the clinically relevant epitopes of HBsAg as being responsive to heat and/or redox treatment. In-solution AFM and cryoTEM determined vaccine particle size distribution, shape, and morphology. Redox-treated rHBsAg enabled 3D reconstruction from CryoTEM images--confirming the previously proposed octahedral structure and the established lipid-to-protein ratio of HBsAg particles. Results from these non-intrusive biophysical and immunochemical analyses coalesced into a comprehensive understanding of rHBsAg vaccine epitope structure and function that was important for assuring the desired epitope formation, determinants for vaccine potency, and particle stability during vaccine design, development, and manufacturing. SIGNIFICANCE: Together, the methods presented here comprise a novel

  8. Introducing the ESAT-6 free IGRA, a companion diagnostic for TB vaccines based on ESAT-6

    DEFF Research Database (Denmark)

    Ruhwald, Morten; de Thurah, Lena; Kuchaka, Davis

    2017-01-01

    tests unspecific after vaccination. This challenge has prompted the development of a companion diagnostic for ESAT-6 based vaccines, an ESAT-6 free IGRA. We screened a panel of seven potential new diagnostic antigens not recognized in BCG vaccinated individuals. Three highly recognized antigens Esp......C, EspF and Rv2348c were identified and combined with CFP10 in an ESAT-6 free antigen cocktail. The cocktail was prepared in a field-friendly format, lyophilized with heparin in ready-to-use vacutainer tubes. The diagnostic performance of the ESAT-6 free IGRA was determined in a cross-validation study....... Compared IGRA, the ESAT-6 free IGRA induced a comparable magnitude of IFN-γ release, and the diagnostic performance was on par with Quantiferon (sensitivity 84% vs 79%; specificity 99% vs 97%). The comparable performance of the ESAT-6 free IGRA to IGRA suggests potential as companion diagnostic for ESAT-6...

  9. A history of fish vaccination: science-based disease prevention in aquaculture.

    Science.gov (United States)

    Gudding, Roar; Van Muiswinkel, Willem B

    2013-12-01

    Disease prevention and control are crucial in order to maintain a sustainable aquaculture, both economically and environmentally. Prophylactic measures based on stimulation of the immune system of the fish have been an effective measure for achieving this goal. Immunoprophylaxis has become an important part in the successful development of the fish-farming industry. The first vaccine for aquaculture, a vaccine for prevention of yersiniosis in salmonid fish, was licensed in USA in 1976. Since then the use of vaccines has expanded to new countries and new species simultaneous with the growth of the aquaculture industry. This paper gives an overview of the achievements in fish vaccinology with particular emphasis on immunoprophylaxis as a practical tool for a successful development of bioproduction of aquatic animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Ethical and legal challenges of vaccines and vaccination: Reflections.

    Science.gov (United States)

    Jesani, Amar; Johari, Veena

    2017-01-01

    Vaccines and vaccination have emerged as key medical scientific tools for prevention of certain diseases. Documentation of the history of vaccination shows that the initial popular resistance to universal vaccination was based on false assumptions and eventually gave way to acceptance of vaccines and trust in their ability to save lives. The successes of the global eradication of smallpox, and now of polio, have only strengthened the premier position occupied by vaccines in disease prevention. However, the success of vaccines and public trust in their ability to eradicate disease are now under challenge, as increasing numbers of people refuse vaccination, questioning the effectiveness of vaccines and the need to vaccinate.

  11. Imitation dynamics of vaccine decision-making behaviours based on the game theory.

    Science.gov (United States)

    Yang, Junyuan; Martcheva, Maia; Chen, Yuming

    2016-01-01

    Based on game theory, we propose an age-structured model to investigate the imitation dynamics of vaccine uptake. We first obtain the existence and local stability of equilibria. We show that Hopf bifurcation can occur. We also establish the global stability of the boundary equilibria and persistence of the disease. The theoretical results are supported by numerical simulations.

  12. Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC

    DEFF Research Database (Denmark)

    Gbédandé, Komi; Fievet, Nadine; Viwami, Firmine

    2017-01-01

    Background  The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC...

  13. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine

    DEFF Research Database (Denmark)

    Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

    2017-01-01

    : PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein...

  14. Association of School-Based Influenza Vaccination Clinics and School Absenteeism--Arkansas, 2012-2013

    Science.gov (United States)

    Gicquelais, Rachel E.; Safi, Haytham; Butler, Sandra; Smith, Nathaniel; Haselow, Dirk T.

    2016-01-01

    Background: Influenza is a major cause of seasonal viral respiratory illness among school-aged children. Accordingly, the Arkansas Department of Health (ADH) coordinates >800 school-based influenza immunization clinics before each influenza season. We quantified the relationship between student influenza vaccination in Arkansas public schools…

  15. Designing and modeling of complex DNA vaccine based on tropomyosin protein of Boophilus genus tick.

    Science.gov (United States)

    Ranjbar, Mohamamd Mahdi; Gupta, Shishir K; Ghorban, Khodayar; Nabian, Sedigheh; Sazmand, Alireza; Taheri, Mohammad; Esfandyari, Sahar; Taheri, Maryam

    2015-01-01

    Boophilus tick is a bloodsucking ectoparasite that transfers some pathogens, reducing production and thus leading to economical losses in the cattle industry. Tropomyosin (TPM) protein is a salivary protein, has actin regulator activity, and plays an important role in immune reactions against parasites. In the current study, besides developing a safe, effective, and broad spectrum protective measure against Boophilus genus tick based on TPM protein, we attempted to minimize possible problems occurring in the design of polytopic vaccines. Briefly, the steps that were followed in the present study were as follows: retrieving sequences and finding the mutational/conservative regions, selecting consensus and high immunogenic epitopes of B and CD4(+) T cells by different approaches, three-dimensional structure (3D structure) prediction and representation of epitopes and highly variable/conserve regions, designing vaccinal construct by fusion of B and T cell epitopes by special patterns and improving immunogenicity, evaluation of the constructs' primary structure and posttranslational modification, calculation of hydrophobic regions, reverse translation, codon optimization, open reading frame checking, insertion of start/end codon, Kozak sequence, and finally constructing the DNA vaccine. Variation plot showed some shared epitopes among the ticks' and mites' species that some might be effective only in some species. Finally, by following the steps mentioned above, two constructs for B and T cells were achieved. Checking constructs revealed their reliability and efficacy for in vitro production and utilization. Successful in silico modeling is an essential step of designing vigorous vaccines. We developed a novel protective and therapeutic vaccine against Boophilus genus (based on TPM protein). At the next step, constructed DNA vaccine would be produced in vitro and administrated to cattle, and its potency to induction of immune response and protection against Boophilus

  16. How to Meet the Last OIE Expert Surveillance Panel Recommendations on Equine Influenza (EI Vaccine Composition: A Review of the Process Required for the Recombinant Canarypox-Based EI Vaccine

    Directory of Open Access Journals (Sweden)

    Romain Paillot

    2016-11-01

    Full Text Available Vaccination is highly effective to prevent, control, and limit the impact of equine influenza (EI, a major respiratory disease of horses. However, EI vaccines should contain relevant equine influenza virus (EIV strains for optimal protection. The OIE expert surveillance panel annually reviews EIV evolution and, since 2010, the use of Florida clade 1 and 2 sub-lineages representative vaccine strains is recommended. This report summarises the development process of a fully- updated recombinant canarypox-based EI vaccine in order to meet the last OIE recommendations, including the vaccine mode of action, production steps and schedule. The EI vaccine ProteqFlu contains 2 recombinant canarypox viruses expressing the haemagglutinin of the A/equine/Ohio/03 and A/equine/Richmond/1/07 isolates (Florida clade 1 and 2 sub-lineages, respectively. The updated EI vaccine was tested for efficacy against the representative Florida clade 2 EIV strain A/equine/Richmond/1/07 in the Welsh mountain pony model. Protective antibody response, clinical signs of disease and virus shedding were compared with unvaccinated control ponies. Significant protection was measured in vaccinated ponies, which supports the vaccine registration. The recombinant canarypox-based EI vaccine was the first fully updated EI vaccine available in the EU, which will help to minimise the increasing risk of vaccine breakdown due to constant EIV evolution through antigenic drift.

  17. Theory-Based Analysis of Interest in an HIV Vaccine for Reasons Indicative of Risk Compensation Among African American Women.

    Science.gov (United States)

    Painter, Julia E; Temple, Brandie S; Woods, Laura A; Cwiak, Carrie; Haddad, Lisa B; Mulligan, Mark J; DiClemente, Ralph J

    2018-06-01

    Licensure of an HIV vaccine could reduce or eliminate HIV among vulnerable populations. However, vaccine effectiveness could be undermined by risk compensation (RC), defined by an increase in risky behavior due to a belief that the vaccine will confer protection. Interest in an HIV vaccine for reasons indicative of RC may serve as an indicator of actual RC in a postlicensure era. This study assessed factors associated with interest in an HIV vaccine for reasons indicative of RC among African American women aged 18 to 55 years, recruited from a hospital-based family planning clinic in Atlanta, Georgia ( N = 321). Data were collected using audio-computer-assisted surveys. Survey items were guided by risk homeostasis theory and social cognitive theory. Multivariable logistic regression was used to assess determinants of interest in an HIV vaccine for reasons indicative of RC. Thirty-eight percent of the sample expressed interest in an HIV vaccine for at least one reason indicative of RC. In the final model, interest in an HIV vaccine for reasons indicative of RC was positively associated with higher impulsivity, perceived benefits of sexual risk behaviors, and perceived benefits of HIV vaccination; it was negatively associated with having at least some college education, positive future orientation, and self-efficacy for sex refusal. Results suggest that demographic, personality, and theory-based psychosocial factors are salient to wanting an HIV vaccine for reasons indicative of RC, and underscore the need for risk-reduction counseling alongside vaccination during the eventual rollout of an HIV vaccine.

  18. PS II model based analysis of transient fluorescence yield measured on whole leaves of Arabidopsis thaliana after excitation with light flashes of different energies.

    Science.gov (United States)

    Belyaeva, N E; Schmitt, F-J; Paschenko, V Z; Riznichenko, G Yu; Rubin, A B; Renger, G

    2011-02-01

    Our recently presented PS II model (Belyaeva et al., 2008) was improved in order to permit a consistent simulation of Single Flash Induced Transient Fluorescence Yield (SFITFY) traces that were earlier measured by Steffen et al. (2005) on whole leaves of Arabidopsis (A.) thaliana at four different energies of the actinic flash. As the essential modification, the shape of the actinic flash was explicitly taken into account assuming that an exponentially decaying rate simulates the time dependent excitation of PS II by the 10 ns actinic flash. The maximum amplitude of this excitation exceeds that of the measuring light by 9 orders of magnitude. A very good fit of the SFITFY data was achieved in the time domain from 100 ns to 10s for all actinic flash energies (the maximum energy of 7.5 × 10¹⁶ photons/(cm²flash) is set to 100%, the relative energies of weaker actinic flashes were of ∼8%, 4%, ∼1%). Our model allows the calculation and visualization of the transient PS II redox state populations ranging from the dark adapted state, via excitation energy and electron transfer steps induced by pulse excitation, followed by final relaxation into the stationary state eventually attained under the measuring light. It turned out that the rate constants of electron transfer steps are invariant to intensity of the actinic laser flash. In marked contrast, an increase of the actinic flash energy by more than two orders of magnitude from 5.4×10¹⁴ photons/(cm²flash) to 7.5×10¹⁶ photons/(cm²flash), leads to an increase of the extent of fluorescence quenching due to carotenoid triplet (³Car) formation by a factor of 14 and of the recombination reaction between reduced primary pheophytin (Phe(-)) and P680(+) by a factor of 3 while the heat dissipation in the antenna complex remains virtually constant. The modified PS II model offers new opportunities to compare electron transfer and dissipative parameters for different species (e.g. for the green algae and the

  19. Vaccination with experimental feline immunodeficiency virus vaccines, based on autologous infected cells, elicits enhancement of homologous challenge infection

    NARCIS (Netherlands)

    J.A. Karlas (Jos); C.H.J. Siebelink (Kees); M.A. Peer; W. Huisman (Willem); A.M. Cuisinier; G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    1999-01-01

    textabstractCats were vaccinated with fixed autologous feline immunodeficiency virus (FIV)-infected cells in order to present viral proteins to the immune system of individual cats in an MHC-matched fashion. Upon vaccination, a humoral response against Gag was induced. Furthermore,

  20. Architectural Insight into Inovirus-Associated Vectors (IAVs and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines

    Directory of Open Access Journals (Sweden)

    Kyriakos A. Hassapis

    2014-12-01

    Full Text Available Inovirus-associated vectors (IAVs are engineered, non-lytic, filamentous bacteriophages that are assembled primarily from thousands of copies of the major coat protein gp8 and just five copies of each of the four minor coat proteins gp3, gp6, gp7 and gp9. Inovirus display studies have shown that the architecture of inoviruses makes all coat proteins of the inoviral particle accessible to the outside. This particular feature of IAVs allows foreign antigenic peptides to be displayed on the outer surface of the virion fused to its coat proteins and for more than two decades has been exploited in many applications including antibody or peptide display libraries, drug design, and vaccine development against infectious and non-infectious diseases. As vaccine carriers, IAVs have been shown to elicit both a cellular and humoral response against various pathogens through the display of antibody epitopes on their coat proteins. Despite their high immunogenicity, the goal of developing an effective vaccine against HIV-1 has not yet materialized. One possible limitation of previous efforts was the use of broadly neutralizing antibodies, which exhibited autoreactivity properties. In the past five years, however, new, more potent broadly neutralizing antibodies that do not exhibit autoreactivity properties have been isolated from HIV-1 infected individuals, suggesting that vaccination strategies aimed at producing such broadly neutralizing antibodies may confer protection against infection. The utilization of these new, broadly neutralizing antibodies in combination with the architectural traits of IAVs have driven the current developments in the design of an inovirus-based vaccine against HIV-1. This article reviews the applications of IAVs in vaccine development, with particular emphasis on the design of inoviral-based vaccines against HIV-1.

  1. History of vaccination.

    Science.gov (United States)

    Plotkin, Stanley

    2014-08-26

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  2. History of vaccination

    OpenAIRE

    Plotkin, Stanley

    2014-01-01

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  3. Beyond the Point Ps Approximation

    OpenAIRE

    Stepanov, Sergey V.; Zvezhinskiy, Dmitry S.; Byakov, Vsevolod M.

    2012-01-01

    In application to positron annihilation spectroscopy, Ps atom is considered not as a point particle, but as a finite size e+ e- pair localized in a bubble-state in a medium. Variation of the internal Coulombic e+ -e- attraction vs. the bubble radius is estimated.

  4. The PS Booster hits 40

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    Many accelerators’ "round" birthdays are being celebrated at CERN these days – the PS turned 50 in 2009, the SPS was 35 in 2011, and this year it's the turn of the PS Booster to mark its 40th anniversary. Originally designed to accelerate 1013 protons to 800 MeV, it has far exceeded its initial design performance over the years.   The PS Booster in the 1970s. Imagine the scene: a group of accelerator physicists staring expectantly at a monitor, when suddenly a shout of joy goes up as a signal flickers across the screen. Does that sound familiar? Well, turn the clock back 40 years (longer hair, wider trouser legs) and you have the situation at the PS Booster on 26 May 1972. On that day, beam was injected into the Booster for the first time. “It was a real buzz,” says Heribert Koziol, then Chairman of the Running-in Committee. “We were very happy – and also a little relieved – when the beam finally...

  5. The PS locomotive runs again

    CERN Multimedia

    2001-01-01

    Over forty years ago, the PS train entered service to steer the magnets of the accelerator into place... ... a service that was resumed last Tuesday. Left to right: Raymond Brown (CERN), Claude Tholomier (D.B.S.), Marcel Genolin (CERN), Gérard Saumade (D.B.S.), Ingo Ruehl (CERN), Olivier Carlier (D.B.S.), Patrick Poisot (D.B.S.), Christian Recour (D.B.S.). It is more than ten years since people at CERN heard the rumbling of the old PS train's steel wheels. Last Tuesday, the locomotive came back into service to be tested. It is nothing like the monstrous steel engines still running on conventional railways -just a small electric battery-driven vehicle employed on installing the magnets for the PS accelerator more than 40 years ago. To do so, it used the tracks that run round the accelerator. In fact, it is the grandfather of the LEP monorail. After PS was commissioned in 1959, the little train was used more and more rarely. This is because magnets never break down, or hardly ever! In fact, the loc...

  6. Alphavirus-based Vaccines Encoding Nonstructural Proteins of Hepatitis C Virus Induce Robust and Protective T-cell Responses

    NARCIS (Netherlands)

    Ip, Peng; Boerma, Annemarie; Regts, Joke; Meijerhof, Tjarko; Wilschut, Jan; Nijman, Hans W.; Daemen, Toos

    An absolute prerequisite for a therapeutic vaccine against hepatitis C virus (HCV) infection is the potency to induce HCV-specific vigorous and broad-spectrum T-cell responses. Here, we generated three HCV vaccines based on a recombinant Semliki Forest virus (rSFV) vector expressing all-or a part of

  7. Performance of the digene LQ, RH and PS HPVs genotyping systems on clinical samples and comparison with HC2 and PCR-based Linear Array.

    Science.gov (United States)

    Godínez, Jose M; Tous, Sara; Baixeras, Nuria; Moreno-Crespi, Judith; Alejo, María; Lejeune, Marylène; Bravo, Ignacio G; Bosch, F Xavier; de Sanjosé, Silvia

    2011-11-18

    Certain Human Papillomaviruses (HPVs) are the infectious agents involved in cervical cancer development. Detection of HPVs DNA is part of the cervical cancer screening protocols and HPVs genotyping has been proposed for its inclusion in these preventive programs. The aim of this study was to evaluate three novel genotyping tests, namely Qiagen LQ, RH and PS, in clinical samples with and without abnormalities. For this, 305 cervical samples were processed and the results of the evaluated techniques were compared with those obtained in the HPVs diagnostic process in our lab, by using HC2 and Linear Array (LA) technologies. The concordances and kappa statistics (k) for each technique compared with HC2 were 98.69% (k = 0.94) for LQ, 98.03% (k = 0.91) for RH and 91.80% (k = 0.82) for PS. There was a very good agreement in HPVs type-specific concordance for the most prevalent types HPV16 (kappa range = 0.83-0.90), HPV18 (k.r.= 0.74-0.80) and HPV45 (k.r.= 0.82-0.90). The three tests showed an overall good concordance for HPVs detection when compared with HR-HC2 system. LQ and RH rendered lower detection rate for multiple infections than LA genotyping. However, our understanding of the clinical significance of multiple HPVs infections is still incomplete and therefore the relevance of the lower ability to detect multiple infections needs to be evaluated.

  8. PERSPECTIVES OF THE DEVELOPMENT OF MUCOSAL VACCINES AGAINST DANGEROUS INFECTIONS ON THE BASE OF TRANSGENIC PLANTS

    Directory of Open Access Journals (Sweden)

    A.V. Tretyakova

    2012-08-01

    Full Text Available Mucosal vaccines created on the base of transgenic plants reacting with mucosal layers of the intestines and other organs are considered to be the perspective method of the vaccination. These vaccines induce both mucosal and general humoral immunogenicity after the peroral administration. The folding of antigenic proteins synthesizing in plants occurs via eukaryotic type and has advantages before yeast and prokaryotic platforms. This feature results to more adequate synthesis of antibodies against pathogens and to the interaction with effector molecules of complement. Earlier we together with The State Scientific Center “Vector”, Institute of chemical biology and fundamental medicine SB RAS and Dr R.Hammond from Laboratory of Plant Pathology (Maryland, USA created two candidate vaccines : one of them against AIDS (HIV-1 and hepatitis B on the base of the chimeric gene TBI-HBS, encoding simultaneously 9 antigenic determinants of HIV-1 and the main surface antigen of hepatitis B (HBsAg. The second candidate vaccine was created against hepatitis B on the base of the genetic construct with the gene preS2-S encoding the synthesis of two subunits of the main surface antigen of hepatitis B and the signal peptide HDEL which directed antigens for the accumulation on ER. Both vaccines were tested on mice and confirmed their immunogenicity as the pronounced antibodies response. Twice vaccinated mice maintained the antibodies response during 11 months after there was little tendency to lowering. It was established that transgenic plants – vaccines (tomato kept the capability to the synthesis of antigenic determinants in seven seed generations during 7 years. The results of the development of the mucosal vaccine against cervical carcinoma (carcinoma of uterine cervix evoked by human papillomaviruses of high oncogenic risks were presented in this report. We created the genetic construct consisting of 35S CaMV promoter, Ώ (omega leader of TMV, the

  9. Lessons from pandemic influenza A(H1N1): the research-based vaccine industry's perspective.

    Science.gov (United States)

    Abelin, Atika; Colegate, Tony; Gardner, Stephen; Hehme, Norbert; Palache, Abraham

    2011-02-01

    As A(H1N1) influenza enters the post-pandemic phase, health authorities around the world are reviewing the response to the pandemic. To ensure this process enhances future preparations, it is essential that perspectives are included from all relevant stakeholders, including vaccine manufacturers. This paper outlines the contribution of R&D-based influenza vaccine producers to the pandemic response, and explores lessons that can be learned to improve future preparedness. The emergence of 2009 A(H1N1) influenza led to unprecedented collaboration between global health authorities, scientists and manufacturers, resulting in the most comprehensive pandemic response ever undertaken, with a number of vaccines approved for use three months after the pandemic declaration. This response was only possible because of the extensive preparations undertaken during the last decade. During this period, manufacturers greatly increased influenza vaccine production capacity, and estimates suggest a further doubling of capacity by 2014. Producers also introduced cell-culture technology, while adjuvant and whole virion technologies significantly reduced pandemic vaccine antigen content. This substantially increased pandemic vaccine production capacity, which in July 2009 WHO estimated reached 4.9 billion doses per annum. Manufacturers also worked with health authorities to establish risk management plans for robust vaccine surveillance during the pandemic. Individual producers pledged significant donations of vaccine doses and tiered-pricing approaches for developing country supply. Based on the pandemic experience, a number of improvements would strengthen future preparedness. Technical improvements to rapidly select optimal vaccine viruses, and processes to speed up vaccine standardization, could accelerate and extend vaccine availability. Establishing vaccine supply agreements beforehand would avoid the need for complex discussions during a period of intense time pressure. Enhancing

  10. 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines.

    Science.gov (United States)

    Liao, Guochao; Zhou, Zhifang; Liao, Jun; Zu, Luning; Wu, Qiuye; Guo, Zhongwu

    2016-02-12

    With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. These glycoconjugates were proved to elicit strong IgG antibody responses in mice. It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates.

  11. A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Caroline Aspord

    Full Text Available BACKGROUND: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy. METHODS AND FINDINGS: Stimulation of PBMC from HLA-A*0201(+ donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+ CD8 T cells. The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment. CONCLUSIONS: These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.

  12. An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge.

    Science.gov (United States)

    Ma, Ji-Hong; Yang, Fu-Ru; Yu, Hai; Zhou, Yan-Jun; Li, Guo-Xin; Huang, Meng; Wen, Feng; Tong, Guangzhi

    2013-07-09

    Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses. Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds' adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus. Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.

  13. Entirely Carbohydrate-Based Vaccines: An Emerging Field for Specific and Selective Immune Responses

    Directory of Open Access Journals (Sweden)

    Sharmeen Nishat

    2016-05-01

    Full Text Available Carbohydrates are regarded as promising targets for vaccine development against infectious disease because cell surface glycans on many infectious agents are attributed to playing an important role in pathogenesis. In addition, oncogenic transformation of normal cells, in many cases, is associated with aberrant glycosylation of the cell surface glycan generating tumor associated carbohydrate antigens (TACAs. Technological advances in glycobiology have added a new dimension to immunotherapy when considering carbohydrates as key targets in developing safe and effective vaccines to combat cancer, bacterial infections, viral infections, etc. Many consider effective vaccines induce T-cell dependent immunity with satisfactory levels of immunological memory that preclude recurrence. Unfortunately, carbohydrates alone are poorly immunogenic as they do not bind strongly to the MHCII complex and thus fail to elicit T-cell immunity. To increase immunogenicity, carbohydrates have been conjugated to carrier proteins, which sometimes can impede carbohydrate specific immunity as peptide-based immune responses can negate antibodies directed at the targeted carbohydrate antigens. To overcome many challenges in using carbohydrate-based vaccine design and development approaches targeting cancer and other diseases, zwitterionic polysaccharides (ZPSs, isolated from the capsule of commensal anaerobic bacteria, will be discussed as promising carriers of carbohydrate antigens to achieve desired immunological responses.

  14. Evaluation of peptide selection approaches for epitope‐based vaccine design

    DEFF Research Database (Denmark)

    Schubert, B.; Lund, Ole; Nielsen, Morten

    2013-01-01

    A major challenge in epitope-based vaccine (EV) design stems from the vast genomic variation of pathogens and the diversity of the host cellular immune system. Several computational approaches have been published to assist the selection of potential T cell epitopes for EV design. So far, no thoro......A major challenge in epitope-based vaccine (EV) design stems from the vast genomic variation of pathogens and the diversity of the host cellular immune system. Several computational approaches have been published to assist the selection of potential T cell epitopes for EV design. So far...... in terms of in silico measurements simulating important vaccine properties like the ability of inducing protection against a multivariant pathogen in a population; the predicted immunogenicity; pathogen, allele, and population coverage; as well as the conservation of selected epitopes. Additionally, we...... evaluate the use of human leukocyte antigen (HLA) supertypes with regards to their applicability for population-spanning vaccine design. The results showed that in terms of induced protection methods that simultaneously aim to optimize pathogen and HLA coverage significantly outperform methods focusing...

  15. Immunotherapy for Alzheimer's disease: DNA- and protein-based epitope vaccines.

    Science.gov (United States)

    Davtyan, Hayk; Petrushina, Irina; Ghochikyan, Anahit

    2014-01-01

    Active immunotherapy for Alzheimer's disease (AD) is aimed to induce antibodies specific to amyloid-beta (Aβ) that are capable to reduce the level of Aβ in the CNS of Alzheimer's disease patients. First clinical trial AN-1792 that was based on vaccination with full-length Aβ42 showed that safe and effective AD vaccine should induce high titers of anti-Aβ antibodies without activation of harmful autoreactive T cells. Replacement of self-T cell epitope with foreign epitope, keeping self-B cell epitope intact, may allow to induce high titers of anti-Aβ antibodies while avoiding the activation of T cells specific to Aβ. Here we describe the protocols for evaluation of AD DNA- or multiple antigenic peptide (MAP)-based epitope vaccines composed of Aβ(1-11) B cell epitope fused to synthetic T cell epitope PADRE (Aβ(1-11)-PADRE). All protocols could be used for testing any epitope vaccine constructed in your lab and composed of other T cell epitopes using the appropriate peptides in tests for evaluation of humoral and cellular immune responses.

  16. Role of trapped and solvated electrons in Ps formation

    International Nuclear Information System (INIS)

    Stepanov, S.V.; Byakov, V.M.; Mikhin, K.V.; He, C.; Hirade, T.

    2005-01-01

    Role of trapped and solvated electrons in Ps formation is discussed. Combination of thermalized positron with such electrons is possible from the view point of the energy balance and may results in Ps formation. This process proceeds during all e = lifetime matter. Fitting of raw experimental e + -e - annihilation spectra has to be based on an adequate physical input, which often leads to necessity of nonexponential deconvolution of the spectra. We have interpreted the Ps formation data in polyethylene, ethylene-methylmethacrylate and polymethylmethacrylate in dark and in light vs. tome of the measurement and temperature. parameters characterized accumulation of trapped electrons and their recombination with counter ions and positrons are obtained. (author)

  17. RF Scenarios for Pb54+ Ions in the PS2

    CERN Document Server

    Benedikt, M; Hancock, S; CERN. Geneva. AB Department

    2008-01-01

    This note analyses some of the rf scenarios that are presently being considered for lead ions in the PS2. An earlier note principally concerning protons [1] highlighted the problem of the large revolution frequency swing of ions in the PS2 and the issue of bunching factor with direct injection from the LEIR machine. We present solutions based on additional rf systems in LEIR and consider the 40 MHz principal rf system proposed for the PS2 in the earlier work to have switchable tuning ranges to cover the large frequency swing required.

  18. Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis.

    Science.gov (United States)

    Rose, Johnie; Hawthorn, Rachael L; Watts, Brook; Singer, Mendel E

    2009-09-25

    To examine the public health impact of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in a birth cohort in India, and to estimate the cost effectiveness and affordability of such a programme. Decision analytical Markov model encompassing all direct medical costs. Infection risk and severity depended on age, number of previous infections, and vaccination history; probabilities of use of inpatient and outpatient health services depended on symptom severity. Published clinical, epidemiological, and economic data. When possible, parameter estimates were based on data specific for India. Population Simulated Indian birth cohort followed for five years. Decrease in rotavirus gastroenteritis episodes (non-severe and severe), deaths, outpatient visits, and admission to hospital; incremental cost effectiveness ratio of vaccination expressed as net cost in 2007 rupees per life year saved. In the base case, vaccination prevented 28,943 (29.7%) symptomatic episodes, 6981 (38.2%) severe episodes, 164 deaths (41.0%), 7178 (33.3%) outpatient visits, and 812 (34.3%) admissions to hospital per 100,000 children. Vaccination cost 8023 rupees (about pound100, euro113, $165) per life year saved, less than India's per capita gross domestic product, a common criterion for cost effectiveness. The net programme cost would be equivalent to 11.6% of the 2006-7 budget of the Indian Department of Health and Family Welfare. Model results were most sensitive to variations in access to outpatient care for those with severe symptoms. If this parameter was increased to its upper limit, the incremental cost effectiveness ratio for vaccination still fell between one and three times the per capita gross domestic product, meeting the World Health Organization's criterion for "cost effective" interventions. Uncertainty analysis indicated a 94.7% probability that vaccination would be cost effective according to a criterion of one times per capita gross domestic product per life

  19. Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review.

    Science.gov (United States)

    Mogasale, Vittal; Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H

    2016-12-01

    Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. No participants are involved, only costs are collected. Oral cholera vaccination and cost estimation. A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in routine immunization systems were lowest from US$ 0.36 (in US$2014) equivalent to I$ 0.99 (in I$2014). The reported cost categories

  20. Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review

    Science.gov (United States)

    Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H.

    2016-01-01

    Background Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. Objectives To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Data sources Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. Study eligibility criteria The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. Participants No participants are involved, only costs are collected. Intervention Oral cholera vaccination and cost estimation. Study appraisal and synthesis method A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Results Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in

  1. Phase II Study of HER-2/neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab

    National Research Council Canada - National Science Library

    Disis, Mary L

    2007-01-01

    The primary purpose of this grant is to determine the overall survival benefit in Stage IV HER2 positive breast cancer patients vaccinated with a HER2 ICD peptide-based vaccine while receiving maintenance trastuzumab...

  2. Phase II Study of HER-2/neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab

    National Research Council Canada - National Science Library

    Disis, Mary L

    2006-01-01

    The primary purpose of this grant is to determine the overall survival benefit in Stage IV HER2 positive breast cancer patients vaccinated with a HER2 ICD peptide-based vaccine while receiving maintenance trastuzumab...

  3. Microneedle-based drug and vaccine delivery via nanoporous microneedle arrays

    OpenAIRE

    Maaden, van der, Koen; Lüttge, R Regina; Vos, PJW; Bouwstra, Joke A; Kersten, Gideon FA; Ploemen, IHJ Ingmar

    2015-01-01

    In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based drug and vaccine delivery and could be a valuable addition to the other microneedle-based drug delivery approaches. To gain more insight into porous microneedle technologies, the scientific an...

  4. Implementation of 40-ps high-speed gated-microchannel-plate based x-ray framing cameras on reentrant SIM's for Nova

    International Nuclear Information System (INIS)

    Bell, P.M.; Kilkenny, J.D.; Landen, O.; Bradley, D.K.

    1994-01-01

    Gated framing cameras used in diagnosing laser produced plasmas have been used on the Nova laser system since 1987. There have been many variations of these systems implemented. All of these cameras have been ultimately limited in response time for two reasons. One being the electrical gating amplitude verses the gate width, this has always limited the detectable gain in the system. The second being the length to diameter (l/d) ratio of standard off the shelf microchannel plates (MCP). This sets the minimum electrical gate pulse that will give detectable gain from a given microchannel plate. The authors have implemented two different types of 40 ps framing camera configurations on the Nova laser system. They will describe the configurations of both systems as well as discuss the advantages of each

  5. Performance of the digene LQ, RH and PS HPVs genotyping systems on clinical samples and comparison with HC2 and PCR-based Linear Array

    Directory of Open Access Journals (Sweden)

    Godínez Jose M

    2011-11-01

    Full Text Available Abstract Background Certain Human Papillomaviruses (HPVs are the infectious agents involved in cervical cancer development. Detection of HPVs DNA is part of the cervical cancer screening protocols and HPVs genotyping has been proposed for its inclusion in these preventive programs. The aim of this study was to evaluate three novel genotyping tests, namely Qiagen LQ, RH and PS, in clinical samples with and without abnormalities. For this, 305 cervical samples were processed and the results of the evaluated techniques were compared with those obtained in the HPVs diagnostic process in our lab, by using HC2 and Linear Array (LA technologies. Results The concordances and kappa statistics (k for each technique compared with HC2 were 98.69% (k = 0.94 for LQ, 98.03% (k = 0.91 for RH and 91.80% (k = 0.82 for PS. There was a very good agreement in HPVs type-specific concordance for the most prevalent types HPV16 (kappa range = 0.83-0.90, HPV18 (k.r.= 0.74-0.80 and HPV45 (k.r.= 0.82-0.90. Conclusions The three tests showed an overall good concordance for HPVs detection when compared with HR-HC2 system. LQ and RH rendered lower detection rate for multiple infections than LA genotyping. However, our understanding of the clinical significance of multiple HPVs infections is still incomplete and therefore the relevance of the lower ability to detect multiple infections needs to be evaluated.

  6. A Novel Virus-Like Particle Based Vaccine Platform Displaying the Placental Malaria Antigen VAR2CSA.

    Directory of Open Access Journals (Sweden)

    Susan Thrane

    Full Text Available Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP based vaccines (e.g., the licensed human papillomavirus vaccines have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of

  7. Novel Plasmodium falciparum malaria vaccines: evidence-based searching for variant surface antigens as candidates for vaccination against pregnancy-associated malaria

    DEFF Research Database (Denmark)

    Staalsoe, Trine; Jensen, Anja T R; Theander, Thor G

    2002-01-01

    Malaria vaccine development has traditionally concentrated on careful molecular, biochemical, and immunological characterisation of candidate antigens. In contrast, evidence of the importance of identified antigens in immunity to human infection and disease has generally been limited to statistic......Malaria vaccine development has traditionally concentrated on careful molecular, biochemical, and immunological characterisation of candidate antigens. In contrast, evidence of the importance of identified antigens in immunity to human infection and disease has generally been limited...... to statistically significant co-variation with protection rather than on demonstration of causal relationships. We have studied the relationship between variant surface antigen-specific antibodies and clinical protection from Plasmodium falciparum malaria in general, and from pregnancy-associated malaria (PAM......) in particular, to provide robust evidence of a causal link between the two in order to allow efficient and evidence-based identification of candidate antigens for malaria vaccine development....

  8. The Meningitis Vaccine Project.

    Science.gov (United States)

    LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre

    2007-09-03

    Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world.

  9. Effective cancer vaccine platform based on attenuated salmonella and a type III secretion system.

    Science.gov (United States)

    Xu, Xin; Hegazy, Wael A H; Guo, Linjie; Gao, Xiuhua; Courtney, Amy N; Kurbanov, Suhrab; Liu, Daofeng; Tian, Gengwen; Manuel, Edwin R; Diamond, Don J; Hensel, Michael; Metelitsa, Leonid S

    2014-11-01

    Vaccines explored for cancer therapy have been based generally on injectable vector systems used to control foreign infectious pathogens, to which the immune system evolved to respond naturally. However, these vectors may not be effective at presenting tumor-associated antigens (TAA) to the immune system in a manner that is sufficient to engender antitumor responses. We addressed this issue with a novel orally administered Salmonella-based vector that exploits a type III secretion system to deliver selected TAA in the cytosol of professional antigen-presenting cells in situ. A systematic comparison of candidate genes from the Salmonella Pathogenicity Island 2 (SPI2) locus was conducted in the vaccine design, using model antigens and a codon-optimized form of the human TAA survivin (coSVN), an oncoprotein that is overexpressed in most human cancers. In a screen of 20 SPI2 promoter:effector combinations, a PsifB::sseJ combination exhibited maximal potency for antigen translocation into the APC cytosol, presentation to CD8 T cells, and murine immunogenicity. In the CT26 mouse model of colon carcinoma, therapeutic vaccination with a lead PsifB::sseJ-coSVN construct (p8032) produced CXCR3-dependent infiltration of tumors by CD8 T cells, reversed the CD8:Treg ratio at the tumor site, and triggered potent antitumor activity. Vaccine immunogenicity and antitumor potency were enhanced by coadministration of the natural killer T-cell ligand 7DW8-5, which heightened the production of IL12 and IFNγ. Furthermore, combined treatment with p8032 and 7DW8-5 resulted in complete tumor regression in A20 lymphoma-bearing mice, where protective memory was demonstrated. Taken together, our results demonstrate how antigen delivery using an oral Salmonella vector can provide an effective platform for the development of cancer vaccines. ©2014 American Association for Cancer Research.

  10. Population-Based Incidence Rates of Cervical Intraepithelial Neoplasia in the Human Papillomavirus Vaccine Era.

    Science.gov (United States)

    Benard, Vicki B; Castle, Philip E; Jenison, Steven A; Hunt, William C; Kim, Jane J; Cuzick, Jack; Lee, Ji-Hyun; Du, Ruofei; Robertson, Michael; Norville, Scott; Wheeler, Cosette M

    2017-06-01

    A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). From 2007 to 2014, a total of 13 520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100 000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], -9.0; 95% CI, -12.0 to -5.8; P women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, -6.3; 95% CI, -10.9 to -1.4; P = .02). Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are reassessed. Evidence is rapidly growing to suggest that further increases in raising the age to start screening are imminent, one step toward integrating screening and vaccination.

  11. Public acceptance of a hypothetical Ebola virus vaccine in Aceh, Indonesia: A hospital-based survey

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    Harapan Harapan

    2017-04-01

    Full Text Available Objective: To determine the acceptance towards a hypothetical Ebola virus vaccine (EVV and associated factors in a non-affected country, Indonesia. Methods: A hospital-based, cross-sectional study was conducted in four regencies of Aceh, Indonesia. A set of pre-tested questionnaires was used to obtain information on acceptance towards EVV and a range of explanatory variables. Associations between EVV acceptance and explanatory variables were tested using multi-steps logistic regression analysis and the Spearman's rank correlation. Results: Participants who had knowledge on Ebola virus disease (EVD were 45.3% (192/424 and none of the participants achieved 80% correct answers on the knowledge regarding to EVD. About 73% of participants expressed their willingness to receive the EVV. Education attainment, occupation, monthly income, have heard regarding to EVD previously, socioeconomic level, attitude towards vaccination practice and knowledge regarding to EVD were associated significantly with acceptance towards EVV in univariate analysis (P < 0.05. In the final multivariate model, socio-economic level, attitude towards vaccination practice and knowledge regarding to EVD were the independent explanatory variables for EVV acceptance. Conclusions: The knowledge of EVD was low, but this minimally affected the acceptance towards EVV. However, to facilitate optimal uptake of EVV, dissemination of vaccine-related information prior to its introduction is required.

  12. Future of an “Asymptomatic” T-cell Epitope-Based Therapeutic Herpes Simplex Vaccine

    Science.gov (United States)

    Dervillez, Xavier; Gottimukkala, Chetan; Kabbara, Khaled W.; Nguyen, Chelsea; Badakhshan, Tina; Kim, Sarah M.; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

    2012-01-01

    Summary Considering the limited success of the recent herpes clinical vaccine trial [1], new vaccine strategies are needed. Infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) in the majority of men and women are usually asymptomatic and results in lifelong viral latency in neurons of sensory ganglia (SG). However, in a minority of men and women HSV spontaneous reactivation can cause recurrent disease (i.e., symptomatic individuals). Our recent findings show that T cells from symptomatic and asymptomatic men and women (i.e. those with and without recurrences, respectively) recognize different herpes epitopes. This finding breaks new ground and opens new doors to assess a new vaccine strategy: mucosal immunization with HSV-1 & HSV-2 epitopes that induce strong in vitro CD4 and CD8 T cell responses from PBMC derived from asymptomatic men and women (designated here as “asymptomatic” protective epitopes”) could boost local and systemic “natural” protective immunity, induced by wild-type infection. Here we highlight the rationale and the future of our emerging “asymptomatic” T cell epitope-based mucosal vaccine strategy to decrease recurrent herpetic disease. PMID:22701511

  13. Vaccine delivery system for tuberculosis based on nano-sized hepatitis B virus core protein particles

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    Dhanasooraj D

    2013-02-01

    Full Text Available Dhananjayan Dhanasooraj, R Ajay Kumar, Sathish MundayoorMycobacterium Research Group, Rajiv Gandhi Centre for Biotechnology, Kerala, IndiaAbstract: Nano-sized hepatitis B virus core virus-like particles (HBc-VLP are suitable for uptake by antigen-presenting cells. Mycobacterium tuberculosis antigen culture filtrate protein 10 (CFP-10 is an important vaccine candidate against tuberculosis. The purified antigen shows low immune response without adjuvant and tends to have low protective efficacy. The present study is based on the assumption that expression of these proteins on HBc nanoparticles would provide higher protection when compared to the native antigen alone. The cfp-10 gene was expressed as a fusion on the major immunodominant region of HBc-VLP, and the immune response in Balb/c mice was studied and compared to pure proteins, a mixture of antigens, and fusion protein-VLP, all without using any adjuvant. The humoral, cytokine, and splenocyte cell proliferation responses suggested that the HBc-VLP bearing CFP-10 generated an antigen-specific immune response in a Th1-dependent manner. By virtue of its self-adjuvant nature and ability to form nano-sized particles, HBc-VLPs are an excellent vaccine delivery system for use with subunit protein antigens identified in the course of recent vaccine research.Keywords: Mycobacterium tuberculosis, VLP, hepatitis B virus core particle, CFP-10, self-adjuvant, vaccine delivery

  14. Measuring HPV vaccination coverage in Australia: comparing two alternative population-based denominators.

    Science.gov (United States)

    Barbaro, Bianca; Brotherton, Julia M L

    2015-08-01

    To compare the use of two alternative population-based denominators in calculating HPV vaccine coverage in Australia by age groups, jurisdiction and remoteness areas. Data from the National HPV Vaccination Program Register (NHVPR) were analysed at Local Government Area (LGA) level, by state/territory and by the Australian Standard Geographical Classification Remoteness Structure. The proportion of females vaccinated was calculated using both the ABS ERP and Medicare enrolments as the denominator. HPV vaccine coverage estimates were slightly higher using Medicare enrolments than using the ABS estimated resident population nationally (70.8% compared with 70.4% for 12 to 17-year-old females, and 33.3% compared with 31.9% for 18 to 26-year-old females, respectively.) The greatest differences in coverage were found in the remote areas of Australia. There is minimal difference between coverage estimates made using the two denominators except in Remote and Very Remote areas where small residential populations make interpretation more difficult. Adoption of Medicare enrolments for the denominator in the ongoing program would make minimal, if any, difference to routine coverage estimates. © 2015 Public Health Association of Australia.

  15. Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

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    Chen Hui-Ming

    2012-04-01

    Full Text Available Abstract Background Shikonin, a phytochemical purified from Lithospermum erythrorhizon, has been shown to confer diverse pharmacological activities, including accelerating granuloma formation, wound healing, anti-inflammation and others, and is explored for immune-modifier activities for vaccination in this study. Transdermal gene-based vaccine is an attractive approach for delivery of DNA transgenes encoding specific tumor antigens to host skin tissues. Skin dendritic cells (DCs, a potent antigen-presenting cell type, is known to play a critical role in transmitting and orchestrating tumor antigen-specific immunities against cancers. The present study hence employs these various components for experimentation. Method The mRNA and protein expression of RANTES were detected by RT-PCR and ELISA, respectively. The regional expression of RANTES and tissue damage in test skin were evaluated via immunohistochemistry assay. Fluorescein isothiocyanate sensitization assay was performed to trace the trafficking of DCs from the skin vaccination site to draining lymph nodes. Adjuvantic effect of shikonin on gene gun-delivered human gp100 (hgp100 DNA cancer vaccine was studied in a human gp100-transfected B16 (B16/hgp100 tumor model. Results Among various phytochemicals tested, shikonin induced the highest level of expression of RANTES in normal skin tissues. In comparison, mouse RANTES cDNA gene transfection induced a higher level of mRANTES expression for a longer period, but caused more extensive skin damage. Topical application of shikonin onto the immunization site before gene gun-mediated vaccination augmented the population of skin DCs migrating into the draining lymph nodes. A hgp100 cDNA gene vaccination regimen with shikonin pretreatment as an adjuvant in a B16/hgp100 tumor model increased cytotoxic T lymphocyte activities in splenocytes and lymph node cells on target tumor cells. Conclusion Together, our findings suggest that shikonin can

  16. Influenza during pregnancy: Incidence, vaccination coverage and attitudes toward vaccination in the French web-based cohort G-GrippeNet.

    Science.gov (United States)

    Loubet, Paul; Guerrisi, Caroline; Turbelin, Clément; Blondel, Béatrice; Launay, Odile; Bardou, Marc; Goffinet, François; Colizza, Vittoria; Hanslik, Thomas; Kernéis, Solen

    2016-04-29

    Pregnancy is a risk factor for severe influenza. However, data on influenza incidence during pregnancy are scarce. Likewise, no data are available on influenza vaccine coverage in France since national recommendation in 2012. We aimed to assess these points using a novel nationwide web-based surveillance system, G-GrippeNet. During the 2014/2015 influenza season, pregnant women living in metropolitan France were enrolled through a web platform (https://www.grippenet.fr/). Throughout the season, participants were asked to report, on a weekly basis, if they had experienced symptoms of influenza-like-illness (ILI). ILI episodes reported were used to calculate incidence density rates based on period of participation from each participant. Vaccination coverage was estimated after weighing on age and education level from national data on pregnant women. Factors associated with higher vaccination coverage were obtained through a logistic regression with Odds Ratio (OR) corrected with the Zhang and Yu method. A total of 153 women were enrolled. ILI incidence density rate was 1.8 per 100 person-week (95% CI, 1.5-2.1). This rate was higher in women older than 40 years (RR = 3.0, 95% CI [1.1-8.3], p = 0.03) and during first/second trimesters compared to third trimester (RR = 4.0, 95% CI [1.4-12.0], p = 0.01). Crude vaccination coverage was 39% (95% CI, 31-47) and weighted vaccination coverage was estimated at 26% (95% CI, 20-34). Health care provider recommendation for vaccination (corrected OR = 7.8; 95% CI [3.0-17.1]) and non-smoking status (cOR = 2.1; 95% CI [1.2-6.9]) were associated with higher vaccine uptake. This original web based longitudinal surveillance study design proved feasible in pregnant women population. First results are of interest and underline that public health policies should emphasize the vaccination promotion through health care providers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Hatchery Spray Cabinet Administration Does Not Damage Avian Coronavirus Infectious Bronchitis Virus Vaccine Based on Analysis by Electron Microscopy and Virus Titration.

    Science.gov (United States)

    Roh, Ha-Jung; Jordan, Brian J; Hilt, Deborah A; Ard, Mary B; Jackwood, Mark W

    2015-03-01

    studies in our laboratory showed that the Arkansas-Delmarva Poultry Industry (Ark-DPI) vaccine given to 1-day-old chickens by hatchery spray cabinet replicated poorly and failed to adequately protect broilers against homologous virus challenge, whereas the same vaccine given by eye-drop did replicate and the birds were protected following homologous virus challenge. To determine if mechanical damage following spray application plays a role in failure of the Ark-DPI vaccine, we examined the morphology of three Ark-DPI vaccines from different manufacturers using an electron microscope and included a Massachusetts (Mass) vaccine as control. One of the Ark-DPI vaccines (vaccine A) and the Mass vaccine had significantly (P vaccines. We also found that the Ark-DPI and Mass vaccines had significantly (P vaccine titer before and after spray in embryonated eggs and found that both Ark-DPI and Mass vaccines had a similar drop in titer, 0.40 logi and 0.310 logi, respec10ively. Based on these data, it appears that mechanical damage to the Ark-DPI vaccine is not occurring when delivered by a hatchery spray cabinet, suggesting that some other factor is contributing to the failure of that vaccine when given by that method.

  18. What Vaccines Do You Need?

    Science.gov (United States)

    ... Recommendations Why Immunize? Vaccines: The Basics The Adult Vaccine Quiz Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Vaccines are recommended for adults based on age, health ...

  19. Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters

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    Joseph Prescott

    2014-01-01

    Full Text Available Andes virus (ANDV is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G. This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure, and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025, but animals were not significantly protected following 1 year of vaccination (p = 0.090. The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.

  20. Challenges in conducting a community-based influenza vaccine trial in a rural community in northern India.

    Science.gov (United States)

    Kumar, Rakesh; Amarchand, Ritvik; Narayan, Venkatesh Vinayak; Saha, Siddhartha; Lafond, Kathryn E; Kapoor, Suresh K; Dar, Lalit; Jain, Seema; Krishnan, Anand

    2018-04-04

    Evidence on influenza vaccine effectiveness from low and middle countries (LMICs) is limited due to limited institutional capacities; lack of adequate resources; and lack of interest by ministries of health for influenza vaccine introduction. There are concerns that the highest ethical standards will be compromised during trials in LMICs leading to mistrust of clinical trials. These factors pose regulatory and operational challenges to researchers in these countries. We conducted a community-based vaccine trial to assess the efficacy of live attenuated influenza vaccine and inactivated influenza vaccine in rural north India. Key regulatory challenges included obtaining regulatory approvals, reporting of adverse events, and compensating subjects for trial-related injuries; all of which were required to be completed in a timely fashion. Key operational challenges included obtaining audio-visual consent; maintaining a low attrition rate; and administering vaccines during a narrow time period before the influenza season, and under extreme heat. We overcame these challenges through advanced planning, and sustaining community engagement. We adapted the trial procedures to cope with field conditions by conducting mock vaccine camps; and planned for early morning vaccination to mitigate threats to the cold chain. These lessons may help investigators to confront similar challenges in other LMICs.

  1. Nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice.

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    Maria A Croyle

    Full Text Available Pre-existing immunity to human adenovirus serotype 5 (Ad5 is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M., nasal (I.N. or oral (P.O. route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-gamma+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-gamma+ CD8+ T cells (3.9+/-1% naïve vs. 3.6+/-1% pre-existing immunity, PEI nor anti-Ebola neutralizing antibody (NAB, 40+/-10 reciprocal dilution, both groups. The number of INF-gamma+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146+/-14, naïve vs. 120+/-16 SFC/million MNCs, PEI. However, pre-existing immunity reduced NAB levels in BAL by approximately 25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-gamma+ CD8+ T cells 10 days after administration (0.3+/-0.3% PEG vs. 1.7+/-0.5% unmodified. PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.

  2. A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus.

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    Yoshimi Tsuda

    2011-08-01

    Full Text Available Human outbreaks of Ebola virus (EBOV are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes.We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a 'proof-of-concept' for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV vector expressing a CD8+ T cell epitope from the nucleoprotein (NP of Zaire ebolavirus (ZEBOV (MCMV/ZEBOV-NP(CTL. MCMV/ZEBOV-NP(CTL induced high levels of long-lasting (>8 months CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection.This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for 'disseminating' CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations.

  3. New safety training for access to the PS complex areas

    CERN Multimedia

    2012-01-01

    Since 10/08/2012, a new course dedicated to the specific radiological risks in the accelerators of the PS complex has been available on SIR (https://sir.cern.ch/). This course complements the general classroom-based Radiation Safety training. Successful completion of the course will be obligatory and verified by the access system as from 01/11/2012 for access to the following accelerator areas: LINAC2, BOOSTER, PS and TT2. Information and reminder e-mails will be sent to all persons currently authorized to access the accelerators of the PS complex. For questions please contact the HSE unit and in particular, the Radiation Protection Group (+41227672504 or safety-rp-ps-complex@cern.ch).

  4. Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Jiangan Xie

    Full Text Available M. bovis strain Bacillus Calmette-Guérin (BCG has been the only licensed live attenuated vaccine against tuberculosis (TB for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis, skin (e.g., skin ulceration and cyanosis, and respiratory system (e.g., cough and pneumonia; in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria. With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG

  5. School nurses' attitudes and experiences regarding the human papillomavirus vaccination programme in Sweden: a population-based survey.

    Science.gov (United States)

    Grandahl, Maria; Tydén, Tanja; Rosenblad, Andreas; Oscarsson, Marie; Nevéus, Tryggve; Stenhammar, Christina

    2014-05-31

    Sweden introduced a school-based human papillomavirus (HPV) vaccination programme in 2012, and school nurses are responsible for managing the vaccinations. The aim of the present study was to investigate the attitudes and experiences of school nurses regarding the school-based HPV vaccination programme 1 year after its implementation. Data were collected using a web-based questionnaire in the spring of 2013, and 83.1% (851/1024) of nurses responded. There were strong associations between the nurses' education about the HPV vaccine and their perceived knowledge about the vaccine and a favourable attitude towards vaccination (both p HPV vaccination compared with nurses with little education about HPV vaccination (adjusted odds ratio [OR] = 9.8; 95% confidence interval [CI]: 3.797-25.132). Nurses with high perceived knowledge were more likely to have a positive attitude compared with those with a low level of perceived knowledge (OR = 2.5; 95% CI: 1.299-4.955). If financial support from the government was used to fund an additional school nurse, nurses were more likely to have a positive attitude than if the financial support was not used to cover the extra expenses incurred by the HPV vaccination (OR = 2.1; 95% CI: 1.051-4.010). The majority, 648 (76.1%), had been contacted by parents with questions about the vaccine, mostly related to adverse effects. In addition, 570 (66.9%) stated that they had experienced difficulties with the vaccinations, and 337 (59.1%) of these considered the task to be time-consuming. A high level of education and perceived good knowledge about HPV are associated with a positive attitude of school nurses to the HPV vaccination programme. Thus, nurses require adequate knowledge, education, skills and time to address the questions and concerns of parents, as well as providing information about HPV. Strategic financial support is required because HPV vaccination is a complex and time-consuming task.

  6. Quality of Web-Based Educational Interventions for Clinicians on Human Papillomavirus Vaccine: Content and Usability Assessment.

    Science.gov (United States)

    Rosen, Brittany L; Bishop, James M; McDonald, Skye L; Kahn, Jessica A; Kreps, Gary L

    2018-02-16

    Human papillomavirus (HPV) vaccination rates fall far short of Healthy People 2020 objectives. A leading reason is that clinicians do not recommend the vaccine consistently and strongly to girls and boys in the age group recommended for vaccination. Although Web-based HPV vaccine educational interventions for clinicians have been created to promote vaccination recommendations, rigorous evaluations of these interventions have not been conducted. Such evaluations are important to maximize the efficacy of educational interventions in promoting clinician recommendations for HPV vaccination. The objectives of our study were (1) to expand previous research by systematically identifying HPV vaccine Web-based educational interventions developed for clinicians and (2) to evaluate the quality of these Web-based educational interventions as defined by access, content, design, user evaluation, interactivity, and use of theory or models to create the interventions. Current HPV vaccine Web-based educational interventions were identified from general search engines (ie, Google), continuing medical education search engines, health department websites, and professional organization websites. Web-based educational interventions were included if they were created for clinicians (defined as individuals qualified to deliver health care services, such as physicians, clinical nurses, and school nurses, to patients aged 9 to 26 years), delivered information about the HPV vaccine and how to increase vaccination rates, and provided continuing education credits. The interventions' content and usability were analyzed using 6 key indicators: access, content, design, evaluation, interactivity, and use of theory or models. A total of 21 interventions were identified, out of which 7 (33%) were webinars, 7 (33%) were videos or lectures, and 7 (33%) were other (eg, text articles, website modules). Of the 21 interventions, 17 (81%) identified the purpose of the intervention, 12 (57%) provided the

  7. Ultrasensitive multi-analyte electrochemical immunoassay based on GNR-modified heated screen-printed carbon electrodes and PS@PDA-metal labels for rapid detection of MMP-9 and IL-6.

    Science.gov (United States)

    Shi, Jian-Jun; He, Ting-Ting; Jiang, Fang; Abdel-Halim, E S; Zhu, Jun-Jie

    2014-05-15

    An ultrasensitive electrochemical immunoassay was developed for rapid detection of interleukin-6 (IL-6) and matrix metallopeptidase-9 (MMP-9); the method utilized PS@PDA-metal nanocomposites based on graphene nanoribbon (GNR)-modified heated screen-printed carbon electrode (HSPCE). Because of the good hydrophilicity and low toxicity, GNRs were used to immobilize antibodies (Ab) and amplify the electrochemical signal. PS@PDA-metal was used to label antibodies and generate a strong electrochemical signal in acetic buffer. A sandwich strategy was adopted to achieve simultaneous detection of MMP-9 and IL-6 based on HSPCE without cross-talk between adjacent electrodes in the range of 10(-5) to 10(3) ng mL(-1) with detection limits of 5 fg mL(-1) and 0.1 pg mL(-1) (S/N=3), respectively. The proposed method showed wide detection range, low detection limit, acceptable stability and good reproducibility. Satisfactory results were also obtained in the practical samples, thus showing this is a promising technique for simultaneous clinical detection of biocomponent proteins. © 2013 Elsevier B.V. All rights reserved.

  8. Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

    Science.gov (United States)

    Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

    2015-07-01

    Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

  9. A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

    Directory of Open Access Journals (Sweden)

    Yang Hong-hui

    2005-05-01

    Full Text Available Abstract Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90% than in adolescents and young adults (70%. Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%, malaise (19% and local redness (19% were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

  10. PROTECTIVE ACTIVITY STUDY OF A CANDIDATE VACCINE AGAINST ROTAVIRUS INFECTION BASED ON RECOMBINANT PROTEIN FliCVP6VP8

    Directory of Open Access Journals (Sweden)

    I. V. Dukhovlinov

    2016-01-01

    Full Text Available Rotavirus infection is among leading causes of severe diarrhea which often leads to severe dehydration, especially, in children under 5 years old. In Russia, the incidence of rotavirus infection is constantly increased, due to higher rates of actual rotavirus infection cases and improved diagnostics of the disease. Immunity to rotavirus is unstable, thus causing repeated infections intra vitam. Anti-infectious resistance in reconvalescents is explained by induction of specific IgM, IgG, and, notably, IgA antibodies. Due to absence of market drugs with direct action against rotavirus, a rational vaccination is considered the most effective way to control the disease. Currently available vaccines for prevention of rotavirus infection are based on live attenuated rotavirus strains, human and/or animal origin, which replicate in human gut. Their implementation may result into different complications. Meanwhile, usage of vaccines based on recombinant proteins is aimed to avoid risks associated with introduction of a complete virus into humans. In this paper, we studied protective activity of candidate vaccines against rotavirus.In this work we studied protective activity of a candidate vaccine against rotavirus infection based on recombinant FliCVP6VP8 protein which includes VP6 and VP8, as well as components of Salmonella typhimurium flagellin (FliC as an adjuvant. Different components are joined by flexible bridges. Efficiency of the candidate vaccine was studied in animal model using Balb/c mice. We have shown high level of protection which occurs when the candidate vaccine is administered twice intramuscularly. Complete protection of animals against mouse rotavirus EDC after intramuscular immunization with a candidate vaccine was associated with arising rotavirus-specific IgA and IgG antibodies in serum and intestine of immunized animals. The efficacy of candidate vaccine based on recombinant protein FliCVP6VP8 against rotavirus infection was

  11. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants.

    Science.gov (United States)

    Rose, N F; Marx, P A; Luckay, A; Nixon, D F; Moretto, W J; Donahoe, S M; Montefiori, D; Roberts, A; Buonocore, L; Rose, J K

    2001-09-07

    We developed an AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AIDS virus (SHIV89.6P). Control monkeys showed a severe loss of CD4+ T cells and high viral loads, and 7/8 progressed to AIDS with an average time of 148 days. All seven vaccinees were initially infected with SHIV89.6P but have remained healthy for up to 14 months after challenge with low or undetectable viral loads. Protection from AIDS was highly significant (p = 0.001). VSV vectors are promising candidates for human AIDS vaccine trials because they propagate to high titers and can be delivered without injection.

  12. Bringing plant-based veterinary vaccines to market: Managing regulatory and commercial hurdles.

    Science.gov (United States)

    MacDonald, Jacqueline; Doshi, Ketan; Dussault, Marike; Hall, J Christopher; Holbrook, Larry; Jones, Ginny; Kaldis, Angelo; Klima, Cassidy L; Macdonald, Phil; McAllister, Tim; McLean, Michael D; Potter, Andrew; Richman, Alex; Shearer, Heather; Yarosh, Oksana; Yoo, Han Sang; Topp, Edward; Menassa, Rima

    2015-12-01

    The production of recombinant vaccines in plants may help to reduce the burden of veterinary diseases, which cause major economic losses and in some cases can affect human health. While there is abundant research in this area, a knowledge gap exists between the ability to create and evaluate plant-based products in the laboratory, and the ability to take these products on a path to commercialization. The current report, arising from a workshop sponsored by an Organisation for Economic Co-operation and Development (OECD) Co-operative Research Programme, addresses this gap by providing guidance in planning for the commercialization of plant-made vaccines for animal use. It includes relevant information on developing business plans, assessing market opportunities, manufacturing scale-up, financing, protecting and using intellectual property, and regulatory approval with a focus on Canadian regulations. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  13. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    International Nuclear Information System (INIS)

    Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

    2013-01-01

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  14. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    Science.gov (United States)

    Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

    2013-05-01

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  15. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Mott, Brittney [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States); Thamake, Sanjay [Radio-Isotope Therapy of America Foundation (United States); Vishwanatha, Jamboor; Jones, Harlan P., E-mail: harlan.jones@unthsc.edu [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States)

    2013-05-15

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 {+-} 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-{gamma} cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  16. Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs

    Directory of Open Access Journals (Sweden)

    Touihri Leila

    2012-12-01

    Full Text Available Abstract Background During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV or distemper virus (CDV after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. Methods We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an “Internal Ribosome Entry Site” (IRES domain. Results The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The

  17. Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs.

    Science.gov (United States)

    Touihri, Leila; Ahmed, Sami Belhaj; Chtourou, Yacine; Daoud, Rahma; Bahloul, Chokri

    2012-12-27

    During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV) or distemper virus (CDV) after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV) 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an "Internal Ribosome Entry Site" (IRES) domain. The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The FMDV 2A was also efficient in the design of multivalent

  18. Novel vaccination approach for dengue infection based on recombinant immune complex universal platform.

    Science.gov (United States)

    Kim, Mi-Young; Reljic, Rajko; Kilbourne, Jacquelyn; Ceballos-Olvera, Ivonne; Yang, Moon-Sik; Reyes-del Valle, Jorge; Mason, Hugh S

    2015-04-08

    Dengue infection is on the rise in many endemic areas of the tropics. Vaccination remains the most realistic strategy for prevention of this potentially fatal viral disease but there is currently no effective vaccine that could protect against all four known serotypes of the dengue virus. This study describes the generation and testing of a novel vaccination approach against dengue based on recombinant immune complexes (RIC). We modelled the dengue RIC on the existing Ebola RIC (Phoolcharoen, et al. Proc Natl Acad Sci USA 2011;108(Dec (51)):20695) but with a key modification that allowed formation of a universal RIC platform that can be easily adapted for use for other pathogens. This was achieved by retaining only the binding epitope of the 6D8 ant-Ebola mAb, which was then fused to the consensus dengue E3 domain (cEDIII), resulting in a hybrid dengue-Ebola RIC (DERIC). We expressed human and mouse versions of these molecules in tobacco plants using a geminivirus-based expression system. Following purification from the plant extracts by protein G affinity chromatography, DERIC bound to C1q component of complement, thus confirming functionality. Importantly, following immunization of mice, DERIC induced a potent, virus-neutralizing anti-cEDIII humoral immune response without exogenous adjuvants. We conclude that these self-adjuvanting immunogens have the potential to be developed as a novel vaccine candidate for dengue infection, and provide the basis for a universal RIC platform for use with other antigens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. EVALUATION OF OIL BASED AVIAN INFLUENZA VACCINE (H5NI PREPARED WITH DIFFERENT CONCENTRATIONS OF ADJUVANT

    Directory of Open Access Journals (Sweden)

    M. IQBAL, M. NISAR, ANWARUL-HAQ, S. NOOR AND Z. J. GILL

    2008-12-01

    Full Text Available Bird flu vaccine from H5N1 strain of avian influenza virus was prepared with two concentrations of adjuvant (Montanide ISA 70MVG. Two vaccines (I and II were prepared containing 50 and 60% Montanide, respectively. Immune response of both the vaccines as single, as well as booster, dose was evaluated in layer birds through haemagglutination inhibition test. Single dose of both vaccines showed poor immune response, while booster dose gave better response with both the vaccines. However, the vaccine prepared with 60% Montanide provided better immune response compared with the vaccine containing 50% montanide.

  20. EDH 'Millionaire' in PS Division

    CERN Multimedia

    2001-01-01

    Christmas cheer! Left to right: Gerard Lobeau receives a bottle of Champagne from Derek Mathieson and Jurgen De Jonghe in recognition of EDH's millionth document. At 14:33 on Monday 3 December a technician in PS division, Gerard Lobeau, unwittingly became part of an important event in the life of CERN's Electronic Document Handling system (EDH). While ordering some pieces of aluminum for one of the PS's 10Mhz RF cavities, he created EDH document number 1,000,000. To celebrate the event Derek Mathieson (EDH Project Leader) and Jurgen De Jonghe (Original EDH Project Leader) presented Mr Lobeau with a bottle of champagne. As with 93% of material requests, Mr Lobeau's order was delivered within 24 hours. 'I usually never win anything' said Mr Lobeau as he accepted his prize, 'I initially though there may have been a problem with EDH when the document number had so many zeros in it, and was then surprised to get a phone call from you a few minutes later.' The EDH team had been monitoring the EDH document number ...

  1. Establishing Correlates of Protection for Vaccine Development: Considerations for the Respiratory Syncytial Virus Vaccine Field.

    Science.gov (United States)

    Kulkarni, Prasad S; Hurwitz, Julia L; Simões, Eric A F; Piedra, Pedro A

    2018-03-01

    Correlates of protection (CoPs) can play a significant role in vaccine development by assisting the selection of vaccine candidates for clinical trials, supporting clinical trial design and implementation, and simplifying tests of vaccine modifications. Because of this important role in vaccine development, it is essential that CoPs be defined by well-designed immunogenicity and efficacy studies, with attention paid to benefits and limitations. The respiratory syncytial virus (RSV) field is unique in that a great deal of information about the humoral response is available from basic research and clinical studies. Polyclonal and monoclonal antibodies have been used routinely in the clinic to protect vulnerable infants from infection, providing a wealth of information about correlations between neutralizing antibodies and disease prevention. Considerations for the establishment of future CoPs to support RSV vaccine development in different populations are therefore discussed.

  2. Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.

    Science.gov (United States)

    Blaney, Joseph E; Marzi, Andrea; Willet, Mallory; Papaneri, Amy B; Wirblich, Christoph; Feldmann, Friederike; Holbrook, Michael; Jahrling, Peter; Feldmann, Heinz; Schnell, Matthias J

    2013-01-01

    We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

  3. Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.

    Directory of Open Access Journals (Sweden)

    Joseph E Blaney

    Full Text Available We have previously described the generation of a novel Ebola virus (EBOV vaccine platform based on (a replication-competent rabies virus (RABV, (b replication-deficient RABV, or (c chemically inactivated RABV expressing EBOV glycoprotein (GP. Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

  4. Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation based on transmission model.

    Science.gov (United States)

    Jit, Mark; Chapman, Ruth; Hughes, Owain; Choi, Yoon Hong

    2011-09-27

    To compare the effect and cost effectiveness of bivalent and quadrivalent human papillomavirus (HPV) vaccination, taking into account differences in licensure indications, protection against non-vaccine type disease, protection against disease related to HPV types 6 and 11, and reported long term immunogenicity. A model of HPV transmission and disease previously used to inform UK vaccination policy, updated with recent evidence and expanded to include scenarios where the two vaccines differ in duration of protection, cross protection, and end points prevented. United Kingdom. Population Males and females aged 12-75 years. Incremental cost effectiveness ratios for both vaccines and additional cost per dose for the quadrivalent vaccine to be equally cost effective as the bivalent vaccine. The bivalent vaccine needs to be cheaper than the quadrivalent vaccine to be equally cost effective, mainly because of its lack of protection against anogenital warts. The price difference per dose ranges from a median of £19 (interquartile range £12-£27) to £35 (£27-£44) across scenarios about vaccine duration, cross protection, and end points prevented (assuming one quality adjusted life year (QALY) is valued at £30,000 and both vaccines can prevent all types of HPV related cancers). The quadrivalent vaccine may have an advantage over the bivalent vaccine in reducing healthcare costs and QALYs lost. The bivalent vaccine may have an advantage in preventing death due to cancer. However, considerable uncertainty remains about the differential benefit of the two vaccines.

  5. Increased humoral immunity by DNA vaccination using an alpha-tocopherol-based adjuvant

    DEFF Research Database (Denmark)

    Karlsson, Ingrid; Borggren, Marie; Nielsen, Jens

    2017-01-01

    approaches. We tested whether the emulsion-based and alpha-tocopherol containing adjuvant Diluvac Forte® has the ability to enhance the immunogenicity of a naked DNA vaccine (i.e., plasmid DNA). As a model vaccine, we used plasmids encoding both a surface-exposed viral glycoprotein (hemagglutinin......) and an internal non-glycosylated nucleoprotein in the Th1/Th2 balanced CB6F1 mouse model. The naked DNA (50 µg) was premixed at a 1:1 volume/volume ratio with Diluvac Forte®, an emulsion containing different concentrations of alpha-tocopherol, the emulsion alone or endotoxin-free phosphate-buffered saline (PBS......). The animals received two intracutaneous immunizations spaced 3 weeks apart. When combined with Diluvac Forte® or the emulsion containing alpha-tocopherol, the DNA vaccine induced a more potent and balanced immunoglobulin G (IgG)1 and IgG2c response, and both IgG subclass responses were significantly enhanced...

  6. Progress of dendritic cell-based cancer vaccines for patients with hematological malignancies.

    Science.gov (United States)

    Ni, Ming; Hoffmann, Jean-Marc; Schmitt, Michael; Schmitt, Anita

    2016-09-01

    Dendritic cells (DCs) are the most professional antigen-presenting cells eliciting cellular and humoral immune responses against cancer cells by expressing these antigens on MHC class I/II complexes to T cells. Therefore, they have been employed in many clinical trials as cancer vaccines for patients with cancer. This review focuses on the use of DCs in leukemia patients expressing leukemia-associated antigens (LAAs). The contribution of both stimulating vs. tolerogenic DCs as well as of other factors to the milieu of anti-leukemia immune responses are discussed. Several DC vaccination strategies like leukemia lysate, proteins and peptides have been developed. Next generation DC vaccines comprise transduction of DCs with retroviral vectors encoding for LAAs, cytokines and costimulatory molecules as well as transfection of DCs with naked RNA encoding for LAAs. Published as well as ongoing clinical trials are reported and critically reviewed. Future results will demonstrate whether next-generation DCs are really superior to conventional pulsing with peptide, protein or tumor lysate. However, currently available methods based on nucleic acid transfection/transduction are tempting in terms of material production costs and time for clinical application according to good manufacturing practice (GMP).

  7. Development of canine herpesvirus based antifertility vaccines for foxes using bacterial artificial chromosomes.

    Science.gov (United States)

    Strive, Tanja; Hardy, Christopher M; French, Nigel; Wright, John D; Nagaraja, Nitin; Reubel, Gerhard H

    2006-02-13

    Using bacterial artificial chromosome (BAC) technology, a canine herpesvirus (CHV)-based recombinant vaccine vector was produced for the development of an antifertility vaccine for foxes. Infectious viruses were recovered following transfection of canid cells with a BAC plasmid carrying the complete CHV genome. In vitro growth characteristics of BAC-derived viruses were similar to that of wildtype (wt)-CHV. Two recombinant antigens, fox zona pellucida protein subunit 3 (fZPC) and enhanced green fluorescent protein (EGFP) as control antigen, were inserted into thymidine kinase (TK) locus of the CHV genome and shown to be efficiently expressed in vitro. Inoculation of foxes with transgenic CHVs induced CHV specific antibodies, but was innocuous and failed to elicit transgene-specific antibody responses. Infectious virus or viral DNA was not detected in mucosal secretions or tissues of vaccinated foxes. The CHV-BAC system proved to be a quick and reliable method to manipulate the CHV genome. It will help to readily apply changes in the vector design in order to improve virus replication in vivo.

  8. Duration of immunity following the administration of oil-based avian influenza H5N1 vaccine in layers

    OpenAIRE

    NISAR, Maryam; RASHID*, Asif; IQBAL, Muhammad

    2014-01-01

    Avian influenza (AI) occurs worldwide and causes tremendous economic losses. The disease is characterised by respiratory signs, depression, and reduced food and water intake. In the present study, an oil-based vaccine created by using Montanide ISA 70 MVG, was prepared and the duration of immunity checked at different time intervals. For this purpose, the cumulative mean titre (CMT) was calculated after employing haemagglutination inhibition test in 50 pullets at day zero before vaccination a...

  9. Microneedle-based drug and vaccine delivery via nanoporous microneedle arrays.

    Science.gov (United States)

    van der Maaden, Koen; Luttge, Regina; Vos, Pieter Jan; Bouwstra, Joke; Kersten, Gideon; Ploemen, Ivo

    2015-08-01

    In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based drug and vaccine delivery and could be a valuable addition to the other microneedle-based drug delivery approaches. To gain more insight into porous microneedle technologies, the scientific and patent literature is reviewed, and we focus on the possibilities and constraints of porous microneedle technologies for dermal drug delivery. Furthermore, we show preliminary data with commercially available porous microneedles and describe future directions in this field of research.

  10. Household-based costs and benefits of vaccinating healthy children in daycare against influenza virus: results from a pilot study.

    Science.gov (United States)

    Pisu, Maria; Meltzer, Martin I; Hurwitz, Eugene S; Haber, Michael

    2005-01-01

    Vaccinating children against influenza virus may reduce infections in immunised children and household contacts, thereby reducing the household-based cost associated with respiratory illnesses. To evaluate the impact of influenza virus vaccination of daycare children on costs of respiratory illnesses of the children and their household contacts from the household and societal perspective. Cost analysis of data from a randomised controlled trial covering the period November to April of 1996-7 and 1998-9. Children (127 in 1996-7 and 133 in 1998-9) from daycare centres in Californian (USA) naval bases received influenza virus vaccine (inactivated) or hepatitis A virus vaccination. Direct and indirect costs (1997 and 1999 US dollars) of respiratory illnesses in households of vaccinated and not vaccinated daycare children, excluding the cost of vaccination. There were no statistically significant differences in household costs of respiratory illness between households with or without influenza virus-vaccinated children (USD 635 vs USD 492: p = 0.98 [1996-7]; USD 412.70 vs USD 499.50: p = 0.42 [1998-9]). In 1996-7, adult and 5- to 17-year-old contacts of vaccinated children had lower household costs than contacts of unvaccinated children (USD 58.50 vs USD 83.20, p = 0.01 and USD 32.80 vs USD 59.50, p = 0.04, respectively), while vaccinated children 0-4 years old had higher household costs than unvaccinated children in the same age group (USD 383 vs USD 236, p = 0.05). In 1998-9, there were no differences within individual age groups. Results from societal perspective were similar. Overall, from both the household and societal perspectives, there were no economic benefits to households from vaccinating daycare children against influenza virus. However, we found some over-time inconsistency in results; this should be considered if changing recommendations about routine influenza virus vaccination of healthy children. Our study size may limit the generalisability of the

  11. Preliminary Evaluation of PS300: A New Self-Lubricating High Temperature Composite Coating for Use to 800 C

    Science.gov (United States)

    Dellacorte, C.; Edmonds, B. J.

    1995-01-01

    This paper introduces PS300, a plasma sprayed, self-lubricating composite coating for use in sliding contacts at temperatures to 800 C. PS300 is a metal bonded chrome oxide coating with silver and BaF2/CaF2 eutectic solid lubricant additives. PS300 is similar to PS200, a chromium carbide based coating, which is currently being investigated for a variety of tribological applications. In pin-on-disk testing up to 650 C, PS300 exhibited comparable friction and wear properties to PS200. The PS300 matrix, which is predominantly chromium oxide rather than chromium carbide, does not require diamond grinding and polishes readily with silicon carbide abrasives greatly reducing manufacturing costs compared to PS200. It is anticipated that PS300 has potential for sliding bearing and seal applications in both aerospace and general industry.

  12. Mimotope-based vaccines of Leishmania infantum antigens and their protective efficacy against visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Lourena Emanuele Costa

    Full Text Available BACKGROUND: The development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL. Epitope-based immunogens, represented by phage-fused peptides that mimic Leishmania infantum antigens, were selected according to their affinity to antibodies from asymptomatic and symptomatic VL dogs' sera. METHODOLOGY/MAIN FINDINGS: Twenty phage clones were selected after three selection cycles, and were evaluated by means of in vitro assays of the immune stimulation of spleen cells derived from naive and chronically infected with L. infantum BALB/c mice. Clones that were able to induce specific Th1 immune response, represented by high levels of IFN-γ and low levels of IL-4 were selected, and based on their selectivity and specificity, two clones, namely B10 and C01, were further employed in the vaccination protocols. BALB/c mice vaccinated with clones plus saponin showed both a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with individual clones or L. infantum extracts. Additionally, these animals, when compared to control groups (saline, saponin, wild-type phage plus saponin, or non-relevant phage clone plus saponin, showed significant reductions in the parasite burden in the liver, spleen, bone marrow, and paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD8+ T cells, against parasite proteins. These animals also presented decreased parasite-mediated IL-4 and IL-10 responses, and increased levels of parasite-specific IgG2a antibodies. CONCLUSIONS/SIGNIFICANCE: This study describes two phage clones that mimic L. infantum antigens, which were directly used as immunogens in vaccines and presented Th1-type immune responses, and that significantly reduced the

  13. Acceptability of School-Based Health Centers for Human Papillomavirus Vaccination Visits: A Mixed-Methods Study.

    Science.gov (United States)

    Hansen, Caitlin E; Okoloko, Edirin; Ogunbajo, Adedotun; North, Anna; Niccolai, Linda M

    2017-09-01

    Countries with high human papillomavirus (HPV) vaccination rates have achieved this success largely through school-based vaccination. Using school-based health centers (SBHCs) in the United States, where HPV vaccine remains underutilized, could improve uptake. In this mixed-methods study, we examined acceptability, facilitators, and barriers of HPV vaccination visits at SBHCs from the perspectives of adolescents and parents. We conducted qualitative interviews and structured surveys with adolescents and parents recruited from an urban, hospital-based clinic. Interviews with parents (N = 20) and adolescents (N = 20) were audio-recorded and transcribed for analysis using an iterative thematic approach. Quantitative measures for a survey administered to parents (N = 131) were derived from the qualitative findings. Survey results were analyzed by chi-square tests. Many participants expressed favorable opinions of HPV vaccination at SBHCs in qualitative interviews. Facilitators included convenience, ease of scheduling, and not missing work or school. However, barriers were noted including concerns about obtaining care outside the medical home, fragmentation of medical records, and negative perceptions about SBHCs. Quantitative findings revealed that a higher proportion of parents with experience using SBHCs were willing to use a middle school (59.5%) or high school (80.5%) SBHC for HPV vaccinations compared with those who had not used SBHCs (p HPV vaccination visits at SBHCs were acceptable, and SBHC users expressed more favorable attitudes. Barriers to HPV vaccination at SBHCs can be addressed through more education about SBHCs' role, and improvement of systems to coordinate care. © 2017, American School Health Association.

  14. Efficacy of a non-updated, Matrix-C-based equine influenza subunit-tetanus vaccine following Florida sublineage clade 2 challenge.

    Science.gov (United States)

    Pouwels, H G W; Van de Zande, S M A; Horspool, L J I; Hoeijmakers, M J H

    2014-06-21

    Assessing the ability of current equine influenza vaccines to provide cross-protection against emerging strains is important. Horses not vaccinated previously and seronegative for equine influenza based on haemagglutination inhibition (HI) assay were assigned at random to vaccinated (n=7) or non-vaccinated (control, n=5) groups. Vaccination was performed twice four weeks apart with a 1 ml influenza subunit (A/eq/Prague/1/56, A/eq/Newmarket/1/93, A/eq/Newmarket/2/93), tetanus toxoid vaccine with Matrix-C adjuvant (EquilisPrequenza Te). All the horses were challenged individually by aerosol with A/eq/Richmond/1/07 three weeks after the second vaccination. Rectal temperature, clinical signs, serology and virus excretion were monitored for 14 days after challenge. There was no pain at the injection site or increases in rectal temperature following vaccination. Increases in rectal temperature and characteristic clinical signs were recorded in the control horses. Clinical signs were minimal in vaccinated horses. Clinical (P=0.0345) and total clinical scores (P=0.0180) were significantly lower in the vaccinated than in the control horses. Vaccination had a significant effect on indicators of viraemia - the extent (P=0.0006) and duration (P=horse was positive or negative for virus excretion during the study. Further research is needed to fully understand the specific properties of this vaccine that may contribute to its cross-protective capacity. British Veterinary Association.

  15. Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

    Directory of Open Access Journals (Sweden)

    Amaya Leunda

    2014-06-01

    Full Text Available Novel efficient vaccines are needed to control tuberculosis (TB, a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine. In this review we provide up to date information on novel tuberculosis (TB vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.

  16. Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations.

    Science.gov (United States)

    Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

    2014-06-16

    Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.

  17. Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

    Science.gov (United States)

    Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

    2014-01-01

    Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. PMID:26344627

  18. High-precision calculation of loosely bound states of LiPs+ and NaPs+

    International Nuclear Information System (INIS)

    Yamashita, Takuma; Kino, Yasushi

    2015-01-01

    A positronic alkali atom would be the first step to investigate behavior of a positronium(Ps) in an external field from atoms/molecules because the system can be regarded as a simple three-body system using model potentials reflecting electron orbitals of the ion core. In order to precisely determine binding energies and structures of positronic alkali atoms (LiPs + and NaPs + ), we improve the model potential so as to reproduce highly excited atomic energy levels of alkali atoms (Li and Na). The polarization potential included by the model potential is expanded in terms of Gaussian functions to finely determine a short range part of the potential which has been assumed to be a simple form. We find better reproducibility not only of atomic levels of the alkali atoms but also of the dipole polarizability of the core ion than previous works. We construct a model potential between a positron and an ion core based on the model potential between the valence electron and ion core. Binding energies associated with a dissociation of the alkali ion core and positronium, and interparticle distances are recalculated. Our results show slightly deeper bound than other previous studies. (paper)

  19. Potential Cost-Effectiveness of RSV Vaccination of Infants and Pregnant Women in Turkey: An Illustration Based on Bursa Data.

    Directory of Open Access Journals (Sweden)

    Koen B Pouwels

    Full Text Available Worldwide, respiratory syncytial virus (RSV is considered to be the most important viral cause of respiratory morbidity and mortality among infants and young children. Although no active vaccine is available on the market yet, there are several active vaccine development programs in various stages. To assess whether one of these vaccines might be a future asset for national immunization programs, modeling the costs and benefits of various vaccination strategies is needed.To evaluate the potential cost-effectiveness of RSV vaccination of infants and/or pregnant women in Turkey.A multi-cohort static Markov model with cycles of one month was used to compare the cost-effectiveness of vaccinated cohorts versus non-vaccinated cohorts. The 2014 Turkish birth cohort was divided by twelve to construct twelve monthly birth cohorts of equal size (111,459 new-borns. Model input was based on clinical data from a multicenter prospective study from Bursa, Turkey, combined with figures from the (international literature and publicly available data from the Turkish Statistical Institute (TÜÏK. Incremental cost-effectiveness ratios (ICERs were expressed in Turkish Lira (TL per quality-adjusted life year (QALY gained.Vaccinating infants at 2 and 4 months of age would prevent 145,802 GP visits, 8,201 hospitalizations and 48 deaths during the first year of life, corresponding to a total gain of 1650 QALYs. The discounted ICER was estimated at 51,969 TL (26,220 US $ in 2013 per QALY gained. Vaccinating both pregnant women and infants would prevent more cases, but was less attractive from a pure economic point of view with a discounted ICER of 61,653 TL (31,106 US $ in 2013 per QALY. Vaccinating only during pregnancy would result in fewer cases prevented than infant vaccination and a less favorable ICER.RSV vaccination of infants and/or pregnant women has the potential to be cost-effective in Turkey. Although using relatively conservative assumptions, all evaluated

  20. A Threat- and Efficacy-Based Framework to Understand Confidence in Vaccines among the Public Health Workforce

    Directory of Open Access Journals (Sweden)

    Lainie Rutkow

    2013-04-01

    Full Text Available The Extended Parallel Process Model (EPPM is an established threat- and efficacy-based behavioral framework for understanding health behaviors in the face of uncertain risk. A growing body of research has applied this model to understand these behaviors among the public health workforce. In this manuscript, we aim to explore the application of this framework to the public health workforce, with a novel focus on their confidence in vaccines and perceptions of vaccine injury compensation mechanisms. We characterize specific connections between EPPM’s threat and efficacy dimensions and relevant vaccine policy frameworks and highlight how these connections can usefully inform training interventions for public health workers to enhance their confidence in these vaccine policy measures.

  1. Can opportunities be enhanced for vaccinating children in home visiting programs? A population-based cohort study.

    Science.gov (United States)

    Isaac, Michael R; Chartier, Mariette; Brownell, Marni; Chateau, Dan; Nickel, Nathan C; Martens, Patricia; Katz, Alan; Sarkar, Joykrishna; Hu, Milton; Burland, Elaine; Goh, ChunYan; Taylor, Carole

    2015-07-07

    Home visiting programs focused on improving early childhood environments are commonplace in North America. A goal of many of these programs is to improve the overall health of children, including promotion of age appropriate vaccination. In this study, population-based data are used to examine the effect of a home visiting program on vaccination rates in children. Home visiting program data from Manitoba, Canada were linked to several databases, including a provincial vaccination registry to examine vaccination rates in a cohort of children born between 2003 and 2009. Propensity score weights were used to balance potential confounders between a group of children enrolled in the program (n = 4,562) and those who were eligible but not enrolled (n = 5,184). Complete and partial vaccination rates for one and two year old children were compared between groups, including stratification into area-level income quintiles. Complete vaccination rates from birth to age 1 and 2 were higher for those enrolled in the Families First program [Average Treatment Effect Risk Ratio (ATE RR) 1.06 (95 % CI 1.03-1.08) and 1.10 (95 % CI 1.05-1.15) respectively]. No significant differences were found between groups having at least one vaccination at age 1 or 2 [ATE RR 1.01 (95 % CI 1.00-1.02) and 1.00 (95 % CI 1.00-1.01) respectively). The interaction between program and income quintiles was not statistically significant suggesting that the program effect did not differ by income quintile. Home visiting programs have the potential to increase vaccination rates for children enrolled, despite limited program content directed towards this end. Evidence-based program enhancements have the potential to increase these rates further, however more research is needed to inform policy makers of optimal approaches in this regard, especially with respect to cost-effectiveness.

  2. Development of a multi-epitope peptide vaccine inducing robust T cell responses against brucellosis using immunoinformatics based approaches.

    Science.gov (United States)

    Saadi, Mahdiye; Karkhah, Ahmad; Nouri, Hamid Reza

    2017-07-01

    Current investigations have demonstrated that a multi-epitope peptide vaccine targeting multiple antigens could be considered as an ideal approach for prevention and treatment of brucellosis. According to the latest findings, the most effective immunogenic antigens of brucella to induce immune responses are included Omp31, BP26, BLS, DnaK and L7-L12. Therefore, in the present study, an in silico approach was used to design a novel multi-epitope vaccine to elicit a desirable immune response against brucellosis. First, five novel T-cell epitopes were selected from Omp31, BP26, BLS, DnaK and L7-L12 proteins using different servers. In addition, helper epitopes selected from Tetanus toxin fragment C (TTFrC) were applied to induce CD4+ helper T lymphocytes (HTLs) responses. Selected epitopes were fused together by GPGPG linkers to facilitate the immune processing and epitope presentation. Moreover, cholera toxin B (CTB) was linked to N terminal of vaccine construct as an adjuvant by using EAAAK linker. A multi-epitope vaccine was designed based on predicted epitopes which was 377 amino acid residues in length. Then, the physico-chemical properties, secondary and tertiary structures, stability, intrinsic protein disorder, solubility and allergenicity of this multi-epitope vaccine were assessed using immunoinformatics tools and servers. Based on obtained results, a soluble, and non-allergic protein with 40.59kDa molecular weight was constructed. Expasy ProtParam classified this chimeric protein as a stable protein and also 89.8% residues of constructed vaccine were located in favored regions of the Ramachandran plot. Furthermore, this multi-epitope peptide vaccine was able to strongly induce T cell and B-cell mediated immune responses. In conclusion, immunoinformatics analysis indicated that this multi-epitope peptide vaccine can be effectively expressed and potentially be used for prophylactic or therapeutic usages against brucellosis. Copyright © 2017 Elsevier B.V. All

  3. Vaccination: problems and perspectives.

    Directory of Open Access Journals (Sweden)

    S. M. Kharit

    2009-01-01

    Full Text Available Massive vaccination had proved its effective morbidity reduction. Today it is necessary to extend vaccination schedule, creation of selective, regional schedules based on epidemiological, clinical, economical substantiation. Development of vaccination needs the profound scientific research, modernization of adverse reaction observing system, betterment training system and awareness of population.

  4. [Mumps vaccine virus transmission].

    Science.gov (United States)

    Otrashevskaia, E V; Kulak, M V; Otrashevskaia, A V; Karpov, I A; Fisenko, E G; Ignat'ev, G M

    2013-01-01

    In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.

  5. Epitope mapping: the first step in developing epitope-based vaccines.

    Science.gov (United States)

    Gershoni, Jonathan M; Roitburd-Berman, Anna; Siman-Tov, Dror D; Tarnovitski Freund, Natalia; Weiss, Yael

    2007-01-01

    Antibodies are an effective line of defense in preventing infectious diseases. Highly potent neutralizing antibodies can intercept a virus before it attaches to its target cell and, thus, inactivate it. This ability is based on the antibodies' specific recognition of epitopes, the sites of the antigen to which antibodies bind. Thus, understanding the antibody/epitope interaction provides a basis for the rational design of preventive vaccines. It is assumed that immunization with the precise epitope, corresponding to an effective neutralizing antibody, would elicit the generation of similarly potent antibodies in the vaccinee. Such a vaccine would be a 'B-cell epitope-based vaccine', the implementation of which requires the ability to backtrack from a desired antibody to its corresponding epitope. In this article we discuss a range of methods that enable epitope discovery based on a specific antibody. Such a reversed immunological approach is the first step in the rational design of an epitope-based vaccine. Undoubtedly, the gold standard for epitope definition is x-ray analyses of crystals of antigen:antibody complexes. This method provides atomic resolution of the epitope; however, it is not readily applicable to many antigens and antibodies, and requires a very high degree of sophistication and expertise. Most other methods rely on the ability to monitor the binding of the antibody to antigen fragments or mutated variations. In mutagenesis of the antigen, loss of binding due to point modification of an amino acid residue is often considered an indication of an epitope component. In addition, computational combinatorial methods for epitope mapping are also useful. These methods rely on the ability of the antibody of interest to affinity isolate specific short peptides from combinatorial phage display peptide libraries. The peptides are then regarded as leads for the definition of the epitope corresponding to the antibody used to screen the peptide library. For

  6. Feasibility of using global system for mobile communication (GSM)-based tracking for vaccinators to improve oral poliomyelitis vaccine campaign coverage in rural Pakistan.

    Science.gov (United States)

    Chandir, Subhash; Dharma, Vijay Kumar; Siddiqi, Danya Arif; Khan, Aamir Javed

    2017-09-05

    Despite multiple rounds of immunization campaigns, it has not been possible to achieve optimum immunization coverage for poliovirus in Pakistan. Supplementary activities to improve coverage of immunization, such as door-to-door campaigns are constrained by several factors including inaccurate hand-drawn maps and a lack of means to objectively monitor field teams in real time, resulting in suboptimal vaccine coverage during campaigns. Global System for Mobile Communications (GSM) - based tracking of mobile subscriber identity modules (SIMs) of vaccinators provides a low-cost solution to identify missed areas and ensure effective immunization coverage. We conducted a pilot study to investigate the feasibility of using GSM technology to track vaccinators through observing indicators including acceptability, ease of implementation, costs and scalability as well as the likelihood of ownership by District Health Officials. The real-time location of the field teams was displayed on a GSM tracking web dashboard accessible by supervisors and managers for effective monitoring of workforce attendance including 'time in-time out', and discerning if all target areas - specifically remote and high-risk locations - had been reached. Direct access to this information by supervisors eliminated the possibility of data fudging and inaccurate reporting by workers regarding their mobility. The tracking cost per vaccinator was USD 0.26/month. Our study shows that GSM-based tracking is potentially a cost-efficient approach, results in better monitoring and accountability, is scalable and provides the potential for improved geographic coverage of health services. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The Challenges and Opportunities for Development of a T-Cell Epitope-Based Herpes Simplex Vaccine

    Science.gov (United States)

    Kuo, Tiffany; Wang, Christine; Badakhshan, Tina; Chilukuri, Sravya; BenMohamed, Lbachir

    2014-01-01

    The infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a half billion individuals worldwide. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. HSV-1 infections are more prevalent than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. While genital herpes in mainly caused by HSV-2 infections, in recent years, there is an increase in the proportion of genital herpes caused by HSV-1 infections in young adults, which reach 50% in some western societies. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries their development has been notoriously difficult. During the most recent National Institute of Health (NIH) workshop titled "Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities", basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One “common denominator” among previously failed clinical herpes vaccine trials is that they either used a whole virus or whole viral proteins, which contain both pathogenic “symptomatic” and protective “asymptomatic” antigens/epitopes. In this report, we continue to advocate that using an “asymptomatic” epitope-based vaccine strategy that selectively incorporates protective epitopes which: (i) are exclusively recognized, in vitro, by effector memory CD4+ and CD8+ TEM cells from “naturally” protected seropositive asymptomatic individuals; and (ii) protect, in vivo, human leukocyte antigen (HLA) transgenic animal models from ocular and genital herpes infections and diseases, could be the answer to many of the scientific challenges facing HSV vaccine

  8. The nature and combination of subunits used in epitope-based Schistosoma japonicum vaccine formulations affect their efficacy

    Directory of Open Access Journals (Sweden)

    Liu Feng

    2010-11-01

    Full Text Available Abstract Background Schistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species. Although there are no vaccines available to date, this strategy appears feasible since natural immunity develops in individuals suffering from repeated infection during a lifetime. Since vaccinations resulting in both Th1- and Th2-type responses have been shown to contribute to protective immunity, a vaccine formulation with the capacity for stimulating multiple arms of the immune response will likely be the most effective. Previously we developed partially protective, single Th- and B cell-epitope-based peptide-DNA dual vaccines (PDDV (T3-PDDV and B3-PDDV, respectively capable of eliciting immune responses against the Schistosoma japonicum 22.6 kDa tegument antigen (Sj22.6 and a 62 kDa fragment of myosin (Sj62, respectively. Results In this study, we developed PDDV cocktails containing multiple epitopes of S. japonicum from Sj22.6, Sj62 and Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated vaccine potential in vivo. Results showed that mice immunized with a single-epitope PDDV elicited either Tc, Th, or B cell responses, respectively, and mice immunized with either the T3- or B3- single-epitope PDDV formulation were partially protected against infection. However, mice immunized with a multicomponent (3 PDDV components formulation elicited variable immune responses that were less immunoprotective than single-epitope PDDV formulations. Conclusions Our data show that combining these different antigens did not result in a more effective vaccine formulation when compared to each component administered individually, and further suggest that immune interference resulting from immunizations with antigenically distinct vaccine targets may be an important consideration in the development of multicomponent vaccine preparations.

  9. Preparation of mucosal nanoparticles and polymer-based inactivated vaccine for Newcastle disease and H9N2 AI viruses

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    Heba M. El Naggar

    2017-02-01

    Full Text Available Aim: To develop a mucosal inactivated vaccines for Newcastle disease (ND and H9N2 viruses to protect against these viruses at sites of infections through mucosal immunity. Materials and Methods: In this study, we prepared two new formulations for mucosal bivalent inactivated vaccine formulations for Newcastle and Avian Influenza (H9N2 based on the use of nanoparticles and polymer adjuvants. The prepared vaccines were delivered via intranasal and spray routes of administration in specific pathogen-free chickens. Cell-mediated and humoral immune response was measured as well as challenge trial was carried out. In addition, ISA71 water in oil was also evaluated. Results: Our results showed that the use of spray route as vaccination delivery method of polymer and nanoparticles MontanideTM adjuvants revealed that it enhanced the cell mediated immune response as indicated by phagocytic activity, gamma interferon and interleukin 6 responses and induced protection against challenge with Newcastle and Avian Influenza (H9N2 viruses. Conclusion: The results of this study demonstrate the potentiality of polymer compared to nanoparticles adjuvantes when used via spray route. Mass application of such vaccines will add value to improve the vaccination strategies against ND virus and Avian influenza viruses.

  10. Protection against Multiple Subtypes of Influenza Viruses by Virus-Like Particle Vaccines Based on a Hemagglutinin Conserved Epitope

    Directory of Open Access Journals (Sweden)

    Shaoheng Chen

    2015-01-01

    Full Text Available We selected the conserved sequence in the stalk region of influenza virus hemagglutinin (HA trimmer, the long alpha helix (LAH, as the vaccine candidate sequence, and inserted it into the major immunodominant region (MIR of hepatitis B virus core protein (HBc, and, by using the E. coli expression system, we prepared a recombinant protein vaccine LAH-HBc in the form of virus-like particles (VLP. Intranasal immunization of mice with this LAH-HBc VLP plus cholera toxin B subunit with 0.2% of cholera toxin (CTB* adjuvant could effectively elicit humoral and cellular immune responses and protect mice against a lethal challenge of homologous influenza viruses (A/Puerto Rico/8/1934 (PR8 (H1N1. In addition, passage of the immune sera containing specific antibodies to naïve mice rendered them resistant against a lethal homologous challenge. Immunization with LAH-HBc VLP vaccine plus CTB* adjuvant could also fully protect mice against a lethal challenge of the 2009 pandemic H1N1 influenza virus or the avian H9N2 virus and could partially protect mice against a lethal challenge of the avian H5N1 influenza virus. This study demonstrated that the LAH-HBc VLP vaccine based on a conserved sequence of the HA trimmer stalk region is a promising candidate vaccine for developing a universal influenza vaccine against multiple influenza viruses infections.

  11. SieveSifter: a web-based tool for visualizing the sieve analyses of HIV-1 vaccine efficacy trials.

    Science.gov (United States)

    Fiore-Gartland, Andrew; Kullman, Nicholas; deCamp, Allan C; Clenaghan, Graham; Yang, Wayne; Magaret, Craig A; Edlefsen, Paul T; Gilbert, Peter B

    2017-08-01

    Analysis of HIV-1 virions from participants infected in a randomized controlled preventive HIV-1 vaccine efficacy trial can help elucidate mechanisms of partial protection. By comparing the genetic sequence of viruses from vaccine and placebo recipients to the sequence of the vaccine itself, a technique called 'sieve analysis', one can identify functional specificities of vaccine-induced immune responses. We have created an interactive web-based visualization and data access tool for exploring the results of sieve analyses performed on four major preventive HIV-1 vaccine efficacy trials: (i) the HIV Vaccine Trial Network (HVTN) 502/Step trial, (ii) the RV144/Thai trial, (iii) the HVTN 503/Phambili trial and (iv) the HVTN 505 trial. The tool acts simultaneously as a platform for rapid reinterpretation of sieve effects and as a portal for organizing and sharing the viral sequence data. Access to these valuable datasets also enables the development of novel methodology for future sieve analyses. Visualization: http://sieve.fredhutch.org/viz . Source code: https://github.com/nkullman/SIEVE . Data API: http://sieve.fredhutch.org/data . agartlan@fredhutch.org. © The Author(s) 2017. Published by Oxford University Press.

  12. Development of a serology-based assay for efficacy evaluation of a lactococcicosis vaccine in Seriola fish.

    Science.gov (United States)

    Nakajima, Nao; Kawanishi, Michiko; Imamura, Saiki; Hirano, Fumiya; Uchiyama, Mariko; Yamamoto, Kinya; Nagai, Hidetaka; Futami, Kunihiko; Katagiri, Takayuki; Maita, Masashi; Kijima, Mayumi

    2014-05-01

    Lactococcicosis is an infection caused by the bacterium Lactococcus garvieae and creates serious economic damage to cultured marine and fresh water fish industries. The use of the assay currently applied to evaluate the potency of the lactococcicosis vaccine is contingent upon meeting specific parameters after statistical analysis of the percent survival of the vaccinated yellowtail or greater amberjack fish after challenge with a virulent strain of L. garvieae. We found that measuring the serological response with a quantitative agglutinating antibody against the L. garvieae antigen (phenotype KG+) was an effective method of monitoring the potency of lactococcicosis vaccines. Vaccinated fish had significantly higher antibody titers than control fish when the L. garvieae Lg2-S strain was used as an antigen. Furthermore, the titer of the KG + agglutinating antibody was correlated with vaccine potency, and the cut-off titer was determined by comparing the data with those from the challenge test. An advantage of the proposed serology-based potency assay is that it will contribute to reduced numbers of animal deaths during vaccine potency evaluations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Comparison of two dose and three dose human papillomavirus vaccine schedules: cost effectiveness analysis based on transmission model.

    Science.gov (United States)

    Jit, Mark; Brisson, Marc; Laprise, Jean-François; Choi, Yoon Hong

    2015-01-06

    To investigate the incremental cost effectiveness of two dose human papillomavirus vaccination and of additionally giving a third dose. Cost effectiveness study based on a transmission dynamic model of human papillomavirus vaccination. Two dose schedules for bivalent or quadrivalent human papillomavirus vaccines were assumed to provide 10, 20, or 30 years' vaccine type protection and cross protection or lifelong vaccine type protection without cross protection. Three dose schedules were assumed to give lifelong vaccine type and cross protection. United Kingdom. Males and females aged 12-74 years. No, two, or three doses of human papillomavirus vaccine given routinely to 12 year old girls, with an initial catch-up campaign to 18 years. Costs (from the healthcare provider's perspective), health related utilities, and incremental cost effectiveness ratios. Giving at least two doses of vaccine seems to be highly cost effective across the entire range of scenarios considered at the quadrivalent vaccine list price of £86.50 (€109.23; $136.00) per dose. If two doses give only 10 years' protection but adding a third dose extends this to lifetime protection, then the third dose also seems to be cost effective at £86.50 per dose (median incremental cost effectiveness ratio £17,000, interquartile range £11,700-£25,800). If two doses protect for more than 20 years, then the third dose will have to be priced substantially lower (median threshold price £31, interquartile range £28-£35) to be cost effective. Results are similar for a bivalent vaccine priced at £80.50 per dose and when the same scenarios are explored by parameterising a Canadian model (HPV-ADVISE) with economic data from the United Kingdom. Two dose human papillomavirus vaccine schedules are likely to be the most cost effective option provided protection lasts for at least 20 years. As the precise duration of two dose schedules may not be known for decades, cohorts given two doses should be closely

  14. Theory-based development of an implementation intervention to increase HPV vaccination in pediatric primary care practices.

    Science.gov (United States)

    Garbutt, Jane M; Dodd, Sherry; Walling, Emily; Lee, Amanda A; Kulka, Katharine; Lobb, Rebecca

    2018-03-13

    The national guideline for use of the vaccine targeting oncogenic strains of the human papillomavirus (HPV) is an evidence-based practice that is poorly implemented in primary care. Recommendations include completion of the vaccine series before the 13th birthday for girls and boys, giving the first dose at the 11- to 12-year-old check-up visit, concurrent with other recommended vaccines. Interventions to increase implementation of this guideline have had little impact, and opportunities to prevent cancer continue to be missed. We used a theory-informed approach to develop a pragmatic intervention for use in primary care settings to increase implementation of the HPV vaccine guideline recommendation. Using a concurrent mixed methods design in 10 primary care practices, we applied the Consolidated Framework for Implementation Research (CFIR) to systematically investigate and characterize factors strongly influencing vaccine use. We then used the Behavior Change Wheel (BCW) and the Theoretical Domains Framework (TDF) to analyze provider behavior and identify behaviors to target for change and behavioral change strategies to include in the intervention. We identified facilitators and barriers to guideline use across the five CFIR domains: most distinguishing factors related to provider characteristics, their perception of the intervention, and their process to deliver the vaccine. Targeted behaviors were for the provider to recommend the HPV vaccine the same way and at the same time as the other adolescent vaccines, to answer parents' questions with confidence, and to implement a vaccine delivery system. To this end, the intervention targeted improving provider's capability (knowledge, communication skills) and motivation (action planning, belief about consequences, social influences) regarding implementing guideline recommendations, and increasing their opportunity to do so (vaccine delivery system). Behavior change strategies included providing information and

  15. Structure-Based Design of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses to a Conserved Epitope

    Energy Technology Data Exchange (ETDEWEB)

    Pierce, Brian G.; Boucher, Elisabeth N.; Piepenbrink, Kurt H.; Ejemel, Monir; Rapp, Chelsea A.; Thomas, William D.; Sundberg, Eric J.; Weng, Zhiping; Wang, Yang; Diamond, Michael S.

    2017-08-09

    Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as well as a bivalent immunogen with two copies of the epitope on the E2 surface. We solved the X-ray structure of a cyclic immunogen in complex with the HCV1 antibody and confirmed preservation of the epitope conformation and the HCV1 interface. Mice vaccinated with our designed immunogens produced robust antibody responses to epitope I, and their serum could neutralize HCV. Notably, the cyclic designs induced greater epitope-specific responses and neutralization than the native peptide epitope. Beyond successfully designing several novel HCV immunogens, this study demonstrates the principle that neutralizing anti-HCV antibodies can be induced by epitope-based, engineered vaccines and provides the basis for further efforts in structure-based design of HCV vaccines.

    IMPORTANCEHepatitis C virus is a leading cause of liver disease and liver cancer, with approximately 3% of the world's population infected. To combat this virus, an effective vaccine would have distinct advantages over current therapeutic options, yet experimental vaccines have not been successful to date, due in part to the virus's high sequence variability leading to immune escape. In this study, we rationally designed several vaccine immunogens based on the structure of a conserved epitope that

  16. Patient reported outcome data following influenza A (H1N1p vaccination in the 2009–2010 season: web-based and telephone evaluation

    Directory of Open Access Journals (Sweden)

    Wade AG

    2011-10-01

    Full Text Available Alan G Wade1, Gordon M Crawford1, Neil Pumford1, Alex McConnachie21Patients Direct, 3 Todd Campus, Glasgow, UK; 2Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UKBackground: There has been worldwide interest in the safety of the pandemic influenza A (H1N1p vaccines, although limited data are available from the vaccine recipients’ perspective. This evaluation was designed to collect data from people who had received an influenza vaccination during the 2009–2010 season using a web-based data collection tool supplemented by telephone reporting (PROBE.Methods: People scheduled to receive the influenza A (H1N1p or seasonal influenza vaccines were recruited through media advertising and campaigns throughout the West of Scotland. Vaccine recipients participated in the evaluation by answering demographic and side effect questions using PROBE methodology on the day of the immunization, after 3 days, 8 days, 6 weeks, 12 weeks, and 26 weeks.Results: A total of 1103 vaccine recipients including 134 young children (0–4 years participated in the evaluation; 694 (63% received H1N1p vaccine only, 135 (12% seasonal vaccine only, 224 (20% both H1N1p and seasonal vaccines, and 50 (5% received H1N1p or seasonal vaccine with a non-influenza vaccine (eg, travel or pneumococcal. Overall, 42% of recipients reported experiencing a side effect after their baseline vaccination; the most commonly reported were general and arm side effects (>20%. Injection site discomfort/pain and flu-like symptoms were reported by 57% and 24% of recipients, respectively. A significantly higher proportion of the 960 H1N1p vaccine recipients experienced a side effect (44% vs 27%, P < 0.001 or injection site discomfort/pain (61% vs 26%, P < 0.001 than those receiving seasonal influenza vaccines. Female sex and H1N1p vaccination were associated with a significantly higher risk of injection site discomfort/pain, whereas the 70+ age group was associated with a

  17. Gold nanocluster-based vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides

    Science.gov (United States)

    Tao, Yu; Zhang, Yan; Ju, Enguo; Ren, Hui; Ren, Jinsong

    2015-07-01

    We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments. Electronic supplementary information (ESI

  18. Immune Monitoring in Cancer Vaccine Clinical Trials: Critical Issues of Functional Flow Cytometry-Based Assays

    Directory of Open Access Journals (Sweden)

    Iole Macchia

    2013-01-01

    Full Text Available The development of immune monitoring assays is essential to determine the immune responses against tumor-specific antigens (TSAs and tumor-associated antigens (TAAs and their possible correlation with clinical outcome in cancer patients receiving immunotherapies. Despite the wide range of techniques used, to date these assays have not shown consistent results among clinical trials and failed to define surrogate markers of clinical efficacy to antitumor vaccines. Multiparameter flow cytometry- (FCM- based assays combining different phenotypic and functional markers have been developed in the past decade for informative and longitudinal analysis of polyfunctional T-cells. These technologies were designed to address the complexity and functional heterogeneity of cancer biology and cellular immunity and to define biomarkers predicting clinical response to anticancer treatment. So far, there is still a lack of standardization of some of these immunological tests. The aim of this review is to overview the latest technologies for immune monitoring and to highlight critical steps involved in some of the FCM-based cellular immune assays. In particular, our laboratory is focused on melanoma vaccine research and thus our main goal was the validation of a functional multiparameter test (FMT combining different functional and lineage markers to be applied in clinical trials involving patients with melanoma.

  19. HiPS - Hierarchical Progressive Survey Version 1.0

    Science.gov (United States)

    Fernique, Pierre; Allen, Mark; Boch, Thomas; Donaldson, Tom; Durand, Daniel; Ebisawa, Ken; Michel, Laurent; Salgado, Jesus; Stoehr, Felix; Fernique, Pierre

    2017-05-01

    This document presents HiPS, a hierarchical scheme for the description, storage and access of sky survey data. The system is based on hierarchical tiling of sky regions at finer and finer spatial resolution which facilitates a progressive view of a survey, and supports multi-resolution zooming and panning. HiPS uses the HEALPix tessellation of the sky as the basis for the scheme and is implemented as a simple file structure with a direct indexing scheme that leads to practical implementations.

  20. The LLL compact 10-ps streak camera

    International Nuclear Information System (INIS)

    Thomas, S.W.; Houghton, J.W.; Tripp, G.R.; Coleman, L.W.

    1975-01-01

    The 10-ps streak camera has been redesigned to simplify its operation, reduce manufacturing costs, and improve its appearance. The electronics have been simplified, a film indexer added, and a contacted slit has been evaluated. Data support a 10-ps resolution. (author)

  1. Enhanced personal protection at the PS

    CERN Multimedia

    Samuel Morier Genoud

    2013-01-01

    Pictures 03, 06, 07 08 : Pierre Ninin, deputy group leader of GS-ASE and responsible for the installation of the new PS complex safety system, in front of a new access control system.Pictures 10, 12 ,13 : View of Building 271, the future control centre of the new PS complex safety system.

  2. PS, SL and LHC Auditoria change names

    CERN Multimedia

    2003-01-01

    Following the replacement of the PS, SL and LHC Divisions by the AB and AT Divisions, the Auditoria are also changing their names. PS Auditorium is renamed AB Meyrin SL Auditorium is renamed AB Prévessin LHC Auditorium is renamed AT

  3. The impact of non-financial and financial encouragements on participation in non school-based human papillomavirus vaccination: a retrospective cohort study.

    Science.gov (United States)

    Lefevere, Eva; Hens, Niel; De Smet, Frank; Beutels, Philippe

    2016-04-01

    Adolescent vaccination coverage under a system of non school-based vaccination is likely to be suboptimal, but might be increased by targeted encouragement campaigns. We analysed the effect on human papillomavirus (HPV) vaccination initiation by girls aged 12-18 of two campaigns set up in Flanders (Belgium) in 2007 and 2009: a personal information campaign and a combined personal information and financial incentive campaign. We analysed (objective) data on HPV vaccination behaviour from the National Alliance of Christian Mutualities (NACM), Flanders' largest sickness fund. We used z-scores to compare the monthly proportion of girls initiating HPV vaccination over time between carefully selected intervention and control groups. Separate analyses were done for older and younger girls. Total sample sizes of the intervention (control) groups were 221 (243) for the personal information campaign and 629 (5,322) for the combined personal information and financial incentive campaign. The personal information campaign significantly increased vaccination initiation, with older girls reacting faster. One year after the campaign the percentages of vaccination initiation for the oldest girls were 64.6 and 42.8 % in the intervention and control group, respectively (z = 3.35, p = 0.0008); for the youngest girls the percentages were 78.4 and 68.1 % (z = 1.71, p = 0.09). The combined personal information and financial incentive campaign increased vaccination initiation among certain age groups. One year after the campaign the difference in percentage points for HPV vaccination initiation between intervention and control groups varied between 18.5 % (z = 3.65, p = 0.0002) and 5.1 % (z = 1.12, p = 0.26). Under a non school-based vaccination system, personal information and removing out-of-pocket costs had a significant positive effect on HPV vaccination initiation, although the effect substantially varied in magnitude. Overall, the obtained vaccination rates remained far below those

  4. Peptide Vaccines for Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Rory C. F. De Brito

    2018-05-01

    Full Text Available Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  5. Peptide Vaccines for Leishmaniasis.

    Science.gov (United States)

    De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B

    2018-01-01

    Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  6. Development and evaluation of a web-based assent for adolescents considering an HIV vaccine trial.

    Science.gov (United States)

    Blake, Diane R; Lemay, Celeste A; Maranda, Louise S; Fortenberry, J Dennis; Kearney, Margaret H; Mazor, Kathleen M

    2015-01-01

    HIV vaccine trials with minors will likely require parental permission and informed assent from adolescents. For this to be a valid process, the information needs to be presented in a manner that promotes adolescent comprehension. Previous studies suggest that adolescent comprehension of assent is often insufficient. We developed an interactive web-based assent that included interspersed quiz questions for a hypothetical HIV vaccine trial. Efficacy of the web-based assent was compared to a standard paper assent with and without interspersed questions. One hundred twenty teen participants, ages 15-17 years, from five community organizations were randomized to self-administered web-based assent (n=60) or investigator-administered paper assent with (n=29) or without (n=31) interspersed quiz questions. After reviewing the assent, participants completed a 27-item comprehension test. Comprehension scores were compared between groups. The mean number of correctly answered questions were 21.2 for the full paper group and 21.1 for the web-based group (t118=-0.08, p=0.94). Scores were 20.2 for the paper without interspersed questions sub-group and 22.1 for the paper with interspersed questions sub-group (t58=1.96, p=0.055). Participants in the web-based group performed as well on the comprehension test as those in the paper group, and those in the paper with questions sub-group performed better than those in the paper without questions sub-group, suggesting that interspersed quiz questions may improve understanding of a traditional paper assent. The minimal investigator time and standardized administration of the web-based assent as well as ability to tailor the assent discussion to topics identified by incorrect comprehension test responses are advantages worthy of further investigation.

  7. Bacterially produced recombinant influenza vaccines based on virus-like particles.

    Directory of Open Access Journals (Sweden)

    Andrea Jegerlehner

    Full Text Available Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains.

  8. Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant

    Directory of Open Access Journals (Sweden)

    Zhao JH

    2017-07-01

    Full Text Available Ji-Hui Zhao,1,* Qi-Bo Zhang,1,* Bao Liu,2 Xiang-Hua Piao,1 Yu-Lu Yan,1 Xiao-Ge Hu,1 Kuan Zhou,1 Yong-Tai Zhang,1 Nian-Ping Feng1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Anethesiology Department, Augusta University, Augusta, GA, USA *These authors contributed equally to this work Purpose: To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA was combined with platycodin (PD, a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array.Methods: OVA- and PD-loaded liposomes (OVA-PD-Lipos were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs, and hemolytic activity to rabbit red blood cells (RBCs were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated.Results: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin.Conclusion: The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant. Keywords: subunit vaccine, saponin adjuvant, liposomes, dissolving microneedle array, intradermal vaccination

  9. Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

    Science.gov (United States)

    Odutola, A; Ota, M O; Ogundare, E O; Antonio, M; Owiafe, P; Worwui, A; Greenwood, B; Alderson, M; Traskine, M; Verlant, V; Dobbelaere, K; Borys, D

    2016-01-01

    Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

  10. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  11. Endoplasmic reticulum targeting sequence enhances HBV-specific cytotoxic T lymphocytes induced by a CTL epitope-based DNA vaccine

    International Nuclear Information System (INIS)

    Xu Wei; Chu Yiwei; Zhang Ruihua; Xu Huanbin; Wang Ying; Xiong Sidong

    2005-01-01

    CD8 + T cells play a critical role in protective immunity against Hepatitis B Virus (HBV). Epitope-based DNA vaccines expressing HBV-dominant CTL epitopes can be used as candidate vaccines capable of inducing cytotoxic T Lymphocytes (CTL) responses. A plasmid DNA encoding a CTL epitope of HBV core antigen, HBc 18-27 , was constructed. Intramuscular immunization of C57BL/6 mice with this DNA vaccine resulted in successful induction of HBV-specific CTL responses. In order to promote transportation of the peptide into endoplasmic reticulum (ER) to bind to MHC class I molecules for optimal class I antigen presentation, an ER targeting sequence (ERTS) was fused with the C 18-27 encoding gene. ERTS fusion significantly enhanced specific CD8 + T cell responses in terms of CTL cytolysis as well as IFN-γ secretion. This enhancement was correlated with promoted epitope presentation on target cell surface. We report here an enhanced immunogenicity of an epitope-based DNA vaccine using an ER targeting signal sequence, which has significant implications for future design of therapeutic HBV vaccine

  12. Preserved immunogenicity of an inactivated vaccine based on foot-and-mouth disease virus particles with improved stability.

    Science.gov (United States)

    Caridi, Flavia; Vázquez-Calvo, Ángela; Borrego, Belén; McCullough, Kenneth; Summerfield, Artur; Sobrino, Francisco; Martín-Acebes, Miguel A

    2017-05-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects important livestock species. Vaccines based on inactivated FMDV virions provide a useful tool for the control of this pathogen. However, long term storage at 4°C (the temperature for vaccine storage) or ruptures of the cold chain, provoke the dissociation of virions, reducing the immunogenicity of the vaccine. An FMDV mutant carrying amino acid replacements VP1 N17D and VP2 H145Y isolated previously rendered virions with increased resistance to dissociation at 4°C. We have evaluated the immunogenicity in swine (a natural FMDV host) of a chemically inactivated vaccine based on this mutant. The presence of these amino acid substitutions did not compromise the immunological potential, including its ability to elicit neutralizing antibodies. These results support the feasibility of this kind of mutants with increased capsid stability as suitable viruses for producing improved FMDV vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Claesson, Mogens Helweg; Nielsen, Hans J

    2009-01-01

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction...... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...... disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels. Conclusion. The increased levels of key pro...

  14. A cucumber mosaic virus based expression system for the production of porcine circovirus specific vaccines.

    Directory of Open Access Journals (Sweden)

    Akos Gellért

    Full Text Available Potential porcine circovirus type 2 (PCV2 capsid protein epitopes, suitable for expression on the surface of cucumber mosaic virus (CMV particles were determined by a thorough analysis of the predicted PCV capsid protein structure. The ab initio protein structure prediction was carried out with fold recognition and threading methods. The putative PCV epitopes were selected on the basis of PCV virion models and integrated into the plant virus coat protein, after amino acid position 131. The recombinants were tested for infectivity and stability on different Nicotiana species and stable recombinant virus particles were purified. The particles were tested for their ability to bind to PCV induced porcine antibodies and used for specific antibody induction in mice and pigs. The results showed that PCV epitopes expressed on the CMV surface were recognized by the porcine antibodies and they were also able to induce PCV specific antibody response. Challenge experiment with PCV2 carried out in immunized pigs showed partial protection against the infection. Based on these results it was concluded that specific antiviral vaccine production for the given pathogen was feasible, offering an inexpensive way for the mass production of such vaccines.

  15. A cucumber mosaic virus based expression system for the production of porcine circovirus specific vaccines.

    Science.gov (United States)

    Gellért, Akos; Salánki, Katalin; Tombácz, Kata; Tuboly, Tamás; Balázs, Ervin

    2012-01-01

    Potential porcine circovirus type 2 (PCV2) capsid protein epitopes, suitable for expression on the surface of cucumber mosaic virus (CMV) particles were determined by a thorough analysis of the predicted PCV capsid protein structure. The ab initio protein structure prediction was carried out with fold recognition and threading methods. The putative PCV epitopes were selected on the basis of PCV virion models and integrated into the plant virus coat protein, after amino acid position 131. The recombinants were tested for infectivity and stability on different Nicotiana species and stable recombinant virus particles were purified. The particles were tested for their ability to bind to PCV induced porcine antibodies and used for specific antibody induction in mice and pigs. The results showed that PCV epitopes expressed on the CMV surface were recognized by the porcine antibodies and they were also able to induce PCV specific antibody response. Challenge experiment with PCV2 carried out in immunized pigs showed partial protection against the infection. Based on these results it was concluded that specific antiviral vaccine production for the given pathogen was feasible, offering an inexpensive way for the mass production of such vaccines.

  16. Dendritic cell-based vaccine in advanced melanoma: update of clinical outcome.

    Science.gov (United States)

    Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Granato, Anna Maria; Ancarani, Valentina; Pancisi, Elena; Brolli, Claudia; Selva, Mirna; Scarpi, Emanuela; Valmorri, Linda; Nicoletti, Stefania Vittoria Luisa; Guidoboni, Massimo; Riccobon, Angela; Ridolfi, Ruggero

    2011-12-01

    Dendritic cells (DCs) are unique specialized antigen-presenting cells capable of priming naive T cells and inducing antigen-specific cytotoxic T lymphocytes. This study presents an update of clinical results from a DC-based phase I-II clinical vaccine trial in stage IV melanoma. From 2003 to 2010, 27 patients with metastatic melanoma were treated with mature DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin and with subcutaneous low-dose interleukin-2. Delayed-type hypersensitivity (DTH) tests for in-vivo immunomonitoring were performed at baseline and every four vaccinations thereafter. Two complete, two mixed and six partial responses, and five stable diseases were observed (overall response, 37.0%; clinical benefit, 55.5%). All 15 responders showed DTH positivity. A median overall survival of 22.9 months [95% confidence interval (CI): 13.4-61.3] for DTH-positive patients (19) and 4.8 months (95% CI: 3.9-11.9) for DTH-negative patients (8; log rank=7.26; P=0.007) was observed. The overall median overall survival was 16 months (95% CI: 9-33). Our results would seem to highlight a relationship between positive-DTH test and an improved survival.

  17. Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.

    Science.gov (United States)

    Zhao, Ji-Hui; Zhang, Qi-Bo; Liu, Bao; Piao, Xiang-Hua; Yan, Yu-Lu; Hu, Xiao-Ge; Zhou, Kuan; Zhang, Yong-Tai; Feng, Nian-Ping

    2017-01-01

    To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.

  18. Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection.

    NARCIS (Netherlands)

    Chaput, N.; Schartz, N.E.; Andre, F.; Taieb, J.; Novault, S.; Bonnaventure, P.; Aubert, N.; Bernard, J.; Lemonnier, F.; Merad, M.; Adema, G.J.; Adams, M.; Ferrantini, M.; Carpentier, A.F.; Escudier, B.; Tursz, T.; Angevin, E.; Zitvogel, L.

    2004-01-01

    Ideal vaccines should be stable, safe, molecularly defined, and out-of-shelf reagents efficient at triggering effector and memory Ag-specific T cell-based immune responses. Dendritic cell-derived exosomes could be considered as novel peptide-based vaccines because exosomes harbor a discrete set of

  19. vQRS Based on Hybrids of CNT with PMMA-POSS and PS-POSS Copolymers to Reach the Sub-PPM Detection of Ammonia and Formaldehyde at Room Temperature Despite Moisture

    Directory of Open Access Journals (Sweden)

    Abhishek Sachan

    2017-07-01

    Full Text Available Nanocomposite-based quantum resistive vapour sensors (vQRS have been developed from the assembly of hybrid copolymers of polyhedral oligomeric silsesquioxane (POSS and poly(methyl methacrylate (PMMA or poly(styrene (PS with carbon nanotubes (CNT. The originality of the resulting conducting architecture is expected to be responsible for the ability of the transducer to detect sub-ppm concentrations of ammonia and formaldehyde at room temperature despite the presence of humidity. In particular, the boosting effect of POSS is evidenced in CNT-based nanocomposite vQRS. The additive fabrication by spraying layer-by-layer provides (sLbL is an effective method to control the reproducibility of the transducers’ chemo-resistive responses. In dry atmosphere, the two types of sensors showed a high sensitivity towards both hazardous gases, as they were able to detect 300 ppb of formaldehyde and 500 ppb of ammonia with a sufficiently good signal to noise ratio (SNR > 10. They also exhibited a quick response times less than 5 s for both vapours and, even in the presence of 100 ppm of water, they were able to detect small amounts of gases (1.5 ppm of NH3 and 9 ppm of CH2O. The results suggest promising applications of POSS-based vQRS for air quality or volatolome monitoring.

  20. [Vaccinal strategies in response to new epidemiological challenges in 2010. Reasonable hope for a "B" meningococcal vaccine].

    Science.gov (United States)

    Nicolas, P

    2010-08-01

    In 2010, vaccines have achieved good effectiveness against invasive meningococcal infection. Development of monovalent and bivalent polysaccharide (PS) vaccines in the 70s and later of tetravalent PS vaccine (ACWY) was followed by development in 2003 of a trivalent ACW vaccine in response to the W135 or mixed A/W135 epidemics that appeared in Africa. More recently PS-conjugated vaccines have shown numerous advantages in comparison with PS vaccines. Mass vaccination campaigns with the C-conjugated vaccine have almost completely eradicated group C meningitis in the UK. It is hoped that introduction of the A-conjugated vaccine MenAfriVac in Africa at the end of year 2010 will end group A meningococcal epidemics in the meningitis belt. The problem of group B meningococcal meningitis has not been completely resolved. For the B strain that has been implicated in hyperendemic waves, a protein vaccine has been produced from outer membrane vesicles (OMV). Use of OMV vaccines achieved good results in Norway and recently in New Zealand. The Norwegian vaccine was also used in Normandy since the strain responsible for the Norman epidemic showed the same PorA as the Norwegian strain. In this regard, a major limitation for OMV vaccines is that they are effective only against the immuno-dominant porin A protein. Current efforts to develop a vaccine against group B meningococci causing sporadic cases are promising. Research is being focused on a blend of surface proteins targeting most of circulating isolates. Field tests will be carried out in the next years, but it is probable that the efficacy of these vaccines will be short-lived since meningococcal antigens vary over time.

  1. Theoretical considerations regarding the existence of PsO and PsS+

    International Nuclear Information System (INIS)

    Farazdel, A.; Cade, P.E.

    1977-01-01

    It has been proposed from experimental studies and in analogy with hydrogen compounds that PsO may be an entity of some importance, or an intermediate, in the reaction of positronium, Ps, with aqueous oxyacid species such as H 2 PO 4 - , HSO 4 - , ClO 4 - , and NO 3 - . This communication explores the stability of PsO and PsS, or [O - :e + ] and [S - :e + ], respectively, relative to dissociation into Ps and O( 3 P) or S( 3 P) on the basis of restricted Hartree-Fock calculations for the PsO and PsS systems and certain correlation correction arguments. A reasonable lower estimate of the dissociation energy to Y+Ps of >-0.47 eV for PsO and >0.70 eV for PsS is obtained. It is suggested that a modest correlation correction to the positron affinity (PA) of O - would very probably lead to a bound state system for PsO. (Auth.)

  2. Innovations in adult influenza vaccination in China, 2014-2015: Leveraging a chronic disease management system in a community-based intervention.

    Science.gov (United States)

    Yi, Bo; Zhou, Suizan; Song, Ying; Chen, Enfu; Lao, Xuyin; Cai, Jian; Greene, Carolyn M; Feng, Luzhao; Zheng, Jiandong; Yu, Hongjie; Dong, Hongjun

    2018-04-03

    To evaluate a community-based intervention that leveraged the non-communicable disease management system to increase seasonal influenza vaccination coverage among older adults in Ningbo, China. From October 2014 - March 2015, we piloted the following on one street in Ningbo, China: educating community healthcare workers (C-HCWs) about influenza and vaccination; requiring C-HCWs to recommend influenza vaccination to older adults during routine chronic disease follow-up; and opening 14 additional temporary vaccination clinics. We selected a non-intervention street for comparison pre- and post-intervention vaccine coverage. In April 2016, we interviewed a random sample of unvaccinated older adults on the intervention street to ask why they remained unvaccinated. Pre-intervention influenza vaccine coverage among adults aged 60 years and older on both streets was 0.3%. Post-intervention, coverage among adults 60 years and older was 19% (1338/7013) on the intervention street and 0.4% (20/5500) on the non-intervention street (phealth (39%); not trusting C-HCWs' recommendations (24%); not knowing where to get vaccinated (17%); and not wanting to pay (9%). Recommending influenza vaccination within a non-communicable disease management system, combined with adding vaccination sites, increased vaccine coverage among older adults in Ningbo, China.

  3. Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate.

    Science.gov (United States)

    Kabanova, Anna; Margarit, Immaculada; Berti, Francesco; Romano, Maria R; Grandi, Guido; Bensi, Giuliano; Chiarot, Emiliano; Proietti, Daniela; Swennen, Erwin; Cappelletti, Emilia; Fontani, Paola; Casini, Daniele; Adamo, Roberto; Pinto, Vittoria; Skibinski, David; Capo, Sabrina; Buffi, Giada; Gallotta, Marilena; Christ, William J; Campbell, A Stewart; Pena, John; Seeberger, Peter H; Rappuoli, Rino; Costantino, Paolo

    2010-12-10

    Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM(197). When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. A SPAD-based 3D imager with in-pixel TDC for 145ps-accuracy ToF measurement

    Science.gov (United States)

    Vornicu, I.; Carmona-Galán, R.; Rodríguez-Vázquez, Á.

    2015-03-01

    The design and measurements of a CMOS 64 × 64 Single-Photon Avalanche-Diode (SPAD) array with in-pixel Time-to-Digital Converter (TDC) are presented. This paper thoroughly describes the imager at architectural and circuit level with particular emphasis on the characterization of the SPAD-detector ensemble. It is aimed to 2D imaging and 3D image reconstruction in low light environments. It has been fabricated in a standard 0.18μm CMOS process, i. e. without high voltage or low noise features. In these circumstances, we are facing a high number of dark counts and low photon detection efficiency. Several techniques have been applied to ensure proper functionality, namely: i) time-gated SPAD front-end with fast active-quenching/recharge circuit featuring tunable dead-time, ii) reverse start-stop scheme, iii) programmable time resolution of the TDC based on a novel pseudo-differential voltage controlled ring oscillator with fast start-up, iv) a global calibration scheme against temperature and process variation. Measurements results of individual SPAD-TDC ensemble jitter, array uniformity and time resolution programmability are also provided.

  5. Brown-Like Adipocyte Progenitors Derived from Human iPS Cells: A New Tool for Anti-obesity Drug Discovery and Cell-Based Therapy?

    Science.gov (United States)

    Yao, Xi; Salingova, Barbara; Dani, Christian

    2018-04-10

    Alternative strategies are urgently required to fight obesity and associated metabolic disorders including diabetes and cardiovascular diseases. Brown and brown-like adipocytes (BAs) store fat, but in contrast to white adipocytes, activated BAs are equipped to dissipate energy stored. Therefore, BAs represent promising cell targets to counteract obesity. However, the scarcity of BAs in adults is a major limitation for a BA-based therapy of obesity, and the notion to increase the BA mass by transplanting BA progenitors (BAPs) in obese patients recently emerged. The next challenge is to identify an abundant and reliable source of BAPs. In this chapter, we describe the capacity of human-induced pluripotent stem cells (hiPSCs) to generate BAPs able to differentiate at a high efficiency with no gene transfer. This cell model represents an unlimited source of human BAPs that in a near future may be a suitable tool for both therapeutic transplantation and for the discovery of novel efficient and safe anti-obesity drugs. The generation of a relevant cell model, such as hiPSC-BAs in 3D adipospheres enriched with macrophages and endothelial cells to better mimic the microenvironment within the adipose tissue, will be the next critical step.

  6. mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

    International Nuclear Information System (INIS)

    Fotin-Mleczek, Mariola; Zanzinger, Kai; Heidenreich, Regina; Lorenz, Christina; Kowalczyk, Aleksandra; Kallen, Karl-Josef; Huber, Stephan M

    2014-01-01

    The eradication of large, established tumors by active immunotherapy is a major challenge because of the numerous cancer evasion mechanisms that exist. This study aimed to establish a novel combination therapy consisting of messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate the effective treatment of established tumors with aggressive growth kinetics. The combination of a tumor-specific mRNA-based vaccination with radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by the combination therapy was evaluated via gene expression arrays as well as flow cytometry analyses of tumor infiltrating cells. In both tumor models we demonstrated that a combination of mRNA-based immunotherapy with radiation results in a strong synergistic anti-tumor effect. This was manifested as either complete tumor eradication or delay in tumor growth. Gene expression analysis of mouse tumors revealed a variety of substantial changes at the tumor site following radiation. Genes associated with antigen presentation, infiltration of immune cells, adhesion, and activation of the innate immune system were upregulated. A combination of radiation and immunotherapy induced significant downregulation of tumor associated factors and upregulation of tumor suppressors. Moreover, combination therapy significantly increased CD4 + , CD8 + and NKT cell infiltration of mouse tumors. Our data provide a scientific rationale for combining immunotherapy with radiation and provide a basis for the development of more potent anti-cancer therapies. The online version of this article (doi:10.1186/1748-717X-9-180) contains supplementary material, which is available to authorized users

  7. A population-based study of measles, mumps and rubella vaccination and autism

    DEFF Research Database (Denmark)

    Madsen, Kreesten Meldgaard; Hviid, Anders; Vestergaard, Mogens

    2002-01-01

    Background It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism. Methods We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish...... Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children’s autism status was obtained from the Danish Psychiatric Central...... the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder. Conclusions This study provides strong evidence against the hypothesis that MMR vaccination causes autism....

  8. Effectiveness and acceptance of a health care-based mandatory vaccination program.

    Science.gov (United States)

    Leibu, Rachel; Maslow, Joel

    2015-01-01

    To decrease the risk of transmission of hospital-associated transmission of influenza and pertussis through mandatory vaccination of staff. A mandatory influenza and toxoid-diphtheria toxoid-acellular pertussis program was implemented systemwide. A structured vaccine exemption program was implemented for those requesting a medical and/or religious/moral/ethical exemption. Systemwide influenza vaccination rates increased from 67% historically, 76.2% in the 2012 to 2013 influenza season, to 94.7% in 2013 to 2014 with an overall compliance rate of 97.8%. Toxoid-diphtheria toxoid-acellular pertussis vaccination rates systemwide reached 94.9%, with an overall compliance rate of 98%. Higher rates were experienced at individual hospital facilities compared with the corporate location. Successful vaccination campaign outcomes can be achieved through diligent enforcement of mandatory vaccination, masking, and other infection prevention procedures.

  9. A population-based study of measles, mumps and rubella vaccination and autism

    DEFF Research Database (Denmark)

    Madsen, Kreesten Meldgaard; Hviid, Anders; Vestergaard, Mogens

    2002-01-01

    Background It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism. Methods We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish...... the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder. Conclusions This study provides strong evidence against the hypothesis that MMR vaccination causes autism....... Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children’s autism status was obtained from the Danish Psychiatric Central...

  10. A systems biology-based approach to deciphering the etiology of steatosis employing patient-derived dermal fibroblasts and iPS cells

    Directory of Open Access Journals (Sweden)

    Justyna eJozefczuk

    2012-09-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD comprises a broad spectrum of disease states ranging from simple steatosis to nonalcoholic steatohepatitis (NASH. As a result of increases in the prevalences of obesity, insulin resistance, and hyperlipidemia, the number of people with hepatic steatosis continues to increase. Differences in susceptibility to steatohepatitis and its progression to cirrhosis have been attributed to a complex interplay of genetic and external factors all addressing the intracellular network. Increase in sugar or refined carbohydrate consumption results in an increase of insulin and insulin resistance that can lead to the accumulation of fat in the liver. Here we demonstrate how a multidisciplinary approach encompassing cellular reprogramming, transcriptomics, proteomics, metabolomics, modeling, network reconstruction and data management can be employed to unveil the mechanisms underlying the progression of steatosis. Proteomics revealed reduced AKT/mTOR signaling in fibroblasts derived from steatosis patients and further establishes that the insulin-resistant phenotype is present not only in insulin-metabolizing central organs, e.g. the liver, but is also manifested in skin fibroblasts. Transcriptome data enabled the generation of a regulatory network based on the transcription factor SREBF1, linked to a metabolic network of glycerolipid and fatty acid biosynthesis including the downstream transcriptional targets of SREBF1 which include LIPIN1 (LPIN and low density lipoprotein receptor (LDLR. Glutathione metabolism was among the pathways enriched in steatosis patients in comparison to healthy controls. By using a model of the glutathione pathway we predict a significant increase in the flux through glutathione synthesis as both gamma-glutamylcysteine synthetase and glutathione synthetase have an increased flux. We anticipate that a larger sample of patients and matching controls will confirm our preliminary findings presented

  11. Development of the Brazilian anti Schistosomiasis vaccine based on the recombinant FABP Sm14 +GLA-SE

    Directory of Open Access Journals (Sweden)

    Miriam eTendler

    2015-05-01

    Full Text Available Data herein reported and discussed refer to vaccination with the recombinant Fatty Acid Binding protein family member of the Schistosomes, called Sm14, discovered and developed under a Brazilian platform leaded by the Oswaldo Cruz Foundation, from the Health Ministry in Brazil, undertaken to assess safety and immunogenicity in healthy volunteers. This paper reviews past and recent outcomes of developmental phases of the Sm14 based anti Schistosomiasis vaccine addressed to, ultimately, impact transmission of the second most prevalent parasitic endemic disease worldwide.

  12. On the crystallization behavior of syndiotactic-b-atactic polystyrene stereodiblock copolymers, atactic/syndiotactic polystyrene blends, and aPS/sPS blends modified with sPS-b-aPS

    Energy Technology Data Exchange (ETDEWEB)

    Annunziata, Liana, E-mail: liana.annunziatta@univ-rennes1.fr [Organométalliques et Catalyse, UMR 6226 Sciences Chimiques CNRS, Université de Rennes 1, Campus de Beaulieu, F-35042 Rennes Cedex (France); Monasse, Bernard, E-mail: bernard.monasse@mines-paristech.fr [Mines-ParisTech, CEMEF, Centre de Mise en Forme des Matériaux, UMR CNRS 7635, Sophia Antipolis (France); Rizzo, Paola; Guerra, Gaetano [Dipartimento di Chimica e Biologia, Università degli studi di Salerno, Via Ponte don Melillo, I-84084 Fisciano, SA (Italy); Duc, Michel [Total Petrochemicals Research Feluy, Zone Industrielle Feluy C, B-7181 Seneffe (Belgium); Carpentier, Jean-François, E-mail: jean-francois.carpentier@univ-rennes1.fr [Organométalliques et Catalyse, UMR 6226 Sciences Chimiques CNRS, Université de Rennes 1, Campus de Beaulieu, F-35042 Rennes Cedex (France)

    2013-09-16

    Crystallization and morphological features of syndiotactic-b-atactic polystyrene stereodiblock copolymers (sPS-b-aPS), atactic/syndiotactic polystyrene blends (aPS/sPS), and aPS/sPS blends modified with sPS-b-aPS, with different compositions in aPS and sPS, have been investigated using differential scanning calorimetry (DSC), polarized light optical microscopy (POM) and wide angle X-ray diffraction (WAXRD) techniques. For comparative purposes, the properties of parent pristine sPS samples were also studied. WAXRD analyses revealed for all the samples, independently from their composition (aPS/sPS ratio) and structure (blends, block copolymers, blends modified with block copolymers), the same polymorphic β form of sPS. The molecular weight of aPS and sPS showed opposite effects on the crystallization of 50:50 aPS/sPS blends: the lower the molecular weight of aPS, the slower the crystallization while the lower the molecular weight of sPS, the faster the crystallization. DSC studies performed under both isothermal and non-isothermal conditions, independently confirmed by POM studies, led to a clear trend for the crystallization rate at a given sPS/aPS ratio (ca. 50:50 and 20:80): sPS homopolymers > sPS-b-aPS block copolymers ∼sPS/aPS blends modified with sPS-b-aPS copolymers > sPS/aPS blends. Interestingly, sPS-b-aPS block copolymers not only crystallized faster than blends, but also affected positively the crystallization behavior of blends. At 50:50 sPS/aPS ratio, blends (Blend-2), block copolymers (Cop-1) and blends modified with block copolymers (Blend-2-mod) crystallized via spherulitic crystalline growth controlled by an interfacial process. In all cases, an instantaneous nucleation was observed. The density of nuclei in block copolymers (160,000−190,000 nuclei mm{sup −3}) was always higher than that in blends and modified blends (30,000−60,000 nuclei mm{sup −3}), even for quite different sPS/aPS ratio. At 20:80 sPS/aPS ratio, the block copolymers

  13. Monitoring the introduction of pneumococcal conjugate vaccines into West Africa: design and implementation of a population-based surveillance system.

    Directory of Open Access Journals (Sweden)

    Grant A Mackenzie

    2012-01-01

    Full Text Available Routine use of pneumococcal conjugate vaccines (PCVs in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings.

  14. Understanding Public Perceptions of the HPV Vaccination Based on Online Comments to Canadian News Articles.

    Directory of Open Access Journals (Sweden)

    Yael Feinberg

    Full Text Available Given the variation in human papillomavirus (HPV vaccine coverage across Canada, and debate regarding delivery of HPV vaccines in Catholic schools, we studied online comments on Canadian news websites to understand public perceptions of HPV and HPV vaccine.We searched English- and French-language Canadian news websites for 2012 articles that contained the terms "HPV" or "human papillomavirus." Articles about HPV vaccinations that contained at least one comment were included. Two researchers independently coded comments, analyzing them for emerging themes.We identified 3073 comments from 1198 individuals in response to 71 news articles; 630 (52.6% individuals expressed positive sentiments about HPV vaccination (2.5 comments/individual, 404 (33.7% were negative (3.0 comments/individual, 34 (2.8% were mixed (1.5 comments/individual and 130 (10.8% were neutral (1.6 comments/individual. Vaccine-supportive commenters believed the vaccine is safe and effective. Common themes in negative comments included concerns regarding HPV vaccine safety and efficacy, distrust of pharmaceutical companies and government, and belief that school-age children are too young for HPV vaccine. Many comments focused on whether the Catholic Church has the right to inform health policy for students, and discussion often evolved into debates regarding HPV and sexual behaviour. We noted that many individuals doubted the credibility of vaccine safety information.The majority of commenters do not appear to be against HPV vaccination, but public health messaging that focuses on both the vaccine's safety profile, and its use as a means to prevent cancer rather than sexually transmitted HPV infection may facilitate its acceptance.

  15. (PS)2: protein structure prediction server version 3.0.

    Science.gov (United States)

    Huang, Tsun-Tsao; Hwang, Jenn-Kang; Chen, Chu-Huang; Chu, Chih-Sheng; Lee, Chi-Wen; Chen, Chih-Chieh

    2015-07-01

    Protein complexes are involved in many biological processes. Examining coupling between subunits of a complex would be useful to understand the molecular basis of protein function. Here, our updated (PS)(2) web server predicts the three-dimensional structures of protein complexes based on comparative modeling; furthermore, this server examines the coupling between subunits of the predicted complex by combining structural and evolutionary considerations. The predicted complex structure could be indicated and visualized by Java-based 3D graphics viewers and the structural and evolutionary profiles are shown and compared chain-by-chain. For each subunit, considerations with or without the packing contribution of other subunits cause the differences in similarities between structural and evolutionary profiles, and these differences imply which form, complex or monomeric, is preferred in the biological condition for the subunit. We believe that the (PS)(2) server would be a useful tool for biologists who are interested not only in the structures of protein complexes but also in the coupling between subunits of the complexes. The (PS)(2) is freely available at http://ps2v3.life.nctu.edu.tw/. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Facile Synthesis of Mono-Dispersed Polystyrene (PS/Ag Composite Microspheres via Modified Chemical Reduction

    Directory of Open Access Journals (Sweden)

    Wen Zhu

    2013-12-01

    Full Text Available A modified method based on in situ chemical reduction was developed to prepare mono-dispersed polystyrene/silver (PS/Ag composite microspheres. In this approach; mono-dispersed PS microspheres were synthesized through dispersion polymerization using poly-vinylpyrrolidone (PVP as a dispersant at first. Then, poly-dopamine (PDA was fabricated to functionally modify the surfaces of PS microspheres. With the addition of [Ag(NH32]+ to the PS dispersion, [Ag(NH32]+ complex ions were absorbed and reduced to silver nanoparticles on the surfaces of PS-PDA microspheres to form PS/Ag composite microspheres. PVP acted both as a solvent of the metallic precursor and as a reducing agent. PDA also acted both as a chemical protocol to immobilize the silver nanoparticles at the PS surface and as a reducing agent. Therefore, no additional reducing agents were needed. The resulting composite microspheres were characterized by TEM, field emission scanning electron microscopy (FESEM, energy-dispersive X-ray spectroscopy (EDS, XRD, UV-Vis and surface-enhanced Raman spectroscopy (SERS. The results showed that Ag nanoparticles (NPs were homogeneously immobilized onto the PS microspheres’ surface in the presence of PDA and PVP. PS/Ag composite microspheres were well formed with a uniform and compact shell layer and were adjustable in terms of their optical property.

  17. Evaluation and validation of a single-dilution potency assay based upon serology of vaccines containing diphtheria toxoid: statistical analysis

    NARCIS (Netherlands)

    Marsman FR; Akkermans AM; Hendriksen CFM; de Jong WH

    1993-01-01

    This document presents the results of a validation study to the use of a single dilution assay in potency testing of the diphtheria component of DPT-polio vaccines. Based on historical data of multi-dilution assays on 27 consecutive batches a simulation study was performed to test the actual

  18. Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy

    Directory of Open Access Journals (Sweden)

    Petra Zieglmayer

    2016-09-01

    Conclusion: The B cell epitope-based recombinant grass pollen allergy vaccine BM32 is well tolerated and few doses are sufficient to suppress immediate allergic reactions as well as allergen-specific T cell responses via a selective induction of allergen-specific IgG antibodies. (ClinicalTrials.gov number, NCT01445002.

  19. A New Method for the Evaluation of Vaccine Safety Based on Comprehensive Gene Expression Analysis

    Directory of Open Access Journals (Sweden)

    Haruka Momose

    2010-01-01

    Full Text Available For the past 50 years, quality control and safety tests have been used to evaluate vaccine safety. However, conventional animal safety tests need to be improved in several aspects. For example, the number of test animals used needs to be reduced and the test period shortened. It is, therefore, necessary to develop a new vaccine evaluation system. In this review, we show that gene expression patterns are well correlated to biological responses in vaccinated rats. Our findings and methods using experimental biology and genome science provide an important means of assessment for vaccine toxicity.

  20. Cost-effectiveness of routine varicella vaccination using the measles, mumps, rubella and varicella vaccine in France: an economic analysis based on a dynamic transmission model for varicella and herpes zoster.

    Science.gov (United States)

    Littlewood, Kavi J; Ouwens, Mario J N M; Sauboin, Christophe; Tehard, Bertrand; Alain, Sophie; Denis, François

    2015-04-01

    Each year in France, varicella and zoster affect large numbers of children and adults, resulting in medical visits, hospitalizations for varicella- and zoster-related complications, and societal costs. Disease prevention by varicella vaccination is feasible, wherein a plausible option involves replacing the combined measles, mumps, and rubella (MMR) vaccine with the combined MMR and varicella (MMRV) vaccine. This study aimed to: (1) assess the cost-effectiveness of adding routine varicella vaccination through MMRV, using different vaccination strategies in France; and (2) address key uncertainties, such as the economic consequences of breakthrough varicella cases, the waning of vaccine-conferred protection, vaccination coverage, and indirect costs. Based on the outputs of a dynamic transmission model that used data on epidemiology and costs from France, a cost-effectiveness model was built. A conservative approach was taken regarding the impact of varicella vaccination on zoster incidence by assuming the validity of the hypothesis of an age-specific boosting of immunity against varicella. The model determined that routine MMRV vaccination is expected to be a cost-effective option, considering a cost-effectiveness threshold of €20,000 per quality-adjusted life-year saved; routine vaccination was cost-saving from the societal perspective. Results were driven by a large decrease in varicella incidence despite a temporary initial increase in the number of zoster cases due to the assumption of exogenous boosting. In the scenario analyses, despite moderate changes in assumptions about incidence and costs, varicella vaccination remained a cost-effective option for France. Routine vaccination with MMRV was associated with high gains in quality-adjusted life-years, substantial reduction in the occurrences of varicella- and zoster-related complications, and few deaths due to varicella. Routine MMRV vaccination is also expected to provide reductions in costs related to

  1. Serology and longevity of immunity against Echinococcus granulosus in sheep and llama induced by an oil-based EG95 vaccine.

    Science.gov (United States)

    Poggio, T V; Jensen, O; Mossello, M; Iriarte, J; Avila, H G; Gertiser, M L; Serafino, J J; Romero, S; Echenique, M A; Dominguez, D E; Barrios, J R; Heath, D

    2016-08-01

    An oil-based formulation of the EG95 vaccine to protect grazing animals against infection with Echinococcus granulosus was formulated in Argentina. The efficacy of the vaccine was monitored by serology in sheep and llama (Lama glama) and was compared to the serology in sheep previously published using a QuilA-adjuvanted vaccine. Long-term efficacy was also tested in sheep by challenging with E. granulosus eggs of the G1 strain 4 years after the beginning of the trial. The serological results for both sheep and llama were similar to those described previously, except that there was a more rapid response after the first vaccination. A third vaccination given after 1 year resulted in a transient boost in serology that lasted for about 12 months, which was similar to results previously described. Sheep challenged after 4 years with three vaccinations presented 84·2% reduction of live cysts counts compared with control group, and after a fourth vaccination prior to challenge, this reduction was 94·7%. The oil-based vaccine appeared to be bio-equivalent to the QuilA vaccine. © 2016 John Wiley & Sons Ltd.

  2. Simultaneous subcutaneous and conjunctival administration of the influenza viral vector based Brucella abortus vaccine to pregnant heifers provides better protection against B. abortus 544 infection than the commercial B. abortus S19 vaccine.

    Science.gov (United States)

    Tabynov, Kaissar; Orynbayev, Mukhit; Renukaradhya, Gourapura J; Sansyzbay, Abylai

    2016-09-30

    In this study, we explored possibility of increasing the protective efficacy of our novel influenza viral vector based B. abortus vaccine (Flu-BA) in pregnant heifers by adapting an innovative method of vaccine delivery. We administered the vaccine concurrently via the conjunctival and subcutaneous routes to pregnant heifers, and these routes were previously tested individually. The Flu-BA vaccination of pregnant heifers (n=9) against a challenge B. abortus 544 infection provided protection from abortion, infection of heifers and fetuses/calves by 88.8%, 100% and 100%, respectively (alpha=0.004-0.0007 vs. negative control; n=7). Our candidate vaccine using this delivery method provided slightly better protection than the commercial B. abortus S19 vaccine in pregnant heifers (n=8), which provided protection from abortion, infection of heifers and fetuses/calves by 87.5%, 75% and 87.5%, respectively. This improved method of the Flu-BA vaccine administration is highly recommended for the recovery of farms which has high prevalence of brucellosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Phase 3 Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

    Science.gov (United States)

    Liao, Guoyang; Li, Rongcheng; Li, Changgui; Sun, Mingbo; Jiang, Shude; Li, Yanping; Mo, Zhaojun; Xia, Jielai; Xie, Zhongping; Che, Yanchun; Yang, Jingsi; Yin, Zhifang; Wang, Jianfeng; Chu, Jiayou; Cai, Wei; Zhou, Jian; Wang, Junzhi; Li, Qihan

    2016-12-01

     The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries.  In this double-blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol.  Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per-protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups.  The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. Synthesis of NiPS3 and CoPS and its hydrogen storage capacity

    International Nuclear Information System (INIS)

    Ismail, N.; Madian, M.; El-Meligi, A.A.

    2014-01-01

    Highlights: • Preparation of NiPS 3 and CoPS using solid state reaction. • Characterization of compounds using XRD, TEM, SEM and IR. • Measuring the compounds thermal stability. • Estimation of the hydrogen storage capacity. -- Abstract: Prepared CoPS and NiPS 3 are studied as new materials for hydrogen energy storage. Single phase of CoPS and NiPS 3 were grown separately in evacuated silicatube via solid state reaction at 650 °C with controlled heating rate 1 °C/min. X-ray diffraction patterns confirm the formation of the desired compounds. Both CoPS and NiPS 3 exhibited high thermal stability up to 700 °C and 630 °C, respectively. The morphology of the prepared samples was investigated using scanning electron microscopy and folded sheets appeared in the transmission electron microscopy. The samples were exposed to 20 bar applied hydrogen pressure at 80 K. Both compounds appear to have feasible hydrogen storage capacity. CoPS was capable to adsorb 1.7 wt% while NiPS 3 storage capacity reached 1.2 wt%

  5. Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN.

    Science.gov (United States)

    He, Yongqun; Xiang, Zuoshuang

    2010-09-27

    Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Bioinformatics curation and ontological representation of Brucella vaccines

  6. Ps 22 in Gospels’ interpretation of Passion

    Directory of Open Access Journals (Sweden)

    Sylwester Jędrzejewski

    2012-09-01

    Full Text Available Ps 22 is a piece of artistically high poetry, clear images and metaphors, historical and prophetic references. The conviction of biblical scholars that the New Testament writers has recognized in Ps 22 prophetic witness of passion, accompanies the Church from its beginnings. The words of Jesus on the cross, taken from Ps 22: 2, have a character of lamentable re-symbolization of the prayer of Israel. These words establish a theological answer in the form of suitable credo as well. Dramatic question “why?” is connected with a proclamation and identification “My God”. The personal experience of oppression and death is included by Jesus in the history of his nation and in the experience of God. Ps 22 in the Gospels’ passion context becomes a proclamation form of prayer and a very personal, expressed in such dramatic circumstances confession of the faith.

  7. PS overcomes two serious magnet failures

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    Two magnets and a bus bar connection in the PS were found to be faulty during high-voltage tests at the end of the accelerator shutdown. A five-week repair schedule was quickly devised. A team of mechanics, technicians and engineers worked at full speed to replace the faulty magnets, succeeding in limiting the delay of the accelerators' spring start-up to two weeks. Here we see the PS magnet string awaiting the replacement no. 6 magnet.

  8. Immune Modulation of NYVAC-Based HIV Vaccines by Combined Deletion of Viral Genes that Act on Several Signalling Pathways

    Directory of Open Access Journals (Sweden)

    Carmen Elena Gómez

    2017-12-01

    Full Text Available An HIV-1 vaccine continues to be a major target to halt the AIDS pandemic. The limited efficacy of the RV144 phase III clinical trial with the canarypox virus-based vector ALVAC and a gp120 protein component led to the conclusion that improved immune responses to HIV antigens are needed for a more effective vaccine. In non-human primates, the New York vaccinia virus (NYVAC poxvirus vector has a broader immunogenicity profile than ALVAC and has been tested in clinical trials. We therefore analysed the HIV immune advantage of NYVAC after removing viral genes that act on several signalling pathways (Toll-like receptors—TLR—interferon, cytokines/chemokines, as well as genes of unknown immune function. We generated a series of NYVAC deletion mutants and studied immune behaviour (T and B cell to HIV antigens and to the NYVAC vector in mice. Our results showed that combined deletion of selected vaccinia virus (VACV genes is a valuable strategy for improving the immunogenicity of NYVAC-based vaccine candidates. These immune responses were differentially modulated, positive or negative, depending on the combination of gene deletions. The deletions also led to enhanced antigen- or vector-specific cellular and humoral responses. These findings will facilitate the development of optimal NYVAC-based vaccines for HIV and other diseases.

  9. Elementary School-Based Influenza Vaccination: Evaluating Impact on Respiratory Illness Absenteeism and Laboratory-Confirmed Influenza

    Science.gov (United States)

    Kjos, Sonia A.; Irving, Stephanie A.; Meece, Jennifer K.; Belongia, Edward A.

    2013-01-01

    Background Studies of influenza vaccine effectiveness in schools have assessed all-cause absenteeism rather than laboratory-confirmed influenza. We conducted an observational pilot study to identify absences due to respiratory illness and laboratory-confirmed influenza in schools with and without school-based vaccination. Methods A local public health agency initiated school-based influenza vaccination in two Wisconsin elementary schools during October 2010 (exposed schools); two nearby schools served as a comparison group (non-exposed schools). Absences due to fever or cough illness were monitored for 12 weeks. During the 4 weeks of peak influenza activity, parents of absent children with fever/cough illness were contacted and offered influenza testing. Results Parental consent for sharing absenteeism data was obtained for 937 (57%) of 1,640 students. Fifty-two percent and 28%, respectively, of all students in exposed and non-exposed schools were vaccinated. Absences due to fever or cough illness were significantly lower in the exposed schools during seven of 12 surveillance weeks. Twenty-seven percent of students at exposed schools and 39% at unexposed schools had one or more days of absence due to fever/cough illness (pabsenteeism due to fever or cough illness, but not absenteeism for other reasons. Although nonspecific, absence due to fever or cough illness may be a useful surrogate endpoint in school-based studies if identification of laboratory confirmed influenza is not feasible. PMID:23991071

  10. A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge.

    Science.gov (United States)

    Pallister, Jackie; Middleton, Deborah; Wang, Lin-Fa; Klein, Reuben; Haining, Jessica; Robinson, Rachel; Yamada, Manabu; White, John; Payne, Jean; Feng, Yan-Ru; Chan, Yee-Peng; Broder, Christopher C

    2011-08-05

    The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5000 TCID₅₀ of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. High prevalence of antibodies against canine adenovirus (CAV) type 2 in domestic dog populations in South Africa precludes the use of CAV-based recombinant rabies vaccines.

    Science.gov (United States)

    Wright, N; Jackson, F R; Niezgoda, M; Ellison, J A; Rupprecht, C E; Nel, L H

    2013-08-28

    Rabies in dogs can be controlled through mass vaccination. Oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. From this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. One such candidate, a recombinant canine adenovirus type 2 vaccine expressing the rabies virus glycoprotein (CAV2-RG), is considered a promising option for dogs, given host specificity and safety. To assess the potential use of this vaccine in domestic dog populations, we investigated the prevalence of antibodies against canine adenovirus type 2 in South African dogs. Blood was collected from 241 dogs from the Gauteng and KwaZulu-Natal provinces. Sampled dogs had not previously been vaccinated against canine adenovirus type 1 (CAV1) or canine adenovirus type 2 (CAV2). Animals from both provinces had a high percentage of seropositivity (45% and 62%), suggesting that CAV2 circulates extensively among domestic dog populations in South Africa. Given this finding, we evaluated the effect of pre-existing CAV-specific antibodies on the efficacy of the CAV2-RG vaccine delivered via the oral route in dogs. Purpose-bred Beagle dogs, which received prior vaccination against canine parvovirus, canine distemper virus and CAV, were immunized by oral administration of CAV2-RG. After rabies virus (RABV) infection all animals, except one vaccinated dog, developed rabies. This study demonstrated that pre-existing antibodies against CAV, such as naturally occurs in South African dogs, inhibits the development of neutralizing antibodies against RABV when immunized with a CAV-based rabies recombinant vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. HPV Vaccine Acceptance in a Clinic-Based Sample of Women in the Rural South

    Science.gov (United States)

    Brandt, Heather M.; Sharpe, Patricia A.; McCree, Donna H.; Wright, Marcie S.; Davis, Jennifer; Hutto, Brent E.

    2009-01-01

    Background: Human papillomavirus (HPV) is a very common sexually transmitted infection linked to cervical disease. Vaccines for some types of HPV were in development at the time of the study. Purpose: The study examined HPV vaccine acceptability among underserved women in a rural region of the southeastern U.S. with high rates of cervical cancer…

  13. Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study

    NARCIS (Netherlands)

    Jaeger, Veronika K.; Hoffman, Hal M.; van der Poll, Tom; Tilson, Hugh; Seibert, Julia; Speziale, Antonio; Junge, Guido; Franke, Kristina; Vritzali, Eleni; Hawkins, Philip N.; Kuemmerle-Deschner, Jasmin; Walker, Ulrich A.

    2017-01-01

    Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. All CAPS

  14. CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion

    DEFF Research Database (Denmark)

    Pedersen, Anders E; Ronchese, Franca

    2007-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells and critical for the priming of CD8+ T cells. Therefore the use of these cells as adjuvant cells has been tested in a large number of experimental and clinical vaccination studies, in particular cancer vaccine studies. A number of protocols...

  15. Association of influenza vaccination and reduced risk of stroke hospitalization among the elderly: a population-based case-control study.

    Science.gov (United States)

    Lin, Hui-Chen; Chiu, Hui-Fen; Ho, Shu-Chen; Yang, Chun-Yuh

    2014-04-02

    The aim of this study was to investigate the effect of influenza vaccination (and annual revaccination) on the risk of stroke admissions. We conducted a population-based case-control study in Taiwan. Cases consisted of patients >65 years of age who had a first-time diagnosis of stroke during the influenza seasons from 2006 to 2009. Controls were selected by matching age, sex, and index date to cases. Multiple logistic regression analysis was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Ever vaccinated individuals in the current vaccination season were associated with a reduced risk of ischemic stroke admissions (OR = 0.76, 95% CI = 0.60-0.97). Compared with individuals never vaccinated against influenza during the past 5 years, the adjusted ORs were 0.92 (95% CI = 0.68-1.23) for the group with 1 or 2 vaccinations, 0.73 (95% CI = 0.54-1.00) for the group with 3 or 4 vaccinations, and 0.56 (95% CI = 0.38-0.83) for the group with 5 vaccinations. There was a significant trend of decreasing risk of ischemic stroke admissions with an increasing number of vaccinations. This study provides evidence that vaccination against influenza may reduce the risk of hospitalization for ischemic stroke and that annual revaccination provides greater protection.

  16. A cell wall protein-based vaccine candidate induce protective immune response against Sporothrix schenckii infection.

    Science.gov (United States)

    Portuondo, Deivys Leandro; Batista-Duharte, Alexander; Ferreira, Lucas Souza; Martínez, Damiana Téllez; Polesi, Marisa Campos; Duarte, Roberta Aparecida; de Paula E Silva, Ana Carolina Alves; Marcos, Caroline Maria; Almeida, Ana Marisa Fusco de; Carlos, Iracilda Zeppone

    2016-02-01

    Sporotrichosis is a subcutaneous mycosis caused by several closely related thermo-dimorphic fungi of the Sporothrix schenckii species complex, affecting humans and other mammals. In the last few years, new strategies have been proposed for controlling sporotrichosis owning to concerns about its growing incidence in humans, cats, and dogs in Brazil, as well as the toxicity and limited efficacy of conventional antifungal drugs. In this study, we assessed the immunogenicity and protective properties of two aluminum hydroxide (AH)-adsorbed S. schenckii cell wall protein (ssCWP)-based vaccine formulations in a mouse model of systemic S. schenckii infection. Fractioning by SDS-PAGE revealed nine protein bands, two of which were functionally characterized: a 44kDa peptide hydrolase and a 47kDa enolase, which was predicted to be an adhesin. Sera from immunized mice recognized the 47kDa enolase and another unidentified 71kDa protein, whereas serum from S. schenckii-infected mice recognized both these proteins plus another unidentified 9.4kDa protein. Furthermore, opsonization with the anti-ssCWP sera led to markedly increased phagocytosis and was able to strongly inhibit the fungus' adhesion to fibroblasts. Immunization with the higher-dose AH-adjuvanted formulation led to increased ex vivo release of IL-12, IFN-γ, IL-4, and IL-17, whereas only IL-12 and IFN-γ were induced by the higher-dose non-adjuvanted formulation. Lastly, passive transference of the higher-dose AH-adjuvanted formulation's anti-ssCWP serum was able to afford in vivo protection in a subsequent challenge with S. schenckii, becoming a viable vaccine candidate for further testing. Copyright © 2015 Elsevier GmbH. All rights reserved.

  17. A PCV2 vaccine based on genotype 2b is more effective than a 2a-based vaccine to protect against PCV2b or combined PCV2a/2b viremia in pigs with concurrent PCV2, PRRSV and PPV infection.

    Science.gov (United States)

    Opriessnig, Tanja; O'Neill, Kevin; Gerber, Priscilla F; de Castro, Alessandra M M G; Gimenéz-Lirola, Luis G; Beach, Nathan M; Zhou, Lei; Meng, Xiang-Jin; Wang, Chong; Halbur, Patrick G

    2013-01-07

    The predominant genotype of porcine circovirus (PCV) in the pig population today is PCV2b yet PCV2a-based commercial vaccines are considered effective in protecting against porcine circovirus associated disease. The objective of this study was to compare the ability of PCV2a- and PCV2b-based vaccines to control PCV2b viremia in a challenge model that mimics the U.S. field situation. Sixty-three pigs were randomly assigned to one of eight groups. Sixteen pigs were vaccinated with an experimental live-attenuated chimeric PCV1-2a vaccine based on genotype 2a and another 16 pigs with a chimeric PCV1-2b vaccine based on genotype 2b. Challenge was done 28 days post vaccination (dpv) using PCV2b (or a combination of PCV2a and PCV2b), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine parvovirus (PPV) to mimic what commonly occurs in the field. The experiment was terminated 21 days post challenge (dpc) or 49dpv. Pigs vaccinated with the chimeric PCV1-2b vaccine had significantly higher levels of PCV1-2b viremia and shedding of the PCV1-2b vaccine virus in feces and nasal secretions but also a more robust humoral immune response as evidenced by significantly higher ELISA S/P ratios compared to the PCV1-2a vaccination. Regardless of challenge, the PCV1-2b vaccination significantly reduced the prevalence and amount of PCV2 viremia compared to the PCV1-2a vaccination. Interestingly, in the non-vaccinated pigs concurrent PCV2a infection resulted in clinical disease and increased macroscopic lung lesions compared to pigs challenged with PCV2b alone, further supporting the idea that concurrent PCV2a/PCV2b infection is necessary for optimal PCV2 replication. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Green revolution vaccines, edible vaccines

    African Journals Online (AJOL)

    Admin

    of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1. Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular ...

  19. Clinical development of a novel inactivated poliomyelitis vaccine based on attenuated Sabin poliovirus strains.

    Science.gov (United States)

    Verdijk, Pauline; Rots, Nynke Y; Bakker, Wilfried A M

    2011-05-01

    Following achievement of polio eradication, the routine use of all live-attenuated oral poliovirus vaccines should be discontinued. However, the costs per vaccine dose for the alternative inactivated poliovirus vaccine (IPV) are significantly higher and the current production capacity is not sufficient for worldwide distribution of the vaccine. In order to achieve cost-prize reduction and improve affordability, IPV production processes and dose-sparing strategies should be developed to facilitate local manufacture at a relatively lower cost. The use of attenuated Sabin instead of wild-type polio strains will provide additional safety during vaccine production and permits production in low-cost settings. Sabin-IPV is under development by several manufacturers. This article gives an overview of results from clinical trials with Sabin-IPV and discusses the requirements and challenges in the clinical development of this novel IPV.

  20. Is hospital based MMR vaccination for children with egg allergy here to stay?

    LENUS (Irish Health Repository)

    Hawkes, C P

    2010-01-01

    Egg allergy is incorrectly considered to constitute a contraindication to MMR in the community, despite a long history of its safe administration to egg allergic children. The product insert perpetuates this misinformation but the Irish guidelines from the RCPI are unequivocal. We reviewed all paediatric cases vaccinated in our hospital in 2007-2008. Forty seven of 91 children receiving vaccinations in hospital, had been referred for MMR due to concerns regarding egg allergy. In 32% (n=15), GP referral for vaccination was made despite correspondence from the clinic advising routine vaccination in the community. Nineteen were second MMR immunisations, which should all have occurred in the community. Unnecessary hospital referral for MMR vaccination is an extra burden on hospital resources, and causes unwarranted anxiety amongst parents of children with egg allergy. A change in practice seems difficult to achieve, as many referrals happen despite individualised correspondence to GPs and other referring clinicians outlining the current guidelines.

  1. Pricing strategies for combination pediatric vaccines based on the lowest overall cost formulary.

    Science.gov (United States)

    Behzad, Banafsheh; Jacobson, Sheldon H; Sewell, Edward C

    2012-10-01

    This paper analyzes pricing strategies for US pediatric combination vaccines by comparing the lowest overall cost formularies (i.e., formularies that have the lowest overall cost). Three pharmaceutical companies compete pairwise over the sale of monovalent and combination vaccines. Particular emphasis is placed on examining the price of Sanofi Pasteur's DTaP-IPV/HIb under different conditions. The main contribution of the paper is to provide the lowest overall cost formularies for different prices of DTaP-IPV/HIb and other Sanofi Pasteur vaccines. The resulting analysis shows that DTaP-IPV/HIb could have been more competitively priced compared with the combination vaccine DTaP-HepB-IPV, for federal contract prices in 2009, 2010 and 2011. This study also proposes the lowest overall cost formularies when shortages of monovalent vaccines occur.

  2. Vaccine Safety

    Science.gov (United States)

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  3. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    International Nuclear Information System (INIS)

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang

    2012-01-01

    Highlights: ► Vero cell-based HPAI H5N1 vaccine with stable high yield. ► Stable high yield derived from the YNVa H3N2 backbone. ► H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  4. Formative research and development of an evidence-based communication strategy: the introduction of Vi typhoid fever vaccine among school-aged children in Karachi, Pakistan.

    Science.gov (United States)

    Pach, Alfred; Tabbusam, Ghurnata; Khan, M Imran; Suhag, Zamir; Hussain, Imtiaz; Hussain, Ejaz; Mumtaz, Uzma; Haq, Inam Ul; Tahir, Rehman; Mirani, Amjad; Yousafzai, Aisha; Sahastrabuddhe, Sushant; Ochiai, R Leon; Soofi, Sajid; Clemens, John D; Favorov, Michael O; Bhutta, Zulfiqar A

    2013-01-01

    The authors conducted formative research (a) to identify stakeholders' concerns related to typhoid fever and the need for disease information and (b) to develop a communication strategy to inform stakeholders and address their concerns and motivate for support of a school-based vaccination program in Pakistan. Data were collected during interactive and semi-structured focus group discussions and interviews, followed by a qualitative analysis and multidisciplinary consultative process to identify an effective social mobilization strategy comprised of relevant media channels and messages. The authors conducted 14 focus group discussions with the parents of school-aged children and their teachers, and 13 individual interviews with school, religious, and political leaders. Parents thought that typhoid fever was a dangerous disease, but were unsure of their children's risk. They were interested in vaccination and were comfortable with a school-based vaccination if conducted under the supervision of trained and qualified staff. Teachers and leaders needed information on typhoid fever, the vaccine, procedures, and sponsors of the vaccination program. Meetings were considered the best form of information dissemination, followed by printed materials and mass media. This study shows how qualitative research findings can be translated into an effective social mobilization and communication approach. The findings of the research indicated the importance of increasing awareness of typhoid fever and the benefits of vaccination against the disease. Identification and dissemination of relevant, community-based disease and vaccination information will increase demand and use of vaccination.

  5. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China); Wang, Yue [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Yingxin Lane 100, Xicheng District, Beijing 100052, People' s Republic of China (China); Liao, Guoyang [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Vero cell-based HPAI H5N1 vaccine with stable high yield. Black-Right-Pointing-Pointer Stable high yield derived from the YNVa H3N2 backbone. Black-Right-Pointing-Pointer H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  6. Perceptions of Community Health Workers (CHWs/PS in the U.S.-Mexico Border HEART CVD Study

    Directory of Open Access Journals (Sweden)

    Hector G. Balcazar

    2014-02-01

    Full Text Available Although prior research has shown that Community Health Workers/Promotores de Salud (CHW/PS can facilitate access to care, little is known about how CHW/PS are perceived in their community. The current study reports the findings of a randomized telephone survey conducted in a high-risk urban community environment along the U.S.-Mexico border. In preparation for a community-based CHW/PS intervention called the HEART ecological study, the survey aimed to assess perceptions of CHW/PS, availability and utilization of community resources (recreational and nutrition related and health behaviors and intentions. A total of 7,155 calls were placed to complete 444 surveys in three zip codes in El Paso, Texas. Results showed that participants felt that healthful community resources were available, but utilization was low and variable: 35% reported going to a park, 20% reported having taken a health class, few reported using a gym (12%, recreation center (8%, or YMCA/YWCA (0.9%. Awareness and utilization of CHW/PS services were low: 20% of respondents had heard of CHW/PS, with 8% reporting previous exposure to CHW/PS services. Upon review of a definition of CHW/PS, respondents expressed positive views of CHW/PS and their value in the healthcare system. Respondents who had previous contact with a CHW/PS reported a significantly more positive perception of the usefulness of CHW/PS (p = 0.006, were more likely to see CHW/PS as an important link between providers and patients (p = 0.008, and were more likely to ask a CHW/PS for help (p = 0.009. Participants who utilized CHW/PS services also had significantly healthier intentions to reduce fast food intake. Future research is needed to evaluate if CHW/PS can facilitate utilization of available community resources such as recreational facilities among Hispanic border residents at risk for CVD.

  7. Emission properties of porphyrin compounds in new polymeric PS:CBP host

    Science.gov (United States)

    Jafari, Mohammad Reza; Bahrami, Bahram

    2015-06-01

    In this study, a device with fundamental structure of ITO/PEDOT:PSS (60 nm)/PS:CBP (70 nm)/Al (150 nm) was fabricated. The electroluminescence spectrum of device designated a red shift rather than PS:CBP photoluminescence spectra. It can be suggested that the electroplex emission occurs at PS:CBP interface. By following this step, red light-emitting devices using porphyrin compounds as a red dopant in a new host material PS:CBP with a configuration of ITO/PEDOT:PSS (60 nm)/PS:CBP:porphyrin compounds(70 nm)/Al (150 nm) have been fabricated and investigated. The electroluminescent spectra of the porphyrin compounds were red-shifted as compared with the PS:CBP blend. OLED devices based on doping 3,4PtTPP and TPPNO2 in PS:CBP showed purer red emission compared with ZnTPP and CoTPP doped devices. We believe that the electroluminescence performance of OLED devices based on porphyrin compounds depends on overlaps between the absorption of the porphyrin compounds and the emission of PS:CBP.

  8. A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS). II. Studies in mice and ferrets and mechanism of adjuvanticity.

    Science.gov (United States)

    Even-Or, Orli; Joseph, Aviva; Itskovitz-Cooper, Noga; Samira, Sarit; Rochlin, Eli; Eliyahu, Hagit; Goldwaser, Itzik; Balasingam, Shobana; Mann, Alex J; Lambkin-Williams, Rob; Kedar, Eli; Barenholz, Yechezkel

    2011-03-16

    We recently showed that lipid assemblies comprised of a novel polycationic sphingolipid (ceramide carbamoyl-spermine, CCS) are an effective adjuvant/carrier when complexed with cholesterol (CCS/C) for influenza and other vaccines administered parenterally and intranasally (i.n.) in mice. Here we expand these studies to ferrets, an established model of influenza infection. We also address the question of why the CCS/C-based liposomal vaccine (also known as VaxiSome™) in mice is superior to vaccines based on liposomes of other lipid compositions (neutral, anionic or cationic). Ferrets immunized i.n. with CCS/C-influenza vaccine produced significantly higher hemagglutination inhibition (HI) antibody titers compared to ferrets immunized intramuscularly with the unadjuvanted influenza vaccine, indicating that the CCS/C-based vaccine is very immunogenic. Furthermore, the i.n. adjuvanted vaccine was shown to significantly reduce the severity of influenza virus infection in ferrets following homologous viral challenge as determined by weight loss, temperature rise and viral titer. No adverse reactions were observed. Pharmacokinetic and biodistribution studies following i.n. administration in mice of CCS/C-based vaccine showed that both the lipids and antigens are retained in the nose and lung for at least 24h, and it appears that this retention correlates with the superior immunogenicity elicited by the adjuvanted vaccine formulation. The CCS lipid also increases production of cytokines (mainly IFN gamma, IL-2 and IL-12) and co-stimulatory molecules' expression, which might further explain the robust adjuvantation of this liposome-based vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Diagnostic tools based on minor groove binder probe technology for rapid identification of vaccinal and field strains of canine parvovirus type 2b.

    Science.gov (United States)

    Decaro, Nicola; Martella, Vito; Elia, Gabriella; Desario, Costantina; Campolo, Marco; Buonavoglia, Domenico; Bellacicco, Anna Lucia; Tempesta, Maria; Buonavoglia, Canio

    2006-12-01

    TaqMan-based diagnostic tests have been developed for the identification of canine parvovirus type 2 (CPV-2) strains in the faeces of dogs with diarrhoea, including a minor groove binder (MGB) probe assay for identification of type 2-based vaccines and field strains (types 2a, 2b and 2c). Since type 2b vaccines have been licensed recently in Europe, two novel MGB assays were developed for discrimination between type 2b vaccines and field strains of CPV. Such assays have been found to be highly sensitive, specific and reproducible, allowing for simultaneous detection of type 2b vaccinal and field strains present in the same specimens. These new assays will help resolution of the diagnostic problems related to the detection of a type 2b strain in the faeces of dogs shortly after the administration of a type 2b vaccine.

  10. Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine.

    Directory of Open Access Journals (Sweden)

    Paul E Makidon

    2008-08-01

    Full Text Available Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg in a novel nanoemulsion (NE adjuvant (HBsAg-NE could be effective with fewer administrations.Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6 titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu. Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2 subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability

  11. Neisseria meningitidis Group A IgG1 and IgG2 Subclass Immune Response in African Children Aged 12–23 Months Following Meningococcal Vaccination

    Science.gov (United States)

    Holme, Daniel; Findlow, Helen; Sow, Samba O.; Idoko, Olubukola T.; Preziosi, Marie-Pierre; Carlone, George; Plikaytis, Brian D.; Borrow, Ray

    2015-01-01

    Background. A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12–23 months of age. Methods. Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A–specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. Results. The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P Group A–specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P vaccines. Conclusions. Vaccination of African children aged 12–24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell–independent immune response commonly associated with polysaccharide antigens. Clinical Trials Registration. SRCTN78147026. PMID:26553689

  12. Current Ebola vaccines

    Science.gov (United States)

    Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

    2012-01-01

    Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible. PMID:22559078

  13. Vaccines in a hurry.

    Science.gov (United States)

    Søborg, Christian; Mølbak, Kåre; Doherty, T Mark; Ulleryd, Peter; Brooks, Tim; Coenen, Claudine; van der Zeijst, Ben

    2009-05-26

    Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public-private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.

  14. Protective immunity conferred by porcine circovirus 2 ORF2-based DNA vaccine in mice.

    Science.gov (United States)

    Sylla, Seydou; Cong, Yan-Long; Sun, Yi-Xue; Yang, Gui-Lian; Ding, Xue-Mei; Yang, Zhan-Qing; Zhou, Yu-Long; Yang, Minnan; Wang, Chun-Feng; Ding, Zhuang

    2014-07-01

    Post-weaning multisystemic wasting syndrome (PMWS) associated with porcine circovirus type 2 (PCV2) has caused the swine industry significant health challenges and economic damage. Although inactivated and subunit vaccines against PMWS have been used widely, so far no DNA vaccine is available. In this study, with the aim of exploring a new route for developing a vaccine against PCV2, the immunogenicity of a DNA vaccine was evaluated in mice. The pEGFP-N1 vector was used to construct a PCV2 Cap gene recombinant vaccine. To assess the immunogenicity of pEGFP-Cap, 80 BALB/c mice were immunized three times at 2 weekly intervals with pEGFP-Cap, LG-strain vaccine, pEGFP-N1 vector or PBS and then challenged with PCV2. IgG and cytokines were assessed by indirect ELISA and ELISA, respectively. Specimens stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC) techniques were examined histopathologically. It was found that vaccination of the mice with the pEGFP-Cap induced solid protection against PCV2 infection through induction of highly specific serum IgG antibodies and cytokines (IFN-γ and IL-10), and a small PCV2 viral load. The mice treated with the pEGFP-Cap and LG-strain developed no histopathologically detectable lesions (HE stain) and IHC techniques revealed only a few positive cells. Thus, this study demonstrated that recombinant pEGFP-Cap substantially alleviates PCV2 infection in mice and provides evidence that a DNA vaccine could be an alternative to PCV2 vaccines against PMWS. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  15. Vaccines.gov

    Science.gov (United States)

    ... Vaccine Safety Vaccines Work Vaccine Types Vaccine Ingredients Vaccines by Disease Chickenpox ... Typhoid Fever Whooping Cough (Pertussis) Yellow Fever Who and When Infants, Children, and Teens ...

  16. Preliminary evaluation of PS300: A new self-lubricating high temperature composite coating for use to 800{degrees}C

    Energy Technology Data Exchange (ETDEWEB)

    DellaCorte, C.; Edmonds, B.J.

    1996-12-31

    This paper introduces PS300, a plasma sprayed, self-lubricating composite coating for use in sliding contacts at temperatures to 800{degrees}C. PS300 is a metal bonded chrome oxide coating with silver and BaF{sub 2}/CaF{sub 2} eutectic solid lubricant additives. PS300 is similar to PS200, a chromium carbide based coating; which is currently being investigated for a variety of tribological applications. In pin-on-disk testing up to 650{degrees}C, PS300 exhibited comparable friction and wear properties to PS200. The PS300 matrix, which is predominantly chromium oxide rather than chromium carbide, does not require diamond grinding and polishes readily with silicon carbide abrasives greatly reducing manufacturing costs compared to PS200. It is anticipated that PS300 has potential for sliding bearing and seal applications in both aerospace and general industry.

  17. A first-generation physiologically based pharmacokinetic (PBPK) model of alpha-tocopherol in human influenza vaccine adjuvant.

    Science.gov (United States)

    Tegenge, Million A; Mitkus, Robert J

    2015-04-01

    Alpha (α)-tocopherol is a component of a new generation of squalene-containing oil-in-water (SQ/W) emulsion adjuvants that have been licensed for use in certain influenza vaccines. Since regulatory pharmacokinetic studies are not routinely required for influenza vaccines, the in vivo fate of this vaccine constituent is largely unknown. In this study, we constructed a physiologically based pharmacokinetic (PBPK) model for emulsified α-tocopherol in human adults and infants. An independent sheep PBPK model was also developed to inform the local preferential lymphatic transfer and for the purpose of model evaluation. The PBPK model predicts that α-tocopherol will be removed from the injection site within 24h and rapidly transfer predominantly into draining lymph nodes. A much lower concentration of α-tocopherol was estimated to peak in plasma within 8h. Any systemically absorbed α-tocopherol was predicted to accumulate slowly in adipose tissue, but not in other tissues. Model evaluation and uncertainty analyses indicated acceptable fit, with the fraction of dose taken up into the lymphatics as most influential on plasma concentration. In summary, this study estimates the in vivo fate of α-tocopherol in adjuvanted influenza vaccine, may be relevant in explaining its immunodynamics in humans, and informs current regulatory risk-benefit analyses. Published by Elsevier Inc.

  18. LS1 Report: PS beams are back!

    CERN Multimedia

    Katarina Anthony & Anaïs Schaeffer

    2014-01-01

    For the first time in over 15 months, there are beams back in the PS. Making their first tour of the accelerator today, 20 June, their injection marks the end of weeks of cold checkouts and hardware commissioning in the PS.   The CERN Control Centre (CCC) is back in business: people gather to restart the LHC injectors, today the PS. Since hardware commissioning was wrapped up on 23 May, the Operations Group (BE-OP) has been conducting cold checkouts on the PS. This involves switching on all of the machine's systems, verifying that they respond to commands by OP and ensuring they are calibrated to beam timings. "These verifications were done, in part, during the hardware commissioning dry runs," says Rende Steerenberg, PS section leader. "But the cold checkouts are on a much larger scale, as we act as if there is beam in the whole machine. We placed a full load on the controls system, cooling, networks, etc. in order to setup the accelerator in the most realis...

  19. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route.

    Science.gov (United States)

    Carey, John B; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V S; Draper, Simon J; Moore, Anne C

    2014-08-21

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.

  20. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

    Science.gov (United States)

    Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

    2014-01-01

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID:25142082

  1. Adenovirus-based vaccine against Listeria monocytogenes

    DEFF Research Database (Denmark)

    Jensen, Søren; Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech

    2013-01-01

    The use of replication-deficient adenoviruses as vehicles for transfer of foreign genes offers many advantages in a vaccine setting, eliciting strong cellular immune responses involving both CD8(+) and CD4(+) T cells. Further improving the immunogenicity, tethering of the inserted target Ag to MHC...... linked to Ii compared with vaccination with the unlinked vaccine. Studies using knockout mice demonstrated that CD8(+) T cells were largely responsible for this protection, which is mediated through perforin-dependent lysis of infected cells and IFN-γ production. Taking the concept a step further...

  2. Tribology and Microstructure of PS212 with a Cr2O3 Seal Coat

    Science.gov (United States)

    Sliney, Harold E.; Benoy, Patricia A.; Korenyi-Both, Andras; Dellacorte, Christopher

    1994-01-01

    PS212 is a plasma sprayed metal bonding chrome carbide coating with solid lubricant additives which has lubricating properties at temperatures up to about 900 deg C. The coating is diamond ground to achieve an acceptable tribological surface. But, as with many plasma spray coatings, PS212 is not fully-dense. In this study, a chromium oxide base seal coating is used in an attempt to seal any porosity that is open to the surface of the PS212 coating, and to study the effect of the sealant on the tribological properties of PS212. The results indicate that the seal coating reduces friction and wear when it is applied and then diamond ground leaving a thin layer of seal coating which fills in the surface pits of the PS212 coating.

  3. Glycoconjugate Vaccines: The Regulatory Framework.

    Science.gov (United States)

    Jones, Christopher

    2015-01-01

    Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

  4. Photodynamic Vaccination of BALB/c Mice for Prophylaxis of Cutaneous Leishmaniasis Caused by Leishmania amazonensis

    Directory of Open Access Journals (Sweden)

    Sayonara M. Viana

    2018-02-01

    Full Text Available Background: Photosensitizers (PS, like porphyrins and phthalocyanines (PC are excitable by light to generate cytotoxic singlet oxygen and other reactive oxygen species in the presence of atmospheric O2. Photodynamic inactivation of Leishmania by this means renders them non-viable, but preserves their effective use as vaccines. Leishmania can be photo-inactivated after PS-sensitization by loading via their endocytic uptake of PC or endogenous induction of transgenic mutants with delta-aminolevulinate (ALA to accumulate cytosolic uroporphyrin I (URO. Here, PS-sensitization and photo-inactivation of Leishmaniaamazonensis was further examined in vitro and in vivo for vaccination against cutaneous leishmaniasis (CL.Methods and Results:Leishmania amazonensis promastigotes were photodynamically inactivated in vitro by PC-loading followed by exposure to red light (1–2 J/cm2 or ALA-induction of uroporphyrinogenic transfectants to accumulate cytosolic URO followed by longwave UV exposure. When applied individually, both strategies of photodynamic inactivation were found to significantly, albeit incompletely abolish the MTT reduction activities of the promastigotes, their uptake by mouse bone marrow-derived macrophages in vitro and their infectivity to mouse ear dermis in vivo. Inactivation of Leishmania to completion by using a combination of both strategies was thus used for the sake of safety as whole-cell vaccines for immunization of BALB/c mice. Different cutaneous sites were assessed for the efficacy of such photodynamic vaccination in vivo. Each site was inoculated first with in vitro doubly PS-sensitized promastigotes and then spot-illuminated with white light (50 J/cm2 for their photo-inactivation in situ. Only in ear dermis parasites were photo-inactivated beyond detection. Mice were thus immunized once in the ear and challenged 3 weeks later at the tail base with virulent L. amazonensis. Prophylaxis was noted in mice photodynamically

  5. The CERN PS/SL Controls Java Application Programming Interface

    International Nuclear Information System (INIS)

    I. Deloose; J. Cuperus; P. Charrue; F. DiMaio; K. Kostro; M. Vanden Eynden; W. Watson

    1999-01-01

    The PS/SL Convergence Project was launched in March 1998. Its objective is to deliver a common control as infrastructure for the CERN accelerators by year 2001. In the framework of this convergence activity, a project was launched to develop a Java Application Programming Interface (API) between programs written in the Java language and the PS and SL accelerator equipment. This Java API was specified and developed in collaboration with TJNAF. It is based on the Java CDEV [1] package that has been extended in order to end up with a CERN/TJNAF common product. It implements a detailed model composed of devices organized in named classes that provide a property-based interface. It supports data subscription and introspection facilities. The device model is presented and the capabilities of the API are described with syntax examples. The software architecture is also described

  6. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

    OpenAIRE

    Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

    2014-01-01

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delive...

  7. Vaccine strategies: Optimising outcomes.

    Science.gov (United States)

    Hardt, Karin; Bonanni, Paolo; King, Susan; Santos, Jose Ignacio; El-Hodhod, Mostafa; Zimet, Gregory D; Preiss, Scott

    2016-12-20

    Successful immunisation programmes generally result from high vaccine effectiveness and adequate uptake of vaccines. In the development of new vaccination strategies, the structure and strength of the local healthcare system is a key consideration. In high income countries, existing infrastructures are usually used, while in less developed countries, the capacity for introducing new vaccines may need to be strengthened, particularly for vaccines administered beyond early childhood, such as the measles or human papillomavirus (HPV) vaccine. Reliable immunisation service funding is another important factor and low income countries often need external supplementary sources of finance. Many regions also obtain support in generating an evidence base for vaccination via initiatives created by organisations including World Health Organization (WHO), the Pan American Health Organization (PAHO), the Agence de Médecine Préventive and the Sabin Vaccine Institute. Strong monitoring and surveillance mechanisms are also required. An example is the efficient and low-cost approaches for measuring the impact of the hepatitis B control initiative and evaluating achievement of goals that have been established in the WHO Western Pacific region. A review of implementation strategies reveals differing degrees of success. For example, in the Americas, PAHO advanced a measles-mumps-rubella vaccine strategy, targeting different population groups in mass, catch-up and follow-up vaccination campaigns. This has had much success but coverage data from some parts of the region suggest that children are still not receiving all appropriate vaccines, highlighting problems with local service infrastructures. Stark differences in coverage levels are also observed among high income countries, as is the case with HPV vaccine implementation in the USA versus the UK and Australia, reflecting differences in delivery settings. Experience and research have shown which vaccine strategies work well and the

  8. A comprehensive analysis of Italian web pages mentioning squalene-based influenza vaccine adjuvants reveals a high prevalence of misinformation.

    Science.gov (United States)

    Panatto, Donatella; Amicizia, Daniela; Arata, Lucia; Lai, Piero Luigi; Gasparini, Roberto

    2018-04-03

    Squalene-based adjuvants have been included in influenza vaccines since 1997. Despite several advantages of adjuvanted seasonal and pandemic influenza vaccines, laypeople's perception of such formulations may be hesitant or even negative under certain circumstances. Moreover, in Italian, the term "squalene" has the same root as such common words as "shark" (squalo), "squalid" and "squalidness" that tend to have negative connotations. This study aimed to quantitatively and qualitatively analyze a representative sample of Italian web pages mentioning squalene-based adjuvants used in influenza vaccines. Every effort was made to limit the subjectivity of judgments. Eighty-four unique web pages were assessed. A high prevalence (47.6%) of pages with negative or ambiguous attitudes toward squalene-based adjuvants was established. Compared with web pages reporting balanced information on squalene-based adjuvants, those categorized as negative/ambiguous had significantly lower odds of belonging to a professional institution [adjusted odds ratio (aOR) = 0.12, p = .004], and significantly higher odds of containing pictures (aOR = 1.91, p = .034) and being more readable (aOR = 1.34, p = .006). Some differences in wording between positive/neutral and negative/ambiguous web pages were also observed. The most common scientifically unsound claims concerned safety issues and, in particular, claims linking squalene-based adjuvants to the Gulf War Syndrome and autoimmune disorders. Italian users searching the web for information on vaccine adjuvants have a high likelihood of finding unbalanced and misleading material. Information provided by institutional websites should be not only evidence-based but also carefully targeted towards laypeople. Conversely, authors writing for non-institutional websites should avoid sensationalism and provide their readers with more balanced information.

  9. Prophylactic Hepatitis E Vaccine.

    Science.gov (United States)

    Zhang, Jun; Zhao, Qinjian; Xia, Ningshao

    2016-01-01

    Hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection-associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals; two of them were tested in human and evidenced to be well tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin ® (HEV 239 vaccine), was licensed in China and launched in 2012.

  10. Vaccines and Kawasaki disease.

    Science.gov (United States)

    Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

    2016-01-01

    The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

  11. Points for Consideration for dengue vaccine introduction - recommendations by the Dengue Vaccine Initiative.

    Science.gov (United States)

    Lim, Jacqueline Kyungah; Lee, Yong-Seok; Wilder-Smith, Annelies; Thiry, Georges; Mahoney, Richard; Yoon, In-Kyu

    2016-01-01

    Dengue is a public health problem in the tropics and subtropics. There are several vaccine candidates in clinical development. However, there may be gaps in the new vaccine introduction after vaccine licensure before it becomes available in developing countries. In anticipation of the first dengue vaccine candidate to be licensed, Dengue Vaccine Initiative (DVI) and, its predecessor, Pediatric Dengue Vaccine Initiative (PDVI) have been working on points for consideration to accelerate evidence-based dengue vaccine introduction, once a vaccine becomes available. In this paper, we review the history of PDVI and its successor, the DVI, and elaborate on the points of consideration for dengue vaccine introduction.

  12. 100-ps framing-camera tube

    International Nuclear Information System (INIS)

    Kalibjian, R.

    1978-01-01

    The optoelectronic framing-camera tube described is capable of recording two-dimensional image frames with high spatial resolution in the <100-ps range. Framing is performed by streaking a two-dimensional electron image across narrow slits. The resulting dissected electron line images from the slits are restored into framed images by a restorer deflector operating synchronously with the dissector deflector. The number of framed images on the tube's viewing screen equals the number of dissecting slits in the tube. Performance has been demonstrated in a prototype tube by recording 135-ps-duration framed images of 2.5-mm patterns at the cathode. The limitation in the framing speed is in the external drivers for the deflectors and not in the tube design characteristics. Faster frame speeds in the <100-ps range can be obtained by use of faster deflection drivers

  13. Respiratory syncytial virus subunit vaccine based on a recombinant fusion protein expressed transiently in mammalian cells.

    Science.gov (United States)

    Nallet, Sophie; Amacker, Mario; Westerfeld, Nicole; Baldi, Lucia; König, Iwo; Hacker, David L; Zaborosch, Christiane; Zurbriggen, Rinaldo; Wurm, Florian M

    2009-10-30

    Although respiratory syncytial virus (RSV) causes severe lower respiratory tract infection in infants and adults at risk, no RSV vaccine is currently available. In this report, efforts toward the generation of an RSV subunit vaccine using recombinant RSV fusion protein (rRSV-F) are described. The recombinant protein was produced by transient gene expression (TGE) in suspension-adapted human embryonic kidney cells (HEK-293E) in 4 L orbitally shaken bioreactors. It was then purified and formulated in immunostimulating reconstituted influenza virosomes (IRIVs). The candidate vaccine induced anti-RSV-F neutralizing antibodies in mice, and challenge studies in cotton rats are ongoing. If successful in preclinical and clinical trials, this will be the first recombinant subunit vaccine produced by large-scale TGE in mammalian cells.

  14. Chimeric avian paramyxovirus-based vector immunization against highly pathogenic avian influenza followed by conventional Newcastle disease vaccination eliminates lack of protection from virulent ND virus

    Directory of Open Access Journals (Sweden)

    C. Steglich

    2014-01-01

    Full Text Available Recently, we described a chimeric, hemagglutinin of highly pathogenic avian influenza virus (HPAIV H5 expressing Newcastle disease virus (NDV-based vector vaccine (chNDVFHNPMV8H5 in which NDV envelope glycoproteins were replaced by those of avian paramyxovirus-8 (APMV-8. This chimeric vaccine induced solid protection against lethal HPAIV H5N1 even in chickens with maternal antibodies against NDV (MDA+. However, due to the absence of the major NDV immunogens it failed to induce protection against Newcastle disease (ND. Here, we report on protection of MDA+ chickens against HPAI H5N1 and ND, by vaccination with chNDVFHNPMV8H5 either on day 1 or day seven after hatch, and subsequent immunization with live attenuated NDV seven days later. Vaccination was well tolerated and three weeks after immunization, challenge infections with highly pathogenic NDV as well as HPAIV H5N1 were carried out. All animals remained healthy without exhibiting any clinical signs, whereas non-vaccinated animals showed morbidity and mortality. Therefore, vaccination with chNDVFHNPMV8H5 can be followed by NDV vaccination to protect chickens from HPAIV as well as NDV, indicating that the antibody response against chNDVFHNPMV8H5 does not interfere with live ND vaccination.

  15. A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Isabela Resende Pereira

    2015-01-01

    , preserved the number of IFNγ+ cells, increased the expression of IFNγ mRNA but reduced inducible NO synthase mRNA. Vaccine-based immunostimulation with rAd might offer a rational alternative for re-programming the immune response to preserve and, moreover, recover tissue injury in Chagas' heart disease.

  16. Knowledge of cervical cancer and HPV vaccine in Bangladeshi women: a population based, cross-sectional study.

    Science.gov (United States)

    Islam, Jessica Yasmine; Khatun, Fatema; Alam, Anadil; Sultana, Farhana; Bhuiyan, Afsana; Alam, Nazmul; Reichenbach, Laura; Marions, Lena; Rahman, Mustafizur; Nahar, Quamrun

    2018-01-11

    The objective of this study was to assess the level of knowledge of cervical cancer among Bangladeshi women and to assess their willingness to receive the human papillomavirus (HPV) vaccine. A population-based, cross-sectional survey was conducted from July to December 2011 in one urban and one rural area of Bangladesh. A total of 2037 ever-married women, aged 14 to 64 years, were interviewed using a structured questionnaire. Data on socio-demographic characteristics and knowledge of cervical cancer were collected. Willingness to receive the HPV vaccine was assessed. Univariate analyses were completed using quantitative data collected. Multivariable logistic regression models were developed to identify factors associated with having heard of cervical cancer and the HPV vaccine. The majority of study participants reported to have heard of cervical cancer (urban: 89.7%, rural 93.4%; P = 0.003). The odds of having heard of cervical cancer were significantly higher in urban women aged 35-44 years (aOR: 2.92 (1.34-6.33) and rural women aged 25-34 years (aOR: 2.90 (1.24-6.73) compared to those aged less than 24 years. Very few women reported to have detailed knowledge on risk factors (urban:9.1%, rural: 8.8%) and prevention (urban: 6.4%, rural: 4.4%) of cervical cancer. In our sample, one in five urban women and one in twenty rural women heard about a vaccine that can prevent cervical cancer. Among urban women, secondary education or higher (aOR: 3.48, 95% CI: 1.67-7.25), age of 20 years and above at marriage (aOR: 2.83, 95% CI: 1.61-5.00), and high socioeconomic status (aOR: 2.25, 95% CI: 1.28-3.95) were factors associated with having heard of the HPV vaccine. Willingness to receive the HPV vaccine among study participants either for themselves (urban: 93.9%, rural: 99.4%) or for their daughters (urban: 91.8%, rural: 99.2%) was high. Detailed knowledge of cervical cancer among Bangladeshi women was found to be poor. Education on cervical cancer must include

  17. Functional testing of an inhalable nanoparticle based influenza vaccine using a human precision cut lung slice technique.

    Directory of Open Access Journals (Sweden)

    Vanessa Neuhaus

    Full Text Available Annual outbreaks of influenza infections, caused by new influenza virus subtypes and high incidences of zoonosis, make seasonal influenza one of the most unpredictable and serious health threats worldwide. Currently available vaccines, though the main prevention strategy, can neither efficiently be adapted to new circulating virus subtypes nor provide high amounts to meet the global demand fast enough. New influenza vaccines quickly adapted to current virus strains are needed. In the present study we investigated the local toxicity and capacity of a new inhalable influenza vaccine to induce an antigen-specific recall response at the site of virus entry in human precision-cut lung slices (PCLS. This new vaccine combines recombinant H1N1 influenza hemagglutinin (HAC1, produced in tobacco plants, and a silica nanoparticle (NP-based drug delivery system. We found no local cellular toxicity of the vaccine within applicable concentrations. However higher concentrations of NP (≥10(3 µg/ml dose-dependently decreased viability of human PCLS. Furthermore NP, not the protein, provoked a dose-dependent induction of TNF-α and IL-1β, indicating adjuvant properties of silica. In contrast, we found an antigen-specific induction of the T cell proliferation and differentiation cytokine, IL-2, compared to baseline level (152±49 pg/mg vs. 22±5 pg/mg, which could not be seen for the NP alone. Additionally, treatment with 10 µg/ml HAC1 caused a 6-times higher secretion of IFN-γ compared to baseline (602±307 pg/mg vs. 97±51 pg/mg. This antigen-induced IFN-γ secretion was further boosted by the adjuvant effect of silica NP for the formulated vaccine to a 12-fold increase (97±51 pg/mg vs. 1226±535 pg/mg. Thus we were able to show that the plant-produced vaccine induced an adequate innate immune response and re-activated an established antigen-specific T cell response within a non-toxic range in human PCLS at the site of virus entry.

  18. How rural and urban parents describe convenience in the context of school-based influenza vaccination: a qualitative study.

    Science.gov (United States)

    Lind, Candace; Russell, Margaret L; Collins, Ramona; MacDonald, Judy; Frank, Christine J; Davis, Amy E

    2015-01-22

    Seasonal influenza vaccine uptake among school-age children has been low, particularly among rural children, even in jurisdictions in Canada where this immunization is publicly funded. Providing this vaccination at school may be convenient for parents and might contribute to increased vaccine uptake, particularly among rural children. We explore the construct of convenience as an advantage of school based influenza vaccination. We also explore for rural urban differences in this construct. Participants were parents of school-aged children from Alberta, Canada. We qualitatively analyzed focus group data from rural parents using a thematic template that emerged from prior work with urban parents. Both groups of parents had participated in focus groups to explore their perspectives on the acceptability of adding an annual influenza immunization to the immunization program that is currently delivered in Alberta schools. Data from within the theme of 'convenience' from both rural and urban parents were then further explored for sub-themes within convenience. Data were obtained from nine rural and nine urban focus groups. The template of themes that had arisen from prior analysis of the urban data applied to the rural data. Convenience was a third level theme under Advantages. Five fourth level themes emerged from within convenience. Four of the five sub-themes were common to both rural and urban participants: reduction of parental burden to schedule, reduction in parental lost time, decrease in parental stress and increase in physical access points for influenza immunization. The fifth subtheme, increases temporal access to influenza immunization, emerged uniquely from the rural data. Both rural and urban parents perceived that convenience would be an advantage of adding an annual influenza immunization to the vaccinations currently given to Alberta children at school. Improving temporal access to such immunization may be a more relevant aspect of convenience to rural

  19. Induction of Protective Immune Responses against Schistosomiasis Haematobium in Hamsters and Mice Using Cysteine Peptidase-Based Vaccine

    Directory of Open Access Journals (Sweden)

    Hatem A M Tallima

    2015-03-01

    Full Text Available One of the major lessons we learned from the radiation-attenuated cercariae (RA vaccine studies is that protective immunity against schistosomiasis is dependent on the induction of T helper (Th1/Th2-related immune responses. Since most schistosome larval and adult-worm-derived molecules used for vaccination uniformly induce a polarized Th1 response, it was essential to include a type 2 immune responses-inducing molecule, such as cysteine peptidases, in the vaccine formula. Here we demonstrate that a single subcutaneous injection of Syrian hamsters with 200 microg active papain 1 h before percutaneous exposure to 150 cercariae of Schistosoma haematobium led to highly significant (P 50% in worm burden and worm egg counts in intestine. Immunization of hamsters with 20 microg recombinant glyceraldehyde 3-phosphate dehydrogenase (rSG3PDH and 20 ug 2-cys peroxiredoxin-derived peptide in a multiple antigen peptide construct (PRX MAP together with papain (20 microg/hamster as adjuvant led to considerable (64% protection against challenge S. haematobium infection, similar to the levels reported with irradiated cercariae. Cysteine peptidases-based vaccination was also effective in protecting outbred mice against a percutaneous challenge infection with S. haematobium cercariae. In two experiments, a mixture of Schistosoma mansoni cathepsin B1 (SmCB1 and Fasciola hepatica cathepsin L1 (FhCL1 led to highly significant (P < 0.005 reduction of 70% in challenge S. haematobium worm burden and 60% reduction in liver egg counts. Mice vaccinated with SmCB1/FhCL1/ rSG3PDH mixture and challenged with S. haematobium cercariae three weeks after the second immunization displayed highly significant (P < 0.005 reduction of 72% in challenge worm burden and no eggs in liver of 8-10 mice/group, as compared to unimmunized mice, associated with production of a mixture of type 1 and type 2-related cytokines and antibody responses.

  20. New Electron Cloud Detectors for the PS Main Magnets

    CERN Document Server

    Yin Vallgren, Ch; Gilardoni, S; Taborelli, M; Neupert, H; Ferreira Somoza, J

    2014-01-01

    Electron cloud (EC) has already been observed during normal operation of the PS, therefore it is necessary to study its in fluence on any beam instability for the future LHC Injector Upgrade (LIU). Two new electron cloud detectors have been discussed, developed and installed during the Long Shutdown (LS1) in one of the PS main magnets. The first measurement method is based on current measurement by using a shielded button-type pick-up. Due to the geometry and space limitation in the PS magnet, the button-type pick-up made of a 96%Al2O3 block coated with a thin layer of solvent-based Ag painting, placed 30 degrees to the bottom part of the vacuum chamber was installed in the horizontal direction where the only opening of the magnet coil is. The other newly developed measurement method is based on detection of photons emitted by the electrons from the electron cloud impinging on the vacuum chamber walls. The emitted photons are reected to a quartz window. A MCP-PMT (Micro-Channel Plate Photomultiplier Tube) wit...

  1. PS Main Control Room (partial view)

    CERN Multimedia

    1974-01-01

    Jean-Pierre Potier (turning buttons) and Bertran Frammery (telephoning) on shift. The 26 GeV Synchrotron and later also its related machines (Linacs 1,2,3; PS-Booster; LEP-Injector Linacs and Electron-Positron Accumulator; Antiproton Accumulator, Antiproton Collector, Low Energy Antiproton Ring and more recently Antiproton Decelerator) were all controlled from the PS control room situated on the Meyrin site. The SPS and LEP were controlled from a separat control centre on the Prevessin site. In 2005 all controls were transferred to the Prevessin centre.

  2. PS overcomes two serious magnet failures

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    Two magnets and a bus bar connection in the PS were found to be faulty during high-voltage tests at the end of the accelerator shutdown. A five-week repair schedule was quickly devised. A team of mechanics, technicians and engineers worked at full speed to replace the faulty magnets, succeeding in limiting the delay of the accelerators' spring start-up to two weeks. These pictures show one of the magnets (no. 19) on the PS locomotive brought back into service for the removal and replacement operations.

  3. Validity and reliability of the Dutch adaptation of the Psoriatic Arthritis Quality of Life (PsAQoL Questionnaire.

    Directory of Open Access Journals (Sweden)

    Freke Wink

    Full Text Available OBJECTIVE: The Psoriatic Arthritis Quality of Life (PsAQoL questionnaire is a disease- specific instrument developed to measure quality of life (QoL in patients with psoriatic arthritis (PsA. The aim of this study was to translate the measure into Dutch and to determine its psychometric properties. METHOD: Translation of the original English PsAQoL into Dutch was performed by bilingual and lay panel. Ten field-test interviews with PsA patients were performed to assess face and content validity. In total, 211 PsA patients were included in a test-retest postal survey to investigate the reliability and construct validity of the Dutch adaptation of the PsAQoL. The PsAQoL, Health Assessment Questionnaire (HAQ and Skindex-17 were administered on two different occasions approximately two weeks apart. RESULTS: The Dutch version of the PsAQoL was found to be relevant, understandable and easy to complete in only a few minutes. It correlated as expected with the HAQ (Spearman's ρ = 0.72 and the 2 subscales of the Skindex-17 (ρ = 0.40 for the psychosocial and ρ = 0.46 for the symptom scale. Furthermore, the measure had good internal consistency (Cronbach's α = 0.92 and test-retest reliability (ρ = 0.89. The PsAQoL was able to define groups of patients based on self-reported general health status, self-reported severity of PsA and flare of arthritis. Duration of PsA did not influence PsAQoL scores. CONCLUSIONS: The Dutch version of the PsAQoL is a valid and reliable questionnaire suitable for use in clinical or research settings to asses PsA-specific QoL.

  4. HPV.edu study protocol: a cluster randomised controlled evaluation of education, decisional support and logistical strategies in school-based human papillomavirus (HPV) vaccination of adolescents.

    Science.gov (United States)

    Skinner, S Rachel; Davies, Cristyn; Cooper, Spring; Stoney, Tanya; Marshall, Helen; Jones, Jane; Collins, Joanne; Hutton, Heidi; Parrella, Adriana; Zimet, Gregory; Regan, David G; Whyte, Patti; Brotherton, Julia M L; Richmond, Peter; McCaffrey, Kirsten; Garland, Suzanne M; Leask, Julie; Kang, Melissa; Braunack-Mayer, Annette; Kaldor, John; McGeechan, Kevin

    2015-09-15

    The National Human Papillomavirus (HPV) Vaccination Program in Australia commenced in 2007 for females and in 2013 for males, using the quadrivalent HPV vaccine (HPV 6,11,16,18). Thus far, we have demonstrated very substantial reductions in genital warts and in the prevalence of HPV among young Australian women, providing early evidence for the success of this public health initiative. Australia has a long history of school-based vaccination programs for adolescents, with comparatively high coverage. However, it is not clear what factors promote success in a school vaccination program. The HPV.edu study aims to examine: 1) student knowledge about HPV vaccination; 2) psycho-social outcomes and 3) vaccination uptake. HPV.edu is a cluster randomised trial of a complex intervention in schools aiming to recruit 40 schools with year-8 enrolments above 100 students (approximately 4400 students). The schools will be stratified by Government, Catholic, and Independent sectors and geographical location, with up to 20 schools recruited in each of two states, Western Australia (WA) and South Australia (SA), and randomly allocated to intervention or control (usual practice). Intervention schools will receive the complex intervention which includes an adolescent intervention (education and distraction); a decisional support tool for parents and adolescents and logistical strategies (consent form returns strategies, in-school mop-up vaccination and vaccination-day guidelines). Careful process evaluation including an embedded qualitative evaluation will be undertaken to explore in depth possible mechanisms for any observed effect of the intervention on primary and secondary outcomes. This study is the first to evaluate the relative effectiveness of various strategies to promote best practice in school-based vaccination against HPV. The study aims to improve vaccination-related psychosocial outcomes, including adolescent knowledge and attitudes, decision-making involvement, self

  5. Outsmart HPV: Acceptability and short-term effects of a web-based HPV vaccination intervention for young adult gay and bisexual men.

    Science.gov (United States)

    McRee, Annie-Laurie; Shoben, Abigail; Bauermeister, Jose A; Katz, Mira L; Paskett, Electra D; Reiter, Paul L

    2018-01-10

    Effective interventions to promote human papillomavirus (HPV) vaccination are needed, particularly among populations at increased risk of HPV-related disease. We developed and pilot tested a web-based intervention, Outsmart HPV, to promote HPV vaccination among young gay and bisexual men (YGBM). In 2016, we recruited a national sample (n = 150) of YGBM ages 18-25 in the United States who had not received any doses of HPV vaccine. Participants were randomized to receive either standard HPV vaccination information (control) or population-targeted, individually-tailored content (Outsmart HPV intervention). We assessed between group differences in HPV vaccination attitudes and beliefs immediately following the intervention using multiple linear regression. There were no differences in HPV vaccination attitudes, beliefs and intentions between groups at baseline. Compared to participants in the control group, intervention participants reported: greater perception that men who have sex with men are at higher risk for anal cancer relative to other men (b = 0.34); greater HPV vaccination self-efficacy (b = 0.15); and fewer perceived harms of HPV vaccine (b = -0.34) on posttest surveys (all p HPV intervention (all > 4.4 on a 5-point scale). Findings from this study provide preliminary support for a brief, tailored web-based intervention in improving HPV vaccination attitudes and beliefs among YGBM. An important next step is to determine the effects of Outsmart HPV on HPV vaccine uptake. ClinicalTrials.gov identifier NCT02835755. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Identification of Novel Potential Vaccine Candidates against Tuberculosis Based on Reverse Vaccinology

    Directory of Open Access Journals (Sweden)

    Gloria P. Monterrubio-López

    2015-01-01

    Full Text Available Tuberculosis (TB is a chronic infectious disease, considered as the second leading cause of death worldwide, caused by Mycobacterium tuberculosis. The limited efficacy of the bacillus Calmette-Guérin (BCG vaccine against pulmonary TB and the emergence of multidrug-resistant TB warrants the need for more efficacious vaccines. Reverse vaccinology uses the entire proteome of a pathogen to select the best vaccine antigens by in silico approaches. M. tuberculosis H37Rv proteome was analyzed with NERVE (New Enhanced Reverse Vaccinology Environment prediction software to identify potential vaccine targets; these 331 proteins were further analyzed with VaxiJen for the determination of their antigenicity value. Only candidates with values ≥0.5 of antigenicity and 50% of adhesin probability and without homology with human proteins or transmembrane regions were selected, resulting in 73 antigens. These proteins were grouped by families in seven groups and analyzed by amino acid sequence alignments, selecting 16 representative proteins. For each candidate, a search of the literature and protein analysis with different bioinformatics tools, as well as a simulation of the immune response, was conducted. Finally, we selected six novel vaccine candidates, EsxL, PE26, PPE65, PE_PGRS49, PBP1, and Erp, from M. tuberculosis that can be used to improve or design new TB vaccines.

  7. Immunogenicity of Yellow Fever Vaccine Coadministered With MenAfriVac in Healthy Infants in Ghana and Mali.

    Science.gov (United States)

    Roy Chowdhury, Panchali; Meier, Christian; Laraway, Hewad; Tang, Yuxiao; Hodgson, Abraham; Sow, Samba O; Enwere, Godwin C; Plikaytis, Brian D; Kulkarni, Prasad S; Preziosi, Marie-Pierre; Niedrig, Matthias

    2015-11-15

    Yellow fever (YF) is still a major public health problem in endemic regions of Africa and South America. In Africa, one of the main control strategies is routine vaccination within the Expanded Programme on Immunization (EPI). A new meningococcal A conjugate vaccine (PsA-TT) is about to be introduced in the EPI of countries in the African meningitis belt, and this study reports on the immunogenicity of the YF-17D vaccines in infants when administered concomitantly with measles vaccine and PsA-TT. Two clinical studies were conducted in Ghana and in Mali among infants who received PsA-TT concomitantly with measles and YF vaccines at 9 months of age. YF neutralizing antibody titers were measured using a microneutralization assay. In both studies, the PsA-TT did not adversely affect the immune response to the concomitantly administered YF vaccine at the age of 9 months. The magnitude of the immune response was different between the 2 studies, with higher seroconversion and seroprotection rates found in Mali vs Ghana. Immunogenicity to YF vaccine is unaffected when coadministered with PsA-TT at 9 months of age. Further studies are warranted to better understand the determinants of the immune response to YF vaccine in infancy. ISRCTN82484612 (PsA-TT-004); PACTR201110000328305 (PsA-TT-007). © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  8. Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier.

    Science.gov (United States)

    Yoshikawa, Tomoaki; Okada, Naoki; Oda, Atsushi; Matsuo, Kazuhiko; Matsuo, Keisuke; Mukai, Yohei; Yoshioka, Yasuo; Akagi, Takami; Akashi, Mitsuru; Nakagawa, Shinsaku

    2008-02-08

    Nanoscopic therapeutic systems that incorporate biomacromolecules, such as protein and peptides, are emerging as the next generation of nanomedicine aimed at improving the therapeutic efficacy of biomacromolecular drugs. In this study, we report that poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent protein delivery carriers for tumor vaccines that delivered antigenic proteins to antigen-presenting cells and elicited potent immune responses. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins through cytosolic translocation from the endosomes, which is a key process of gamma-PGA NP-mediated anti-tumor immune responses. Our findings suggest that the gamma-PGA NP system is suitable for the intracellular delivery of protein-based drugs as well as tumor vaccines.

  9. Efficacy of oral immunotherapy with a rice-based edible vaccine containing hypoallergenic Japanese cedar pollen allergens for treatment of established allergic conjunctivitis in mice

    Directory of Open Access Journals (Sweden)

    Ken Fukuda

    2018-01-01

    Conclusions: Oral administration of transgenic rice seeds expressing hypoallergenic allergens ameliorated allergic conjunctivitis in the established setting. Such a rice-based edible vaccine is potentially both safe and effective for oral immunotherapy in individuals with allergic conjunctivitis.

  10. Analysis of PSA-Specific T-Cell Responses of Prostate Cancer Patients Given a PSA-Based Vaccine on a Clinical Trial

    National Research Council Canada - National Science Library

    Gulley, James

    2003-01-01

    .... This randomized, phase II clinical trial was designed to determine if a PSA-based vaccine could induce a specific immune response when combined with radiotherapy in patients with localized prostate cancer...

  11. School-based vaccination programmes: a systematic review of the evidence on organisation and delivery in high income countries

    Directory of Open Access Journals (Sweden)

    Sarah Perman

    2017-03-01

    Full Text Available Abstract Background Many countries have recently expanded their childhood immunisation programmes. Schools are an increasingly attractive setting for delivery of these new immunisations because of their ability to reach large numbers of children in a short period of time. However, there are organisational challenges to delivery of large-scale vaccination programmes in schools. Understanding the facilitators and barriers is important for improving the delivery of future school-based vaccination programmes. Methods We undertook a systematic review of evidence on school-based vaccination programmes in order to understand the influence of organisational factors on the delivery of programmes. Our eligibility criteria were studies that (1 focused on childhood or adolescent vaccination programmes delivered in schools; (2 considered organisational factors that influenced the preparation or delivery of programmes; (3 were conducted in a developed or high-income country; and (4 had been peer reviewed. We searched for articles published in English between 2000 and 2015 using MEDLINE and HMIC electronic databases. Additional studies were identified by searching the Cochrane Library and bibliographies. We extracted data from the studies, assessed quality and the risk of bias, and categorised findings using a thematic framework of eight organisational factors. Results We found that most of the recent published literature is from the United States and is concerned with the delivery of pandemic or seasonal flu vaccination programmes at a regional (state or local level. We found that the literature is largely descriptive and not informed by the use of theory. Despite this, we identified common factors that influence the implementation of programmes. These factors included programme leadership and governance, organisational models and institutional relationships, workforce capacity and roles particularly concerning the school nurse, communication with parents and

  12. Vaccine process technology.

    Science.gov (United States)

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

  13. Chitosan-Poly (I:C-PADRE Based Nanoparticles as Delivery Vehicles for Synthetic Peptide Vaccines

    Directory of Open Access Journals (Sweden)

    Jorge F. Correia-Pinto

    2015-09-01

    Full Text Available The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C (pIC and a T-Helper peptide (PADRE, integrated into a chitosan (CS based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm, a high positive surface charge (>40 mV and high pIC association efficiency (>96%. They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen.

  14. Hepatitis Vaccines

    OpenAIRE

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

  15. Laboratory spectrum of the PS radical and related astronomical search

    International Nuclear Information System (INIS)

    Ohishi, M.; Yamamoto, S.; Saito, S.; Kawaguchi, K.; Suzuki, H.

    1988-01-01

    The millimeter-wave rotational spectrum of the PS radical (X 2Pi r) was observed in the laboratory for the first time in the frequency region of 79-293 GHz by discharging the mixture of PSCl3 and He. Some 44 lines were measured, and the rotational constant, the centrifugal distortion constant, the centrifugal distortion term of the spin-orbit coupling constant, the Lambda-type doubling constants, and the hyperfine coupling constants were determined. Based on the measured and calculated frequencies, an astronomical search for the interstellar and circumstellar PS radical was made without success in Orion KL, Sgr B2, L134N,IRC + 10216, VY CMa, and OH 231.8 + 4.2. 29 references

  16. Successful online learning – the five Ps

    Directory of Open Access Journals (Sweden)

    Jim FLOOD

    2004-04-01

    hardware or software problems when trying to access their learning materials, tend to blame themselves for the errors - and consequently suffer a blow to their self-esteem. They rarely return to the scene of their humiliation and could account for a significant part of the 70% who gets ‘killed off’. So technical support, especially in the early stages is essential. Also essential is the support of colleagues–both those taking part and those who are providing ‘cover’ while the learning takes place. This is particularly critical in work-based learning situations in which learners tend to feel that they are ‘letting colleagues down’ by not contributing to the ongoing work. “I’m too busy to do it” is the most common reason for non-completion of online courses – for which read; “I can’t be seen not being busy”. An important prop for learners is the manner in which the culture of an organisation is both overtly and institutionally supportive. Any discussion environment whether real or virtual needs to be one in which the learner can have trust and confidence–and this is where skilled facilitation can help. Effective facilitation of an online discussion in which the only medium of communication is text is not impossible–but it does require additional competencies that are not within the skill set of most trainers and teachers. Skilled facilitation does enable people to learn from each other and becoming effective members of a learning community. This type of interaction also gives access to the tacit knowledge that is often more valuable that the explicit content in the learning materials. So think about ‘props’ in terms of the 3 Ts: Technical, Trust and Teamwork. Summary The five Ps outlined above are closely interdependent and require an integrated approach to the design of a learning architecture in which online learners are more likely to flourish than to perish. Designing and implementing an appropriate blend of these Ps should enable learners, and their

  17. Effectiveness of a Web-Based Tailored Intervention With Virtual Assistants Promoting the Acceptability of HPV Vaccination Among Mothers of Invited Girls: Randomized Controlled Trial.

    Science.gov (United States)

    Pot, Mirjam; Paulussen, Theo Gwm; Ruiter, Robert Ac; Eekhout, Iris; de Melker, Hester E; Spoelstra, Maxine Ea; van Keulen, Hilde M

    2017-09-06

    In 2010, the human papillomavirus (HPV) vaccination was introduced in the Dutch National Immunization Program for 12-year-old girls, aiming to reduce the incidence of cervical cancer in women. HPV vaccination uptake turned out to be lower than expected: 61% versus 70%, respectively. Mothers were shown to play the most important role in the immunization decision about this vaccination. They had also expressed their need for interactive personal information about the HPV vaccination over and above the existing universal general information. To improve the effectiveness of the existing education about the HPV vaccination, we systematically developed a Web-based tailored intervention with virtual assistants providing mothers of girls to be invited with tailored feedback on their decision making about the HPV vaccination. The aim of this study was to evaluate the effectiveness of the Web-based tailored intervention for promoting HPV vaccination acceptance by means of a randomized controlled trial (RCT). Mothers were recruited via the Dutch vaccination register (Praeventis) (n=36,000) and three Web-based panels (n=2483). Those who gave informed consent (N=8062) were randomly assigned to the control (n=4067) or intervention condition (n=3995). HPV vaccination uptake, as registered by Praeventis once the HPV vaccination round was completed, was used as the primary outcome. Secondary outcomes were differential scores across conditions between baseline (before the provided access to the new tailored intervention) and follow-up (just before the first vaccination) regarding the mothers' degree of informed decision making (IDM), decisional conflict, and critical determinants of HPV vaccination uptake among which are intention, attitude, risk perception, and outcome beliefs. Intention-to-treat analysis (N=8062) showed a significant positive effect of the intervention on IDM, decisional conflict, and nearly all determinants of HPV vaccination uptake (Padmin/rctview.asp?TC=4935

  18. Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

    Science.gov (United States)

    Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

    1999-03-01

    We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

  19. Back to work for the PS

    CERN Multimedia

    2006-01-01

    On 22 June, the PS's rotating machine started turning again for the first time since its enforced shutdown one month ago (see Bulletin No. 23-24/2006) - and the PS was back in operation the very next day! A team from Siemens worked their socks off, 6 days a week for one month (including public holidays), to repair the electrical power supply in collaboration with the AB/PO Group's Main Power Converters (MPC) Section. The generator's faulty rotor was dismantled and replaced by the renovated spare rotor. The multitude of electrical and mechanical connections together with the sheer weight of the rotor (80 tonnes) made this an extremely complex job. The AB/PO Group used the shutdown to test a back-up solution for the PS power supply. The accelerator was directly wired up to the 18 kV electrical network via a 13 MVA transformer, installed at the end of the 1970s but never used. This solution succeeded in bringing the PS back into operation but at limited energy and frequency. Just 14 GeV could be achieved, whic...

  20. CNA-motion in a PS - Fn

    International Nuclear Information System (INIS)

    Singh, M.P.; Mishra, C.K.

    1989-12-01

    A Finsler space Fn (n > 2), throughout with the projective curvature tensor possessing vanishing covariant derivative, has been called a ''projectively symmetric Finsler space'' and such a space is denoted PS-Fn. The conditions in which an infinitesimal transformation defines non-affine motion with a contra-field, briefly called CNA-motion, are discussed. 7 refs

  1. Beyond metric gravity: Progress on PS-200

    International Nuclear Information System (INIS)

    Goldman, T.; Brown, R.E.; Camp, J.B.; Darling, T.; Dyer, P.; Holzscheiter, M.H.; Hughes, R.J.; Jarmie, N.; King, N.S.P.; Lizon, D.C.; Nieto, M.M.; Schauer, M.M.M.; Schecker, J.A.; Cornford, S.; Hosea, K.; Kenefick, R.A.; Hoibraaten, S.; Midzor, M.M.; Parry, S.P.; Ristenen, R.A.; Witteborn, F.C.

    1993-01-01

    The reconciliation of quantum mechanics and gravity on varying distance scales requires changes to General Relativity that may be testable implications. We briefly review the status of tests with matter of the inverse square law and the principle of equivalence, then report on progress on the drift-tube measurement section of PS- 200, the experiment to measure the gravitational acceleration of antiprotons

  2. NIKHEF: AmPS of electron beam

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Now operational at the Dutch National Institute for Nuclear Physics and High Energy Physics (NIKHEF), Amsterdam, is a new tool for studying the electromagnetic properties of nuclei. Called AmPS - Amsterdam pulse stretcher - this ring provides experiments with a smoother, almost continuous supply of electrons

  3. Human Papillomavirus vaccination in general practice in France, three years after the implementation of a targeted vaccine recommendation based on age and sexual history : Targeted HPV vaccine recommendation in France

    OpenAIRE

    Thierry , Pascale; Lasserre , Andrea; Rossignol , Louise; Kernéis , Solen; Blaizeau , Fanette; Stheneur , Chantal; Blanchon , Thierry; Levy-Bruhl , Daniel; Hanslik , Thomas

    2015-01-01

    International audience; IntroductionIn France, vaccination against human papilloma virus (HPV) was recommended in 2007 for all 14-year-old girls as well as “catch-up” vaccination for girls between 15-23 years of age either before or within one year of becoming sexually active. We evaluated the vaccine coverage according to the eligibility for vaccination in a sample of young girls aged 14 to 23 years, who were seen in general practices. Patients and methodsA survey was proposed to 706 general...

  4. Induction of complex immune responses and strong protection against retrovirus challenge by adenovirus-based immunization depends on the order of vaccine delivery.

    Science.gov (United States)

    Kaulfuß, Meike; Wensing, Ina; Windmann, Sonja; Hrycak, Camilla Patrizia; Bayer, Wibke

    2017-02-06

    In the Friend retrovirus mouse model we developed potent adenovirus-based vaccines that were designed to induce either strong Friend virus GagL 85-93 -specific CD8 + T cell or antibody responses, respectively. To optimize the immunization outcome we evaluated vaccination strategies using combinations of these vaccines. While the vaccines on their own confer strong protection from a subsequent Friend virus challenge, the simple combination of the vaccines for the establishment of an optimized immunization protocol did not result in a further improvement of vaccine effectivity. We demonstrate that the co-immunization with GagL 85-93 /leader-gag encoding vectors together with envelope-encoding vectors abrogates the induction of GagL 85-93 -specific CD8 + T cells, and in successive immunization protocols the immunization with the GagL 85-93 /leader-gag encoding vector had to precede the immunization with an envelope encoding vector for the efficient induction of GagL 85-93 -specific CD8 + T cells. Importantly, the antibody response to envelope was in fact enhanced when the mice were adenovirus-experienced from a prior immunization, highlighting the expedience of this approach. To circumvent the immunosuppressive effect of envelope on immune responses to simultaneously or subsequently administered immunogens, we developed a two immunizations-based vaccination protocol that induces strong immune responses and confers robust protection of highly Friend virus-susceptible mice from a lethal Friend virus challenge.

  5. ps-ro Fuzzy Open(Closed Functions and ps-ro Fuzzy Semi-Homeomorphism

    Directory of Open Access Journals (Sweden)

    Pankaj Chettri

    2015-11-01

    Full Text Available The aim of this paper is to introduce and characterize some new class of functions in a fuzzy topological space termed as ps-ro fuzzy open(closed functions, ps-ro fuzzy pre semiopen functions and ps-ro fuzzy semi-homeomorphism. The interrelation among these concepts and also their relations with the parallel existing concepts are established. It is also shown with the help of examples that these newly introduced concepts are independent of the well known existing allied concepts.

  6. An Investigation of Immunogenicity of Chitosan-Based Botulinum Neurotoxin E Binding Domain Recombinant Candidate Vaccine via Mucosal Route

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Bagheripour

    2017-01-01

    Full Text Available Background and Objectives: Botulism syndrome is caused by serotypes A-G of neurotoxins of Clostridium genus. Neurotoxin binding domain is an appropriate vaccine candidate due to its immunogenic activity. In this study, the immunogenicity of chitosan-based botulinum neurotoxin E binding domain recombinant candidate vaccine was investigated via mucosal route of administration. Methods: In this experimental study, chitosan nanoparticles containing rBoNT/E protein were synthesized by ionic gelation method and were administered orally and intranasally to mice. After each administration, IgG antibody titer was measured by ELISA method. Finally, all groups were challenged with active botulinum neurotoxin type E. Data were analyzed using Duncan and repeated ANOVA tests. The significance level was considered as p0.05, even intranasal route reduced the immunogenicity.

  7. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

    Science.gov (United States)

    van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W.; Daemen, Toos

    2015-01-01

    The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus. PMID:26343186

  8. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

    Directory of Open Access Journals (Sweden)

    Stephanie van de Wall

    2015-03-01

    Full Text Available The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV targeting human papillomavirus (HPV. Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7 via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

  9. Risk Management Capability Maturity and Performance of Complex Product and System (CoPS Projects with an Asian Perspective

    Directory of Open Access Journals (Sweden)

    Ren, Y.

    2014-07-01

    Full Text Available Complex Products and Systems (CoPS are high value, technology and engineering-intensive capital goods. The motivation of this study is the persistent high failure rate of CoPS projects, Asian CoPS provider’s weak capability and lack of specific research on CoPS risk management. This paper evaluates risk management maturity level of CoPS projects against a general CoPS risk management capability maturity model (RM-CMM developed by the authors. An Asian based survey was conducted to investigate the value of RM to project performance, and Asian (non-Japanese CoPS implementers’ perceived application of RM practices, their strengths and weaknesses. The survey result shows that higher RM maturity level leads to higher CoPS project performance. It also shows project complexity and uncertainty moderates the relationship between some RM practices and project performance, which implies that a contingency approach should be adopted to manage CoPS risks effectively. In addition, it shows that Asian CoPS implementers are weak in RM process and there are also rooms for improvement in the softer aspects of organizational capabilities and robustness.

  10. A Model International Partnership for Community-based Research on Vaccine-preventable Diseases: the Kamphaeng Phet-AFRIMS Virology Research Unit (KAVRU)

    Science.gov (United States)

    2013-01-01

    4500 Table 3 Acknowledgment of contributions. Participant Role Albert Sabin Led effort to make JEV Vaccine during WWII Richard Mason Member of...R A v R R K D S a b c d e f g h i j a A R R A A K V S J H D I C T P p ( C t 0 h Vaccine 31 (2013) 4487– 4500 Contents lists available at...ScienceDirect Vaccine jou rn al hom ep age: www.elsev ier .com/ locat e/vacc ine eview model international partnership for community-based research on

  11. An oral Sindbis virus replicon-based DNA vaccine containing VP2 gene of canine parvovirus delivered by Escherichia coli elicits immune responses in dogs.

    Science.gov (United States)

    Dahiya, S S; Saini, M; Kumar, P; Gupta, P K

    2011-01-01

    A Sindbis virus replicon-based DNA vaccine containing VP2 gene of canine parvovirus (CPV) was delivered by Escherichia coli to elicit immune responses. The orally immunized dogs developed CPV-specific serum IgG and virus neutralizing antibody responses. The cellular immune responses analyzed using lymphocyte proliferation test and flow cytometry indicated CPV-specific sensitization of both CD3+CD4+ and CD3+CD8+ lymphocytes. This study demonstrated that the oral CPV DNA vaccine delivered by E. coli can be considered as a promising approach for vaccination of dogs against CPV.

  12. Rotavirus vaccines

    Science.gov (United States)

    Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

    2014-01-01

    Rotavirus is the leading cause of severe diarrhea among children rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

  13. Macromolecular systems for vaccine delivery.

    Science.gov (United States)

    MuŽíková, G; Laga, R

    2016-10-20

    Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.

  14. A new strategy based on SmRho protein loaded chitosan nanoparticles as a candidate oral vaccine against schistosomiasis.

    Directory of Open Access Journals (Sweden)

    Carolina R Oliveira

    Full Text Available BACKGROUND: Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticles containing the antigen SmRho and coated with sodium alginate. METHODS AND FINDINGS: Our results showed an efficient performance of protein loading of nanoparticles before and after coating with alginate. Characterization of the resulting nanoparticles reported a size around 430 nm and a negative zeta potential. In vitro release studies of protein showed great stability of coated nanoparticles in simulated gastric fluid (SGF and simulated intestinal fluid (SIF. Further in vivo studies was performed with different formulations of chitosan nanoparticles and it showed that oral immunization was not able to induce high levels of antibodies, otherwise intramuscular immunization induced high levels of both subtypes IgG1 and IgG2a SmRho specific antibodies. Mice immunized with nanoparticles associated to CpG showed significant modulation of granuloma reaction. Mice from all groups immunized orally with nanoparticles presented significant levels of protection against infection challenge with S. mansoni worms, suggesting an important role of chitosan in inducing a protective immune response. Finally, mice immunized with nanoparticles associated with the antigen SmRho plus CpG had 38% of the granuloma area reduced and also presented 48% of protection against of S. mansoni infection. CONCLUSIONS: Taken together, this results support this new strategy as an efficient delivery system and a potential vaccine against schistosomiasis.

  15. Comprehensive safety assessment of a human inactivated diploid enterovirus 71 vaccine based on a phase III clinical trial.

    Science.gov (United States)

    Zhang, Wei; Kong, Yujia; Jiang, Zhiwei; Li, Chanjuan; Wang, Ling; Xia, Jielai

    2016-04-02

    Human enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease (HFMD). In a previous phase III trial in children, a human diploid cell-based inactivated EV71 vaccine elicited EV71 specific immune responses and protection against EV71 associated HFMD. This study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. This was a randomized, double-blinded, placebo-controlled, phase III clinical trial of a human diploid vaccine carried out in 12,000 children in Guangxi Zhuang Autonomous Region, China (ClinicalTrials.gov: NCT01569581). Solicited events were recorded for 7 days and unsolicited events were reported for 28 days after each injection. Age trend analysis of adverse reaction was conducted in each treatment group. Multiple logistic regression models were built to identify factors influencing the severity of adverse reactions. Fewer solicited adverse reactions were observed in older participants within the first 7 days after vaccination (P < 0.0001), except local pain and pruritus. More severe adverse reactions were observed after the initial injection than after the booster injection. Serious cold or respiratory tract infections (RTI) were observed more often in children aged 6-36 months than in older children. Only the severity of local swelling was associated with body mass index. Children with throat discomfort before injection had a higher risk of serious cold or RTI. These results indicated that the human diploid cell-based vaccine achieved a satisfactory safety profile.

  16. Phosphorene-directed self-assembly of asymmetric PS-b-PMMA block copolymer for perpendicularly-oriented sub-10 nm PS nanopore arrays

    Science.gov (United States)

    Zhang, Ziming; Zheng, Lu; Khurram, Muhammad; Yan, Qingfeng

    2017-10-01

    Few-layer black phosphorus, also known as phosphorene, is a new two-dimensional material which is of enormous interest for applications, mainly in electronics and optoelectronics. Herein, we for the first time employ phosphorene for directing the self-assembly of asymmetric polystyrene-block-polymethylmethacrylate (PS-b-PMMA) block copolymer (BCP) thin film to form the perpendicular orientation of sub-10 nm PS nanopore arrays in a hexagonal fashion normal to the interface. We experimentally demonstrate that none of the PS and PMMA blocks exhibit preferential affinity to the phosphorene-modified surface. Furthermore, the perpendicularly-oriented PS nanostructures almost stay unchanged with the variation of number of layers of few-layer phosphorene nanoflakes between 15-30 layers. Differing from the neutral polymer brushes which are widely used for chemical modification of the silicon substrate, phosphorene provides a novel physical way to control the interfacial interactions between the asymmetric PS-b-PMMA BCP thin film and the silicon substrate. Based on our results, it is possible to build a new scheme for producing sub-10 nm PS nanopore arrays oriented perpendicularly to the few-layer phosphorene nanoflakes. Furthermore, the nanostructural microdomains could serve as a promising nanolithography template for surface patterning of phosphorene nanoflakes.

  17. Phosphorene-directed self-assembly of asymmetric PS-b-PMMA block copolymer for perpendicularly-oriented sub-10 nm PS nanopore arrays.

    Science.gov (United States)

    Zhang, Ziming; Zheng, Lu; Khurram, Muhammad; Yan, Qingfeng

    2017-10-20

    Few-layer black phosphorus, also known as phosphorene, is a new two-dimensional material which is of enormous interest for applications, mainly in electronics and optoelectronics. Herein, we for the first time employ phosphorene for directing the self-assembly of asymmetric polystyrene-block-polymethylmethacrylate (PS-b-PMMA) block copolymer (BCP) thin film to form the perpendicular orientation of sub-10 nm PS nanopore arrays in a hexagonal fashion normal to the interface. We experimentally demonstrate that none of the PS and PMMA blocks exhibit preferential affinity to the phosphorene-modified surface. Furthermore, the perpendicularly-oriented PS nanostructures almost stay unchanged with the variation of number of layers of few-layer phosphorene nanoflakes between 15-30 layers. Differing from the neutral polymer brushes which are widely used for chemical modification of the silicon substrate, phosphorene provides a novel physical way to control the interfacial interactions between the asymmetric PS-b-PMMA BCP thin film and the silicon substrate. Based on our results, it is possible to build a new scheme for producing sub-10 nm PS nanopore arrays oriented perpendicularly to the few-layer phosphorene nanoflakes. Furthermore, the nanostructural microdomains could serve as a promising nanolithography template for surface patterning of phosphorene nanoflakes.

  18. POPS: the 60MW power converter for the PS accelerator: Control strategy and performances

    CERN Document Server

    Boattini, Fulvio; Skawinski, Gregory

    2015-01-01

    The main power supply of Proton-Synchrotron (PS) accelerator is one of the biggest at CERN. The old rotating machine system has been replaced with a new NPC based DC/DC power supply named POPS (Power system for PS main magnets) with capacitor banks as energy storage mean. POPS is in operation since February 2011. The operation of the PS accelerator requires a specific design of the control system with very high performance requirements in term of accuracy and precision. This paper describes the main lines of the control strategies analyzing the problems encountered and the solutions adopted. The performances of the converter are presented throughout the paper.

  19. 基于时序InSAR的京津高铁北京段地面沉降监测%The Subsidence Monitoring of Beijing-Tianjin High-speed Railway Based on PS-InSAR

    Institute of Scientific and Technical Information of China (English)

    周玉营; 陈蜜; 宫辉力; 李小娟; 余洁; 祝秀星

    2017-01-01

    The Beijing-Tianjin high-speed railway is the first high-speed railway in China. The stability of the geological environment is crucial for the safe operation of the high-speed railway. Land subsidence especially uneven subsidence will probably cause the deformation of the roadbed and bridge, which may affect the safety of high-speed railway operation. Therefore, it has very important significance for land subsidence monitoring along the high-speed railway. Interferometric synthetic aperture radar (InSAR) is an effective way for monitoring land subsidence with high precision. Based on 45 high-resolution TerraSAR-X images acquired from 2010 to 2015, the Permanent Scatter Interferometry (PS-InSAR) is empolyed to obtain land subsidence information along Beijing-Tianjin high-speed railway in Beijing section. The results indicate that there exist different spatial distributions of the land subsidence along the high-speed railway, the annual subsidence rate from Beijing south railway station to Shilihe interval is less than 10 mm/a, and from Shilihe to Shibalidian interval the annual subsidence rate ranges from 10 to 40 mm/a. And the maximum annual subsidence rate reaches 90mm/a from Yizhuang station to the east interval. The comprehensive analysis of static- dynamic loadings and hydrogeological data can help to understand the causes of land subsidence along high-speed railway. Over-exploitation of groundwater is the main factor of land subsidence in the study area, and the combination of dynamic and static loadings have certain influence on land subsidence. To some extent, the land subsidence along the high-speed railway is controlled by the Nanyuan-Tongzhou fault and the Jiugong fault, and most parts of the land subsidence are located in the Daxing uplifted belt with thick clay layer.%京津高铁是中国第一条高速运行的城际铁路,其安全运行对轨道的平顺性有着严格的要求.地面沉降,尤其是不均匀地面沉降会引起部分路基和桥

  20. Vaccine Hesitancy.

    Science.gov (United States)

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vac