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Sample records for ten leading vaccine-candidate

  1. Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models.

    Science.gov (United States)

    Rivera-Hernandez, Tania; Pandey, Manisha; Henningham, Anna; Cole, Jason; Choudhury, Biswa; Cork, Amanda J; Gillen, Christine M; Ghaffar, Khairunnisa Abdul; West, Nicholas P; Silvestri, Guido; Good, Michael F; Moyle, Peter M; Toth, Istvan; Nizet, Victor; Batzloff, Michael R; Walker, Mark J

    2016-06-14

    Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i) streptolysin O (SLO), interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), group A streptococcal C5a peptidase (SCPA), arginine deiminase (ADI), and trigger factor (TF); (ii) the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii) group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a "gold standard" for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model. This set of experiments demonstrates the inherent variability of mouse models for the characterization of GAS vaccine candidate protective efficacy. Such variability poses an important challenge for GAS vaccine development, as advancement of candidates to human clinical trials requires strong evidence of efficacy. This study highlights the need for an open discussion within the field regarding standardization of animal models for GAS vaccine development. Copyright © 2016 Rivera-Hernandez et al.

  2. Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models

    Directory of Open Access Journals (Sweden)

    Tania Rivera-Hernandez

    2016-06-01

    Full Text Available Group A Streptococcus (GAS is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i streptolysin O (SLO, interleukin 8 (IL-8 protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP], group A streptococcal C5a peptidase (SCPA, arginine deiminase (ADI, and trigger factor (TF; (ii the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model.

  3. Leishmaniasis: vaccine candidates and perspectives.

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    Singh, Bhawana; Sundar, Shyam

    2012-06-06

    Leishmania is a protozoan parasite and a causative agent of the various clinical forms of leishmaniasis. High cost, resistance and toxic side effects of traditional drugs entail identification and development of therapeutic alternatives. The sound understanding of parasite biology is key for identifying novel drug targets, that can induce the cell mediated immunity (mainly CD4+ and CD8+ IFN-gamma mediated responses) polarized towards a Th1 response. These aspects are important in designing a new vaccine along with the consideration of the candidates with respect to their ability to raise memory response in order to improve the vaccine performance. This review is an effort to identify molecules according to their homology with the host and their ability to be used as potent vaccine candidates. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  4. Nonclinical Development of BCG Replacement Vaccine Candidates

    OpenAIRE

    Bernd Eisele; Martin Gengenbacher; Reginald Kidd; David McCown; Sheldon Morris; Steven Derrick; David Hokey; Dominick Laddy; Rosemary Chang; Megan Fitzpatrick; Leander Grode; Kamalakannan Velmurugan; Kaufmann,Stefan H. E.; John Fulkerson; Brennan, Michael J.

    2013-01-01

    The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both ...

  5. Vaccine candidates for malaria: what's new?

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    Takashima, Eizo; Morita, Masayuki; Tsuboi, Takafumi

    2016-01-01

    Although it is more than a decade since the parasite genome information was obtained, standardized novel genome-wide selection/prioritization strategies for candidacy of malaria vaccine antigens are still sought. In the quest to systematically identify candidates, it is impossible to overemphasize the usefulness of wheat germ cell-free technology in expressing quality proteins for the post-genome vaccine candidate discovery.

  6. Promising new vaccine candidates against Campylobacter in broilers.

    Directory of Open Access Journals (Sweden)

    Marine Meunier

    Full Text Available Campylobacter is the leading cause of human bacterial gastroenteritis in the European Union. Birds represent the main reservoir of the bacteria, and human campylobacteriosis mainly occurs after consuming and/or handling poultry meat. Reducing avian intestinal Campylobacter loads should impact the incidence of human diseases. At the primary production level, several measures have been identified to reach this goal, including vaccination of poultry. Despite many studies, however, no efficient vaccine is currently available. We have recently identified new vaccine candidates using the reverse vaccinology strategy. This study assessed the in vivo immune and protective potential of six newly-identified vaccine antigens. Among the candidates tested on Ross broiler chickens, four (YP_001000437.1, YP_001000562.1, YP_999817.1, and YP_999838.1 significantly reduced cecal Campylobacter loads by between 2 and 4.2 log10 CFU/g, with the concomitant development of a specific humoral immune response. In a second trial, cecal load reductions results were not statistically confirmed despite the induction of a strong immune response. These vaccine candidates need to be further investigated since they present promising features.

  7. Advanced Vaccine Candidates for Lassa Fever

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    Igor S. Lukashevich

    2012-10-01

    Full Text Available Lassa virus (LASV is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF. LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered.

  8. Nonclinical Development of BCG Replacement Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Bernd Eisele

    2013-04-01

    Full Text Available The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  9. Nonclinical Development of BCG Replacement Vaccine Candidates.

    Science.gov (United States)

    Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H E; Fulkerson, John; Brennan, Michael J

    2013-04-16

    The failure of current Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  10. Advanced vaccine candidates for Lassa fever.

    Science.gov (United States)

    Lukashevich, Igor S

    2012-10-29

    Lassa virus (LASV) is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF). LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever) with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered.

  11. Computational Vaccinology: An Important Strategy to Discover New Potential S. mansoni Vaccine Candidates

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    Carina S. Pinheiro

    2011-01-01

    Full Text Available The flatworm Schistosoma mansoni is a blood fluke parasite that causes schistosomiasis, a debilitating disease that occurs throughout the developing world. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control schistosomiasis is through immunization with an antischistosomiasis vaccine combined with drug treatment. Several papers on Schistosoma mansoni vaccine and drug development have been published in the past few years, representing an important field of study. The advent of technologies that allow large-scale studies of genes and proteins had a remarkable impact on the screening of new and potential vaccine candidates in schistosomiasis. In this postgenomic scenario, bioinformatic technologies have emerged as important tools to mine transcriptomic, genomic, and proteomic databases. These new perspectives are leading to a new round of rational vaccine development. Herein, we discuss different strategies to identify potential S. mansoni vaccine candidates using computational vaccinology.

  12. Blood-stage malaria vaccines: post-genome strategies for the identification of novel vaccine candidates.

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    Ntege, Edward H; Takashima, Eizo; Morita, Masayuki; Nagaoka, Hikaru; Ishino, Tomoko; Tsuboi, Takafumi

    2017-08-01

    An efficacious malaria vaccine is necessary to advance the current control measures towards malaria elimination. To-date, only RTS,S/AS01, a leading pre-erythrocytic stage vaccine completed phase 3 trials, but with an efficacy of 28-36% in children, and 18-26% in infants, that waned over time. Blood-stage malaria vaccines protect against disease, and are considered effective targets for the logical design of next generation vaccines to improve the RTS,S field efficacy. Therefore, novel blood-stage vaccine candidate discovery efforts are critical, albeit with several challenges including, high polymorphisms in vaccine antigens, poor understanding of targets of naturally protective immunity, and difficulties in the expression of high AT-rich plasmodial proteins. Areas covered: PubMed ( www.ncbi.nlm.nih.gov/pubmed ) was searched to review the progress and future prospects of malaria vaccine research and development. We focused on post-genome vaccine candidate discovery, malaria vaccine development, sequence diversity, pre-clinical and clinical trials. Expert commentary: Post-genome high-throughput technologies using wheat germ cell-free protein synthesis technology and immuno-profiling with sera from malaria patients with clearly defined outcomes are highlighted to overcome current challenges of malaria vaccine candidate discovery.

  13. A novel live-attenuated vaccine candidate for mayaro Fever.

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    William J Weise

    2014-08-01

    Full Text Available Mayaro virus (MAYV is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

  14. The fimbrial protein FlfA from Gallibacterium anatis is a virulence factor and vaccine candidate

    DEFF Research Database (Denmark)

    Bager, Ragnhild Jørgensen; Nesta, Barbara; Pors, Susanne Elisabeth

    2013-01-01

    The Gram-negative bacterium Gallibacterium anatis is a major cause of salpingitis and peritonitis in egg-laying chickens, leading to decreased egg production worldwide. Widespread multidrug resistance largely prevents treatment of this organism using traditional antimicrobial agents, while antige......-independent vaccine candidate This is the first study describing a fimbrial subunit protein of G. anatis with a clear potential as a vaccine antigen....... antigenic diversity hampers disease prevention by classical vaccines. Thus, insight into its pathogenesis and knowledge about important virulence factors is urgently required. A key event during the colonization and invasion of mucosal surfaces is adherence, and recently, at least three F17-like fimbrial...

  15. Vaccine candidate discovery for the next generation of malaria vaccines.

    Science.gov (United States)

    Tuju, James; Kamuyu, Gathoni; Murungi, Linda M; Osier, Faith H A

    2017-10-01

    Although epidemiological observations, IgG passive transfer studies and experimental infections in humans all support the feasibility of developing highly effective malaria vaccines, the precise antigens that induce protective immunity remain uncertain. Here, we review the methodologies applied to vaccine candidate discovery for Plasmodium falciparum malaria from the pre- to post-genomic era. Probing of genomic and cDNA libraries with antibodies of defined specificities or functional activity predominated the former, whereas reverse vaccinology encompassing high throughput in silico analyses of genomic, transcriptomic or proteomic parasite data sets is the mainstay of the latter. Antibody-guided vaccine design spanned both eras but currently benefits from technological advances facilitating high-throughput screening and downstream applications. We make the case that although we have exponentially increased our ability to identify numerous potential vaccine candidates in a relatively short space of time, a significant bottleneck remains in their validation and prioritization for evaluation in clinical trials. Longitudinal cohort studies provide supportive evidence but results are often conflicting between studies. Demonstration of antigen-specific antibody function is valuable but the relative importance of one mechanism over another with regards to protection remains undetermined. Animal models offer useful insights but may not accurately reflect human disease. Challenge studies in humans are preferable but prohibitively expensive. In the absence of reliable correlates of protection, suitable animal models or a better understanding of the mechanisms underlying protective immunity in humans, vaccine candidate discovery per se may not be sufficient to provide the paradigm shift necessary to develop the next generation of highly effective subunit malaria vaccines. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

  16. Japanese encephalitis virus vaccine candidates generated by chimerization with dengue virus type 4.

    Science.gov (United States)

    Gromowski, Gregory D; Firestone, Cai-Yen; Hanson, Christopher T; Whitehead, Stephen S

    2014-05-23

    Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide and vaccination is one of the most effective ways to prevent disease. A suitable live-attenuated JEV vaccine could be formulated with a live-attenuated tetravalent dengue vaccine for the control of these viruses in endemic areas. Toward this goal, we generated chimeric virus vaccine candidates by replacing the precursor membrane (prM) and envelope (E) protein structural genes of recombinant dengue virus type 4 (rDEN4) or attenuated vaccine candidate rDEN4Δ30 with those of wild-type JEV strain India/78. Mutations were engineered in E, NS3 and NS4B protein genes to improve replication in Vero cells. The chimeric viruses were attenuated in mice and some elicited modest but protective levels of immunity after a single dose. One particular chimeric virus, bearing E protein mutation Q264H, replicated to higher titer in tissue culture and was significantly more immunogenic in mice. The results are compared with live-attenuated JEV vaccine strain SA14-14-2. Published by Elsevier Ltd.

  17. In silico identification of vaccine candidates against Klebsiella oxytoca.

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    Talukdar, Sandipan; Bayan, Udeshna; Saikia, Kandarpa Kr

    2017-08-01

    Klebsiella oxytoca causes several diseases in immunocompromised as well as healthy individuals. Increasing resistance to a number of antibiotics makes treatment options limited. Prevention using vaccine could be an important solution to get rid of infections caused by Klebsiella oxytoca. In recent time, genome based approaches have contributed significantly in vaccine development. Our aim was to identify the most conserved and immunogenic antigens that can be considered as potential vaccine candidates. KEGG database was used to find out pathways unique to the bacteria. Subcellular localization of the protein sequences taken from the selected 36 pathways were predicted using PSORTb v3.0.2 and CELLO v2.5. Prediction of B cell epitope and the probability of the antigenicity were evaluated by using IEDB and Vaxijen respectively. BLASTp was done to find out the similarity of the selected proteins with the human proteome. Proteins failing to comply with the set parameters were filtered at each step. Finally, we identified 6 surface exposed proteins as potential vaccine candidates against Klebsiella oxytoca. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Generation of a parvovirus B19 vaccine candidate.

    Science.gov (United States)

    Chandramouli, Sumana; Medina-Selby, Angelica; Coit, Doris; Schaefer, Mary; Spencer, Terika; Brito, Luis A; Zhang, Pu; Otten, Gillis; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Settembre, Ethan C

    2013-08-20

    Parvovirus B19 is the causative agent of fifth disease in children, aplastic crisis in those with blood dyscrasias, and hydrops fetalis. Previous parvovirus B19 virus-like-particle (VLP) vaccine candidates were produced by co-infection of insect cells with two baculoviruses, one expressing wild-type VP1 and the other expressing VP2. In humans, the VLPs were immunogenic but reactogenic. We have developed new VLP-based parvovirus B19 vaccine candidates, produced by co-expressing VP2 and either wild-type VP1 or phospholipase-negative VP1 in a regulated ratio from a single plasmid in Saccharomyces cerevisiae. These VLPs are expressed efficiently, are very homogeneous, and can be highly purified. Although VP2 alone can form VLPs, in mouse immunizations, VP1 and the adjuvant MF59 are required to elicit a neutralizing response. Wild-type VLPs and those with phospholipase-negative VP1 are equivalently potent. The purity, homogeneity, yeast origin, and lack of phospholipase activity of these VLPs address potential causes of previously observed reactogenicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. KSAC, the first defined polyprotein vaccine candidate for visceral leishmaniasis.

    Science.gov (United States)

    Goto, Yasuyuki; Bhatia, Ajay; Raman, Vanitha S; Liang, Hong; Mohamath, Raodoh; Picone, Alessandro F; Vidal, Silvia E Z; Vedvick, Thomas S; Howard, Randall F; Reed, Steven G

    2011-07-01

    A subunit vaccine using a defined antigen(s) may be one effective solution for controlling leishmaniasis. Because of genetic diversity in target populations, including both dogs and humans, a multiple-antigen vaccine will likely be essential. However, the cost of a vaccine to be used in developing countries must be considered. We describe herein a multiantigen vaccine candidate comprised of antigens known to be protective in animal models, including dogs, and to be recognized by humans immune to visceral leishmaniasis. The polyprotein (KSAC) formulated with monophosphoryl lipid A, a widely used adjuvant in human vaccines, was found to be immunogenic and capable of inducing protection against Leishmania infantum, responsible for human and canine visceral leishmaniasis, and against L. major, responsible for cutaneous leishmaniasis. The results demonstrate the feasibility of producing a practical, cost-effective leishmaniasis vaccine capable of protecting both humans and dogs against multiple Leishmania species.

  20. Evaluation of Lethal Giant Larvae as a Schistosomiasis Vaccine Candidate

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    Yufan Cao

    2016-01-01

    Full Text Available Schistosomiasis is a neglected tropical disease of humans, and it is considered to be the second most devastating parasitic disease after malaria. Eggs produced by normally developed female worms are important in the transmission of the parasite, and they responsible for the pathogenesis of schistosomiasis. The tumor suppressor gene lethal giant larvae (lgl has an essential function in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. In our earlier study, downregulation of the lgl gene induced a significant reduction in the egg hatching rate of Schistosoma japonicum (Sj eggs. In this study, the Sjlgl gene was used as a vaccine candidate against schistosomiasis, and vaccination achieved and maintained a stable reduction of the egg hatching rate, which is consistent with previous studies, in addition to reducing the worm burden and liver egg burden in some trials.

  1. Extracellular vesicles secreted by Schistosoma mansoni contain protein vaccine candidates.

    Science.gov (United States)

    Sotillo, Javier; Pearson, Mark; Potriquet, Jeremy; Becker, Luke; Pickering, Darren; Mulvenna, Jason; Loukas, Alex

    2016-01-01

    Herein we show for the first time that Schistosoma mansoni adult worms secrete exosome-like extracellular vesicles ranging from 50 to 130nm in size. Extracellular vesicles were collected from the excretory/secretory products of cultured adult flukes and purified by Optiprep density gradient, resulting in highly pure extracellular vesicle preparations as confirmed by transmission electron microscopy and Nanosight tracking analysis. Extracellular vesicle proteomic analysis showed numerous known vaccine candidates, potential virulence factors and molecules implicated in feeding. These findings provide new avenues for the exploration of host-schistosome interactions and offer a potential mechanism by which some vaccine antigens exert their protective efficacy. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Immune subdominant antigens as vaccine candidates against Mycobacterium tuberculosis.

    Science.gov (United States)

    Orr, Mark T; Ireton, Gregory C; Beebe, Elyse A; Huang, Po-Wei D; Reese, Valerie A; Argilla, David; Coler, Rhea N; Reed, Steven G

    2014-09-15

    Unlike most pathogens, many of the immunodominant epitopes from Mycobacterium tuberculosis are under purifying selection. This startling finding suggests that M. tuberculosis may gain an evolutionary advantage by focusing the human immune response against selected proteins. Although the implications of this to vaccine development are incompletely understood, it has been suggested that inducing strong Th1 responses against Ags that are only weakly recognized during natural infection may circumvent this evasion strategy and increase vaccine efficacy. To test the hypothesis that subdominant and/or weak M. tuberculosis Ags are viable vaccine candidates and to avoid complications because of differential immunodominance hierarchies in humans and experimental animals, we defined the immunodominance hierarchy of 84 recombinant M. tuberculosis proteins in experimentally infected mice. We then combined a subset of these dominant or subdominant Ags with a Th1 augmenting adjuvant, glucopyranosyl lipid adjuvant in stable emulsion, to assess their immunogenicity in M. tuberculosis-naive animals and protective efficacy as measured by a reduction in lung M. tuberculosis burden of infected animals after prophylactic vaccination. We observed little correlation between immunodominance during primary M. tuberculosis infection and vaccine efficacy, confirming the hypothesis that subdominant and weakly antigenic M. tuberculosis proteins are viable vaccine candidates. Finally, we developed two fusion proteins based on strongly protective subdominant fusion proteins. When paired with the glucopyranosyl lipid adjuvant in stable emulsion, these fusion proteins elicited robust Th1 responses and limited pulmonary M. tuberculosis for at least 6 wk postinfection with a single immunization. These findings expand the potential pool of M. tuberculosis proteins that can be considered as vaccine Ag candidates. Copyright © 2014 by The American Association of Immunologists, Inc.

  3. Rotavirus VP6 preparations as a non-replicating vaccine candidates.

    Science.gov (United States)

    Jalilvand, Somayeh; Marashi, Sayed Mahdi; Shoja, Zabihollah

    2015-06-26

    Rotavirus (RV) structural proteins VP4 and VP7, located on the surface of viral particles, elicit neutralizing antibodies (Abs) and are therefore considered to be important components of RV vaccines. However, despite inducing neutralizing Abs, limits of cross-neutralizing activity and lack of full correlation with protection limit the usefulness of these proteins as protective agents against RV disease. VP6 protein, which forms the middle layer of RV particles, is discussed as an alternative vaccine candidate since it can induce cross-protective immune responses against different RV strains although the Ab raised is not neutralizing. This report reviews different functions of VP6 that can lead to considering it as an alternative vaccine against RV disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Ascaris suum enolase is a potential vaccine candidate against ascariasis.

    Science.gov (United States)

    Chen, Ning; Yuan, Zi-Guo; Xu, Min-Jun; Zhou, Dong-Hui; Zhang, Xiu-Xiang; Zhang, Yan-Zhong; Wang, Xiao-Wei; Yan, Chao; Lin, Rui-Qing; Zhu, Xing-Quan

    2012-05-14

    Ascariasis caused by Ascaris is the most common parasite problem in humans and pigs worldwide. No vaccines are available for the prevention of Ascaris infections. In the present study, the gene encoding Ascaris suum enolase (As-enol-1) was amplified, cloned and sequenced. Amino acid sequence alignment indicated that As-enol-1 was highly conserved between different nematodes and shared the highest identity (87%) with enolase from Anisakis simplex s.l. The recombinant pVAX-Enol was successfully expressed in Marc-145 cells. The ability of the pVAX-Enol for inducing immune protective responses against challenge infection with A. suum L3 was evaluated in Kunming mice. The immune response was evaluated by lymphoproliferative assay, cytokine and antibody measurements, and the reduction rate of recovery larvae. The results showed that the mice immunized with pVAX-Enol developed a high level of specific antibody responses against A. suum, a strong lymphoproliferative response, and significant levels of IFN-γ, IL-2, IL-4 and IL-10 production, compared with the other groups immunized with empty plasmid or blank controls, respectively. There was a 61.13% reduction (Psuum enolase is a potential vaccine candidate against A. suum infection. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  5. Novel approaches to identify protective malaria vaccine candidates

    Directory of Open Access Journals (Sweden)

    Wan Ni eChia

    2014-11-01

    Full Text Available Efforts to develop vaccines against malaria have been the focus of substantial research activities for decades. Several categories of candidate vaccines are currently being developed for protection against malaria, based on antigens corresponding to the pre-erythrocytic, blood-stage or sexual stages of the parasite. Long lasting sterile protection from Plasmodium falciparum sporozoite challenge has been observed in human following vaccination with whole parasite formulations, clearly demonstrating that a protective immune response targeting predominantly the pre-erythrocytic stages can develop against malaria. However, most of vaccine candidates currently being investigated, which are mostly subunits vaccines, have not been able to induce substantial (>50% protection thus far. This is due to the fact that the antigens responsible for protection against the different parasite stages are still yet to be known and relevant correlates of protection have remained elusive. For a vaccine to be developed in a timely manner, novel approaches are required. In this article, we review the novel approaches that have been developed to identify the antigens for the development of an effective malaria vaccine.

  6. Identification of Novel Vaccine Candidates against Campylobacter through Reverse Vaccinology

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    Marine Meunier

    2016-01-01

    Full Text Available Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union. Human cases are mainly due to Campylobacter jejuni or Campylobacter coli, and contamination is associated with the handling and/or consumption of poultry meat. In fact, poultry constitutes the bacteria’s main reservoir. A promising way of decreasing the incidence of campylobacteriosis in humans would be to decrease avian colonization. Poultry vaccination is of potential for this purpose. However, despite many studies, there is currently no vaccine available on the market to reduce the intestinal Campylobacter load in chickens. It is essential to identify and characterize new vaccine antigens. This study applied the reverse vaccinology approach to detect new vaccine candidates. The main criteria used to select immune proteins were localization, antigenicity, and number of B-epitopes. Fourteen proteins were identified as potential vaccine antigens. In vitro and in vivo experiments now need to be performed to validate the immune and protective power of these newly identified antigens.

  7. Study on Theileria lestoquardi antigens as potential vaccine candidates.

    Science.gov (United States)

    Namavari, Mehdi; Hosseini, Mohammad H; Seghatoleslam, Atefeh; Lotfi, Mohsen; Shirazi, Ali; Sparagano, Olivier A E

    2008-12-01

    Theileria lestoquardi is the causative agent of malignant theileriosis of sheep and goats, causing morbidity and mortality in these animals worldwide. Western blot analysis based on T. lestoquardi schizont antigens was carried out using sera collected from Iranian sheep, which had been immunized with T. lestoquardi schizont-infected cells. The results of Western blot analysis demonstrated that schizont-immunized animals produced antibodies reacting with protein bands at 73, 42, 20, 14, and 12 kDa. Comparison of the results of the current Western blotting test with earlier studies of Theileria spp. revealed two immunogenic schizont proteins with molecular weights of 73 and 42 kDa shared between T. annulata and T. lestoquardi. Two other proteins with molecular weights of 14 and 12 kDa have not been previously found in other Theileria species. Our results suggest that the 73-kDa protein could be a potential vaccine candidate and that the 14- and 12-kDa proteins could be considered as diagnostic antigens.

  8. Identification of peptidoglycan-associated proteins as vaccine candidates for enterococcal infections.

    Directory of Open Access Journals (Sweden)

    Felipe Romero-Saavedra

    Full Text Available Infections by opportunistic bacteria have significant contributions to morbidity and mortality of hospitalized patients and also lead to high expenses in healthcare. In this setting, one of the major clinical problems is caused by Gram-positive bacteria such as enterococci and staphylococci. In this study we extract, purify, identify and characterize immunogenic surface-exposed proteins present in the vancomycin resistant enterococci (VRE strain Enterococcus faecium E155 using three different extraction methods: trypsin shaving, biotinylation and elution at high pH. Proteomic profiling was carried out by gel-free and gel-nanoLC-MS/MS analyses. The total proteins found with each method were 390 by the trypsin shaving, 329 by the elution at high pH, and 45 using biotinylation. An exclusively extracytoplasmic localization was predicted in 39 (10% by trypsin shaving, in 47 (15% by elution at high pH, and 27 (63% by biotinylation. Comparison between the three extraction methods by Venn diagram and subcellular localization predictors (CELLO v.2.5 and Gpos-mPLoc allowed us to identify six proteins that are most likely surface-exposed: the SCP-like extracellular protein, a low affinity penicillin-binding protein 5 (PBP5, a basic membrane lipoprotein, a peptidoglycan-binding protein LysM (LysM, a D-alanyl-D-alanine carboxypeptidase (DdcP and the peptidyl-prolyl cis-trans isomerase (PpiC. Due to their close relationship with the peptidoglycan, we chose PBP5, LysM, DdcP and PpiC to test their potential as vaccine candidates. These putative surface-exposed proteins were overexpressed in Escherichia coli and purified. Rabbit polyclonal antibodies raised against the purified proteins were able to induce specific opsonic antibodies that mediated killing of the homologous strain E. faecium E155 as well as clinical strains E. faecium E1162, Enterococcus faecalis 12030, type 2 and type 5. Passive immunization with rabbit antibodies raised against these proteins

  9. Attenuated strains of Mycobacterium avium subspecies paratuberculosis as vaccine candidates against Johne's disease.

    Science.gov (United States)

    Settles, Erik W; Kink, John A; Talaat, Adel

    2014-04-11

    Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease in ruminants. Johne's disease has a severe economic impact on the dairy industry in the USA and worldwide. In an effort to combat this disease, we screened several transposon mutants that were attenuated in the murine model of paratuberculosis for the potential use as live attenuated vaccines. Using the murine model, two vaccine candidates (pgs1360, pgs3965 with mutations of fabG2_2 and umaA1, respectively) were at or below the limit of detection for tissue colonization suggesting their low level persistence and hence safety. Prior to challenge, both candidates induced a M. paratuberculosis-specific IFN-γ, an indication of eliciting cell-mediated immunity. Following challenge with a virulent strain of M. paratuberculosis, the two vaccine candidates significantly reduced bacterial colonization in organs with reduced histological scores compared to control animals. In addition, one of the vaccine candidates (pgs3965) also induced IL-17a, a cytokine associated with protective immunity in mycobacterial infection. Our analysis suggested that the pgs3965 vaccine candidate is a potential live-attenuated vaccine that could be tested further in ruminant models of paratuberculosis. The analysis also validated our screening strategy to identify effective vaccine candidates against intracellular pathogens. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Genetic Stability of Parainfluenza Virus 5-Vectored Human Respiratory Syncytial Virus Vaccine Candidates after In Vitro and In Vivo Passage.

    Science.gov (United States)

    Phan, Shannon I; Adam, Carolyn M; Chen, Zhenhai; Citron, Michael; Liang, Xiaoping; Espeseth, Amy S; Wang, Dai; He, Biao

    2017-10-01

    Human respiratory syncytial virus (RSV) is the leading etiologic agent of lower respiratory tract infections in children, but no licensed vaccine exists. Previously, we developed two parainfluenza virus 5 (PIV5)-based RSV vaccine candidates that protect mice against RSV challenge. PIV5 was engineered to express either the RSV fusion protein (F) or the RSV major attachment glycoprotein (G) between the hemagglutinin-neuraminidase (HN) and RNA-dependent RNA polymerase (L) genes of the PIV5 genome [PIV5-RSV-F (HN-L) and PIV5-RSV-G (HN-L), respectively]. To investigate the stability of the vaccine candidates in vitro, they were passaged in Vero cells at high and low multiplicities of infection (MOIs) for 11 generations and the genome sequences, growth kinetics, and protein expression of the resulting viruses were compared with those of the parent viruses. Sporadic mutations were detected in the consensus sequences of the viruses after high-MOI passages, and mutation rates increased under low-MOI-passage conditions. None of the mutations abolished antigen expression. Increased numbers of mutations correlated with increased growth rates in vitro, indicating that the viruses evolved through the course of serial passages. We also examined the in vivo stability of the vaccine candidates after a single passage in African green monkeys. No mutations were detected in the consensus sequences of viruses collected from the bronchoalveolar lavage (BAL) fluid of the animals. In vivo, mutations in RSV G and PIV5 L were found in individual isolates of PIV5-RSV-G (HN-L), but plaque isolates of PIV5-RSV-F (HN-L) had no mutations. To improve upon the PIV5-RSV-F (HN-L) candidate, additional vaccine candidates were generated in which the gene for RSV F was inserted into earlier positions in the PIV5 genome. These insertions did not negatively impact the sequence stability of the vaccine candidates. The results suggest that the RSV F and G gene insertions are stable in the PIV5 genome

  12. Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate

    DEFF Research Database (Denmark)

    Esen, Meral; Kremsner, Peter G; Schleucher, Regina

    2009-01-01

    Malaria is a major public health problem in Sub-Saharan Africa. In highly endemic regions infants, children and pregnant women are mostly affected. An effective malaria vaccine would complement existing malaria control strategies because it can be integrated in existing immunization programs easily....... Here we present the results of the first phase Ia clinical trial of GMZ2 adjuvanted in aluminium hydroxide. GMZ2 is a malaria vaccine candidate, designed upon the rationale to induce immune responses against asexual blood stages of Plasmodium falciparum similar to those encountered in semi...... is a safe and immunogenic malaria vaccine candidate suitable for further clinical development....

  13. Efficacy of chimeric Pestivirus vaccine candidates against Classical Swine Fever: protection and DIVA characteristics

    NARCIS (Netherlands)

    Eble, P.L.; Geurts, Y.; Quak, J.; Moonen-Leusen, H.W.M.; Blome, S.; Hofmann, M.A.; Koenen, F.; Beer, M.; Loeffen, W.L.A.

    2013-01-01

    Currently no live DIVA (Differentiating Infected from Vaccinated Animals) vaccines against classical swine fever (CSF) are available. The aim of this study was to investigate whether chimeric pestivirus vaccine candidates (CP7_E2alf, Flc11 and Flc9) are able to protect pigs against clinical signs,

  14. A full-length Plasmodium falciparum recombinant circumsporozoite protein expressed by Pseudomonas fluorescens platform as a malaria vaccine candidate.

    Directory of Open Access Journals (Sweden)

    Amy R Noe

    Full Text Available The circumsporozoite protein (CSP of Plasmodium falciparum is a major surface protein, which forms a dense coat on the sporozoite's surface. Preclinical research on CSP and clinical evaluation of a CSP fragment-based RTS, S/AS01 vaccine have demonstrated a modest degree of protection against P. falciparum, mediated in part by humoral immunity and in part by cell-mediated immunity. Given the partial protective efficacy of the RTS, S/AS01 vaccine in a recent Phase 3 trial, further improvement of CSP-based vaccines is crucial. In this report, we describe the preclinical development of a full-length, recombinant CSP (rCSP-based vaccine candidate against P. falciparum malaria suitable for current Good Manufacturing Practice (cGMP production. Utilizing a novel high-throughput Pseudomonas fluorescens expression platform, we demonstrated greater efficacy of full-length rCSP as compared to N-terminally truncated versions, rapidly down-selected a promising lead vaccine candidate, and developed a high-yield purification process to express immunologically active, intact antigen for clinical trial material production. The rCSP, when formulated with various adjuvants, induced antigen-specific antibody responses as measured by enzyme-linked immunosorbent assay (ELISA and immunofluorescence assay (IFA, as well as CD4+ T-cell responses as determined by ELISpot. The adjuvanted rCSP vaccine conferred protection in mice when challenged with transgenic P. berghei sporozoites containing the P. falciparum repeat region of CSP. Furthermore, heterologous prime/boost regimens with adjuvanted rCSP and an adenovirus type 35-vectored CSP (Ad35CS showed modest improvements in eliciting CSP-specific T-cell responses and anti-malarial protection, depending on the order of vaccine delivery. Collectively, these data support the importance of further clinical development of adjuvanted rCSP, either as a stand-alone product or as one of the components in a heterologous prime

  15. Characterization of Two Metal Binding Lipoproteins as Vaccine Candidates for Enterococcal Infections.

    Science.gov (United States)

    Romero-Saavedra, Felipe; Laverde, Diana; Budin-Verneuil, Aurélie; Muller, Cécile; Bernay, Benoit; Benachour, Abdellah; Hartke, Axel; Huebner, Johannes

    2015-01-01

    Enterococcus faecium and faecalis are Gram-positive opportunistic pathogens that have become leading causes of nosocomial infections over the last decades. Especially multidrug resistant enterococci have become a challenging clinical problem worldwide. Therefore, new treatment options are needed and the identification of alternative targets for vaccine development has emerged as a feasible alternative to fight the infections caused by these pathogens. We extrapolate the transcriptomic data from a mice peritonitis infection model in E. faecalis to identify putative up-regulated surface proteins under infection conditions in E. faecium. After the bionformatic analyses two metal binding lipoproteins were identified to have a high homology (>72%) between the two species, the manganese ABC transporter substrate-binding lipoprotein (PsaAfm,) and the zinc ABC transporter substrate-binding lipoprotein (AdcAfm). These candidate lipoproteins were overexpressed in Escherichia coli and purified. The recombinant proteins were used to produce rabbit polyclonal antibodies that were able to induce specific opsonic antibodies that mediated killing of the homologous strain E. faecium E155 as well as clinical strains E. faecium E1162, Enterococcus faecalis 12030, type 2 and type 5. Mice were passively immunized with the antibodies raised against recombinant lipoproteins, showing significant reduction of colony counts in mice livers after the bacterial challenge and demonstrating the efficacy of these metal binding lipoproteins as promising vaccine candidates to treat infections caused by these enterococcal pathogens. Overall, our results demonstrate that these two metal binding lipoproteins elicited specific, opsonic and protective antibodies, with an extensive cross-reactivity and serotype-independent coverage among these two important nocosomial pathogens. Pointing these two protein antigens as promising immunogens, that can be used as single components or as carrier proteins

  16. Characterization of Two Metal Binding Lipoproteins as Vaccine Candidates for Enterococcal Infections.

    Directory of Open Access Journals (Sweden)

    Felipe Romero-Saavedra

    Full Text Available Enterococcus faecium and faecalis are Gram-positive opportunistic pathogens that have become leading causes of nosocomial infections over the last decades. Especially multidrug resistant enterococci have become a challenging clinical problem worldwide. Therefore, new treatment options are needed and the identification of alternative targets for vaccine development has emerged as a feasible alternative to fight the infections caused by these pathogens.We extrapolate the transcriptomic data from a mice peritonitis infection model in E. faecalis to identify putative up-regulated surface proteins under infection conditions in E. faecium. After the bionformatic analyses two metal binding lipoproteins were identified to have a high homology (>72% between the two species, the manganese ABC transporter substrate-binding lipoprotein (PsaAfm, and the zinc ABC transporter substrate-binding lipoprotein (AdcAfm. These candidate lipoproteins were overexpressed in Escherichia coli and purified. The recombinant proteins were used to produce rabbit polyclonal antibodies that were able to induce specific opsonic antibodies that mediated killing of the homologous strain E. faecium E155 as well as clinical strains E. faecium E1162, Enterococcus faecalis 12030, type 2 and type 5. Mice were passively immunized with the antibodies raised against recombinant lipoproteins, showing significant reduction of colony counts in mice livers after the bacterial challenge and demonstrating the efficacy of these metal binding lipoproteins as promising vaccine candidates to treat infections caused by these enterococcal pathogens.Overall, our results demonstrate that these two metal binding lipoproteins elicited specific, opsonic and protective antibodies, with an extensive cross-reactivity and serotype-independent coverage among these two important nocosomial pathogens. Pointing these two protein antigens as promising immunogens, that can be used as single components or as carrier

  17. In-silico Hierarchical Approach for the Identification of Potential Universal Vaccine Candidates (PUVCs) from Neisseria gonorrhoeae.

    Science.gov (United States)

    Jain, Ravi; Sonkar, Subash C; Chaudhry, Uma; Bala, Manju; Saluja, Daman

    2016-12-07

    Resistance to the currently recommended extended-spectrum cephalosporins, which is used to treat Gonorrhea, is increasing continuously and leading to a threat of untreatable infection. It is, therefore, becoming extremely essential to search for new therapeutic strategies to control Gonorrhea. Vaccination may be considered as an effective control measure to control this disease, which is caused by Neisseria gonorrhoeae. In-silico hierarchical approach was used to help identify candidate proteins of N. gonorrhoeae that might contribute significantly in vaccine research. In contrast to the conventional vaccine research which requires at least 10-12 years, the present approach would reduce the time period drastically and help to identify Potential Universal Vaccine Candidates (PUVCs). These proteins were further analyzed for the presence of T-cell and linear B-cell epitopes, by using HLAPred and ABCpred servers respectively, in order to facilitate the identification of Multi Epitope Peptide Vaccine Constructs. We have identified 23 non-host candidate proteins, using the proteomic information of four sequenced strains of N. gonorrhoeae namely FA 1090, TCDC_NG08107, NCCP11945 and MS11 and labeled them as PUVCs. Since all these identified 23 PUVCs contained both T cell and B cell epitopes, these have been further reiterated as PUVCs which could be used as promising leads for vaccine development. This hierarchical approach is the first comprehensive study to identify potential vaccine candidates which once utilized for vaccine development would surely serve as promising tools for effective control of Gonorrhea. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Reduced antibody responses against Plasmodium falciparum vaccine candidate antigens in the presence of Trichuris trichiura

    DEFF Research Database (Denmark)

    Esen, Meral; Mordmüller, Benjamin; de Salazar, Pablo Martinez

    2012-01-01

    BACKGROUND: Helminth infections are highly prevalent in the tropics and may have an effect on immune responses to vaccines due to their immunomodulatory effect. The prevalence of helminth infections in young children, the target group for malaria and most other vaccines, is high. Therefore we...... assessed the influence of helminth infection on vaccine-induced immune responses in a phase I clinical trial of the malaria vaccine candidate GMZ2. METHODS: Twenty Gabonese preschool-age children were vaccinated with GMZ2, a blood stage malaria vaccine candidate. Humoral immune response against the vaccine...... antigens and parasitological status were assessed. Vaccine-specific antibody concentrations and memory B-cell numbers were compared in worm infected and non-infected participants. RESULTS: Antibody response to GMZ2 was 3.4-fold (95% confidence interval: 1.6, 7.4) higher in Trichuris trichiura negative...

  19. Characterization nanoparticles-based vaccines and vaccine candidates: a Transmission Electron Microscopy study

    Directory of Open Access Journals (Sweden)

    I. Menéndez I

    2016-05-01

    Full Text Available Transmission Electron Microscopy (TEM is a valuable tool for the biotech industry. This paper summarizes some of the contributions of MET in the characterization of the recombinant antigens are part of vaccines or vaccine candidates obtained in the CIGB. It mentions the use of complementary techniques MET (Negative staining, and immunoelectron that enhance visualization and ultrastructural characterization of the recombinant proteins obtained by Genetic Engineering.

  20. Development of a BCG challenge model for the testing of vaccine candidates against tuberculosis in cattle.

    Science.gov (United States)

    Villarreal-Ramos, Bernardo; Berg, Stefan; Chamberlain, Laura; McShane, Helen; Hewinson, R Glyn; Clifford, Derek; Vordermeier, Martin

    2014-09-29

    Vaccination is being considered as part of a sustainable strategy for the control of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle against BTB. However, BCG confers partial protection against BTB and therefore, there is a need to develop improved vaccines. BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates. One indicator of the induction of protective responses would be the ability of the host's immune response to control/kill mycobacteria. In this work we have evaluated an intranodal BCG challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses. To our knowledge, this is the first such report. Whilst BCG only confers partial protection, it is still the standard against which other vaccines are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu counts than naïve cattle at 14 and 21 days after intranodal challenge with BCG (Tokyo strain). This model could help prioritize competing TB vaccine candidates and exploration of primary and secondary immune responses to mycobacteria. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  1. Theiler's murine encephalomyelitis virus as a vaccine candidate for immunotherapy.

    Science.gov (United States)

    Pavelko, Kevin D; Girtman, Megan A; Mitsunaga, Yoshihiro; Mendez-Fernandez, Yanice V; Bell, Michael P; Hansen, Michael J; Allen, Kathleen S; Rodriguez, Moses; Pease, Larry R

    2011-01-01

    The induction of sterilizing T-cell responses to tumors is a major goal in the development of T-cell vaccines for treating cancer. Although specific components of anti-viral CD8+ immunity are well characterized, we still lack the ability to mimic viral CD8+ T-cell responses in therapeutic settings for treating cancers. Infection with the picornavirus Theiler's murine encephalomyelitis virus (TMEV) induces a strong sterilizing CD8+ T-cell response. In the absence of sterilizing immunity, the virus causes a persistent infection. We capitalized on the ability of TMEV to induce strong cellular immunity even under conditions of immune deficiency by modifying the virus to evaluate its potential as a T-cell vaccine. The introduction of defined CD8+ T-cell epitopes into the leader sequence of the TMEV genome generates an attenuated vaccine strain that can efficiently drive CD8+ T-cell responses to the targeted antigen. This virus activates T-cells in a manner that is capable of inducing targeted tissue damage and glucose dysregulation in an adoptive T-cell transfer model of diabetes mellitus. As a therapeutic vaccine for the treatment of established melanoma, epitope-modified TMEV can induce strong cytotoxic T-cell responses and promote infiltration of the T-cells into established tumors, ultimately leading to a delay in tumor growth and improved survival of vaccinated animals. We propose that epitope-modified TMEV is an excellent candidate for further development as a human T-cell vaccine for use in immunotherapy.

  2. Characterisation of tropomyosin and paramyosin as vaccine candidate molecules for the poultry red mite, Dermanyssus gallinae.

    Science.gov (United States)

    Wright, Harry W; Bartley, Kathryn; Huntley, John F; Nisbet, Alasdair J

    2016-10-12

    Dermanyssus gallinae is the most economically important haematophagous ectoparasite in commercial egg laying flocks worldwide. It infests the hens during the night where it causes irritation leading to restlessness, pecking and in extreme cases anaemia and increased cannibalism. Due to an increase in the occurrence of acaricide-resistant D. gallinae populations, new control strategies are required and vaccination may offer a sustainable alternative to acaricides. In this study, recombinant forms of D. gallinae tropomyosin (Der g 10) and paramyosin (Der g 11) were produced, characterised and tested as vaccine candidate molecules. The D. gallinae paramyosin (Der g 11) coding sequence was characterised and recombinant versions of Der g 11 and D. gallinae tropomyosin (Der g 10) were produced. Hens were immunised with the recombinant proteins and the resulting antibodies were fed to D. gallinae and mite mortality evaluated. Sections of mites were probed with anti- Der g 11 and Der g 10 antibodies to identify the tissue distribution of these protein in D. gallinae. The entire coding sequence of Der g 11 was 2,622 bp encoding 874 amino acid residues. Immunohistochemical staining of mite sections revealed that Der g 10 and Der g 11 were located throughout D. gallinae tissues. In phylogenetic analyses of these proteins both clustered with orthologues from tick species rather than with orthologues from astigmatid mites. Antibodies raised in hens against recombinant forms of these proteins significantly increased D. gallinae mortality, by 19 % for Der g 10 (P < 0.001) and by 23 % for Der g 11 (P = 0.009) when fed to the mites using an in vitro feeding device. This study has shown that Der g 10 and Der g 11 were located ubiquitously throughout D. gallinae and that antibodies raised against recombinant versions of these proteins can be used to significantly increase D. gallinae mortality in an in vitro feeding assay. When comparing archived data for all recombinant

  3. Immunogenicity of multi-epitope-based vaccine candidates administered with the adjuvant Gp96 against rabies.

    Science.gov (United States)

    Niu, Yange; Liu, Ye; Yang, Limin; Qu, Hongren; Zhao, Jingyi; Hu, Rongliang; Li, Jing; Liu, Wenjun

    2016-04-01

    Rabies, a zoonotic disease, causes > 55,000 human deaths globally and results in at least 500 million dollars in losses every year. The currently available rabies vaccines are mainly inactivated and attenuated vaccines, which have been linked with clinical diseases in animals. Thus, a rabies vaccine with high safety and efficacy is urgently needed. Peptide vaccines are known for their low cost, simple production procedures and high safety. Therefore, in this study, we examined the efficacy of multi-epitope-based vaccine candidates against rabies virus. The ability of various peptides to induce epitope-specific responses was examined, and the two peptides that possessed the highest antigenicity and conservation, i.e., AR16 and hPAB, were coated with adjuvant canine-Gp96 and used to prepare vaccines. The peptides were prepared as an emulsion of oil in water (O/W) to create three batches of bivalent vaccine products. The vaccine candidates possessed high safety. Virus neutralizing antibodies were detected on the day 14 after the first immunization in mice and beagles, reaching 5-6 IU/mL in mice and 7-9 IU/mL in beagles by day 28. The protective efficacy of the vaccine candidates was about 70%-80% in mice challenged by a virulent strain of rabies virus. Thus, a novel multi-epitope-based rabies vaccine with Gp96 as an adjuvant was developed and validated in mice and dogs. Our results suggest that synthetic peptides hold promise for the development of novel vaccines against rabies.

  4. Recombinant baculovirus associated with bilosomes as an oral vaccine candidate against HEV71 infection in mice.

    Directory of Open Access Journals (Sweden)

    Balraj Premanand

    Full Text Available BACKGROUND: Human enterovirus 71 (HEV71 is one of the major pathogen responsible for hand, foot and mouth disease (HFMD. Currently no effective vaccine or antiviral drugs are available. Like poliovirus, EV71 is transmitted mainly by the feco-oral route. To date the majority of the studied EV71 vaccine candidates are administered parenterally. Injectable vaccines induce good systemic immunity but mucosal responses are often unsatisfactory, whereas mucosal vaccines provide both systemic and mucosal immunity. Therefore, oral immunization appears to be an attractive alternative to parenteral immunization. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we studied the efficacy of an orally administered vaccine candidate developed using recombinant baculovirus displaying VP1 (Bac-VP1 in a murine model. Gastrointestinal delivery of Bac-VP1 significantly induced VP1-specific humoral (IgG and mucosal (IgA immune responses. Further, we studied the efficacy of the Bac-VP1 associated with bilosomes and observed that the Bac-VP1 associated with bilosomes elicited significantly higher immune responses compared to bilosomes non-associated with Bac-VP1. However, mice immunized subcutaneously with live Bac-VP1 had significantly enhanced VP1 specific serum IgG levels and higher neutralizing antibody titers compared with mice orally immunized with live Bac-VP1 alone or associated with bilosomes. CONCLUSION: Bilosomes have been shown to possess inherent adjuvant properties when associated with antigen. Therefore Bac-VP1 with bilosomes could be a promising oral vaccine candidate against EV71 infections. Thus, Bac-VP1 loaded bilosomes may provide a needle free, painless approach for immunization against EV71, thereby increasing patient compliance and consequently increasing vaccination coverage.

  5. Discovery of Novel Leptospirosis Vaccine Candidates Using Reverse and Structural Vaccinology

    Directory of Open Access Journals (Sweden)

    Alan John Alexander McBride

    2017-04-01

    Full Text Available Leptospira spp. are diderm (two membranes bacteria that infect mammals causing leptospirosis, a public health problem with global implications. Thousands of people die every year due to leptospirosis, especially in developing countries with tropical climates. Prophylaxis is difficult due to multiple factors, including the large number of asymptomatic hosts that transmit the bacteria, poor sanitation, increasing numbers of slum dwellers, and the lack of an effective vaccine. Several leptospiral recombinant antigens were evaluated as a replacement for the inactivated (bacterin vaccine; however, success has been limited. A prospective vaccine candidate is likely to be a surface-related protein that can stimulate the host immune response to clear leptospires from blood and organs. In this study, a comprehensive bioinformatics approach based on reverse and structural vaccinology was applied toward the discovery of novel leptospiral vaccine candidates. The Leptospira interrogans serovar Copenhageni strain L1-130 genome was mined in silico for the enhanced identification of conserved β-barrel (βb transmembrane proteins and outer membrane (OM lipoproteins. Orthologs of the prospective vaccine candidates were screened in the genomes of 20 additional Leptospira spp. Three-dimensional structural models, with a high degree of confidence, were created for each of the surface-exposed proteins. Major histocompatibility complex II (MHC-II epitopes were identified, and their locations were mapped on the structural models. A total of 18 βb transmembrane proteins and 8 OM lipoproteins were identified. These proteins were conserved among the pathogenic Leptospira spp. and were predicted to have epitopes for several variants of MHC-II receptors. A structural and functional analysis of the sequence of these surface proteins demonstrated that most βb transmembrane proteins seem to be TonB-dependent receptors associated with transportation. Other proteins

  6. An update on smallpox vaccine candidates and their role in bioterrorism related vaccination strategies.

    Science.gov (United States)

    Wiser, Itay; Balicer, Ran D; Cohen, Dani

    2007-01-22

    The threat of using variola virus in a bioterrorist attack urged different countries to renew the production of traditional vaccines and develop new generations of smallpox vaccines. Manufacturers try to combine smallpox vaccine past experience with technological advances in vaccine development to achieve protection similar to that of the traditional vaccines with a higher level of safety and fewer contraindications. In light of the reported immunogenicity and reactogenicity of the stockpiled smallpox vaccines employed in the last immunization campaigns of "first responders", we review recently accumulated data on the assessment of new smallpox vaccine candidates and discuss their role in possible vaccination policies.

  7. Jenner-predict server: prediction of protein vaccine candidates (PVCs) in bacteria based on host-pathogen interactions

    Science.gov (United States)

    2013-01-01

    Background Subunit vaccines based on recombinant proteins have been effective in preventing infectious diseases and are expected to meet the demands of future vaccine development. Computational approach, especially reverse vaccinology (RV) method has enormous potential for identification of protein vaccine candidates (PVCs) from a proteome. The existing protective antigen prediction software and web servers have low prediction accuracy leading to limited applications for vaccine development. Besides machine learning techniques, those software and web servers have considered only protein’s adhesin-likeliness as criterion for identification of PVCs. Several non-adhesin functional classes of proteins involved in host-pathogen interactions and pathogenesis are known to provide protection against bacterial infections. Therefore, knowledge of bacterial pathogenesis has potential to identify PVCs. Results A web server, Jenner-Predict, has been developed for prediction of PVCs from proteomes of bacterial pathogens. The web server targets host-pathogen interactions and pathogenesis by considering known functional domains from protein classes such as adhesin, virulence, invasin, porin, flagellin, colonization, toxin, choline-binding, penicillin-binding, transferring-binding, fibronectin-binding and solute-binding. It predicts non-cytosolic proteins containing above domains as PVCs. It also provides vaccine potential of PVCs in terms of their possible immunogenicity by comparing with experimentally known IEDB epitopes, absence of autoimmunity and conservation in different strains. Predicted PVCs are prioritized so that only few prospective PVCs could be validated experimentally. The performance of web server was evaluated against known protective antigens from diverse classes of bacteria reported in Protegen database and datasets used for VaxiJen server development. The web server efficiently predicted known vaccine candidates reported from Streptococcus pneumoniae and

  8. Jenner-predict server: prediction of protein vaccine candidates (PVCs) in bacteria based on host-pathogen interactions.

    Science.gov (United States)

    Jaiswal, Varun; Chanumolu, Sree Krishna; Gupta, Ankit; Chauhan, Rajinder S; Rout, Chittaranjan

    2013-07-01

    Subunit vaccines based on recombinant proteins have been effective in preventing infectious diseases and are expected to meet the demands of future vaccine development. Computational approach, especially reverse vaccinology (RV) method has enormous potential for identification of protein vaccine candidates (PVCs) from a proteome. The existing protective antigen prediction software and web servers have low prediction accuracy leading to limited applications for vaccine development. Besides machine learning techniques, those software and web servers have considered only protein's adhesin-likeliness as criterion for identification of PVCs. Several non-adhesin functional classes of proteins involved in host-pathogen interactions and pathogenesis are known to provide protection against bacterial infections. Therefore, knowledge of bacterial pathogenesis has potential to identify PVCs. A web server, Jenner-Predict, has been developed for prediction of PVCs from proteomes of bacterial pathogens. The web server targets host-pathogen interactions and pathogenesis by considering known functional domains from protein classes such as adhesin, virulence, invasin, porin, flagellin, colonization, toxin, choline-binding, penicillin-binding, transferring-binding, fibronectin-binding and solute-binding. It predicts non-cytosolic proteins containing above domains as PVCs. It also provides vaccine potential of PVCs in terms of their possible immunogenicity by comparing with experimentally known IEDB epitopes, absence of autoimmunity and conservation in different strains. Predicted PVCs are prioritized so that only few prospective PVCs could be validated experimentally. The performance of web server was evaluated against known protective antigens from diverse classes of bacteria reported in Protegen database and datasets used for VaxiJen server development. The web server efficiently predicted known vaccine candidates reported from Streptococcus pneumoniae and Escherichia coli

  9. Combined semi-empirical screening and design of experiments (DOE) approach to identify candidate formulations of a lyophilized live attenuated tetravalent viral vaccine candidate.

    Science.gov (United States)

    Patel, Ashaben; Erb, Steven M; Strange, Linda; Shukla, Ravi S; Kumru, Ozan S; Smith, Lee; Nelson, Paul; Joshi, Sangeeta B; Livengood, Jill A; Volkin, David B

    2017-05-12

    A combination experimental approach, utilizing semi-empirical excipient screening followed by statistical modeling using design of experiments (DOE), was undertaken to identify stabilizing candidate formulations for a lyophilized live attenuated Flavivirus vaccine candidate. Various potential pharmaceutical compounds used in either marketed or investigative live attenuated viral vaccine formulations were first identified. The ability of additives from different categories of excipients, either alone or in combination, were then evaluated for their ability to stabilize virus against freeze-thaw, freeze-drying, and accelerated storage (25°C) stresses by measuring infectious virus titer. An exploratory data analysis and predictive DOE modeling approach was subsequently undertaken to gain a better understanding of the interplay between the key excipients and stability of virus as well as to determine which combinations were interacting to improve virus stability. The lead excipient combinations were identified and tested for stabilizing effects using a tetravalent mixture of viruses in accelerated and real time (2-8°C) stability studies. This work demonstrates the utility of combining semi-empirical excipient screening and DOE experimental design strategies in the formulation development of lyophilized live attenuated viral vaccine candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Cell biological characterization of the malaria vaccine candidate trophozoite exported protein 1.

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    Caroline Kulangara

    Full Text Available In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1. In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.

  11. Genomic analysis of chimeric human cytomegalovirus vaccine candidates derived from strains Towne and Toledo.

    Science.gov (United States)

    Suárez, Nicolás M; Lau, Betty; Kemble, George M; Lee, Ronzo; Mocarski, Edward S; Wilkinson, Gavin W G; Adler, Stuart P; McVoy, Michael A; Davison, Andrew J

    2017-08-01

    Human cytomegalovirus (HCMV) is an important opportunistic pathogen in immunocompromised patients and a major cause of congenital birth defects when acquired in utero. In the 1990s, four chimeric viruses were constructed by replacing genome segments of the high passage Towne strain with segments of the low passage Toledo strain, with the goal of obtaining live attenuated vaccine candidates that remained safe but were more immunogenic than the overly attenuated Towne vaccine. The chimeras were found to be safe when administered to HCMV-seronegative human volunteers, but to differ significantly in their ability to induce seroconversion. This suggests that chimera-specific genetic differences impacted the ability to replicate or persist in vivo and the consequent ability to induce an antibody response. To identify specific genomic breakpoints between Towne and Toledo sequences and establish whether spontaneous mutations or rearrangements had occurred during construction of the chimeras, complete genome sequences were determined. No major deletions or rearrangements were observed, although a number of unanticipated mutations were identified. However, no clear association emerged between the genetic content of the chimeras and the reported levels of vaccine-induced HCMV-specific humoral or cellular immune responses, suggesting that multiple genetic determinants are likely to impact immunogenicity. In addition to revealing the genome organization of the four vaccine candidates, this study provided an opportunity to probe the genetics of HCMV attenuation in humans. The results may be valuable in the future design of safe live or replication-defective vaccines that optimize immunogenicity and efficacy.

  12. Identification and characterization of antigens as vaccine candidates against Klebsiella pneumoniae

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    Lundberg, Urban; Senn, Beatrice M.; Schüler, Wolfgang; Meinke, Andreas; Hanner, Markus

    2013-01-01

    Nosocomial infections, also called “hospital acquired infections,” occur worldwide and affect both developed and resource-poor countries, thus having a major impact on their health care systems. Klebsiella pneumoniae, which is an opportunistic Gram-negative pathogen, is responsible for causing pneumonia, urinary tract infections and septicemia in immune compromised hosts such as neonates. Unfortunately, there is no vaccine or mAb available for prophylactic or therapeutic use against K. pneumoniae infections. For this reason, we sought for a protein-based subunit vaccine capable of combating K. pneumoniae infections, by applying our ANTIGENome technology for the identification of potential vaccine candidates, focusing on conserved protein antigens present in strains with different serotypes. We identified numerous novel immunogenic proteins using genomic surface display libraries and human serum antibodies from donors exposed to or infected by K. pneumoniae. Vaccine candidate antigens were finally selected based on animal protection in a murine lethal-sepsis model. The protective and highly conserved antigens identified in this study are promising candidates for the development of a protein-based vaccine to prevent infection by K. pneumoniae. PMID:23250007

  13. Production of a Recombinant Vaccine Candidate against Burkholderia pseudomallei Exploiting the Bacterial N-Glycosylation Machinery

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    Fatima eGarcia-Quintanilla

    2014-07-01

    Full Text Available Vaccines developing immune responses towards surface carbohydrates conjugated to proteins are effective in preventing infection and death by bacterial pathogens. Traditional production of these vaccines utilizes complex synthetic chemistry to acquire and conjugate the glycan to a protein. However, glycoproteins produced by bacterial protein glycosylation systems are significantly easier to produce, and could possible be used as vaccine candidates. In this work we functionally expressed the B. pseudomallei O polysaccharide (OPS II, the C. jejuni oligosaccharyltransferase (OTase, and a suitable glycoprotein (AcrA in a designer E. coli strain with a higher efficiency for production of glycoconjugates. We were able to produce and purify the OPS II-AcrA glycoconjugate, and MS analysis confirmed correct glycan was produced and attached. We observed the attachment of the O-acetylated deoxyhexose directly to the acceptor protein, which expands the range of substrates utilized by the OTase PglB. Injection of the glycoprotein into mice generated an IgG immune response against B. pseudomallei, and this response was partially protective against an intranasal challenge. Our experiments show that bacterial engineered glycoconjugates can be utilized as vaccine candidates against B. pseudomallei. Additionally, our new E. coli strain SDB1 is more efficient in glycoprotein production, and could have additional applications in the future.

  14. Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets.

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    Min-Yuan Chia

    Full Text Available Avian-origin influenza A (H7N9 viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300 μg aluminum hydroxide, 1.5 μg HA, and 1.5 μg HA plus 300 μg aluminum hydroxide were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA inhibition and neutralizing antibodies were <10 and <40 for the control group (adjuvant only, 17 and 80 for the unadjuvanted (HA only group, and 190 and 640 for the adjuvanted group (HA plus adjuvant, respectively. After challenge with wild-type influenza H7N9 viruses, virus titers in respiratory tracts of the adjuvanted group were significantly lower than that in the control, and unadjuvanted groups. MDCK cell-derived influenza H7N9 whole virus vaccine candidate is immunogenic and protective in ferrets and clinical development is highly warranted.

  15. Evaluation of ribosomal P0 peptide as a vaccine candidate against Argulus siamensis in Labeo rohita

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    Kar Banya

    2017-04-01

    Full Text Available Argulus spp. are important ectoparasites of fish, and the current approach of their control using chemical pesticides has numerous drawbacks. Vaccination is a promising alternative but identification of protective antigens is a limiting step. The ribosomal protein P0, essential for protein synthesis, has been studied as a vaccine candidate. We generated sequence information of the P0 protein of the ectoparasite Argulus siamensis and the host Labeo rohita. The region of the parasite P0 protein with less sequence similarity with that of the host P0 protein and high predicted antigenicity was used for peptide synthesis. The peptide was conjugated with keyhole limpet hemocyanin (KLH for immunization of rohu at a dose of 1.5 μg/g body weight. Dot blot assays confirmed production of antibodies against pP0-KLH in immunized fish. We evaluated the efficiency of pP0-KLH as a vaccine antigen by challenge of the immunized fish with A. siamensis. Although there was no significant difference in parasite load between both groups, a reduced and delayed mortality of 59% (15 days post-infection in immunized group was noticed as compared to 75% mortality (within 7–15 days post-infection in control group. The partial protection observed indicated the need for further optimization of this molecule to develop it into a vaccine candidate.

  16. Prediction of vaccine candidates against Pseudomonas aeruginosa: An integrated genomics and proteomics approach.

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    Rashid, Muhammad Ibrahim; Naz, Anam; Ali, Amjad; Andleeb, Saadia

    2017-07-01

    Pseudomonas aeruginosa is among top critical nosocomial infectious agents due to its persistent infections and tendency for acquiring drug resistance mechanisms. To date, there is no vaccine available for this pathogen. We attempted to exploit the genomic and proteomic information of P. aeruginosa though reverse-vaccinology approaches to unveil the prospective vaccine candidates. P. aeruginosa strain PAO1 genome was subjected to sequential prioritization approach following genomic, proteomics and structural analyses. Among, the predicted vaccine candidates: surface components of antibiotic efflux pumps (Q9HY88, PA2837), chaperone-usher pathway components (CupC2, CupB3), penicillin binding protein of bacterial cell wall (PBP1a/mrcA), extracellular component of Type 3 secretory system (PscC) and three uncharacterized secretory proteins (PA0629, PA2822, PA0978) were identified as potential candidates qualifying all the set criteria. These proteins were then analyzed for potential immunogenic surface exposed epitopes. These predicted epitopes may provide a basis for development of a reliable subunit vaccine against P. aeruginosa. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Pilot Scale Production of Highly Efficacious and Stable Enterovirus 71 Vaccine Candidates

    Science.gov (United States)

    Chang, Cheng-Peng; Guo, Meng-Shin; Hsieh, Shih-Yang; Yang, Wen-Hsueh; Chao, Hsin-Ju; Wu, Chien-Long; Huang, Ju-Lan; Lee, Min-Shi; Hu, Alan Yung-Chi; Lin, Sue-Chen; Huang, Yu-Yun; Hu, Mei-Hua; Chow, Yen-Hung; Chiang, Jen-Ron; Chang, Jui-Yuan; Chong, Pele

    2012-01-01

    Background Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. Principal Finding In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7–10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30–43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37°C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4°C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and

  18. Whole genome identification of Mycobacterium tuberculosis vaccine candidates by comprehensive data mining and bioinformatic analyses

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    Sadoff Jerald C

    2008-05-01

    Full Text Available Abstract Background Mycobacterium tuberculosis, the causative agent of tuberculosis (TB, infects ~8 million annually culminating in ~2 million deaths. Moreover, about one third of the population is latently infected, 10% of which develop disease during lifetime. Current approved prophylactic TB vaccines (BCG and derivatives thereof are of variable efficiency in adult protection against pulmonary TB (0%–80%, and directed essentially against early phase infection. Methods A genome-scale dataset was constructed by analyzing published data of: (1 global gene expression studies under conditions which simulate intra-macrophage stress, dormancy, persistence and/or reactivation; (2 cellular and humoral immunity, and vaccine potential. This information was compiled along with revised annotation/bioinformatic characterization of selected gene products and in silico mapping of T-cell epitopes. Protocols for scoring, ranking and prioritization of the antigens were developed and applied. Results Cross-matching of literature and in silico-derived data, in conjunction with the prioritization scheme and biological rationale, allowed for selection of 189 putative vaccine candidates from the entire genome. Within the 189 set, the relative distribution of antigens in 3 functional categories differs significantly from their distribution in the whole genome, with reduction in the Conserved hypothetical category (due to improved annotation and enrichment in Lipid and in Virulence categories. Other prominent representatives in the 189 set are the PE/PPE proteins; iron sequestration, nitroreductases and proteases, all within the Intermediary metabolism and respiration category; ESX secretion systems, resuscitation promoting factors and lipoproteins, all within the Cell wall category. Application of a ranking scheme based on qualitative and quantitative scores, resulted in a list of 45 best-scoring antigens, of which: 74% belong to the dormancy

  19. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

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    Ai-Hsiang Chou

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration, a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice

  20. Carbohydrate moieties as vaccine candidates: targeting the sweet spot in the immune response.

    Science.gov (United States)

    Taylor, Christopher E; Cobb, Brian A; Rittenhouse-Olson, Kate; Paulson, James C; Schreiber, John R

    2012-06-22

    Advances in the use of carbohydrates as vaccine candidates for the prevention of infectious and malignant diseases was the topic for a meeting in Rockville, MD, sponsored by the National Institute of Allergy and Infectious Diseases involving a diverse group of scientists. Participants included research scientists and clinicians from academia and industry, and representatives from the National Institutes of Health and US Food and Drug Administration. This workshop was the third in a series of meetings designed to address issues relating to the immune response to carbohydrate antigens and how this information is used in the development of vaccines. Participants also identified roadblocks, research opportunities and resource needs. The meeting was organized into sessions that focused on recent advances in the immune response to microbial and cancer carbohydrate antigens, glycomics, novel vaccine approaches, novel adjuvants and delivery systems. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

  1. A defined syphilis vaccine candidate inhibits dissemination of Treponema pallidum subspecies pallidum

    Science.gov (United States)

    Lithgow, Karen V.; Hof, Rebecca; Wetherell, Charmaine; Phillips, Drew; Houston, Simon; Cameron, Caroline E.

    2017-01-01

    Syphilis is a prominent disease in low- and middle-income countries, and a re-emerging public health threat in high-income countries. Syphilis elimination will require development of an effective vaccine that has thus far remained elusive. Here we assess the vaccine potential of Tp0751, a vascular adhesin from the causative agent of syphilis, Treponema pallidum subsp. pallidum. Tp0751-immunized animals exhibit a significantly reduced bacterial organ burden upon T. pallidum challenge compared with unimmunized animals. Introduction of lymph nodes from Tp0751-immunized, T. pallidum-challenged animals to naive animals fails to induce infection, confirming sterile protection. These findings provide evidence that Tp0751 is a promising syphilis vaccine candidate. PMID:28145405

  2. GapA, a potential vaccine candidate antigen against Streptococcus agalactiae in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Zhang, Ze; Yu, Angen; Lan, Jiangfeng; Zhang, Hua; Hu, Minqiang; Cheng, Jiewei; Zhao, Lijuan; Lin, Li; Wei, Shun

    2017-04-01

    Streptococcosis due to the bacterium Streptococcus agalactiae (S. agalactiae) has resulted in enormous economic losses in aquaculture worldwide, especially in the tilapia culture industry. Previously, there were limited vaccines that could be employed against streptococcosis in tilapia. This study aimed to develop a vaccine candidate using the glyceraldehyde-phosphate dehydrogenase protein (GapA) of S. agalactiae encoded by the gapA gene. Tilapia were intraperitoneally injected with PBS, PBS + Freund's adjuvant, PBS + Montanide's adjuvant, GapA + Freund's adjuvant, GapA + Montanide's adjuvant, killed S. agalactiae whole cells (WC)+Freund's adjuvant, or killed S. agalactiae whole cells (WC)+ Montanide's adjuvant. They were then challenged with S. agalactiae, and the relative percentage survival (RPS) was monitored 14 days after the challenge. The highest RPSs were observed in the WC groups, with 76.7% in WC + Freund's adjuvant and 74.4% in WC + Montanide's adjuvant groups; these were followed by the GapA groups, with 63.3% in GapA + Freund's adjuvant and 45.6% in GapA + Montanide's adjuvant groups. The RPS of the PBS group was 0%, and those of PBS + Freund's adjuvant and PBS + Montanide's adjuvant groups were 6.7% and 3.3%, respectively. Additionally, the IgM antibody responses elicited in GapA groups and WC groups were significantly higher than those in PBS groups. Furthermore, the expressions of cytokine (IL-1β and TNF-α) mRNAs in the GapA groups and WC groups were significantly higher than those in the PBS groups. Taken together, these results reveal that the GapA protein is a promising vaccine candidate that could be used to prevent streptococcosis in tilapia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Genetic diversity of vaccine candidate antigens in Plasmodium falciparum isolates from the Amazon basin of Peru

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    Lucas Carmen M

    2008-05-01

    Full Text Available Abstract Background Several of the intended Plasmodium falciparum vaccine candidate antigens are highly polymorphic and could render a vaccine ineffective if their antigenic sites were not represented in the vaccine. In this study, characterization of genetic variability was performed in major B and T-cell epitopes within vaccine candidate antigens in isolates of P. falciparum from Peru. Methods DNA sequencing analysis was completed on 139 isolates of P. falciparum collected from endemic areas of the Amazon basin in Loreto, Peru from years 1998 to 2006. Genetic diversity was determined in immunological important regions in circumsporozoite protein (CSP, merozoite surface protein-1 (MSP-1, apical membrane antigen-1 (AMA-1, liver stage antigen-1 (LSA-1 and thrombospondin-related anonymous protein (TRAP. Alleles identified by DNA sequencing were aligned with the vaccine strain 3D7 and DNA polymorphism analysis and FST study-year pairwise comparisons were done using the DnaSP software. Multilocus analysis (MLA was performed and average of expected heterozygosity was calculated for each loci and haplotype over time. Results Three different alleles for CSP, seven for MSP-1 Block 2, one for MSP-1 Block 17, three for AMA-1 and for LSA-1 each and one for TRAP were identified. There were 24 different haplotypes in 125 infections with complete locus typing for each gene. Conclusion Characterization of the genetic diversity in Plasmodium isolates from the Amazon Region of Peru showed that P. falciparum T and B cell epitopes in these antigens have polymorphisms more similar to India than to Africa. These findings are helpful in the formulation of a vaccine considering restricted repertoire populations.

  4. Construction and screening of attenuated ΔphoP/Q Salmonella typhimurium vectored plague vaccine candidates.

    Science.gov (United States)

    Sizemore, Donata R; Warner, Elizabeth A; Lawrence, Julie A; Thomas, Lawrence J; Roland, Kenneth L; Killeen, Kevin P

    2012-03-01

    Preclinical studies evaluating plague vaccine candidates have demonstrated that the F1 and V protein antigens of Yersinia pestis confer protection against challenge from virulent strains. Live-attenuated ΔphoP/Q Salmonella typhimurium recombinants were constructed expressing either F1, V antigens, F1 and V antigens, or a F1-V fusion from Asd (+) balanced-lethal plasmids. To improve antigen delivery, genes encoding plague antigens were modified in order to localize antigens to specific bacterial cellular compartments which include cytoplasmic, outer membrane, or secreted. Candidate vaccine strains were evaluated for growth characteristics, full-length lipopolysaccharide (LPS), plasmid stability, and antigen expression in vitro. Plague vaccine candidate strains with favorable in vitro profiles were evaluated in murine or rabbit preclinical oral immunogenicity studies. Attenuated S. typhimurium strains expressing cytoplasmically localized F1-V and V antigen antigens were more immunogenic than strains that secreted or localized plague antigens to the outer membrane. In particular, S. typhimurium M020 and M023, which express Asd(+)-plasmid derived soluble F1-V and soluble V antigen, respectively, at high levels in the bacterial cell cytoplasm were found to induce the highest levels of plague-specific serum antibodies. To further evaluate balanced-lethal plasmid retention capacity, ΔphoP/Q S. typhimurium PurB(+) and GlnA(+) balanced-lethal plasmid systems harboring F1-V were compared with M020 in vitro and in BALB/c mice in a immunogenicity study. Although there was no detectable difference in plague antigen expression in vitro, S. typhimurium M020 was the most immunogenic plague antigen vector strain evaluated, inducing high-titer serum IgG antibodies specific against F1, V and F1-V.

  5. Genetic variation in vitro and in vivo of an attenuated Lassa vaccine candidate.

    Science.gov (United States)

    Zapata, Juan C; Goicochea, Marco; Nadai, Yuka; Eyzaguirre, Lindsay M; Carr, Jean K; Tallon, Luke J; Sadzewicz, Lisa; Myers, Garry; Fraser, Claire M; Su, Qi; Djavani, Mahmoud; Lukashevich, Igor S; Salvato, Maria S

    2014-03-01

    The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo.

  6. A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats.

    Science.gov (United States)

    Rostad, Christina A; Stobart, Christopher C; Gilbert, Brian E; Pickles, Ray J; Hotard, Anne L; Meng, Jia; Blanco, Jorge C G; Moin, Syed M; Graham, Barney S; Piedra, Pedro A; Moore, Martin L

    2016-08-15

    Although respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log10 total PFU and 2.7 log10 PFU/g of tissue, respectively, compared to those in unvaccinated animals (P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity. RSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by

  7. A chimeric protein-based malaria vaccine candidate induces robust T cell responses against Plasmodium vivax MSP119.

    Science.gov (United States)

    Fonseca, Jairo Andres; Cabrera-Mora, Monica; Singh, Balwan; Oliveira-Ferreira, Joseli; da Costa Lima-Junior, Josué; Calvo-Calle, J Mauricio; Lozano, Jose Manuel; Moreno, Alberto

    2016-10-06

    The most widespread Plasmodium species, Plasmodium vivax, poses a significant public health threat. An effective vaccine is needed to reduce global malaria burden. Of the erythrocytic stage vaccine candidates, the 19 kDa fragment of the P. vivax Merozoite Surface Protein 1 (PvMSP119) is one of the most promising. Our group has previously defined several promiscuous T helper epitopes within the PvMSP1 protein, with features that allow them to bind multiple MHC class II alleles. We describe here a P. vivax recombinant modular chimera based on MSP1 (PvRMC-MSP1) that includes defined T cell epitopes genetically fused to PvMSP119. This vaccine candidate preserved structural elements of the native PvMSP119 and elicited cytophilic antibody responses, and CD4+ and CD8+ T cells capable of recognizing PvMSP119. Although CD8+ T cells that recognize blood stage antigens have been reported to control blood infection, CD8+ T cell responses induced by P. falciparum or P. vivax vaccine candidates based on MSP119 have not been reported. To our knowledge, this is the first time a protein based subunit vaccine has been able to induce CD8+ T cell against PvMSP119. The PvRMC-MSP1 protein was also recognized by naturally acquired antibodies from individuals living in malaria endemic areas with an antibody profile associated with protection from infection. These features make PvRMC-MSP1 a promising vaccine candidate.

  8. Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds.

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    Debmalya Barh

    Full Text Available Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC for most of the pathogenic Vibrio strains. Two targets (uppP and yajC are novel to Vibrio, and two targets (uppP and ompU can be used to develop both drugs and vaccines (dual targets against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.

  9. Limitations of Murine Models for Assessment of Antibody-Mediated Therapies or Vaccine Candidates against Staphylococcus epidermidis Bloodstream Infection

    Science.gov (United States)

    Zhang, Jinrong; Kesselly, Augustus; Lam, Hubert; Kleanthous, Harry; Yethon, Jeremy A.

    2016-01-01

    Staphylococcus epidermidis is normally a commensal colonizer of human skin and mucus membranes, but, due to its ability to form biofilms on indwelling medical devices, it has emerged as a leading cause of nosocomial infections. Bacteremia or bloodstream infection is a frequent and costly complication resulting from biofilm fouling of medical devices. Our goal was to develop a murine model of S. epidermidis infection to identify potential vaccine targets for the prevention of S. epidermidis bacteremia. However, assessing the contribution of adaptive immunity to protection against S. epidermidis challenge was complicated by a highly efficacious innate immune response in mice. Naive mice rapidly cleared S. epidermidis infections from blood and solid organs, even when the animals were immunocompromised. Cyclophosphamide-mediated leukopenia reduced the size of the bacterial challenge dose required to cause lethality but did not impair clearance after a nonlethal challenge. Nonspecific innate immune stimulation, such as treatment with a Toll-like receptor 4 (TLR4) agonist, enhanced bacterial clearance. TLR2 signaling was confirmed to accelerate the clearance of S. epidermidis bacteremia, but TLR2−/− mice could still resolve a bloodstream infection. Furthermore, TLR2 signaling played no role in the clearance of bacteria from the spleen. In conclusion, these data suggest that S. epidermidis bloodstream infection is cleared in a highly efficient manner that is mediated by both TLR2-dependent and -independent innate immune mechanisms. The inability to establish a persistent infection in mice, even in immunocompromised animals, rendered these murine models unsuitable for meaningful assessment of antibody-mediated therapies or vaccine candidates. PMID:26857577

  10. Large extracellular loop of tetraspanin as a potential vaccine candidate for filariasis.

    Directory of Open Access Journals (Sweden)

    Gajalakshmi Dakshinamoorthy

    Full Text Available Lymphatic filariasis affects nearly 120 million people worldwide and mass preventive chemotherapy is currently used as a strategy to control this infection. This has substantially reduced the incidence of the infection in several parts of the world. However, a prophylactic vaccine would be more effective in preventing future infections and will supplement the mass chemotherapy efforts. Unfortunately, there is no licensed vaccine available currently to prevent this infection. Molecules expressed on the surface of the parasite are potential candidates for vaccine development as they are exposed to the host immune system. In this study we show that the large extracellular loop of tetraspanin (TSP LEL, a protein expressed on the cuticle of Brugia malayi and Wuchereria bancrofti is a potential vaccine candidate. Our results showed that BmTSP LEL is expressed on the surface of B. malayi infective third stage larvae (L3 and sera from human subjects who are putatively immune to lymphatic filariasis carry high titer of IgG1 and IgG3 antibodies against BmTSP LEL and WbTSP LEL. We also showed that these antibodies in the sera of human subjects can participate in the killing of B. malayi L3 in an antibody dependent cell-mediated cytotoxicity mechanism. Vaccination trials in mice showed that close to 64% protection were achieved against challenge infections with B. malayi L3. Immunized animals showed high titer of anti-WbTSP LEL IgG1, IgG2a and IgG2b antibodies in the sera and IFN-γ secreting cells in the spleen. Onchocerca volvulus another filarial parasite also expresses TSP LEL. Cross-reactivity studies showed that IgG1 antibody in the sera of endemic normal subjects, recognize OvTSP LEL. Similarly, anti-OvTSP LEL antibodies in the sera of subjects who are immune to O. volvulus were also shown to cross-react with rWbTSP LEL and rBmTSP LEL. These findings thus suggested that rTSP LEL can be developed as a potential vaccine candidate against multiple

  11. Stability and CTL-activity of P40/ELA melanoma vaccine candidate.

    Science.gov (United States)

    Beck, A; Goetsch, L; Champion, T; Bussat, M C; Aubry, J P; Klinguer-Hamour, C; Haeuw, J F; Bonnefoy, J Y; Corvaïa, N

    2001-01-01

    The decapeptide ELA (ELAGIGILTV), a Melan-A/MART-1 antigen immunodominant peptide analogue, is an interesting melanoma vaccine candidate alone or in combination with other tumour antigens. P40, the recombinant outer membrane protein A of Klebsiella pneumoniae (kpOmpA), was recently shown to target dendritic cells and to induce peptide-specific CTLs. Here we investigated the adjuvant role of P40 mixed or chemically conjugated to ELA. This compound is an N-terminal glutamic acid-containing peptide. However, it has been reported that the amino group and the gamma-carboxylic group of glutamic acids easily condense to form pyroglutamic derivatives. Usually, to overcome this stability problem, peptides of pharmaceutical interest were developed with a pyroglutamic acid instead of N-terminal glutamic acid, without loss of pharmacological properties. Unfortunately, the pyroglutamic acid derivative (PyrELA) as well as the N-terminal acetyl capped derivative (AcELA) failed to elicit CTL activity when mixed with P40 adjuvant protein. Despite the apparent minor modifications introduced by PyrELA and AcELA, these two derivatives have probably lower affinity than ELA for the class I Major Histocompatibility Complex. Furthermore, this stability problem is worse in the case of clinical grade ELA, produced as an acetate salt, like most of the pharmaceutical grade peptides. We report here that the hydrochloride shows a higher stability than the acetate and may be suitable for use in man. Copyright 2001 The International Association for Biologicals.

  12. Plant expressed coccidial antigens as potential vaccine candidates in protecting chicken against coccidiosis.

    Science.gov (United States)

    Sathish, Kota; Sriraman, Rajan; Subramanian, B Mohana; Rao, N Hanumantha; Kasa, Balaji; Donikeni, Jagan; Narasu, M Lakshmi; Srinivasan, V A

    2012-06-22

    Coccidiosis is a disease caused by intracellular parasites belonging to the genus Eimeria. In the present study, we transiently expressed two coccidial antigens EtMIC1 and EtMIC2 as poly histidine-tagged fusion proteins in tobacco. We have evaluated the protective efficacy of plant expressed EtMIC1 as monovalent and as well as bi-valent formulation where EtMIC1 and EtMIC2 were used in combination. The protective efficacy of these formulations was evaluated using homologous challenge in chickens. We observed better serum antibody response, weight gain and reduced oocyst shedding in birds immunized with EtMIC1 and EtMIC2 as bivalent formulation compared to monovalent formulation. However, IFN-γ response was not significant in birds immunized with EtMIC1 compared to the birds immunized with EtMIC2. Our results indicate the potential use of these antigens as vaccine candidates. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Characterization of a novel vaccine candidate and serine proteinase inhibitor from Schistosoma japonicum (Sj serpin).

    Science.gov (United States)

    Yan, Yutao; Liu, Shuxian; Song, Guangcheng; Xu, Yixin; Dissous, Colette

    2005-07-15

    Serine proteinase inhibitors (serpins) represent an important superfamily of endogenous inhibitors that regulate proteolytic events active in a variety of physiological functions. Immunological screening of a Schistosoma japonicum adult worm cDNA expression library with sera of Microtus fortis, a naturally resistant vertebrate host, has identified one clone that encoded for a sequence homologous to those of the serpin superfamily. The full-length sequence encoding S. japonicum serpin (Sj serpin) was amplified from adult worm cDNA by using 5'-RACE-PCR and subsequently cloned into the prokaryotic expression vector pET28c. The full-length Sj serpin fusion-protein with his-tag was expressed in E. coli, purified by affinity chromatography and used to immunize New Zealand white rabbits. Sj serpin is located on the tegument in S. japonicum adult worms. C57BL/6 mice immunized with Sj serpin induced the production of high levels of specific IgE and IgG1 subclass antibodies as well as a marked IL-4 response. Lymphocyte surface marker analysis revealed proliferation of CD19 expressing B cells, indicating a predominant Th2-type response to Sj serpin. Immunized mice developed moderate protection against infection of S. japonicum as demonstrated by a 36 and 39% reduction in the recovery of adult worms and eggs, respectively. These data suggested a role for Sj serpin as a vaccine candidate or as a novel target for anti-schistosome drugs.

  14. Characterization of Brucella abortus mutant strain Δ22915, a potential vaccine candidate.

    Science.gov (United States)

    Bao, Yanqing; Tian, Mingxing; Li, Peng; Liu, Jiameng; Ding, Chan; Yu, Shengqing

    2017-04-04

    Brucellosis, caused by Brucella spp., is an important zoonosis worldwide. Vaccination is an effective strategy for protection against Brucella infection in livestock in developing countries and in wildlife in developed countries. However, current vaccine strains including S19 and RB51 are pathogenic to humans and pregnant animals, limiting their use. In this study, we constructed the Brucella abortus (B. abortus) S2308 mutant strain Δ22915, in which the putative lytic transglycosylase gene BAB_RS22915 was deleted. The biological properties of mutant strain Δ22915 were characterized and protection of mice against virulent S2308 challenge was evaluated. The mutant strain Δ22915 showed reduced survival within RAW264.7 cells and survival in vivo in mice. In addition, the mutant strain Δ22915 failed to escape fusion with lysosomes within host cells, and caused no observable pathological damage. RNA-seq analysis indicated that four genes associated with amino acid/nucleotide transport and metabolism were significantly upregulated in mutant strain Δ22915. Furthermore, inoculation of ∆22915 at 10 5 colony forming units induced effective host immune responses and long-term protection of BALB/c mice. Therefore, mutant strain ∆22915 could be used as a novel vaccine candidate in the future to protect animals against B. abortus infection.

  15. Immunogenic virus-like particles continuously expressed in mammalian cells as a veterinary rabies vaccine candidate.

    Science.gov (United States)

    Fontana, Diego; Kratje, Ricardo; Etcheverrigaray, Marina; Prieto, Claudio

    2015-08-20

    Rabies is one of the most lethal infectious diseases in the world, with a mortality approaching 100%. There are between 60,000 and 70,000 reported annual deaths, but this is probably an underestimation. Despite the fact that there are vaccines available for rabies, there is a real need of developing more efficacious and cheaper vaccines. This is particularly true for veterinary vaccines because dogs are still the main vector for rabies transmission to human beings. In a previous work, we described the development and characterization of rabies virus-like particles (RV-VLPs) expressed in HEK293 cells. We showed that RV-VLPs are able to induce a specific antibodies response. In this work, we show that VLPs are able to protect mice against virus challenge. Furthermore, we developed a VLPs expressing HEK-293 clone (sP2E5) that grows in serum free medium (SFM) reaching high cell densities. sP2E5 was cultured in perfusion mode in a 5 L bioreactor for 20 days, and the RV-VLPs produced were capable of triggering a protective immune response without the need of concentration or adjuvant addition. Further, these VLPs are able to induce the production of rabies virus neutralizing antibodies. These results demonstrate that RV-VLPs are a promising rabies vaccine candidate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. In Silico Analysis of Epitope-Based Vaccine Candidates against Hepatitis B Virus Polymerase Protein.

    Science.gov (United States)

    Zheng, Juzeng; Lin, Xianfan; Wang, Xiuyan; Zheng, Liyu; Lan, Songsong; Jin, Sisi; Ou, Zhanfan; Wu, Jinming

    2017-05-16

    Hepatitis B virus (HBV) infection has persisted as a major public health problem due to the lack of an effective treatment for those chronically infected. Therapeutic vaccination holds promise, and targeting HBV polymerase is pivotal for viral eradication. In this research, a computational approach was employed to predict suitable HBV polymerase targeting multi-peptides for vaccine candidate selection. We then performed in-depth computational analysis to evaluate the predicted epitopes' immunogenicity, conservation, population coverage, and toxicity. Lastly, molecular docking and MHC-peptide complex stabilization assay were utilized to determine the binding energy and affinity of epitopes to the HLA-A0201 molecule. Criteria-based analysis provided four predicted epitopes, RVTGGVFLV, VSIPWTHKV, YMDDVVLGA and HLYSHPIIL. Assay results indicated the lowest binding energy and high affinity to the HLA-A0201 molecule for epitopes VSIPWTHKV and YMDDVVLGA and epitopes RVTGGVFLV and VSIPWTHKV, respectively. Regions 307 to 320 and 377 to 387 were considered to have the highest probability to be involved in B cell epitopes. The T cell and B cell epitopes identified in this study are promising targets for an epitope-focused, peptide-based HBV vaccine, and provide insight into HBV-induced immune response.

  17. An assessment of enterotoxigenic Escherichia coli and Shigella vaccine candidates for infants and children.

    Science.gov (United States)

    Walker, Richard I

    2015-02-18

    Despite improvements to water quality, sanitation, and the implementation of current prevention and treatment interventions, diarrhea remains a major cause of illness and death, especially among children less than five years of age in the developing world. Rotavirus vaccines have already begun making a real impact on diarrhea, but several more enteric vaccines will be necessary to achieve broader reductions of illness and death. Among the many causes of diarrheal disease, enterotoxigenic Escherichia coli (ETEC) and Shigella are the two most important bacterial pathogens for which there are no currently licensed vaccines. Vaccines against these two pathogens could greatly reduce the impact of disease caused by these infections. This review describes the approaches to ETEC and Shigella vaccines that are currently under development, including a range of both cellular and subunit approaches for each pathogen. In addition, the review discusses strategies for maximizing the potential benefit of these vaccines, which includes the feasibility of co-administration, consolidation, and combination of vaccine candidates, as well as issues related to effective administration of enteric vaccines to infants. Recent impact studies indicate that ETEC and Shigella vaccines could significantly benefit global public health. Either vaccine, particularly if they could be combined together or with another enteric vaccine, would be an extremely valuable tool for saving lives and promoting the health of infants and children in the developing world, as well as potentially providing protection to travelers and military personnel visiting endemic areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Attenuated Mycobacterium tuberculosis SO2 vaccine candidate is unable to induce cell death.

    Directory of Open Access Journals (Sweden)

    Adriana Aporta

    Full Text Available It has been proposed that Mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. As part of the characterization of a novel tuberculosis vaccine candidate, the M. tuberculosis phoP mutant SO2, we sought to evaluate its potential to induce host cell death. The parental M. tuberculosis MT103 strain and the current vaccine against tuberculosis Bacillus Calmette-Guérin (BCG were used as comparators in mouse models in vitro and in vivo. Our data reveal that attenuated SO2 was unable to induce apoptotic events neither in mouse macrophages in vitro nor during lung infection in vivo. In contrast, virulent MT103 triggers typical apoptotic events with phosphatidylserine exposure, caspase-3 activation and nuclear condensation and fragmentation. BCG strain behaved like SO2 and did not induce apoptosis. A clonogenic survival assay confirmed that viability of BCG- or SO2-infected macrophages was unaffected. Our results discard apoptosis as the protective mechanism induced by SO2 vaccine and provide evidence for positive correlation between classical apoptosis induction and virulent strains, suggesting apoptosis as a possible virulence determinant during M. tuberculosis infection.

  19. Lipoprotein NMB0928 from Neisseria meningitidis serogroup B as a novel vaccine candidate.

    Science.gov (United States)

    Delgado, Maité; Yero, Daniel; Niebla, Olivia; González, Sonia; Climent, Yanet; Pérez, Yusleydis; Cobas, Karem; Caballero, Evelín; García, Darien; Pajón, Rolando

    2007-12-05

    Polysaccharide-based vaccines for serogroup B Neisseria meningitidis have failed to induce protective immunity. As a result, efforts to develop vaccines for serogroup B meningococcal disease have mostly focused on outer membrane proteins (OMP). Vaccine candidates based on meningococcal OMP have emerged in the form of outer membrane vesicles (OMVs) or, more recently, purified recombinant proteins, as alternative strategies for serogroup B vaccine development. In our group, the protein composition of the Cuban OMVs-based vaccine VA-MENGOC-BC was elucidated using two-dimensional gel electrophoresis and mass spectrometry. The proteomic map of this product allowed the identification of new putative protective proteins not previously reported as components of an antimeningococcal vaccine. In the present study, we have determined the immunogenicity and protective capacity of NMB0928, one of those proteins present in the OMVs. The antigen was obtained as a recombinant protein in Escherichia coli, purified and used to immunize mice. The antiserum produced against the protein was capable to recognize the natural protein in different meningococcal strains by whole-cell ELISA and Western blotting. After immunization, recombinant NMB0928 induced bactericidal antibodies, and when the protein was administered inserted into liposomes, the elicited antibodies were protective in the infant rat model. These results suggest that NMB0928 is a novel antigen worth to be included in a broadly protective meningococcal vaccine.

  20. Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates

    DEFF Research Database (Denmark)

    Jones, Sophie; Grignard, Lynn; Nebie, Issa

    2015-01-01

    for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. METHODS: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso......OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences....... CONCLUSIONS: We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity....

  1. Evaluation of the potential of Mycobacterium smegmatis as vaccine Candidate against tuberculosis by in silico and in vivo studies

    Directory of Open Access Journals (Sweden)

    Le Thuy Nguyen Thi

    2010-04-01

    Full Text Available In this study, we scanned multiple published databases of gene expression in vivo of M. tuberculosis at different phases of infection in animals and humans, to select 38 proteins that are highly expressed in the active, latent and reactivation phases. The selected proteins were predicted for T and B epitopes. For each proteins, the regions containing T and B epitopes were selected at the same time to look for identical epitopes on M. smegmatis based on sequence alignments. Preliminary studies of humoral immunogenicity and cross-reactivity with M. tuberculosis in mice using two M. smegmatis-derived experimental vaccines were carried out, demonstrating the immunogenicity of M. smegmatis proteoliposomes and the recognition of M. tuberculosis proteins by the sera of animals immunized with this vaccine candidate. The conjunction of in silico and in vivo studies suggested the potential for future evaluation of M. smegmatis as vaccine candidate against tuberculosis using different strategies

  2. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    KAUST Repository

    Pahil, Sapna

    2017-08-02

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  3. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Science.gov (United States)

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G P S

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  4. A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria

    Directory of Open Access Journals (Sweden)

    José Manuel Lozano

    2017-11-01

    Full Text Available Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of PfCSP, STARP; MSA1 and Pf155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei-ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems.

  5. 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.

  6. Structure of SALO, a leishmaniasis vaccine candidate from the sand fly Lutzomyia longipalpis.

    Directory of Open Access Journals (Sweden)

    Oluwatoyin A Asojo

    2017-03-01

    Full Text Available Immunity to the sand fly salivary protein SALO (Salivary Anticomplement of Lutzomyia longipalpis protected hamsters against Leishmania infantum and L. braziliensis infection and, more recently, a vaccine combination of a genetically modified Leishmania with SALO conferred strong protection against L. donovani infection. Because of the importance of SALO as a potential component of a leishmaniasis vaccine, a plan to produce this recombinant protein for future scale manufacturing as well as knowledge of its structural characteristics are needed to move SALO forward for the clinical path.Recombinant SALO was expressed as a soluble secreted protein using Pichia pastoris, rSALO(P, with yields of 1g/L and >99% purity as assessed by SEC-MALS and SDS-PAGE. Unlike its native counterpart, rSALO(P does not inhibit the classical pathway of complement; however, antibodies to rSALO(P inhibit the anti-complement activity of sand fly salivary gland homogenate. Immunization with rSALO(P produces a delayed type hypersensitivity response in C57BL/6 mice, suggesting rSALO(P lacked anti-complement activity but retained its immunogenicity. The structure of rSALO(P was solved by S-SAD at Cu-Kalpha to 1.94 Å and refined to Rfactor 17%. SALO is ~80% helical, has no appreciable structural similarities to any human protein, and has limited structural similarity in the C-terminus to members of insect odorant binding proteins. SALO has three predicted human CD4+ T cell epitopes on surface exposed helices.The results indicate that SALO as expressed and purified from P. pastoris is suitable for further scale-up, manufacturing, and testing. SALO has a novel structure, is not similar to any human proteins, is immunogenic in rodents, and does not have the anti-complement activity observed in the native salivary protein which are all important attributes to move this vaccine candidate forward to the clinical path.

  7. Structure of SALO, a leishmaniasis vaccine candidate from the sand fly Lutzomyia longipalpis.

    Science.gov (United States)

    Asojo, Oluwatoyin A; Kelleher, Alan; Liu, Zhuyun; Pollet, Jeroen; Hudspeth, Elissa M; Rezende, Wanderson C; Groen, Mallory Jo; Seid, Christopher A; Abdeladhim, Maha; Townsend, Shannon; de Castro, Waldione; Mendes-Sousa, Antonio; Bartholomeu, Daniella Castanheira; Fujiwara, Ricardo Toshio; Bottazzi, Maria Elena; Hotez, Peter J; Zhan, Bin; Oliveira, Fabiano; Kamhawi, Shaden; Valenzuela, Jesus G

    2017-03-01

    Immunity to the sand fly salivary protein SALO (Salivary Anticomplement of Lutzomyia longipalpis) protected hamsters against Leishmania infantum and L. braziliensis infection and, more recently, a vaccine combination of a genetically modified Leishmania with SALO conferred strong protection against L. donovani infection. Because of the importance of SALO as a potential component of a leishmaniasis vaccine, a plan to produce this recombinant protein for future scale manufacturing as well as knowledge of its structural characteristics are needed to move SALO forward for the clinical path. Recombinant SALO was expressed as a soluble secreted protein using Pichia pastoris, rSALO(P), with yields of 1g/L and >99% purity as assessed by SEC-MALS and SDS-PAGE. Unlike its native counterpart, rSALO(P) does not inhibit the classical pathway of complement; however, antibodies to rSALO(P) inhibit the anti-complement activity of sand fly salivary gland homogenate. Immunization with rSALO(P) produces a delayed type hypersensitivity response in C57BL/6 mice, suggesting rSALO(P) lacked anti-complement activity but retained its immunogenicity. The structure of rSALO(P) was solved by S-SAD at Cu-Kalpha to 1.94 Å and refined to Rfactor 17%. SALO is ~80% helical, has no appreciable structural similarities to any human protein, and has limited structural similarity in the C-terminus to members of insect odorant binding proteins. SALO has three predicted human CD4+ T cell epitopes on surface exposed helices. The results indicate that SALO as expressed and purified from P. pastoris is suitable for further scale-up, manufacturing, and testing. SALO has a novel structure, is not similar to any human proteins, is immunogenic in rodents, and does not have the anti-complement activity observed in the native salivary protein which are all important attributes to move this vaccine candidate forward to the clinical path.

  8. Force Spectroscopy of the Plasmodium falciparum Vaccine Candidate Circumsporozoite Protein Suggests a Mechanically Pliable Repeat Region.

    Science.gov (United States)

    Patra, Aditya Prasad; Sharma, Shobhona; Ainavarapu, Sri Rama Koti

    2017-02-10

    The most effective vaccine candidate of malaria is based on the Plasmodium falciparum circumsporozoite protein (CSP), a major surface protein implicated in the structural strength, motility, and immune evasion properties of the infective sporozoites. It is suspected that reversible conformational changes of CSP are required for infection of the mammalian host, but the detailed structure and dynamic properties of CSP remain incompletely understood, limiting our understanding of its function in the infection. Here, we report the structural and mechanical properties of the CSP studied using single-molecule force spectroscopy on several constructs, one including the central region of CSP, which is rich in NANP amino acid repeats (CSPrep), and a second consisting of a near full-length sequence without the signal and anchor hydrophobic domains (CSPΔHP). Our results show that the CSPrep is heterogeneous, with 40% of molecules requiring virtually no mechanical force to unfold (<10 piconewtons (pN)), suggesting that these molecules are mechanically compliant and perhaps act as entropic springs, whereas the remaining 60% are partially structured with low mechanical resistance (∼70 pN). CSPΔHP having multiple force peaks suggests specifically folded domains, with two major populations possibly indicating the open and collapsed forms. Our findings suggest that the overall low mechanical resistance of the repeat region, exposed on the outer surface of the sporozoites, combined with the flexible full-length conformations of CSP, may provide the sporozoites not only with immune evasion properties, but also with lubricating capacity required during its navigation through the mosquito and vertebrate host tissues. We anticipate that these findings would further assist in the design and development of future malarial vaccines. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Potential of recombinant inorganic pyrophosphatase antigen as a new vaccine candidate against Baylisascaris schroederi in mice

    Science.gov (United States)

    2013-01-01

    The intestinal nematode Baylisascaris schroederi is an important cause of death for wild and captive giant pandas. Inorganic pyrophosphatases (PPases) are critical for development and molting in nematode parasites and represent potential targets for vaccination. Here, a new PPase homologue, Bsc-PYP-1, from B. schroederi was identified and characterized, and its potential as a vaccine candidate was evaluated in a mouse challenge model. Sequence alignment of PPases from nematode parasites and other organisms show that Bsc-PYP-1 is a nematode-specific member of the family I soluble PPases. Immunohistochemistry revealed strong localization of native Bsc-PYP-1 to the body wall, gut epithelium, ovary and uterus of adult female worms. Additionally, Bsc-PYP-1 homologues were found in roundworms infecting humans (Ascaris lumbricoides), swine (Ascaris suum) and dogs (Toxocara canis). In two vaccine trials, recombinant Bsc-PYP-1 (rBsc-PYP-1) formulated with Freund complete adjuvant induced significantly high antigen-specific immunoglobulin (Ig)G but no IgE or IgM responses. Analysis of IgG-subclass profiles revealed a greater increase of IgG1 than IgG2a. Splenocytes from rBsc-PYP-1/FCA-immunized mice secreted low levels of T helper (Th)1-type cytokines, interferon-γ and interleukin (IL)-2, while producing significantly high levels of IL-10 and significantly elevated levels of IL-4 (Th2 cytokines) after stimulation with rBsc-PYP-1 in vitro. Finally, vaccinated mice had 69.02–71.15% reductions (in 2 experiments) in larval recovery 7 days post-challenge (dpc) and 80% survival at 80 dpc. These results suggest that Th2-mediated immunity elicited by rBsc-PYP-1 provides protection against B. schroederi, and the findings should contribute to further development of Bsc-PYP-1 as a candidate vaccine against baylisascariasis. PMID:24090087

  10. Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates.

    Directory of Open Access Journals (Sweden)

    E M D L van der Heijden

    Full Text Available Conventional control and eradication strategies for bovine tuberculosis (BTB face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331, formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control. Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study

  11. Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates.

    Science.gov (United States)

    van der Heijden, E M D L; Chileshe, J; Vernooij, J C M; Gortazar, C; Juste, R A; Sevilla, I; Crafford, J E; Rutten, V P M G; Michel, A L

    2017-01-01

    Conventional control and eradication strategies for bovine tuberculosis (BTB) face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus) aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331), formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control). Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study, urging further

  12. Recombinant Mip-PilE-FlaA dominant epitopes vaccine candidate against Legionella pneumophila.

    Science.gov (United States)

    He, Jinlei; Huang, Fan; Chen, Han; Chen, Qiwei; Zhang, Junrong; Li, Jiao; Chen, Dali; Chen, Jianping

    2017-06-01

    Legionella pneumophila is the main causative agent of Legionnaires' disease, which is a severe multi-system disease with pneumonia as the primary manifestation. We designed a recombinant Mip-PilE-FlaA dominant epitopes vaccine against Legionella pneumophila to prevent the disease and evaluated its immunogenicity and protective immunity. The protein structures of Mip, PilE and FlaA were analyzed using a computer, and the gene sequences of the dominant epitopes of the three proteins were selected to construct and optimize the vaccine. The optimized mip, pilE, flaA and recombinant mip-pilE-flaA gene sequences were cloned, expressed and purified. The purified proteins were used as dominant epitopes vaccines to immunize BALB/c mice and determine the protective immunity and immunogenicity of these purified proteins. The identification confirmed that the recombinant mip-pilE-flaA was successfully cloned and expressed. ELISA revealed that the Mip-PilE-FlaA group produced the highest IgG response, and this protein may considerably improve the production of some cytokines in BALB/c mice. Histopathology analyses of lungs from mice immunized with Mip-PilE-FlaA revealed a certain protective effect. Our work demonstrated that the recombinant dominant epitopes of Mip-PilE-FlaA exhibited strong immunogenicity and immune protection, and this protein may be an efficient epitopes vaccine candidate against Legionella pneumophila. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  13. The Vaccine Candidate Vibrio cholerae 638 Is Protective against Cholera in Healthy Volunteers

    Science.gov (United States)

    García, Luis; Jidy, Manuel Díaz; García, Hilda; Rodríguez, Boris L.; Fernández, Roberto; Año, Gemma; Cedré, Bárbara; Valmaseda, Tania; Suzarte, Edith; Ramírez, Margarita; Pino, Yadira; Campos, Javier; Menéndez, Jorge; Valera, Rodrigo; González, Daniel; González, Irma; Pérez, Oliver; Serrano, Teresita; Lastre, Miriam; Miralles, Fernando; del Campo, Judith; Maestre, Jorge Luis; Pérez, José Luis; Talavera, Arturo; Pérez, Antonio; Marrero, Karen; Ledón, Talena; Fando, Rafael

    2005-01-01

    Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXΦ prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 109 CFU of freshly harvested 638 buffered with 1.3% NaHCO3, while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 109 CFU of ΔCTXΦ attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 × 105 CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO3. Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (109 CFU) of strain

  14. Limited variation in vaccine candidate Plasmodium falciparum Merozoite Surface Protein-6 over multiple transmission seasons

    Directory of Open Access Journals (Sweden)

    Branch OraLee H

    2010-05-01

    same community. By contrast, PfMSP6 was highly stable at the sequence level, with no SNPs detected in the 506 samples analysed. This limited diversity supports further investigation of PfMSP6 as a blood stage vaccine candidate, with the clear caveat that any such vaccine must either contain both alleles or generate cross-protective responses that react against both allele classes. Detailed immunoepidemiology studies are needed to establish the viability of these approaches before PfMSP6 advances further down the vaccine development pipeline.

  15. Leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.

    Science.gov (United States)

    Lakshmi, Bhavana Sethu; Wang, Ruobing; Madhubala, Rentala

    2014-06-24

    Leishmaniasis is a neglected tropical disease caused by Leishmania species. It is a major health concern affecting 88 countries and threatening 350 million people globally. Unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. The emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. The genome sequence of Leishmania, provides access to novel genes that hold potential as chemotherapeutic targets or vaccine candidates. In this study, we selected 19 antigenic genes from about 8000 common Leishmania genes based on the Leishmania major and Leishmania infantum genome information available in the pathogen databases. Potential vaccine candidates thus identified were screened using an in vitro high throughput immunological platform developed in the laboratory. Four candidate genes coding for tuzin, flagellar glycoprotein-like protein (FGP), phospholipase A1-like protein (PLA1) and potassium voltage-gated channel protein (K VOLT) showed a predominant protective Th1 response over disease exacerbating Th2. We report the immunogenic properties and protective efficacy of one of the four antigens, tuzin, as a DNA vaccine against Leishmania donovani challenge. Our results show that administration of tuzin DNA protected BALB/c mice against L. donovani challenge and that protective immunity was associated with higher levels of IFN-γ and IL-12 production in comparison to IL-4 and IL-10. Our study presents a simple approach to rapidly identify potential vaccine candidates using the exhaustive information stored in the genome and an in vitro high-throughput immunological platform. Copyright © 2014. Published by Elsevier Ltd.

  16. Increased efficacy of inactivated vaccine candidates prepared with Salmonella enterica serovar Typhimurium strains of predominant genotypes in ducks.

    Science.gov (United States)

    Youn, S Y; Kwon, Y K; Song, C S; Lee, H J; Jeong, O M; Choi, B K; Jung, S C; Kang, M S

    2016-08-01

    Salmonella enterica serovar Typhimurium has been a major causative agent of food-borne human disease, mainly due to consumption of contaminated food animal products. In particular, ducks serve as a reservoir of serovar Typhimurium, and are one of the common sources of human infection. To prevent infection of ducks, and therefore minimize human infection, it is critical to control the persistent epidemic strains in ducks. Here, we analyzed the genetic diversity and virulence of serovar Typhimurium isolates from ducks in Korea to identify the predominant strains that might be used as efficient vaccine candidates for ducks. Among the isolates, 2 representative isolates (ST26 and ST76) of predominant genotypes were selected as vaccine strains on the basis of genotypic analysis by pulsed-field gel electrophoresis and DNA microarrays. Two-week-old ducks were then injected intramuscularly with inactivated vaccine candidates prepared using ST26 or ST76 (10(8) cfu/0.5 mL/duck or 10(9) cfu/0.5 mL/duck), and oral challenge with a highly virulent serovar Typhimurium strain (10(9) cfu/0.5 mL/duck) was carried out 2 wk later. Shedding of the challenge strain was significantly decreased in group 2 after vaccination. The antibody levels by enzyme-linked immunosorbent assay in all vaccinated groups were enhanced significantly (P < 0.05) compared to the unvaccinated control group. Overall, vaccination with ST26 or ST76 reduced bacterial shedding and colonization in internal organs, and induced elevated antibody response. In particular, serovar Typhimurium ST26 (10(8) cfu/0.5 mL/duck) was the most effective vaccine candidate, which can provide efficient protection against serovar Typhimurium in ducks with higher effectiveness compared to a commercial vaccine currently used worldwide. © 2016 Poultry Science Association Inc.

  17. Inferior immunogenicity and efficacy of respiratory syncytial virus fusion protein-based subunit vaccine candidates in aged versus young mice.

    Directory of Open Access Journals (Sweden)

    Corinne Cayatte

    Full Text Available Respiratory syncytial virus (RSV is recognized as an important cause of lower and upper respiratory tract infections in older adults, and a successful vaccine would substantially lower morbidity and mortality in this age group. Recently, two vaccine candidates based on soluble purified glycoprotein F (RSV F, either alone or adjuvanted with glucopyranosyl lipid A formulated in a stable emulsion (GLA-SE, failed to reach their primary endpoints in clinical efficacy studies, despite demonstrating the desired immunogenicity profile and efficacy in young rodent models. Here, one of the RSV F vaccine candidates (post-fusion conformation, RSV post-F, and a stabilized pre-fusion form of RSV F (RSV pre-F, DS-Cav1 were evaluated in aged BALB/c mice. Humoral and cellular immunogenicity elicited after immunization of naïve, aged mice was generally lower compared to young animals. In aged mice, RSV post-F vaccination without adjuvant poorly protected the respiratory tract from virus replication, and addition of GLA-SE only improved protection in the lungs, but not in nasal turbinates. RSV pre-F induced higher neutralizing antibody titers compared to RSV post-F (as previously reported but interestingly, RSV F-specific CD8 T cell responses were lower compared to RSV post-F responses regardless of age. The vaccines were also tested in RSV seropositive aged mice, in which both antigen forms similarly boosted neutralizing antibody titers, although GLA-SE addition boosted neutralizing activity only in RSV pre-F immunized animals. Cell-mediated immune responses in the aged mice were only slightly boosted and well below levels induced in seronegative young mice. Taken together, the findings suggest that the vaccine candidates were not able to induce a strong anti-RSV immune response in recipient mice with an aged immune system, in agreement with recent human clinical trial results. Therefore, the aged mouse model could be a useful tool to evaluate improved vaccine

  18. Comparative testing of six antigen-based malaria vaccine candidates directed toward merozoite-stage Plasmodium falciparum

    DEFF Research Database (Denmark)

    Arnot, David E; Cavanagh, David R; Remarque, Edmond J

    2008-01-01

    Immunogenicity testing of Plasmodium falciparum antigens being considered as malaria vaccine candidates was undertaken in rabbits. The antigens compared were recombinant baculovirus MSP-1(19) and five Pichia pastoris candidates, including two versions of MSP-1(19), AMA-1 (domains I and II), AMA-1......G concentrations. The two P. pastoris-produced MSP-1(19)-induced IgGs conferred the lowest growth inhibition. Comparative analysis of immunogenicity of vaccine antigens can be used to prioritize candidates before moving to expensive GMP production and clinical testing. The assays used have given discriminating...

  19. The meningococcal vaccine candidate neisserial surface protein A (NspA binds to factor H and enhances meningococcal resistance to complement.

    Directory of Open Access Journals (Sweden)

    Lisa A Lewis

    2010-07-01

    Full Text Available Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH to fH-binding protein (fHbp is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a approximately 17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA, a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep I chain of lipooligosaccharide (LOS, or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6-7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components.

  20. Identification of New Virulence Factors and Vaccine Candidates for Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Jourdan A. Andersson

    2017-10-01

    -type CO92 in a pneumonic model. Further, evaluation of the attenuated T6SS mutant strains in vitro revealed significant alterations in phagocytosis, intracellular survival in murine macrophages, and their ability to induce cytotoxic effects on macrophages. The results reported here provide further evidence of the utility of the STM screening approach for the identification of novel virulence factors and to possibly target such genes for the development of novel live-attenuated vaccine candidates for plague.

  1. Ten strategies to lower costs, improve quality, and engage patients: the view from leading health system CEOs.

    Science.gov (United States)

    Cosgrove, Delos M; Fisher, Michael; Gabow, Patricia; Gottlieb, Gary; Halvorson, George C; James, Brent C; Kaplan, Gary S; Perlin, Jonathan B; Petzel, Robert; Steele, Glenn D; Toussaint, John S

    2013-02-01

    Patient-centeredness--the idea that care should be designed around patients' needs, preferences, circumstances, and well-being--is a central tenet of health care delivery. For CEOs of health care organizations, patient-centered care is also quickly becoming a business imperative, with payments tied to performance on measures of patient satisfaction and engagement. In A CEO Checklist for High-Value Health Care, we, as executives of eleven leading health care delivery institutions, outlined ten key strategies for reducing costs and waste while improving outcomes. In this article we describe how implementation of these strategies benefits both health care organizations and patients. For example, Kaiser Permanente's Healthy Bones Program resulted in a 30 percent reduction in hip fracture rates for at-risk patients. And at Virginia Mason Health System in Seattle, nurses reorganized care patterns and increased the time they spent on direct patient care to 90 percent. Our experiences show that patient-engaged care can be delivered in ways that simultaneously improve quality and reduce costs.

  2. Ten-Year Monitored Natural Recovery of Lead-Contaminated Mine Tailing in Klity Creek, Kanchanaburi Province, Thailand.

    Science.gov (United States)

    Phenrat, Tanapon; Otwong, Ashijya; Chantharit, Aphichart; Lowry, Gregory V

    2016-10-01

    Klity Creek has become Thailand's first official remediation ordered by the court in 2013, 15 years after the spill of lead (Pb)-contaminated mine tailing into the creek. The Pollution Control Department (PCD) decided to restore the creek through monitored natural recovery (MNR) since 2006 but has not been successful. Interestingly, the most recent remediation plan in 2015 will still apply MNR to five out of the seven portions of the creek, despite no scientific feasibility evaluation of using MNR to restore the creek. This study qualitatively and quantitatively evaluated the feasibility of using MNR to clean up the creek in order to protect the Klity children from excess Pb exposure. We analyzed the physical and chemical transformation of Pb contaminated sediment in the creek and developed a remedial action goal and cleanup level using the Integrated Exposure Uptake Biokinetic model (IEUBK). We empirically determined the natural recovery (NR) potentials and rates using 10 years of data monitoring the water and sediment samples from eight monitoring stations (KC1 to KC8). Klity Creek has NR potential for water except at KC2, which is closest to the spill and the other improperly managed Pb sources. However, the creek has no NR potential for sediment except at the KC8 location (NR rate = 11.1 ± 3.0 × 10-3 month-1) farthest from the spill. The MNR method is not suitable to use as the sole remedial approach for Klity Creek (KC2 to KC7). Although MNR is applicable at KC8, it may require up to 377 ± 76 years to restore the sediment to the background Pb concentration. Phenrat T, Otwong A, Chantharit A, Lowry GV. 2016. Ten-year monitored natural recovery of lead-contaminated mine tailing in Klity Creek, Kanchanaburi Province, Thailand. Environ Health Perspect 124:1511-1520; http://dx.doi.org/10.1289/EHP215.

  3. Tomatine Adjuvantation of Protective Immunity to a Major Pre-erythrocytic Vaccine Candidate of Malaria is Mediated via CD8+ T Cell Release of IFN-γ

    Directory of Open Access Journals (Sweden)

    Karen G. Heal

    2010-01-01

    Full Text Available The glycoalkaloid tomatine, derived from the wild tomato, can act as a powerful adjuvant to elicit an antigen-specific cell-mediated immune response to the circumsporozoite (CS protein, a major pre-erythrocytic stage malaria vaccine candidate antigen. Using a defined MHC-class-I-restricted CS epitope in a Plasmodium berghei rodent model, antigen-specific cytotoxic T lymphocyte activity and IFN-γ secretion ex vivo were both significantly enhanced compared to responses detected from similarly stimulated splenocytes from naive and tomatine-saline-immunized mice. Further, through lymphocyte depletion it is demonstrated that antigen-specific IFN-γ is produced exclusively by the CD8+ T cell subset. We conclude that the processing of the P. berghei CS peptide as an exogenous antigen and its presentation via MHC class I molecules to CD8+ T cells leads to an immune response that is an in vitro correlate of protection against pre-erythrocytic malaria. Further characterization of tomatine as an adjuvant in malaria vaccine development is indicated.

  4. Evaluation of Borrelia burgdorferi BbHtrA Protease as a Vaccine Candidate for Lyme Borreliosis in Mice.

    Directory of Open Access Journals (Sweden)

    Amy J Ullmann

    Full Text Available Borrelia burgdorferi synthesizes an HtrA protease (BbHtrA which is a surface-exposed, conserved protein within Lyme disease spirochetes with activity toward CheX and BmpD of Borrelia spp, as well as aggrecan, fibronectin and proteoglycans found in skin, joints and neural tissues of vertebrates. An antibody response against BbHtrA is observed in Lyme disease patients and in experimentally infected laboratory mice and rabbits. Given the surface location of BbHtrA on B. burgdorferi and its ability to elicit an antibody response in infected hosts, we explored recombinant BbHtrA as a potential vaccine candidate in a mouse model of tick-transmitted Lyme disease. We immunized mice with two forms of BbHtrA: the proteolytically active native form and BbHtrA ablated of activity by a serine to alanine mutation at amino acid 226 (BbHtrA(S226A. Although inoculation with either BbHtrA or BbHtrA(S226A produced high-titer antibody responses in C3H/HeJ mice, neither antigen was successful in protecting mice from B. burgdorferi challenge. These results indicate that the search for novel vaccine candidates against Lyme borreliosis remains a challenge.

  5. Identification of L. infantum chagasi proteins in VL patients' urine: a promising antigen discovery approach of vaccine candidates

    Science.gov (United States)

    Kashino, Suely S.; Abeijon, Claudia; Qin, Lizeng; Kanunfre, Kelly A.; Kubrusly, Flávia S.; Silva, Fernando O.; Costa, Dorcas L.; Campos, Dioclécio; Costa, Carlos H.N.; Raw, Isaias; Campos-Neto, Antonio

    2012-01-01

    Visceral leishmaniasis (VL) is a serious lethal parasitic disease caused by Leishmania donovani in Asia and by Leishmania infantum chagasi in Southern Europe and South America. VL is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. This high incidence is due in part to the lack of an efficacious vaccine. Here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with VL. We combined RP-HPLC and mass spectrometry and categorized three L. infantum chagasi proteins, presumably produced in spleen, liver, and bone marrow lesions and excreted in the patients’ urine. Specifically, these proteins were the following: Li-isd1 (XP_001467866.1), Li-txn1 (XP_001466642.1), and Li-ntf2 (XP_001463738.1). Initial vaccine validation studies were performed with the rLi-ntf2 protein produced in E. coli mixed with the adjuvant BpMPLA-SE. This formulation stimulated potent Th1 response in BALB/c mice. Compared to control animals, mice immunized with Li-ntf2 + BpMPLASE had a marked parasite burden reduction in spleens at 40 days post-challenge with virulent L. infantum chagasi. These results strongly support the proposed antigen discovery strategy of vaccine candidates to kala-azar and opens novel possibilities for vaccine development to other serious infectious diseases. PMID:22443237

  6. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roger Le Grand

    2013-07-01

    Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  7. Identification of putative vaccine candidates against Helicobacter pylori exploiting exoproteome and secretome: a reverse vaccinology based approach.

    Science.gov (United States)

    Naz, Anam; Awan, Faryal Mehwish; Obaid, Ayesha; Muhammad, Syed Aun; Paracha, Rehan Zafar; Ahmad, Jamil; Ali, Amjad

    2015-06-01

    Helicobacter pylori (H. pylori) is an important pathogen associated with diverse gastric disorders ranging from peptic ulcer to malignancy. It has also been recognized by the World Health Organization (WHO) as class I carcinogen. Conventional treatment regimens for H. pylori seem to be ineffective, possibly due to antibiotic resistance mechanisms acquired by the pathogen. In this study we have successfully employed a reverse vaccinology approach to predict the potential vaccine candidates against H. pylori. The predicted potential vaccine candidates include vacA, babA, sabA, fecA and omp16. Host-pathogen interactions analysis elaborated their direct or indirect role in the specific signaling pathways including epithelial cell polarity, metabolism, secretion system and transport. Furthermore, surface-exposed antigenic epitopes were predicted and analyzed for conservation among 39 complete genomes of H. pylori (Genbank) for all the candidate proteins. These epitopes may serve as a base for the development of broad spectrum peptide or multi-component vaccines against H. pylori. We also believe that the proposed pipeline can be extended to other pathogens and for the identification of novel candidates for the development of effective vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Immunoprotective efficacy of Acinetobacter baumannii outer membrane protein, FilF, predicted in silico as a potential vaccine candidate

    Directory of Open Access Journals (Sweden)

    Ravinder eSingh

    2016-02-01

    Full Text Available Acinetobacter baumannii is emerging as a serious nosocomial pathogen with multidrug resistance that has made it difficult to cure and development of efficacious treatment against this pathogen is direly needed. This has led to investigate vaccine approach to prevent and treat A. baumannii infections. In this work, an outer membrane putative pilus assembly protein, FilF, was predicted as vaccine candidate by in silico analysis of A. baumannii proteome and was found to be conserved among the A. baumannii strains. It was cloned and expressed in E. coli BL21(DE3 and purified by Ni-NTA chromatography. Immunization with FilF generated high antibody titer (>64000 and provided 50% protection against a standardized lethal dose (10*8 CFU of A. baumannii in murine pneumonia model. FilF immunization reduced the bacterial load in lungs by 2 and 4 log cycles, 12 and 24 h post infection as compared to adjuvant control; reduced the levels of pro-inflammatory cytokines TNF-α, IL-6, IL-33, IFN-γ and IL-1β significantly and histology of lung tissue supported the data by showing considerably reduced damage and infiltration of neutrophils in lungs. These results demonstrate the in vivo validation of immunoprotective efficacy of a protein predicted as a vaccine candidate by in silico proteomic analysis and open the possibilities for exploration of a large array of uncharacterized proteins.

  9. Advances in the characterization of a proteol iposome derived from Mycobacterium bovis BCG as vaccine candidate against tuberculosis

    Directory of Open Access Journals (Sweden)

    Nadine Alvarez-Cabrera

    2014-12-01

    Full Text Available Despite efforts to eradicate tuberculosis (TB worldwide, this remains a serious health problem. The Bacillus Calmette-Guerin (BCG, the only available vaccine against TB, has variable efficacy and though protects against severe forms of the disease in childhood, has a questionable role in the protection against pulmonary tuberculosis in adults. In recent years, new TB vaccine candidates are being developed using multiple vaccine strategies. Taking into account the antigenic similarity of M. bovis BCG and M. tuberculosis, and the history of the use of proteoliposomes in vaccine formulations, we aimed to study the potentialities of a proteoliposome derived from M. bovis BCG (PLBCG as a potential vaccine candidate against TB. The results demonstrate that a PLBCG was obtained, which was observed by different techniques and that is composed of nanoparticulate vesicles. Additionally, analysis by SDSPAGE followed by Coomassie stained showed the presence of several protein bands on PLBCG whose molecular size may correspond with that reported for M. bovis BCG protein having homology to M. tuberculosis.

  10. Development and evaluation of two subunit vaccine candidates containing antigens of hepatitis E virus, rotavirus, and astrovirus.

    Science.gov (United States)

    Xia, Ming; Wei, Chao; Wang, Leyi; Cao, Dianjun; Meng, Xiang-Jin; Jiang, Xi; Tan, Ming

    2016-05-19

    Hepatitis E virus (HEV), rotavirus (RV), and astrovirus (AstV) are important pathogens that transmit through a common fecal-oral route, causing hepatitis (HEV) and gastroenteritis (RV and AstV) respectively in humans. In this study, we developed and evaluated two subunit vaccine candidates that consisted of the same protruding or spike protein antigens of the three viruses in two formats, a fusion of the three antigens into one molecule (fused vaccine) vs. a mixture of the three free antigens together (mixed vaccine). Both vaccines were easily made via E. coli expression system. Mouse immunization experiments showed that the fused vaccine elicited significantly higher antibody responses against the three viral antigens than those induced by the mixed vaccine. In addition, the mouse post-immune antisera of the fused vaccine revealed significantly higher neutralizing titers against HEV infection in cell culture, as well as significantly higher 50% blocking titers (BT50) against RV VP8-HBGA receptor interactions than those of the post-immune antisera after immunization of the mixed vaccine. Thus, the fused vaccine is a promising trivalent vaccine candidate against HEV, RV, and AstV, which is worth for further development.

  11. Sequential chemoimmunotherapy of experimental visceral leishmaniasis using a single low dose of liposomal amphotericin B and a novel DNA vaccine candidate.

    Science.gov (United States)

    Seifert, Karin; Juhls, Christiane; Salguero, Francisco J; Croft, Simon L

    2015-09-01

    Combination therapies for leishmaniasis, including drugs and immunomodulators, are one approach to shorten treatment courses and to improve the treatment of complex manifestations of the disease. We evaluated a novel T-cell-epitope-enriched DNA vaccine candidate (LEISHDNAVAX) as host-directed immunotherapy in combination with a standard antileishmanial drug in experimental visceral leishmaniasis. Here we show that the DNA vaccine candidate can boost the efficacy of a single suboptimal dose of liposomal amphotericin B in C57BL/6 mice. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Neospora caninum immune mapped protein 1 (NcIMP1 is a novel vaccine candidate against neosporosis

    Directory of Open Access Journals (Sweden)

    Xia CUI,Daoyu YANG,Tao LEI,Hui WANG,Pan HAO,Qun LIU

    2015-03-01

    Full Text Available The Neospora caninum immune mapped protein 1 (NcIMP1 was identified as a membrane protein, and a previous study indicated that NcIMP1 could be a promising vaccine candidate against neosporosis. In this study, the immune response and protection efficacy of NcIMP1 were evaluated. The coding sequence of NcIMP1 was inserted into the eukaryotic expression vector pcDNA 3.1(+, resulting in the recombination plasmid pcDNA-IMP1, which was used for the intramuscular immunization of BALB/c mice. After immunization, the immune response was evaluated using a lymphoproliferative assay and cytokine and antibody measurements. Quantification of the cerebral parasite burden of mice challenged with 2 × 106N. caninum was performed 14 days after the last immunization. The results showed that the mice immunized with pcDNA-IMP1 developed a high level of specific antibody responses against recombinant NcIMP1, with a mixed IgG1/IgG2a response and a predominance of IgG2a production. The cellular immune response was associated with the production of IFN-&Ggr;, IL-2, IL-4 and IL-10 cytokines. The experiment was terminated 30 days p.i., and the cerebral parasite burden in each mouse was assessed by quantitative PCR. The parasite burden was significantly reduced in the pcDNA-IMP1-vaccinated mice. These data suggest that IMP1 is a promising vaccine candidate against neosporosis.

  13. Predicted Coverage and Immuno-Safety of a Recombinant C-Repeat Region Based Streptococcus pyogenes Vaccine Candidate.

    Science.gov (United States)

    McNeilly, Celia; Cosh, Samantha; Vu, Therese; Nichols, Jemma; Henningham, Anna; Hofmann, Andreas; Fane, Anne; Smeesters, Pierre R; Rush, Catherine M; Hafner, Louise M; Ketheesan, Natkuman; Sriprakash, Kadaba S; McMillan, David J

    2016-01-01

    The C-terminal region of the M-protein of Streptococcus pyogenes is a major target for vaccine development. The major feature is the C-repeat region, consisting of 35-42 amino acid repeat units that display high but not perfect identity. SV1 is a S. pyogenes vaccine candidate that incorporates five 14mer amino acid sequences (called J14i variants) from differing C-repeat units in a single recombinant construct. Here we show that the J14i variants chosen for inclusion in SV1 are the most common variants in a dataset of 176 unique M-proteins. Murine antibodies raised against SV1 were shown to bind to each of the J14i variants present in SV1, as well as variants not present in the vaccine. Antibodies raised to the individual J14i variants were also shown to bind to multiple but different combinations of J14i variants, supporting the underlying rationale for the design of SV1. A Lewis Rat Model of valvulitis was then used to assess the capacity of SV1 to induce deleterious immune response associated with rheumatic heart disease. In this model, both SV1 and the M5 positive control protein were immunogenic. Neither of these antibodies were cross-reactive with cardiac myosin or collagen. Splenic T cells from SV1/CFA and SV1/alum immunized rats did not proliferate in response to cardiac myosin or collagen. Subsequent histological examination of heart tissue showed that 4 of 5 mice from the M5/CFA group had valvulitis and inflammatory cell infiltration into valvular tissue, whereas mice immunised with SV1/CFA, SV1/alum showed no sign of valvulitis. These results suggest that SV1 is a safe vaccine candidate that will elicit antibodies that recognise the vast majority of circulating GAS M-types.

  14. Immunogenicity of a virosomally-formulated Plasmodium falciparum GLURP-MSP3 chimeric protein-based malaria vaccine candidate in comparison to adjuvanted formulations

    DEFF Research Database (Denmark)

    Tamborrini, Marco; Stoffel, Sabine A; Westerfeld, Nicole

    2011-01-01

    In clinical trials, immunopotentiating reconstituted influenza virosomes (IRIVs) have shown great potential as a versatile antigen delivery platform for synthetic peptides derived from Plasmodium falciparum antigens. This study describes the immunogenicity of a virosomally-formulated recombinant ...... fusion protein comprising domains of the two malaria vaccine candidate antigens MSP3 and GLURP....

  15. A virus-like particle vaccine candidate for influenza A virus based on multiple conserved antigens presented on hepatitis B tandem core particles.

    Science.gov (United States)

    Ramirez, Alejandro; Morris, Stephen; Maucourant, Sophie; D'Ascanio, Isabella; Crescente, Vincenzo; Lu, I-Na; Farinelle, Sophie; Muller, Claude P; Whelan, Michael; Rosenberg, William

    2018-02-01

    Existing Influenza A virus (IAV) vaccines target variable parts of the virus that may change between seasons. Vaccine design relies on predicting the predominant circulating influenza strains but when there is a mismatch between vaccine and circulating strains, efficacy is sub-optimal. Furthermore, current approaches provide limited protection against emerging influenza strains that may cause pandemics. One solution is to design vaccines that target conserved protein domains of influenza, which remain largely unchanged over time and are likely to be found in emergent variants. We present a virus-like particle (VLP), built using the hepatitis B virus tandem core platform, as an IAV vaccine candidate containing multiple conserved antigens. Hepatitis B core protein spontaneously assembles into a VLP that is immunogenic and confers immunogenicity to proteins incorporated into the major insertion region (MIR) of core monomers. However, insertion of antigen sequences may disrupt particle assembly preventing VLP formation or result in unstable particles. We have overcome these problems by genetically manipulating the hepatitis B core to express core monomers in tandem, ligated with a flexible linker, incorporating different antigens at each of the MIRs. Immunisation with this VLP, named Tandiflu1, containing 4 conserved antigens from matrix protein 2 ectodomain and hemagglutinin stalk, leads to production of cross-reactive and protective antibodies. The polyclonal antibodies induced by Tandiflu1 can bind IAV Group 1 hemagglutinin types H1, H5, H11, H9, H16 and a conserved epitope on matrix protein 2 expressed by most strains of IAV. Vaccination with Tandiflu1 results in 100% protection from a lethal influenza challenge with H1N1 IAV. Serum transfer from vaccinated animals is sufficient to confer protection from influenza-associated illness in naïve mice. These data suggest that a Tandem Core based IAV vaccine might provide broad protection against common and emergent H1

  16. Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates.

    Science.gov (United States)

    Todd, Thomas E; Tibi, Omar; Lin, Yu; Sayers, Samantha; Bronner, Denise N; Xiang, Zuoshuang; He, Yongqun

    2013-01-01

    Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and challenge pathogen strain

  17. Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

    Science.gov (United States)

    2013-01-01

    Background Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. Results Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and

  18. Enzymatic shaving of the tegument surface of live schistosomes for proteomic analysis: a rational approach to select vaccine candidates.

    Directory of Open Access Journals (Sweden)

    William Castro-Borges

    2011-03-01

    Full Text Available The membrane-associated and membrane-spanning constituents of the Schistosoma mansoni tegument surface, the parasite's principal interface with the host bloodstream, have recently been characterized using proteomic techniques. Biotinylation of live worms using membrane-impermeant probes revealed that only a small subset of the proteins was accessible to the reagents. Their position within the multilayered architecture of the surface has not been ascertained.An enzymatic shaving approach on live worms has now been used to release the most accessible components, for analysis by MS/MS. Treatment with trypsin, or phosphatidylinositol-specific phospholipase C (PiPLC, only minimally impaired membrane integrity. PiPLC-enriched proteins were distinguished from those released in parasite vomitus or by handling damage, using isobaric tagging. Trypsin released five membrane proteins, Sm200, Sm25 and three annexins, plus host CD44 and the complement factors C3 and C4. Nutrient transporters and ion channels were absent from the trypsin fraction, suggesting a deeper location in the surface complex; surprisingly, two BAR-domain containing proteins were released. Seven parasite and two host proteins were enriched by PiPLC treatment, the vaccine candidate Sm29 being the most prominent along with two orthologues of human CD59, potentially inhibitors of complement fixation. The enzymes carbonic anhydrase and APD-ribosyl cyclase were also enriched, plus Sm200 and alkaline phosphatase. Host GPI-anchored proteins CD48 and CD90, suggest 'surface painting' during worm peregrination in the portal system.Our findings suggest that the membranocalyx secreted over the tegument surface is not the inert barrier previously proposed, some tegument proteins being externally accessible to enzymes and thus potentially located within it. Furthermore, the detection of C3 and C4 indicates that the complement cascade is initiated, while two CD59 orthologues suggest a potential

  19. Polymorphism in liver-stage malaria vaccine candidate proteins: immune evasion and implications for vaccine design.

    Science.gov (United States)

    Flanagan, Katie L; Wilson, Kirsty L; Plebanski, Magdalena

    2016-01-01

    The pre-erythrocytic stage of infection by malaria parasites represents a key target for vaccines that aim to eradicate malaria. Two important broad immune evasion strategies that can interfere with vaccine efficacy include the induction of dendritic cell (DC) dysfunction and regulatory T cells (Tregs) by blood-stage malaria parasites, leading to inefficient priming of T cells targeting liver-stage infections. The parasite also uses 'surgical strike' strategies, whereby polymorphism in pre-erythrocytic antigens can interfere with host immunity. Specifically, we review how even single amino acid changes in T cell epitopes can lead to loss of binding to major histocompatibility complex (MHC), lack of cross-reactivity, or antagonism and immune interference, where simultaneous or sequential stimulation with related variants of the same T cell epitope can cause T cell anergy or the conversion of effector to immunosuppressive T cell phenotypes.

  20. Comparative evaluation of two vaccine candidates against experimental leishmaniasis due to Leishmania major infection in four inbred mouse strains.

    Science.gov (United States)

    Benhnini, Fouad; Chenik, Mehdi; Laouini, Dhafer; Louzir, Hechmi; Cazenave, Pierre André; Dellagi, Koussay

    2009-11-01

    Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders that also support the development of experimental leishmaniasis due to L. major. In this study, we sought to determine whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins, namely, LACK (for Leishmania homolog of receptor for activated C kinase) and LmPDI (for L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c, and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in outbred human populations and should be selected for clinical trials.

  1. Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due to Leishmania major Infection in Four Inbred Mouse Strains▿

    Science.gov (United States)

    Benhnini, Fouad; Chenik, Mehdi; Laouini, Dhafer; Louzir, Hechmi; Cazenave, Pierre André; Dellagi, Koussay

    2009-01-01

    Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders that also support the development of experimental leishmaniasis due to L. major. In this study, we sought to determine whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins, namely, LACK (for Leishmania homolog of receptor for activated C kinase) and LmPDI (for L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c, and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in outbred human populations and should be selected for clinical trials. PMID:19726616

  2. Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs.

    Science.gov (United States)

    Avishek, Kumar; Kaushal, Himanshu; Gannavaram, Sreenivas; Dey, Ranadhir; Selvapandiyan, Angamuthu; Ramesh, V; Negi, Narender Singh; Dubey, Uma S; Nakhasi, Hira L; Salotra, Poonam

    2016-09-14

    Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1(-/-) and Ldp27(-/-)) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1(-/-) and Ldp27(-/-) in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1(-/-) and Ldp27(-/-) strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4(+) and CD8(+) T cells and IL-17 secreting CD4(+) cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1(-/-) and Ldp27(-/-) are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure.

  3. Immunogenicity of a new recombinant IpaC from Shigella dysenteriae type I in guinea pig as a vaccine candidate.

    Science.gov (United States)

    Malaei, Fatemeh; Hesaraki, Mahdi; Saadati, Mojtaba; Ahdi, Ali Mohammad; Sadraeian, Mohammad; Honari, Hussein; Nazarian, Shahram

    2013-06-01

    Recombinant vaccine technology is one of the most developed means in controlling infectious diseases. However, an effective vaccine against Shigella is still missing. To evaluate recombinant IpaC protein of Shigella as a vaccine candidate. In this study we cloned IpaC gene into an expression vector in prokaryotic system. The protein expression was evaluated by SDS-PAGE and Western-Blotting analysis. The recombinant protein was purified using Ni-NTA affinity chromatography. Guinea pigs were immunized with the recombinant protein and the level of immunogenicity was examined by ELISA and Western blotting of IpaC. Challenge test was done through the intraoculary injection of Shigella dysenteriae (6×108 CFU/eye) and after 48 hours was scored for keratoconjunctivitis. The results showed a remarkable level of immunogenicity in terms of antibody response and protection against keratoconjunctivitis in tested animals. The recombinant IpaC protein provided a protective system against Shigella dysenteriae type I during the challenge test. The results showed the potential of using recombinant IpaC in preparation of vaccine in perspective studies.

  4. Comparative assessment of transmission-blocking vaccine candidates against Plasmodium falciparum.

    Science.gov (United States)

    Kapulu, M C; Da, D F; Miura, K; Li, Y; Blagborough, A M; Churcher, T S; Nikolaeva, D; Williams, A R; Goodman, A L; Sangare, I; Turner, A V; Cottingham, M G; Nicosia, A; Straschil, U; Tsuboi, T; Gilbert, S C; Long, Carole A; Sinden, R E; Draper, S J; Hill, A V S; Cohuet, A; Biswas, S

    2015-06-11

    Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species, and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform.

  5. Discovery of novel vaccine candidates and drug targets against visceral leishmaniasis using proteomics and transcriptomics.

    Science.gov (United States)

    Kumari, Shraddha; Kumar, Awanish; Samant, Mukesh; Singh, Neeloo; Dube, Anuradha

    2008-11-01

    Among the three clinical forms (cutaneous, mucosal and visceral) of leishmaniasis visceral (VL) one is the most devastating type caused by the invasion of the reticuloendothelial system of human by Leishmania donovani, L. infantum and L. chagasi. India and Sudan account for about half the world's burden of VL. Current control strategy is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. An understanding of resistance mechanism(s) operating in clinical isolates might provide additional leads for the development of new drugs. Further, due to the lack of fully effective treatment the search for novel immune targets is also needed. So far, no vaccine exists for VL despite indications of naturally developing immunity. Therefore, an urgent need for new and effective leishmanicidal agents and for this identification of novel drug and vaccine targets is imperative. The availability of the complete genome sequence of Leishmania has revolutionised many areas of leishmanial research and facilitated functional genomic studies as well as provided a wide range of novel targets for drug designing. Most notably, proteomics and transcriptomics have become important tools in gaining increased understanding of the biology of Leishmania to be explored on a global scale, thus accelerating the pace of discovery of vaccine/drug targets. In addition, these approaches provide the information regarding genes and proteins that are expressed and under which conditions. This review provides a comprehensive view about those proteins/genes identified using proteomics and transcriptomic tools for the development of vaccine/drug against VL.

  6. Recombinant prohibitin protein of Leishmania infantum acts as a vaccine candidate and diagnostic marker against visceral leishmaniasis.

    Science.gov (United States)

    Dias, Daniel S; Ribeiro, Patrícia A F; Martins, Vívian T; Lage, Daniela P; Ramos, Fernanda F; Dias, Anna L T; Rodrigues, Marcella R; Portela, Áquila S B; Costa, Lourena E; Caligiorne, Rachel B; Steiner, Bethina T; Chávez-Fumagalli, Miguel A; Salles, Beatriz C S; Santos, Thaís T O; Silveira, Julia A G; Magalhães-Soares, Danielle F; Roatt, Bruno M; Machado-de-Ávila, Ricardo A; Duarte, Mariana C; Menezes-Souza, Daniel; Silva, Eduardo S; Galdino, Alexsandro S; Coelho, Eduardo A F

    2017-11-09

    Visceral leishmaniasis (VL) represents a serious public health problem, as Leishmania infantum is one of main disease causative agents in the Americas. In a previous immunoproteomic study, the prohibitin (PHB) protein was identified in L. infantum promastigote and amastigote extracts by antibodies in asymptomatic and symptomatic VL dog sera. This protein was found to be highly conserved between different Leishmania spp., but it presented a low identity with amino acid sequences of other organisms. The aim of the present study was to evaluate the cellular response induced by the recombinant PHB (rPHB) protein in BALB/c mice, as well as in PBMCs purified from untreated and treated VL patients, as well as to evaluate its protective efficacy against an infection by L. infantum promastigotes. Our data showed that there was a Th1 cellular response to rPHB, based on high levels of IFN-γ, IL-12, and GM-CSF in the immunized animals, as well as a proliferative response specific to the protein and higher IFN-γ levels induced in PBMCs from individuals who had recovered from the disease. The protection was represented by significant reductions in the parasite load in the animals' spleen, liver, bone marrow, and draining lymph nodes, as compared to results found in the control groups. In addition, an anti-rPHB serology, using a canine and human serological panel, showed a high performance of this protein when diagnosing VL based on high sensitivity and specificity values, as compared to results found for the rA2 antigen and the soluble Leishmania antigenic extract. Our data suggest that PHB has a potential application for the diagnosis of canine and human VL through antibody detection, as well as an application as a vaccine candidate to protect against disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Evaluation of the Schistosoma mansoni Y-box-binding protein (SMYB1 potential as a vaccine candidate against schistosomiasis

    Directory of Open Access Journals (Sweden)

    Silvia Regina Costa Dias

    2014-06-01

    Full Text Available Schistosomiasis is a neglected tropical disease, and after malaria, is the second most important tropical disease in public health. A vaccine that reduces parasitemia is desirable to achieve mass treatment with a low cost. Although potential antigens have been identified and tested in clinical trials, no effective vaccine against schistosomiasis is available. Y-box-binding proteins (YBPs regulate gene expression and participate in a variety of cellular processes, including transcriptional and translational regulation, DNA repair, cellular proliferation, drug resistance and stress responses. The Schistosoma mansoni ortholog of the human YB-1, SMYB1, is expressed in all stages of the parasite life cycle. Although SMYB1 binds to DNA or RNA oligonucleotides, immunohistochemistry assays demonstrated that it is primarily localized in the cytoplasm of parasite cells. In addition, SMYB1 interacts with a protein involved in mRNA processing, suggesting that SMYB1 functions in the turnover, transport and/or stabilization of RNA molecules during post-transcriptional gene regulation. Here we report the potential of SMYB1 as a vaccine candidate. We demonstrate that recombinant SMYB1 stimulates the production of high levels of specific IgG1 antibodies in a mouse model. The observed levels of specific IgG1 and IgG2a antibodies indicate an actual protection against cercariae challenge. Animals immunized with rSMYB1 exhibited a 26% reduction in adult worm burden and a 28% reduction in eggs retained in the liver. Although proteins from the worm tegument are considered optimal targets for vaccine development, this study demonstrates that unexposed cytoplasmic proteins can reduce the load of intestinal worms and the number of eggs retained in the liver.

  8. Evaluation of the Schistosoma mansoni Y-box-binding protein (SMYB1) potential as a vaccine candidate against schistosomiasis.

    Science.gov (United States)

    Dias, Sílvia R C; Boroni, Mariana; Rocha, Elizângela A; Dias, Thomaz L; de Laet Souza, Daniela; Oliveira, Fabrício M S; Bitar, Mainá; Macedo, Andrea M; Machado, Carlos R; Caliari, Marcelo V; Franco, Glória R

    2014-01-01

    Schistosomiasis is a neglected tropical disease, and after malaria, is the second most important tropical disease in public health. A vaccine that reduces parasitemia is desirable to achieve mass treatment with a low cost. Although potential antigens have been identified and tested in clinical trials, no effective vaccine against schistosomiasis is available. Y-box-binding proteins (YBPs) regulate gene expression and participate in a variety of cellular processes, including transcriptional and translational regulation, DNA repair, cellular proliferation, drug resistance, and stress responses. The Schistosoma mansoni ortholog of the human YB-1, SMYB1, is expressed in all stages of the parasite life cycle. Although SMYB1 binds to DNA or RNA oligonucleotides, immunohistochemistry assays demonstrated that it is primarily localized in the cytoplasm of parasite cells. In addition, SMYB1 interacts with a protein involved in mRNA processing, suggesting that SMYB1 functions in the turnover, transport, and/or stabilization of RNA molecules during post-transcriptional gene regulation. Here we report the potential of SMYB1 as a vaccine candidate. We demonstrate that recombinant SMYB1 stimulates the production of high levels of specific IgG1 antibodies in a mouse model. The observed levels of specific IgG1 and IgG2a antibodies indicate an actual protection against cercariae challenge. Animals immunized with rSMYB1 exhibited a 26% reduction in adult worm burden and a 28% reduction in eggs retained in the liver. Although proteins from the worm tegument are considered optimal targets for vaccine development, this study demonstrates that unexposed cytoplasmic proteins can reduce the load of intestinal worms and the number of eggs retained in the liver.

  9. Ex vivo transfection of trout pronephros leukocytes, a model for cell culture screening of fish DNA vaccine candidates.

    Science.gov (United States)

    Ortega-Villaizan, M; Martinez-Lopez, A; Garcia-Valtanen, P; Chico, V; Perez, L; Coll, J M; Estepa, A

    2012-09-07

    DNA vaccination opened a new era in controlling and preventing viral diseases since DNA vaccines have shown to be very efficacious where some conventional vaccines have failed, as it occurs in the case of the vaccines against fish novirhabdoviruses. However, there is a big lack of in vitro model assays with immune-related cells for preliminary screening of in vivo DNA vaccine candidates. In an attempt to solve this problem, rainbow trout pronephros cells in early primary culture were transfected with two plasmid DNA constructions, one encoding the green fluorescent protein (GFP) and another encoding the viral haemorrhagic septicaemia virus (VHSV) glycoprotein G (G(VHSV)) - the only viral antigen which has conferred in vivo protection. After assessing the presence of GFP- and G(VHSV)-expressing cells, at transcription and protein levels, the immune response in transfected pronephros cells was evaluated. At 24h post-transfection, G(VHSV) up-regulated migm and tcr transcripts expression, suggesting activation of B and T cells, as well, a high up-regulation of tnfα gene was observed. Seventy-two hours post-transfection, we detected the up-regulation of mx and tnfα genes transcripts and Mx protein which correlated with the induction of an anti-VHSV state. All together we have gathered evidence for successful transfection of pronephros cells with pAE6G, which correlates with in vivo protection results, and is less time-consuming and more rapid than in vivo assays. Therefore, this outcome opens the possibility to use pronephros cells in early primary culture for preliminary screening fish DNA vaccines as well as to further investigate the function that these cells perform in fish immune response orchestration after DNA immunisation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. CFP10: mFcγ2 as a novel tuberculosis vaccine candidate increases immune response in mouse.

    Science.gov (United States)

    Baghani, Ali Asghar; Soleimanpour, Saman; Farsiani, Hadi; Mosavat, Arman; Yousefi, Masoud; Meshkat, Zahra; Rezaee, Seyed Abdolrahim; Jamehdar, Saeid Amel; Eydgahi, Mohammad Reza Akbari; Sadeghian, Hamid; Ghazvini, Kiarash

    2017-02-01

    Despite treatment with antibiotics and vaccination with BCG, tuberculosis (TB) is still considered as one of the most important public health problems in the world. Therefore, designing and producing a more effective vaccine against TB seems urgently. In this study, immunogenicity of a fusion protein which consisting or comprising CFP-10 from Mycobacterium tuberculosis and the Fc-domain of mouse IgG2a was evaluated as a novel subunit vaccine candidate against TB. The genetic constructs were cloned in pPICZαA expression vector and recombinant vectors (pPICZαA-CFP-10: Fcγ2a and pPICZαA-CFP-10:His) were transformed into Pichia pastoris. To evaluate the expression of recombinant proteins, SDS-PAGE and immunoblotting were used. The immunogenicity of recombinant proteins, with and without BCG were assessed in BALB/c mice and specific cytokines against recombinant proteins (IFN-γ, IL-12, IL-4, IL-17 and TGF-β) were evaluated. The levels of IFN-γ and IL-12 in mice that received recombinant proteins was higher than the control groups (BCG and PBS). Thus, both recombinant proteins (CFP-10:Fcγ2a and CFP-10:His) could excite good response in Th1-cells. The Fc-tagged protein had a stronger Th1 response with low levels of IL-4, as compared to CFP-10:His. However, the highest level of Th1 response was observed in groups that were vaccinated with BCG (prime) and then received recombinant protein CFP-10: Fcγ2a (booster). The results demonstrated that binding mice Fc-domain to CFP-10 protein can increase the immunogenicity of the subunit vaccine. Further studies, might be able to design and produce a new generation of subunit vaccines based on the Fc-fused immunogen.

  11. Optimization and scale-up of cell culture and purification processes for production of an adenovirus-vectored tuberculosis vaccine candidate.

    Science.gov (United States)

    Shen, Chun Fang; Jacob, Danielle; Zhu, Tao; Bernier, Alice; Shao, Zhongqi; Yu, Xuefeng; Patel, Mehul; Lanthier, Stephane; Kamen, Amine

    2016-06-17

    Tuberculosis (TB) is the second leading cause of death by infectious disease worldwide. The only available TB vaccine is the Bacille Calmette-Guerin (BCG). However, parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. AdAg85A, an adenoviral vector expressing the mycobacterial protein Ag85A, is a new tuberculosis vaccine candidate, and has shown promising results in pre-clinical studies and phase I trial. This adenovirus vectored vaccine is produced using HEK 293 cell culture. Here we report on the optimization of cell culture conditions, scale-up of production and purification of the AdAg85A at different scales. Four commercial serum-free media were evaluated under various conditions for supporting the growth of HEK293 cell and production of AdAg85A. A culturing strategy was employed to take advantages of two culture media with respective strengths in supporting the cell growth and virus production, which enabled to maintain virus productivity at higher cell densities and resulted in more than two folds of increases in culture titer. The production of AdAg85A was successfully scaled up and validated at 60L bioreactor under the optimal conditions. The AdAg85A generated from the 3L and 60L bioreactor runs was purified through several purification steps. More than 98% of total cellular proteins was removed, over 60% of viral particles was recovered after the purification process, and purity of AdAg85A was similar to that of the ATCC VR-1516 Ad5 standard. Vaccination of mice with the purified AdAg85A demonstrated a very good level of Ag85A-specific antibody responses. The optimized production and purification conditions were transferred to a GMP facility for manufacturing of AdAg85A for generation of clinical grade material to support clinical trials. Crown Copyright © 2016. Published by Elsevier Ltd. All rights

  12. Serum-free microcarrier based production of replication deficient Influenza vaccine candidate virus lacking NS1 using Vero cells

    Directory of Open Access Journals (Sweden)

    Yan Mylene L

    2011-08-01

    Full Text Available Abstract Background Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1 gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Results Five commercially available animal-component free, serum-free media (SFM were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 μg/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. Conclusions We describe for the

  13. Serum-free microcarrier based production of replication deficient influenza vaccine candidate virus lacking NS1 using Vero cells.

    Science.gov (United States)

    Chen, Allen; Poh, Swan Li; Dietzsch, Christian; Roethl, Elisabeth; Yan, Mylene L; Ng, Say Kong

    2011-08-11

    Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1) gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Five commercially available animal-component free, serum-free media (SFM) were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 μg/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. We describe for the first time the production of Influenza viruses using Vero

  14. In vitro evaluation of a soluble Leishmania promastigote surface antigen as a potential vaccine candidate against human leishmaniasis.

    Science.gov (United States)

    Chamakh-Ayari, Rym; Bras-Gonçalves, Rachel; Bahi-Jaber, Narges; Petitdidier, Elodie; Markikou-Ouni, Wafa; Aoun, Karim; Moreno, Javier; Carrillo, Eugenia; Salotra, Poonam; Kaushal, Himanshu; Negi, Narender Singh; Arevalo, Jorge; Falconi-Agapito, Francesca; Privat, Angela; Cruz, Maria; Pagniez, Julie; Papierok, Gérard-Marie; Rhouma, Faten Bel Haj; Torres, Pilar; Lemesre, Jean-Loup; Chenik, Mehdi; Meddeb-Garnaoui, Amel

    2014-01-01

    PSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L. braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals were subdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantum infection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high or low levels of IFN-γ in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detected in sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more. No significant cytokine response was observed in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increase in CD4+ T cells producing IFN-γ after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ. We showed that the LaPSA-38S protein was able to induce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infection indicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection.

  15. A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions.

    Directory of Open Access Journals (Sweden)

    Jessica B Hostetler

    2015-12-01

    Full Text Available A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC, and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion.We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further suggesting that the proteins

  16. Recoding of the vesicular stomatitis virus L gene by computer-aided design provides a live, attenuated vaccine candidate.

    Science.gov (United States)

    Wang, Bingyin; Yang, Chen; Tekes, Gergely; Mueller, Steffen; Paul, Aniko; Whelan, Sean P J; Wimmer, Eckard

    2015-03-31

    analyzed in both cell culture and an animal model. One such recombinant virus, L1(sdmax), contained extra overrepresented codon pairs in its L gene open reading frame (ORF) and showed promise as an effective vaccine candidate because of a favorable balance between virulence and immunogenicity. Our study not only contributes to the understanding of the underlying mechanism of codon pair bias but also may facilitate the development of live attenuated vaccines for other viruses in the order Mononegavirales. Copyright © 2015 Wang et al.

  17. In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

    Science.gov (United States)

    Bahi-Jaber, Narges; Petitdidier, Elodie; Markikou-Ouni, Wafa; Aoun, Karim; Moreno, Javier; Carrillo, Eugenia; Salotra, Poonam; Kaushal, Himanshu; Negi, Narender Singh; Arevalo, Jorge; Falconi-Agapito, Francesca; Privat, Angela; Cruz, Maria; Pagniez, Julie; Papierok, Gérard-Marie; Rhouma, Faten Bel Haj; Torres, Pilar; Lemesre, Jean-Loup; Chenik, Mehdi; Meddeb-Garnaoui, Amel

    2014-01-01

    PSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L. braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals were subdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantum infection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high or low levels of IFN-γ in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detected in sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more. No significant cytokine response was observed in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increase in CD4+ T cells producing IFN-γ after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ. We showed that the LaPSA-38S protein was able to induce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infection indicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection. PMID:24786587

  18. In vitro evaluation of a soluble Leishmania promastigote surface antigen as a potential vaccine candidate against human leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Rym Chamakh-Ayari

    Full Text Available PSA (Promastigote Surface Antigen belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L. species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm or L. braziliensis (CCLb or visceral leishmaniasis due to L. donovani (CVLd and in healthy individuals. Healthy individuals were subdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantum infection or non immune/naive individuals (HLR: Healthy Low Responders, depending on whether they produce high or low levels of IFN-γ in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detected in sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more. No significant cytokine response was observed in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increase in CD4+ T cells producing IFN-γ after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ. We showed that the LaPSA-38S protein was able to induce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infection indicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection.

  19. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    Directory of Open Access Journals (Sweden)

    Li Pinghua

    2012-05-01

    wild O/HN/CHA/93 virus. Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China.

  20. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    Science.gov (United States)

    2012-01-01

    . Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China. PMID:22591597

  1. Recombinant α-actinin subunit antigens of Trichomonas vaginalis as potential vaccine candidates in protecting against trichomoniasis.

    Science.gov (United States)

    Xie, Yi-Ting; Gao, Jiang-Mei; Wu, Ya-Ping; Tang, Petrus; Hide, Geoff; Lai, De-Hua; Lun, Zhao-Rong

    2017-02-16

    stimulation with the corresponding antigens in vitro. Immunization with both ACT-F and ACT-T could confer partial to complete protection and trigger strong Th1/Th2 mixed humoral and cellular immune responses in the mouse host. This suggested that recombinant α-actinin subunit antigens may be promising vaccine candidates against trichomoniasis.

  2. Pulmonary immunity and durable protection induced by the ID93/GLA-SE vaccine candidate against the hyper-virulent Korean Beijing Mycobacterium tuberculosis strain K.

    Science.gov (United States)

    Cha, Seung Bin; Kim, Woo Sik; Kim, Jong-Seok; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Cho, Sang-Nae; Coler, Rhea N; Reed, Steven G; Shin, Sung Jae

    2016-04-27

    The majority of tuberculosis (TB) vaccine candidates advanced to clinical trials have been evaluated preclinically using laboratory-adapted strains. However, it has been proposed that challenge with clinical isolates in preclinical vaccine testing could provide further and more practical validation. Here, we tested the ID93/GLA-SE TB vaccine candidate against the clinical Mycobacterium tuberculosis (Mtb) strain K (Mtb K) belonging to the Beijing family, the most prevalent Mtb strain in South Korea. Mice immunized with ID93/GLA-SE exhibited a significant reduction in bacteria and reduced lung inflammation against Mtb K when compared to non-immunized controls. In addition, we analyzed the immune responses in the lungs of ID93/GLA-SE-immunized mice, and showed that ID93/GLA-SE was able to elicit sustained Th1-biased immune responses including antigen-specific multifunctional CD4(+) T cell co-producing IFN-γ, TNF-α, and IL-2 as well as a high magnitude of IFN-γ response for up to 10 weeks post-challenge. Notably, further investigation of T cell subsets in the lung following challenge showed remarkable generation of CD8(+) central memory T cells by ID93/GLA-SE-immunization. Our findings showed that ID93/GLA-SE vaccine confers a high level of robust protection against the hypervirulent Mtb Beijing infection which was characterized by pulmonary Th1-polarized T-cell immune responses. These findings may also provide relevant information for potential utility of this vaccine candidate in East-Asian countries where the Beijing genotype is highly prevalent. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Optimized blanching reduces the host cell protein content and substantially enhances the recovery and stability of two plant derived malaria vaccine candidates

    Directory of Open Access Journals (Sweden)

    Stephan eMenzel

    2016-02-01

    Full Text Available Plants provide an advantageous expression platform for biopharmaceutical proteins because of their low pathogen burden and potential for inexpensive, large-scale production. However, the purification of target proteins can be challenging due to issues with extraction, the removal of host cell proteins (HCPs, and low expression levels. The heat treatment of crude extracts can reduce the quantity of HCPs by precipitation thus increasing the purity of the target protein and streamlining downstream purification. In the overall context of downstream process development for plant-derived malaria vaccine candidates, we applied a design-of-experiments approach to enhance HCP precipitation from Nicotiana benthamiana extracts generated after transient expression, using temperatures in the 20−80°C range, pH values of 3.0−8.0 and incubation times of 0−60 min. We also investigated the recovery of two protein-based malaria vaccine candidates under these conditions and determined their stability in the heat-treated extract while it was maintained at room temperature for 24 h. The heat precipitation of HCPs was also carried out by blanching intact plants in water or buffer prior to extraction in a blender. Our data show that all the heat precipitation methods reduced the amount of HCP in the crude plant extracts by more than 80%, simplifying the subsequent downstream processing steps. Furthermore, when the heat treatment was performed at 80°C rather than 65°C, both malaria vaccine candidates were more stable after extraction and the recovery of both proteins increased by more than 30%.

  4. Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia

    DEFF Research Database (Denmark)

    Mamo, Hassen; Esen, Meral; Ajua, Anthony

    2013-01-01

    to investigate the nature of humoral immune response to malaria in two ethnic groups in two endemic localities: Shewa Robit in north, and Boditi in south Ethiopia which are characterized by varying levels of malaria transmission and altitude. In a cross-sectional study, the study participants were diagnosed...... for malaria infection microscopically and by the rapid diagnostic test (RDT). Sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate GMZ2 and its subunits (Glutamate-rich protein (GLURP-R0), merozoite surface...

  5. Lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Cashman Kathleen A

    2010-10-01

    virion, electron microscopy analysis demonstrated that LASV VLP appeared structurally similar to native virions, with pleiomorphic distribution in size and shape. LASV VLP that displayed GPC or GPC+NP were immunogenic in mice, and generated a significant IgG response to individual viral proteins over the course of three immunizations, in the absence of adjuvants. Furthermore, sera from convalescent Lassa fever patients recognized VLP in ELISA format, thus affirming the presence of native epitopes displayed by the recombinant pseudoparticles. Conclusions These results established that modular LASV VLP can be generated displaying high levels of immunogenic viral proteins, and that small laboratory scale mammalian expression systems are capable of producing multi-milligram quantities of pseudoparticles. These VLP are structurally and morphologically similar to native LASV virions, but lack replicative functions, and thus can be safely generated in low biosafety level settings. LASV VLP were immunogenic in mice in the absence of adjuvants, with mature IgG responses developing within a few weeks after the first immunization. These studies highlight the relevance of a VLP platform for designing an optimal vaccine candidate against Lassa hemorrhagic fever, and warrant further investigation in lethal challenge animal models to establish their protective potential.

  6. Identification of Leishmania infantum chagasi proteins in urine of patients with visceral leishmaniasis: a promising antigen discovery approach of vaccine candidates.

    Science.gov (United States)

    Kashino, S S; Abeijon, C; Qin, L; Kanunfre, K A; Kubrusly, F S; Silva, F O; Costa, D L; Campos, D; Costa, C H N; Raw, I; Campos-Neto, A

    2012-07-01

    Visceral leishmaniasis (VL) is a serious lethal parasitic disease caused by Leishmania donovani in Asia and by Leishmania infantum chagasi in southern Europe and South America. VL is endemic in 47 countries with an annual incidence estimated to be 500,000 cases. This high incidence is due in part to the lack of an efficacious vaccine. Here, we introduce an innovative approach to directly identify parasite vaccine candidate antigens that are abundantly produced in vivo in humans with VL. We combined RP-HPLC and mass spectrometry and categorized three L. infantum chagasi proteins, presumably produced in spleen, liver and bone marrow lesions and excreted in the patients' urine. Specifically, these proteins were the following: Li-isd1 (XP_001467866.1), Li-txn1 (XP_001466642.1) and Li-ntf2 (XP_001463738.1). Initial vaccine validation studies were performed with the rLi-ntf2 protein produced in Escherichia coli mixed with the adjuvant BpMPLA-SE. This formulation stimulated potent Th1 response in BALB/c mice. Compared to control animals, mice immunized with Li-ntf2+ BpMPLA-SE had a marked parasite burden reduction in spleens at 40 days post-challenge with virulent L. infantum chagasi. These results strongly support the proposed antigen discovery strategy of vaccine candidates to VL and opens novel possibilities for vaccine development to other serious infectious diseases. © 2012 Blackwell Publishing Ltd.

  7. Improved Prefusion Stability, Optimized Codon Usage, and Augmented Virion Packaging Enhance the Immunogenicity of Respiratory Syncytial Virus Fusion Protein in a Vectored-Vaccine Candidate.

    Science.gov (United States)

    Liang, Bo; Ngwuta, Joan O; Surman, Sonja; Kabatova, Barbora; Liu, Xiang; Lingemann, Matthias; Liu, Xueqiao; Yang, Lijuan; Herbert, Richard; Swerczek, Joanna; Chen, Man; Moin, Syed M; Kumar, Azad; McLellan, Jason S; Kwong, Peter D; Graham, Barney S; Collins, Peter L; Munir, Shirin

    2017-08-01

    Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but it lacks a licensed vaccine or suitable antiviral drug. A live attenuated chimeric bovine/human parainfluenza virus type 3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naive children, rB/HPIV3 was well tolerated but the immunogenicity of wild-type RSV F was unsatisfactory. We previously modified RSV F with a designed disulfide bond (DS) to increase stability in the prefusion (pre-F) conformation and to be efficiently packaged in the vector virion. Here, we further stabilized pre-F by adding both disulfide and cavity-filling mutations (DS-Cav1), and we also modified RSV F codon usage to have a lower CpG content and a higher level of expression. This RSV F open reading frame was evaluated in rB/HPIV3 in three forms: (i) pre-F without vector-packaging signal, (ii) pre-F with vector-packaging signal, and (iii) secreted pre-F ectodomain trimer. Despite being efficiently expressed, the secreted pre-F was poorly immunogenic. DS-Cav1 stabilized pre-F, with or without packaging, induced higher titers of pre-F specific antibodies in hamsters, and improved the quality of RSV-neutralizing serum antibodies. Codon-optimized RSV F containing fewer CpG dinucleotides had higher F expression, replicated more efficiently in vivo, and was more immunogenic. The combination of DS-Cav1 pre-F stabilization, optimized codon usage, reduced CpG content, and vector packaging significantly improved vector immunogenicity and protective efficacy against RSV. This provides an improved vectored RSV vaccine candidate suitable for pediatric clinical evaluation.IMPORTANCE RSV and HPIV3 are the first and second leading viral causes of severe pediatric respiratory disease worldwide. Licensed vaccines or suitable antiviral drugs are not available. We

  8. Strain-specific Plasmodium falciparum multifunctional CD4(+) T cell cytokine expression in Malian children immunized with the FMP2.1/AS02A vaccine candidate.

    Science.gov (United States)

    Graves, Shawna F; Kouriba, Bourema; Diarra, Issa; Daou, Modibo; Niangaly, Amadou; Coulibaly, Drissa; Keita, Yamoussa; Laurens, Matthew B; Berry, Andrea A; Vekemans, Johan; Ripley Ballou, W; Lanar, David E; Dutta, Sheetij; Gray Heppner, D; Soisson, Lorraine; Diggs, Carter L; Thera, Mahamadou A; Doumbo, Ogobara K; Plowe, Christopher V; Sztein, Marcelo B; Lyke, Kirsten E

    2016-05-17

    Based on Plasmodium falciparum (Pf) apical membrane antigen 1 (AMA1) from strain 3D7, the malaria vaccine candidate FMP2.1/AS02A showed strain-specific efficacy in a Phase 2 clinical trial in 400 Malian children randomized to 3 doses of the AMA1 vaccine candidate or control rabies vaccine on days 0, 30 and 60. A subset of 10 Pf(-) (i.e., no clinical malaria episodes) AMA1 recipients, 11 Pf(+) (clinical malaria episodes with parasites with 3D7 or Fab9-type AMA1 cluster 1 loop [c1L]) AMA1 recipients, and 10 controls were randomly chosen for analysis. Peripheral blood mononuclear cells (PBMCs) isolated on days 0, 90 and 150 were stimulated with full-length 3D7 AMA1 and c1L from strains 3D7 (c3D7) and Fab9 (cFab9). Production of IFN-γ, TNF-α, IL-2, and/or IL-17A was analyzed by flow cytometry. Among AMA1 recipients, 18/21 evaluable samples stimulated with AMA1 demonstrated increased IFN-γ, TNF-α, and IL-2 derived from CD4(+) T cells by day 150 compared to 0/10 in the control group (pvaccines, CD4(+) cells expressing both TNF-α and IL-2 were increased in Pf(-) children compared to Pf(+) children. When PBMCs were stimulated with c3D7 and cFab9 separately, 4/18 AMA1 recipients with an AMA1-specific CD4(+) response had a significant response to one or both c1L. This suggests that recognition of the AMA1 antigen is not dependent upon c1L alone. In summary, AMA1-specific T cell responses were notably increased in children immunized with an AMA1-based vaccine candidate. The role of CD4(+)TNF-α(+)IL-2(+)-expressing T cells in vaccine-induced strain-specific protection against clinical malaria requires further exploration. Clinicaltrials.gov Identifier: NCT00460525. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Lead

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    ... is serious about making sure companies that break the law are held accountable In the past year, EPA ... the health effects of lead in drinking water The law mandates no-lead products for drinking water after ...

  10. Short- and long-term immunogenicity and protection induced by non-replicating smallpox vaccine candidates in mice and comparison with the traditional 1st generation vaccine.

    Science.gov (United States)

    Ferrier-Rembert, Audrey; Drillien, Robert; Tournier, Jean-Nicolas; Garin, Daniel; Crance, Jean-Marc

    2008-03-25

    This study assessed three non-replicating smallpox vaccine candidates (modified vaccinia Ankara (MVA), NYVAC and HR) for their immunogenicity and ability to protect mice against an intranasal cowpox virus challenge and compared them with the traditional replicating vaccine. A single immunisation with the non-replicating vaccines induced a complete protection from death at short-term, but was not fully protective when mice were challenged 150 days post-vaccination with protection correlated with the specific neutralizing antibodies and CD4(+) T-cells responses. Prime-boost vaccination enabled effective long-term protection from death for mice vaccinated with MVA, but protection from disease and CD4(+) T-cell level were lower than the ones induced by the traditional vaccine over the long-term period. Further investigations are necessary with MVA to determine the optimal conditions of immunisation to induce at long-term immunogenicity and protection observed with the 1st generation smallpox vaccine.

  11. The Use of Microwave-Assisted Solid-Phase Peptide Synthesis and Click Chemistry for the Synthesis of Vaccine Candidates Against Hookworm Infection.

    Science.gov (United States)

    Fuaad, Abdullah A H Ahmad; Skwarczynski, Mariusz; Toth, Istvan

    2016-01-01

    A protein-based vaccine approach against hookworm infection has failed to deliver the expected outcome, due to a problem with an allergic response in the patient or difficulties in the proteins' production. This implication could be overcome by using a chemically synthesized peptide-based vaccine approach. This approach utilizes minimal pathogenic components that are necessary for the stimulation of the immune response without triggering adverse side effects. To boost the peptide's immunogenicity, a lipid core peptide (LCP) system can be utilized as a carrier molecule/immunostimulant. This chapter describes in detail the synthesizing of protected lipoamino acid, the self-adjuvanting moiety (LCP core), the peptide epitope, and the final vaccine candidate. The subunit peptide and the LCP core were synthesized using microwave-assisted solid-phase peptide synthesis (SPPS). Then the final hookworm vaccine construct was assembled using the copper-catalyzed azide-alkyne cycloaddition, or "click," reaction.

  12. Naturally acquired immune responses to malaria vaccine candidate antigens MSP3 and GLURP in Guahibo and Piaroa indigenous communities of the Venezuelan Amazon

    DEFF Research Database (Denmark)

    Baumann, Andreas; Magris, Magda M; Urbaez, Marie-Luz

    2012-01-01

    ABSTRACT: BACKGROUND: Malaria transmission in most of Latin America can be considered as controlled. In such a scenario, parameters of baseline immunity to malaria antigens are of specific interest with respect to future malaria eradication efforts. METHODS: A cross-sectional study was carried out...... in two indigenous population groups in Amazonas/Venezuela. Data from the regional malaria documentation system were extracted and participants from the ethnic groups of the Guahibo (n = 180) and Piaroa (n = 295) were investigated for the presence of Plasmodium parasites and naturally acquired antibodies...... to Plasmodium falciparum antigens in serum. The GMZ2 vaccine candidate proteins MSP3 and GLURP were chosen as serological markers. RESULTS: The incidence of P. falciparum in both communities was found to be less than 2%, and none of the participants harboured P. falciparum at the time of the cross...

  13. Protection against shigellosis caused by Shigella dysenteriae serotype 4 in guinea pigs using Escherichia albertii DM104 as a live vaccine candidate strain.

    Science.gov (United States)

    Chowdhury, Fatema Moni; Rahman, Mohammed Ziaur; Sarkar, Md Murshed Hasan; Rabbi, Fazle; Khan, Sirajul Islam; Ahsan, Chowdhury Rafiqul; Birkeland, Nils-Kåre

    2017-06-01

    Recently, we reported the induction of protective immunity by environmental Escherichia albertii strain DM104 against Shigella dysenteriae in guinea pig model. In this study, we assessed three different immunization routes, such as intranasal, oral, and intrarectal routes, and revealed differences in immune responses by measuring both the serum IgG and mucosal IgA antibody titers. Protective efficacy of different routes of immunization was also determined by challenging immunized guinea pigs against live S. dysenteriae. It was found that intranasal immunization showed promising results in terms of antibody response and protective efficacy. All these results reconfirm our previous findings and additionally point out that the intranasal immunization of the environmental E. albertii strain DM104 in guinea pig model can be a better live vaccine candidate against shigellosis.

  14. Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: results of a randomised controlled trial.

    Science.gov (United States)

    Bhandari, Nita; Sharma, Pooja; Glass, Roger I; Ray, Pratima; Greenberg, Harry; Taneja, Sunita; Saksena, Manju; Rao, C Durga; Gentsch, Jon R; Parashar, Umesh; Maldonado, Yvonne; Ward, Richard L; Bhan, M K

    2006-07-26

    We evaluated safety and immunogenicity of two orally administered human rotavirus vaccine candidates 116E and I321. Ninety healthy infants aged 8 weeks received a single dose of 116E (10(5)FFu (florescence focus units)), I321 (10(5)FFu) or placebo. There were no significant differences in the number of adverse events. Fever was reported by 6/30, 1/30 and 5/30 in the 116E, I321 and placebo groups; the corresponding figures for diarrhoea were 5/30, 8/29 and 3/30. Serum IgA seroconversion rates were 73%, 39% and 20% in the 116E, I321 and placebo groups, respectively. Vaccine virus was shed on days 3, 7 or 28 in 11/30 infants of the 116E and none in the other two groups. The 116E strain is attenuated, clinically safe and highly immunogenic with a single dose.

  15. Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.

    Science.gov (United States)

    Chen, Wen-Hsiang; Du, Lanying; Chag, Shivali M; Ma, Cuiqing; Tricoche, Nancy; Tao, Xinrong; Seid, Christopher A; Hudspeth, Elissa M; Lustigman, Sara; Tseng, Chien-Te K; Bottazzi, Maria Elena; Hotez, Peter J; Zhan, Bin; Jiang, Shibo

    2014-01-01

    Development of vaccines for preventing a future pandemic of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and for biodefense preparedness is urgently needed. Our previous studies have shown that a candidate SARS vaccine antigen consisting of the receptor-binding domain (RBD) of SARS-CoV spike protein can induce potent neutralizing antibody responses and protection against SARS-CoV challenge in vaccinated animals. To optimize expression conditions for scale-up production of the RBD vaccine candidate, we hypothesized that this could be potentially achieved by removing glycosylation sites in the RBD protein. In this study, we constructed two RBD protein variants: 1) RBD193-WT (193-aa, residues 318-510) and its deglycosylated forms (RBD193-N1, RBD193-N2, RBD193-N3); 2) RBD219-WT (219-aa, residues 318-536) and its deglycosylated forms (RBD219-N1, RBD219-N2, and RBD219-N3). All constructs were expressed as recombinant proteins in yeast. The purified recombinant proteins of these constructs were compared for their antigenicity, functionality and immunogenicity in mice using alum as the adjuvant. We found that RBD219-N1 exhibited high expression yield, and maintained its antigenicity and functionality. More importantly, RBD219-N1 induced significantly stronger RBD-specific antibody responses and a higher level of neutralizing antibodies in immunized mice than RBD193-WT, RBD193-N1, RBD193-N3, or RBD219-WT. These results suggest that RBD219-N1 could be selected as an optimal SARS vaccine candidate for further development.

  16. Construction of a Salmonella Gallinarum ghost as a novel inactivated vaccine candidate and its protective efficacy against fowl typhoid in chickens

    Directory of Open Access Journals (Sweden)

    Chaudhari Atul A

    2012-05-01

    Full Text Available Abstract In order to develop a novel, safe and immunogenic fowl typhoid (FT vaccine candidate, a Salmonella Gallinarum ghost with controlled expression of the bacteriophage PhiX174 lysis gene E was constructed using pMMP99 plasmid in this study. The formation of the Salmonella Gallinarum ghost with tunnel formation and loss of cytoplasmic contents was observed by scanning electron microscopy and transmission electron microscopy. No viable cells were detectable 24 h after the induction of gene E expression by an increase in temperature from 37 °C to 42 °C. The safety and protective efficacy of the Salmonella Gallinarum ghost vaccine was tested in chickens that were divided into four groups: group A (non-immunized control, group B (orally immunized, group C (subcutaneously immunized and group D (intramuscularly immunized. The birds were immunized at day 7 of age. None of the immunized animals showed any adverse reactions such as abnormal behavior, mortality, or signs of FT such as anorexia, depression, or diarrhea. These birds were subsequently challenged with a virulent Salmonella Gallinarum strain at 3 weeks post-immunization (wpi. Significant protection against the virulent challenge was observed in all immunized groups based on mortality and post-mortem lesions compared to the non-immunized control group. In addition, immunization with the Salmonella Gallinarum ghosts induced significantly high systemic IgG response in all immunized groups. Among the groups, orally-vaccinated group B showed significantly higher levels of secreted IgA. A potent antigen-specific lymphocyte activation response along with significantly increased percentages of CD4+ and CD8+ T lymphocytes found in all immunized groups clearly indicate the induction of cellular immune responses. Overall, these findings suggest that the newly constructed Salmonella Gallinarum ghost appears to be a safe, highly immunogenic, and efficient non-living bacterial vaccine

  17. Protection efficacy of the Brucella abortus ghost vaccine candidate lysed by the N-terminal 24-amino acid fragment (GI24) of the 36-amino acid peptide PMAP-36 (porcine myeloid antimicrobial peptide 36) in murine models.

    Science.gov (United States)

    Kwon, Ae Jeong; Moon, Ja Young; Kim, Won Kyong; Kim, Suk; Hur, Jin

    2016-11-01

    Brucella abortus cells were lysed by the N-terminal 24-amino acid fragment (GI24) of the 36-amino acid peptide PMAP-36 (porcine myeloid antimicrobial peptide 36). Next, the protection efficacy of the lysed fragment as a vaccine candidate was evaluated. Group A mice were immunized with sterile PBS, group B mice were intraperitoneally (ip) immunized with 3 × 10 8 colony-forming units (CFUs) of B. abortus strain RB51, group C mice were immunized ip with 3 × 10 8 cells of the B. abortus vaccine candidate, and group D mice were orally immunized with 3 × 10 9 cells of the B. abortus vaccine candidate. Brucella lipopolysaccharide (LPS)-specific serum IgG titers were considerably higher in groups C and D than in group A. The levels of interleukin (IL)-4, IL-10, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) were significantly higher in groups B-D than in group A. After an ip challenge with B. abortus 544, only group C mice showed a significant level of protection as compared to group A. Overall, these results show that ip immunization with a vaccine candidate lysed by GI24 can effectively protect mice from systemic infection with virulent B. abortus.

  18. Lead

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    ... Test Safety Alert: Learn about CDC Recommendations Second Informational Call (CDC-RFA-17-1701PPHF17), April 5, 2017, ... CLPPP CAP Healthy Homes Assessment Tools Lead Health Literacy Initiative Refugee Tool Kit Resources Healthy Homes and ...

  19. Immunoglobulin GM 3 23 5,13,14 phenotype is strongly associated with IgG1 antibody responses to Plasmodium vivax vaccine candidate antigens PvMSP1-19 and PvAMA-1

    Directory of Open Access Journals (Sweden)

    Fontes Cor JF

    2010-08-01

    Full Text Available Abstract Background Humoral immune responses play a key role in the development of immunity to malaria, but the host genetic factors that contribute to the naturally occurring immune responses to malarial antigens are not completely understood. The aim of the present investigation was to determine whether, in subjects exposed to malaria, GM and KM allotypes--genetic markers of immunoglobulin γ and κ-type light chains, respectively--contribute to the magnitude of natural antibody responses to target antigens that are leading vaccine candidates for protection against Plasmodium vivax. Methods Sera from 210 adults, who had been exposed to malaria transmission in the Brazilian Amazon endemic area, were allotyped for several GM and KM determinants by a standard hemagglutination-inhibition method. IgG subclass antibodies to P. vivax apical membrane antigen 1 (PvAMA-1 and merozoite surface protein 1 (PvMSP1-19 were determined by an enzyme-linked immunosorbent assay. Multiple linear regression models and the non-parametric Mann-Whitney test were used for data analyses. Results IgG1 antibody levels to both PvMSP1-19 and PvAMA-1 antigens were significantly higher (P = 0.004, P = 0.002, respectively in subjects with the GM 3 23 5,13,14 phenotype than in those who lacked this phenotype. Conclusions Results presented here show that immunoglobulin GM allotypes contribute to the natural antibody responses to P. vivax malaria antigens. These findings have important implications for the effectiveness of vaccines containing PvAMA-1 or PvMSP1-19 antigens. They also shed light on the possible role of malaria as one of the evolutionary selective forces that may have contributed to the maintenance of the extensive polymorphism at the GM loci.

  20. Molecular characterization of thyroid hormone receptor beta from Schistosoma japonicum and assessment of its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Qiu Chunhui

    2012-08-01

    Full Text Available Abstract Background Thyroid hormones (TH modulate growth, development and differentiation and metabolic processes by interacting with thyroid hormone receptors (THRs. The purpose of this study was to identify a novel thyroid hormone receptor beta encoding gene of Schistosoma japonicum (SjTHRβ and to investigate its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice. Methods The full-length cDNA sequence of SjTHRβ, its gene organization, and its transcript levels were characterized, and the phylogenetic relationship between THR, RAR and RXR from other organisms were analysis, the ability of this protein binding to a conserved DNA core motif, and its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice were evaluated. Results The SjTHRβ cDNA was cloned, verified by 5’ and 3’ Rapid Amplification of cDNA Ends and shown to be polyadenylated at the 3’end, suggesting the transcript is full-length. SjTHRβ is homologous to THRs from other species and has a predicted conservative DNA binding domain and ligand binding domain that normally characterizes these receptors. A comparative quantitative PCR analysis showed that SjTHRβ was the highest expressed in 21d worms and the lowest in 7 d and 13 d schistosomula. The cDNA corresponding to DNA binding domain (SjTHRβ-DBD and ligand binding domain (SjTHRβ-LBD were cloned and subsequently expressed in E coli. The expressed proteins were used to immunize mice and generate specific serum against recombinant SjTHRβ (rSjTHRβ. Western blotting revealed that anti-rSjTHRβ-LBD serum recognized two protein bands in extracts from 21 d worm with molecular sizes of approximately 95 kDa and 72 kDa. Electrophoretic mobility shift assay (EMSA analysis showed that rSjTHRβ-DBD could bind to a conserved DNA core motif. Immunization of BALB/c mice with rSjTHRβ-LBD could induce partial protective efficacy(27.52% worm reduction and 29.50% liver eggs

  1. Safety and immunogenicity of rSh28GST antigen in humans: phase 1 randomized clinical study of a vaccine candidate against urinary schistosomiasis.

    Science.gov (United States)

    Riveau, Gilles; Deplanque, Dominique; Remoué, Franck; Schacht, Anne-Marie; Vodougnon, Hubert; Capron, Monique; Thiry, Michel; Martial, Joseph; Libersa, Christian; Capron, André

    2012-01-01

    Treatment of urinary schistosomiasis by chemotherapy remains challenging due to rapid re-infection and possibly to limited susceptibility to praziquantel treatment. Therefore, therapeutic vaccines represent an attractive alternative control strategy. The objectives of this study were to assess the safety and tolerability profile of the recombinant 28 kDa glutathione S-transferase of Schistosoma haematobium (rSh28GST) in healthy volunteers, and to determine its immunogenicity. Volunteers randomly received 100 µg rSh28GST together with aluminium hydroxide (Alum) as adjuvant (n = 8), or Alum alone as a comparator (n = 8), twice with a 28-day interval between doses. A third dose of rSh28GST or Alum alone was administered to this group at day 150. In view of the results obtained, another group of healthy volunteers (n = 8) received two doses of 300 µg of rSh28GST, again with a 28-day interval. A six-month follow-up was performed with both clinical and biological evaluations. Immunogenicity of the vaccine candidate was evaluated in terms of specific antibody production, the capacity of sera to inhibit enzymatic activity of the antigen, and in vitro cytokine production. Among the 24 healthy male participants no serious adverse events were reported in the days or weeks after administration. Four subjects under rSh28GST reported mild reactions at the injection site while a clinically insignificant increase in bilirubin was observed in 8/24 subjects. No hematological nor biochemical evidence of toxicity was detected. Immunological analysis showed that rSh28GST was immunogenic. The induced Th2-type response was characterized by antibodies capable of inhibiting the enzymatic activity of rSh28GST. rSh28GST in Alum did not induce any significant toxicity in healthy adults and generated a Th2-type immune response. Together with previous preclinical results, the data of safety, tolerability and quality of the specific immune response provide evidence that clinical

  2. Safety and immunogenicity of rSh28GST antigen in humans: phase 1 randomized clinical study of a vaccine candidate against urinary schistosomiasis.

    Directory of Open Access Journals (Sweden)

    Gilles Riveau

    Full Text Available Treatment of urinary schistosomiasis by chemotherapy remains challenging due to rapid re-infection and possibly to limited susceptibility to praziquantel treatment. Therefore, therapeutic vaccines represent an attractive alternative control strategy. The objectives of this study were to assess the safety and tolerability profile of the recombinant 28 kDa glutathione S-transferase of Schistosoma haematobium (rSh28GST in healthy volunteers, and to determine its immunogenicity.Volunteers randomly received 100 µg rSh28GST together with aluminium hydroxide (Alum as adjuvant (n = 8, or Alum alone as a comparator (n = 8, twice with a 28-day interval between doses. A third dose of rSh28GST or Alum alone was administered to this group at day 150. In view of the results obtained, another group of healthy volunteers (n = 8 received two doses of 300 µg of rSh28GST, again with a 28-day interval. A six-month follow-up was performed with both clinical and biological evaluations. Immunogenicity of the vaccine candidate was evaluated in terms of specific antibody production, the capacity of sera to inhibit enzymatic activity of the antigen, and in vitro cytokine production.Among the 24 healthy male participants no serious adverse events were reported in the days or weeks after administration. Four subjects under rSh28GST reported mild reactions at the injection site while a clinically insignificant increase in bilirubin was observed in 8/24 subjects. No hematological nor biochemical evidence of toxicity was detected. Immunological analysis showed that rSh28GST was immunogenic. The induced Th2-type response was characterized by antibodies capable of inhibiting the enzymatic activity of rSh28GST.rSh28GST in Alum did not induce any significant toxicity in healthy adults and generated a Th2-type immune response. Together with previous preclinical results, the data of safety, tolerability and quality of the specific immune response provide evidence that

  3. Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate.

    Science.gov (United States)

    Ntege, Edward H; Arisue, Nobuko; Ito, Daisuke; Hasegawa, Tomoyuki; Palacpac, Nirianne M Q; Egwang, Thomas G; Horii, Toshihiro; Takashima, Eizo; Tsuboi, Takafumi

    2016-11-04

    Genetic variability in Plasmodium falciparum malaria parasites hampers current malaria vaccine development efforts. Here, we hypothesize that to address the impact of genetic variability on vaccine efficacy in clinical trials, conserved antigen targets should be selected to achieve robust host immunity across multiple falciparum strains. Therefore, suitable vaccine antigens should be assessed for levels of polymorphism and genetic diversity. Using a total of one hundred and two clinical isolates from a region of high malaria transmission in Uganda, we analyzed extent of polymorphism and genetic diversity in four recently reported novel blood-stage malaria vaccine candidate proteins: Rh5 interacting protein (PfRipr), GPI anchored micronemal antigen (PfGAMA), rhoptry-associated leucine zipper-like protein 1 (PfRALP1) and Duffy binding-like merozoite surface protein 1 (PfMSPDBL1). In addition, utilizing the wheat germ cell-free system, we expressed recombinant proteins for the four candidates based on P. falciparum laboratory strain 3D7 sequences, immunized rabbits to obtain specific antibodies (Abs) and performed functional growth inhibition assay (GIA). The GIA activity of the raised Abs was demonstrated using both homologous 3D7 and heterologous FVO strains in vitro. Both pfripr and pfralp1 are less polymorphic but the latter is comparatively more diverse, with varied number of regions having insertions and deletions, asparagine and 6-mer repeats in the coding sequences. Pfgama and pfmspdbl1 are polymorphic and genetically diverse among the isolates with antibodies against the 3D7-based recombinant PfGAMA and PfMSPDBL1 inhibiting merozoite invasion only in the 3D7 but not FVO strain. Moreover, although Abs against the 3D7-based recombinant PfRipr and PfRALP1 proteins potently inhibited merozoite invasion of both 3D7 and FVO, the GIA activity of anti-PfRipr was much higher than that of anti-PfRALP1. Thus, PfRipr is regarded as a promising blood-stage vaccine

  4. Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

    Science.gov (United States)

    Bennett, Jason W; Yadava, Anjali; Tosh, Donna; Sattabongkot, Jetsumon; Komisar, Jack; Ware, Lisa A; McCarthy, William F; Cowden, Jessica J; Regules, Jason; Spring, Michele D; Paolino, Kristopher; Hartzell, Joshua D; Cummings, James F; Richie, Thomas L; Lumsden, Joanne; Kamau, Edwin; Murphy, Jittawadee; Lee, Cynthia; Parekh, Falgunee; Birkett, Ashley; Cohen, Joe; Ballou, W Ripley; Polhemus, Mark E; Vanloubbeeck, Yannick F; Vekemans, Johan; Ockenhouse, Christian F

    2016-02-01

    A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use. We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls. The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period. This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.

  5. Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

    Directory of Open Access Journals (Sweden)

    Jason W Bennett

    2016-02-01

    Full Text Available A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001, a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP and a truncated repeat region that contains repeat sequences from both the VK210 (type 1 and the VK247 (type 2 parasites, was developed as a vaccine candidate for global use.We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.

  6. Safety and Immunogenicity of the Malaria Vaccine Candidate MSP3 Long Synthetic Peptide in 12–24 Months-Old Burkinabe Children

    Science.gov (United States)

    Sirima, Sodiomon B.; Tiono, Alfred B.; Ouédraogo, Alphonse; Diarra, Amidou; Ouédraogo, André Lin; Yaro, Jean Baptiste; Ouédraogo, Espérance; Gansané, Adama; Bougouma, Edith C.; Konaté, Amadou T.; Kaboré, Youssouf; Traoré, Abdoulaye; Roma, Chilengi; Soulama, Issiaka; Luty, Adrian J. F.; Cousens, Simon; Nébié, Issa

    2009-01-01

    Background A Phase Ia trial in European volunteers of the candidate vaccine merozoite surface protein 3 (MSP3), a Plasmodium falciparum blood stage membrane, showed that it induces biologically active antibodies able to achieve parasite killing in vitro, while a phase Ib trial in semi-immune adult volunteers in Burkina Faso confirmed that the vaccine was safe. The aim of this study was to assess the safety and immunogenicity of this vaccine candidate in children aged 12–24 months living in malaria endemic area of Burkina Faso. Methods The study was a double-blind, randomized, controlled, dose escalation phase Ib trial, designed to assess the safety, reactogenicity and immunogenicity of three doses of either 15 or 30 µg of MSP3-LSP adsorbed on aluminum hydroxide in 45 children 12 to 24 months of age randomized into three equal groups. Each group received 3 vaccine doses (on days 0, 28 and 56) of either 15 µg of MSP3-LSP, 30 µg of MSP3-LSP or of the Engerix B hepatitis B vaccine. Children were visited at home daily for the 6 days following each vaccination to solicit symptoms which might be related to vaccination. Serious adverse events occurring during the study period (1 year) were recorded. Antibody responses to MSP3-LSP were measured on days 0, 28, 56 and 84. Results All 45 enrolled children received three MSP3 vaccine doses. No serious adverse events were reported. Most of the adverse events reported were mild to moderate in severity. The only reported local symptoms with grade 3 severity were swelling and induration, with an apparently dose related response. All grade 3 adverse events resolved without any sequelae. Both MSP3 doses regimens were able to elicit high levels of anti-MSP3 specific IgG1 and IgG3 antibodies in the volunteers with very little or no increase in IgG2, IgG4 and IgM classes: i.e. vaccination induced predominantly the isotypes involved in the monocyte-dependent mechanism of P. falciparum parasite-killing. Conclusion Our results support

  7. Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials.

    Science.gov (United States)

    Norrby, Maria; Vesikari, Timo; Lindqvist, Lars; Maeurer, Markus; Ahmed, Raija; Mahdavifar, Shahnaz; Bennett, Sean; McClain, J Bruce; Shepherd, Barbara M; Li, Daner; Hokey, David A; Kromann, Ingrid; Hoff, Søren T; Andersen, Peter; de Visser, Adriëtte W; Joosten, Simone A; Ottenhoff, Tom H M; Andersson, Jan; Brighenti, Susanna

    2017-03-14

    Novel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant. BCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150μg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland. The subjects were followed for adverse events and CD4+ T cell responses. H4:IC31 vaccination was well tolerated with a safety profile consisting of mostly mild to moderate self-limited injection site pain, myalgia, arthralgia, fever and post-vaccination inflammatory reaction at the screening tuberculin skin test injection site. The H4:IC31 vaccine elicited antigen-specific CD4+ T cell proliferation and cytokine production that persisted 18weeks after the last vaccination. CD4+ T cell expansion, IFN-γ production and multifunctional CD4+ Th1 responses were most prominent after two doses of H4:IC31 containing 5, 15, or 50μg of H4 in combination with the 500nmol IC31 adjuvant dose. The novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4+ T cell responses in previously BCG-vaccinated healthy individuals. These dose-escalation trials provided evidence that the optimal antigen-adjuvant dose combinations are 5, 15, or 50μg of H4 and 500nmol of IC31. ClinicalTrials.gov, NCT02066428 and NCT02074956. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Deletion of nuoG from the Vaccine Candidate Mycobacterium bovis BCG ΔureC::hly Improves Protection against Tuberculosis.

    Science.gov (United States)

    Gengenbacher, Martin; Nieuwenhuizen, Natalie; Vogelzang, Alexis; Liu, Haipeng; Kaiser, Peggy; Schuerer, Stefanie; Lazar, Doris; Wagner, Ina; Mollenkopf, Hans-Joachim; Kaufmann, Stefan H E

    2016-05-24

    The current tuberculosis (TB) vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), provides insufficient protection against pulmonary TB. Previously, we generated a listeriolysin-expressing recombinant BCG strain, which to date has successfully completed phase I and phase IIa clinical trials. In an attempt to further improve efficacy, we deleted the antiapoptotic virulence gene nuoG, encoding NADH dehydrogenase 1 subunit G, from BCG ΔureC::hly In vitro, deletion of nuoG unexpectedly led to strongly increased recruitment of the autophagosome marker LC3 to the engulfed vaccine, suggesting that nuoG also affects xenophagic pathways. In mice, BCG ΔureC::hly ΔnuoG vaccination was safer than BCG and improved protection over that of parental BCG ΔureC::hly, significantly reducing TB load in murine lungs, ameliorating pulmonary pathology, and enhancing immune responses. Transcriptome analysis of draining lymph nodes after vaccination with either BCG ΔureC::hly or BCG ΔureC::hly ΔnuoG demonstrated earlier and stronger induction of immune responses than that with BCG SSI and suggested upregulation of inflammasome activation and interferon-induced GTPases. In summary, BCG ΔureC::hly ΔnuoG is a promising next-generation TB vaccine candidate with excellent efficacy and safety. Autophagy and apoptosis are fundamental processes allowing cells to degrade their components or kill themselves, respectively. The immune system has adopted these mechanisms to eliminate intracellular pathogens. Residing in host cells, the causative agent of tuberculosis, Mycobacterium tuberculosis, has evolved strategies to set cellular programs of autophagy and apoptosis "on hold." The mycobacterial gene nuoG was found to prevent host cell apoptosis. We have deleted nuoG in the live vaccine candidate BCG ΔureC::hly, which is in phase II clinical development, to leave cellular apoptosis "on go" upon immunization. In preclinical models, this strategy boosted immunity and improved

  9. The therapeutic HIV Env C5/gp41 vaccine candidate Vacc-C5 induces specific T cell regulation in a phase I/II clinical study.

    Science.gov (United States)

    Brekke, Kristin; Sommerfelt, Maja; Ökvist, Mats; Dyrhol-Riise, Anne Margarita; Kvale, Dag

    2017-03-24

    Levels of non-neutralising antibodies (AB) to the C5 domain of HIV Env gp120 are inversely related to progression of HIV infection. In this phase I/II clinical study we investigated safety of Vacc-C5, a peptide-based therapeutic vaccine candidate corresponding to C5/gp41732-744 as well as the effects on pre-existing AB levels to C5/gp41732-744, immune activation and T cell responses including exploratory assessments of Vacc-C5-induced T cell regulation. Our hypothesis was that exposure of the C5 peptide motif may have detrimental effects due to several of its HLA-like features and that enhancement of non-neutralising anti-C5 AB by vaccination could reduce C5 exposure and thereby chronic immune activation. Thirty-six HIV patients on effective antiretroviral therapy were randomised to one of three dose levels of Vacc-C5 administered intramuscularly with Alhydrogel or intradermally with GM-CSF as adjuvant through initial immunisation and two booster periods over 26 weeks. Vacc-C5-specific AB were measured by ELISA and T cell responses by both IFN-γ ELISPOT and proliferative assays analysed by flow cytometry. Immune regulation was assessed by functional blockade of the two inhibitory cytokines IL-10 and TGF-β in parallel cultures. Non-parametric statistical tests were applied. Vacc-C5 was found safe and well tolerated in all patients. Only marginal changes in humoral and cellular responses were induced, without any effect on immune activation. Overall, anti-Vacc-C5 AB levels seemed to decrease compared to pre-existing levels. Whereas Vacc-C5-specific CD8+ T cell proliferative responses increased after the first booster period (p = 0.020; CD4+, p = 0.057), they were reduced after the second. In contrast, Vacc-C5-induced T cell regulation increased after completed vaccination (p ≤ 0.027) and was lower at baseline in the few AB responders identified (p = 0.027). The therapeutic HIV vaccine candidate Vacc-C5 safely induced only marginal immune responses

  10. 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, E-mail: euy-tokyo@umin.ac.jp [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, E-mail: liaogy@21cn.com [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.

  11. Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein.

    Science.gov (United States)

    Schepens, Bert; Sedeyn, Koen; Vande Ginste, Liesbeth; De Baets, Sarah; Schotsaert, Michael; Roose, Kenny; Houspie, Lieselot; Van Ranst, Marc; Gilbert, Brian; van Rooijen, Nico; Fiers, Walter; Piedra, Pedro; Saelens, Xavier

    2014-11-01

    Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcγRI and FcγRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  12. Identification of ribosomal phosphoprotein P0 of Neospora caninum as a potential common vaccine candidate for the control of both neosporosis and toxoplasmosis.

    Science.gov (United States)

    Zhang, Houshuang; Lee, Eung-goo; Liao, Min; Compaore, Muller K A; Zhang, Guohong; Kawase, Osamu; Fujisaki, Kozo; Sugimoto, Chihiro; Nishikawa, Yoshifumi; Xuan, Xuenan

    2007-06-01

    The characterization of the cross-reactive antigens of two closely related apicomplexan parasites, Neospora caninum and Toxoplasma gondii, is important to elucidate the common mechanisms of parasite-host interactions. In this context, a gene encoding N. caninum ribosomal phosphoprotein P0 (NcP0) was identified by immunoscreening of a N. caninum tachyzoite cDNA expression library with antisera from mice immunized with T. gondii tachyzoites. The NcP0 was encoded by a gene with open reading frame of 936 bp, which encoded a protein of 311 amino acids. The NcP0 gene existed as a single copy in the genome and was interrupted by a 432 bp intron. The NcP0 showed 94.5% amino acid identity to T. gondii P0 (TgP0). Anti-recombinant NcP0 (rNcP0) sera recognized a native parasite protein with a molecular mass of 34 kDa in Western blot analysis. Immunofluorescence analysis showed that the NcP0 was localized to the surface of N. caninum tachyzoites. A purified anti-rNcP0 IgG antibody inhibited the growth of N. caninum and T. gondii in vitro in a concentration-dependent manner. These results indicate that P0 is a cross-reactive antigen between N. caninum and T. gondii and a potential common vaccine candidate to control both parasites.

  13. Deletion of nuoG from the Vaccine Candidate Mycobacterium bovis BCG ΔureC::hly Improves Protection against Tuberculosis

    Science.gov (United States)

    Gengenbacher, Martin; Nieuwenhuizen, Natalie; Vogelzang, Alexis; Liu, Haipeng; Kaiser, Peggy; Schuerer, Stefanie; Lazar, Doris; Wagner, Ina; Mollenkopf, Hans-Joachim

    2016-01-01

    ABSTRACT The current tuberculosis (TB) vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), provides insufficient protection against pulmonary TB. Previously, we generated a listeriolysin-expressing recombinant BCG strain, which to date has successfully completed phase I and phase IIa clinical trials. In an attempt to further improve efficacy, we deleted the antiapoptotic virulence gene nuoG, encoding NADH dehydrogenase 1 subunit G, from BCG ΔureC::hly. In vitro, deletion of nuoG unexpectedly led to strongly increased recruitment of the autophagosome marker LC3 to the engulfed vaccine, suggesting that nuoG also affects xenophagic pathways. In mice, BCG ΔureC::hly ΔnuoG vaccination was safer than BCG and improved protection over that of parental BCG ΔureC::hly, significantly reducing TB load in murine lungs, ameliorating pulmonary pathology, and enhancing immune responses. Transcriptome analysis of draining lymph nodes after vaccination with either BCG ΔureC::hly or BCG ΔureC::hly ΔnuoG demonstrated earlier and stronger induction of immune responses than that with BCG SSI and suggested upregulation of inflammasome activation and interferon-induced GTPases. In summary, BCG ΔureC::hly ΔnuoG is a promising next-generation TB vaccine candidate with excellent efficacy and safety. PMID:27222470

  14. UV and X-ray structural studies of a 101-residue long Tat protein from a HIV-1 primary isolate and of its mutated, detoxified, vaccine candidate.

    Science.gov (United States)

    Foucault, Marine; Mayol, Katia; Receveur-Bréchot, Véronique; Bussat, Marie-Claire; Klinguer-Hamour, Christine; Verrier, Bernard; Beck, Alain; Haser, Richard; Gouet, Patrice; Guillon, Christophe

    2010-05-01

    The 101-residue long Tat protein of primary isolate 133 of the human immunodeficiency virus type 1 (HIV-1), wt-Tat(133) displays a high transactivation activity in vitro, whereas the mutant thereof, STLA-Tat(133), a vaccine candidate for HIV-1, has none. These two proteins were chemically synthesized and their biological activity was validated. Their structural properties were characterized using circular dichroism (CD), fluorescence emission, gel filtration, dynamic light scattering, and small angle X-ray scattering (SAXS) techniques. SAXS studies revealed that both proteins were extended and belong to the family of intrinsically unstructured proteins. CD measurements showed that wt-Tat(133) or STLA-Tat(133) underwent limited structural rearrangements when complexed with specific fragments of antibodies. Crystallization trials have been performed on the two forms, assuming that the Tat(133) proteins might have a better propensity to fold in supersaturated conditions, and small crystals have been obtained. These results suggest that biologically active Tat protein is natively unfolded and requires only a limited gain of structure for its function. 2009 Wiley-Liss, Inc.

  15. Expression, purification, immunogenicity and protective efficacy of a recombinant nucleoside hydrolase from Leishmania donovani, a vaccine candidate for preventing cutaneous leishmaniasis.

    Science.gov (United States)

    McAtee, C Patrick; Seid, Christopher A; Hammond, Molly; Hudspeth, Elissa; Keegan, Brian P; Liu, Zhuyun; Wei, Junfei; Zhan, Bin; Arjona-Sabido, Raul; Cruz-Chan, Vladimir; Dumonteil, Eric; Hotez, Peter J; Bottazzi, Maria Elena

    2017-02-01

    The nucleoside hydrolase gene from Leishmania donovani was cloned and expressed in Escherichia coli as a full length 36-kDa protein (LdNH36). Following lysis and extraction, the protein was purified by anion exchange and gel filtration chromatography. The purified protein had a molecular mass of approximately 36-kDa and was confirmed to be >99% pure. Using a nucleoside hydrolase assay, the protein was found to exhibit a Km of 741 ± 246 μM. Protein integrity was confirmed by lithium dodecyl sulfate polyacrylamide gel electrophoresis (LDS-PAGE), mass spectrometry (MS), and enzymatic assay. Analysis of antibody levels from immunized mice indicated that LdNH36 alone or in a stable emulsion with the Toll-like receptor-4 ligand glucopyranosyl lipid adjuvant (GLA-SE) as immunostimulant induced high levels of antigen-specific IgG antibodies. The cellular immune response indicated a T h 1 response in mice immunized with LdNH36, but only when formulated with GLA-SE. Mice immunized with the LdNH36 antigen in combination with the GLA-SE adjuvant and challenged with Leishmania mexicana showed significant reductions (>20 fold) in parasite burden, confirming the protective efficacy of this vaccine candidate. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Protection of mice against Staphylococcus aureus infection by a recombinant protein ClfA-IsdB-Hlg as a vaccine candidate.

    Science.gov (United States)

    Delfani, Somayeh; Mohabati Mobarez, Ashraf; Imani Fooladi, Abbas Ali; Amani, Jafar; Emaneini, Mohammad

    2016-02-01

    Staphylococcus aureus is one of the most important causes of nosocomial infections. An effective vaccine to prevent S. aureus infections is urgently required due to the dramatic increase in the number of antibiotic-resistant strains. In this report, we evaluated a newly recombinant protein composed of selected antigenic regions of clumping factor A (ClfA), iron surface determinant B (IsdB) and gamma hemolysin B (HlgB) of S. aureus and sequence coding for hydrophobic linkers between three domains. The recombinant gene was constructed in pET-28a (+) and expressed in Escherichia coli BL21. In addition, sequence coding for a His(6)-tag was added followed by a hybrid procedure of nickel chelate protein purification. Immunization of BALB/c mice with the recombinant protein ClfA-IsdB-Hlg evoked antigen-specific antibodies that could opsonize S. aureus cells, enhancing in vitro phagocytosis by macrophages. Vaccination with the recombinant protein also reduced the bacterial load recovered from mice spleen samples and increased survival following the intraperitoneal challenge with pathogenic S. aureus compared to the control mice. Our results showed that the recombinant protein ClfA-IsdB-Hlg is a promising vaccine candidate for the prevention of S. aureus bacteremia infections.

  17. Attenuation and Immunogenicity of a Live High Pathogenic PRRSV Vaccine Candidate with a 32-Amino Acid Deletion in the nsp2 Protein

    Directory of Open Access Journals (Sweden)

    Wenhui Lu

    2014-01-01

    Full Text Available A porcine reproductive and respiratory syndrome virus (PRRSV QY1 was serially passed on Marc-145 cells. Virulence of different intermediate derivatives of QY1 (P5, P60, P80, and P100 were determined. The study found that QY1 had been gradually attenuated during the in vitro process. Pathogenicity study showed that pigs inoculated with QY1 P100 and P80 did not develop any significant PRRS clinic symptoms. However, mild-to-moderate clinical signs and acute HP-PRRSV symptoms of infection were observed in pigs inoculated with QY1 P60 and P5, respectively. Furthermore, we determined the whole genome sequences of these four intermediate viruses. The results showed that after 100 passages, compared to QY1 P5, a total of 32 amino acid mutations were found. Moreover, there were one nucleotide deletion and a unique 34-amino acid deletion found at 5′UTR and in nsp2 gene during the attenuation process, respectively. Such deletions were genetically stable in vivo. Following PRRSV experimental challenge, pigs inoculated with a single dose of QY1 P100 developed no significant clinic symptoms and well tolerated lethal challenge, while QY1 P80 group still developed mild fever in the clinic trial after challenge. Thus, we concluded that QY1 P100 was a promising and highly attenuated PRRSV vaccine candidate.

  18. Transcriptome analysis of human peripheral blood mononuclear cells exposed to Lassa virus and to the attenuated Mopeia/Lassa reassortant 29 (ML29), a vaccine candidate.

    Science.gov (United States)

    Zapata, Juan Carlos; Carrion, Ricardo; Patterson, Jean L; Crasta, Oswald; Zhang, Yan; Mani, Sachin; Jett, Marti; Poonia, Bhawna; Djavani, Mahmoud; White, David M; Lukashevich, Igor S; Salvato, Maria S

    2013-01-01

    Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.

  19. MtrR control of a transcriptional regulatory pathway in Neisseria meningitidis that influences expression of a gene (nadA) encoding a vaccine candidate.

    Science.gov (United States)

    Cloward, Jason M; Shafer, William M

    2013-01-01

    The surface-exposed NadA adhesin produced by a subset of capsular serogroup B strains of Neisseria meningitidis is currently being considered as a vaccine candidate to prevent invasive disease caused by a hypervirulent lineage of meningococci. Levels of NadA are known to be controlled by both transcriptional regulatory factors and a component of human saliva, 4-hydroxyphenylacetic acid. Herein, we confirmed the capacity of a DNA-binding protein termed FarR to negatively control nadA expression. We also found that a known transcriptional regulator of farR in N. gonorrhoeae termed MtrR can have a negative regulatory impact on farR and nadA expression, especially when over-expressed. MtrR-mediated repression of nadA was found to be direct, and its binding to a target DNA sequence containing the nadA promoter influenced formation and/or stability of FarR::nadA complexes. The complexity of the multi-layered regulation of nadA uncovered during this investigation suggests that N. meningitidis modulates NadA adhesin protein levels for the purpose of interacting with host cells yet avoiding antibody directed against surface exposed epitopes.

  20. Evidence for globally shared, cross-reacting polymorphic epitopes in the pregnancy-associated malaria vaccine candidate VAR2CSA

    DEFF Research Database (Denmark)

    Avril, Marion; Kulasekara, Bridget R; Gose, Severin O

    2008-01-01

    Pregnancy-associated malaria (PAM) is characterized by the placental sequestration of Plasmodium falciparum-infected erythrocytes (IEs) with the ability to bind to chondroitin sulfate A (CSA). VAR2CSA is a leading candidate for a pregnancy malaria vaccine, but its large size ( approximately 350 k......Da) and extensive polymorphism may pose a challenge to vaccine development. In this study, rabbits were immunized with individual VAR2CSA Duffy binding-like (DBL) domains expressed in Pichia pastoris or var2csa plasmid DNA and sera were screened on different CSA-binding parasite lines. Rabbit antibodies to three...

  1. Deficiencies of effectiveness of intervention studies in veterinary medicine: a cross-sectional survey of ten leading veterinary and medical journals

    NARCIS (Netherlands)

    Di Girolamo, Nicola; Meursinge Reynders, Reint

    2016-01-01

    The validity of studies that assess the effectiveness of an intervention (EoI) depends on variables such as the type of study design, the quality of their methodology, and the participants enrolled. Five leading veterinary journals and 5 leading human medical journals were hand-searched for EoI

  2. Subcutaneous administration CpG-ODNs acts as a potent adjuvant for an HIV-1-tat-based vaccine candidate to elicit cellular immunity in BALB/c mice.

    Science.gov (United States)

    Panahi, Zeinab; Abdoli, Asghar; Mosayebi, Ghasem; Mahdavi, Mehdi; Bahrami, Fariborz

    2018-01-08

    To evaluate the combined effects of CpG oligodeoxynucleotides (CpG-ODNs) adjuvant and subcutaneous injection route on efficacy of a HIV-1-tat DNA vaccine candidate using BALB/c mice as an animal model. Evaluation of cellular and humoral immunity of mice injected subcutaneously with HIV-1-tat gene cloned into a pcDNA3.1 vector indicated that significant levels of IFN-γ cytokine secretion (900 pg/ml), lymphocyte proliferation (2.5 stimulation index) and IgG2a (1.45 absorbance 450 nm) production could be achieved. These indicators of stimulated cellular immunity were elicited 2 weeks after the last injection (P < 0.05). Formulation of HIV-1-tat DNA vaccine candidate with CpG-ODNs as an adjuvant while administrated subcutaneously are a promising approach to induce effective cellular immunity responses against HIV-1 infection.

  3. The C-terminal domain of Clostridium perfringens alpha toxin as a vaccine candidate against bovine necrohemorrhagic enteritis.

    Science.gov (United States)

    Goossens, Evy; Verherstraeten, Stefanie; Valgaeren, Bonnie R; Pardon, Bart; Timbermont, Leen; Schauvliege, Stijn; Rodrigo-Mocholí, Diego; Haesebrouck, Freddy; Ducatelle, Richard; Deprez, Piet R; Van Immerseel, Filip

    2016-04-27

    Bovine necrohemorrhagic enteritis is caused by Clostridium perfringens and leads to sudden death. Alpha toxin, together with perfringolysin O, has been identified as the principal toxin involved in the pathogenesis. We assessed the potential of alpha toxin as a vaccine antigen. Using an intestinal loop model in calves, we investigated the protection afforded by antisera raised against native alpha toxin or its non-toxic C-terminal fragment against C. perfringens-induced intestinal necrosis. Immunization of calves with either of the vaccine preparations induced a strong antibody response. The resulting antisera were able to neutralize the alpha toxin activity and the C. perfringens-induced endothelial cytotoxicity in vitro. The antisera raised against the native toxin had a stronger neutralizing activity than those against the C-terminal fragment. However, antibodies against alpha toxin alone were not sufficient to completely neutralize the C. perfringens-induced necrosis in the intestinal loop model. The development of a multivalent vaccine combining the C-terminal fragment of alpha toxin with other C. perfringens virulence factors might be necessary for complete protection against bovine necrohemorrhagic enteritis.

  4. Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia.

    Science.gov (United States)

    Mamo, Hassen; Esen, Meral; Ajua, Anthony; Theisen, Michael; Mordmüller, Benjamin; Petros, Beyene

    2013-02-05

    In Ethiopia, the general population is vulnerable to unpredictable epidemics of Plasmodium falciparum malaria. However, there is little information on the anti-malaria immune profile of the population in the endemic regions of the country. The study was designed to investigate the nature of humoral immune response to malaria in two ethnic groups in two endemic localities: Shewa Robit in north, and Boditi in south Ethiopia which are characterized by varying levels of malaria transmission and altitude. In a cross-sectional study, the study participants were diagnosed for malaria infection microscopically and by the rapid diagnostic test (RDT). Sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate GMZ2 and its subunits (Glutamate-rich protein (GLURP-R0), merozoite surface protein 3 (MSP3); as well as IgG subclasses against GLURP-R0 and MSP3. Whereas 23(8.6%) blood smear-positive cases for P. falciparum were detected in Boditi, all Shewa Robit study participants had no detectable P. falciparum infection. In both localities, total IgG prevalence and levels to GMZ2 were significantly higher than the response to the component domains indicating the strong recognition of GMZ2 by antibodies acquired through natural exposure. Total IgG and subclass prevalence and levels were higher in Shewa Robit than Boditi, suggesting difference in the intensity of malaria transmission in the two localities and/or genetic differences between the two populations in their response to the antigens. In both study sites, IgG subclass levels to GLURP-R0 were significantly higher than that to MSP3 for all corresponding subclasses in most individuals, indicating the higher relative antigenicity and probably protective potential of GLURP-R0 compared to MSP3. Against both GLURP-R0 and MSP3, the ratio of cytophilic to noncytophilic antibodies was >1 in the majority of the study participants, in both

  5. Immunogenicity and Efficacy of Live L. tarentolae Expressing KMP11-NTGP96-GFP Fusion as a Vaccine Candidate against Experimental Visceral Leishmaniasis Caused by L. infantum

    Directory of Open Access Journals (Sweden)

    Vahid NASIRI

    2016-10-01

    Full Text Available Background: The aim of present study was to evaluate the protective efficacy of live recombinant L. tarentolae expressing KMP11-NTGP96-GFP fusion as candidates for live engineered recombinant vaccine against visceral leishmaniasis in BALB/c mice.Methods: KMP-11 and NT-GP96 genes cloned into the pJET1.2/blunt cloning vector and then into pEGFP-N1 expression vector. The KMP-11, NT-GP96 and GFP fused in pEGFP-N1 and subcloned into Leishmanian pLEXSY-neo vector. Finally this construct was transferred to L. tarentolae by electroporation. Tranfection was confirmed by SDS-PAGE, WESTERN blot, flowcytometry and RT-PCR. Protective efficacy of this construct was evaluated as a vaccine candidate against visceral leishmaniasis. Parasite burden, humoral and cellular immune responses were assessed before and at 4 weeks after challenge.Results: KMP- NT-Gp96-GFP Fusion was cloned successfully into pLEXSY -neo vector and this construct successfully transferred to L. tarentolae. Finding indicated that immunization with L. tarentolae tarentolae-KMP11-NTGP96-GFP provides significant protection against visceral leishmaniasis and was able to induce an increased expression of IFN-γ and IgG2a. Following challenge, a reduced parasite load in the spleen of the KMP11-NTGP96-GFP immunized group was detected.Conclusion: The present study is the first to use a combination of a Leishmania antigen with an immunologic antigen in live recombinant L. tarentolae and results suggest that L. tarentolae-KMP11-NTGP96-GFP could be considered as a potential tool in vaccination against visceral leishmaniasis and this vaccination strategy could provide a potent rout for future vaccine development. 

  6. Testing of four Leishmania vaccine candidates in a mouse model of infection with Leishmania (Viannia) braziliensis, the main causative agent of cutaneous leishmaniasis in the New World.

    Science.gov (United States)

    Salay, G; Dorta, M L; Santos, N M; Mortara, R A; Brodskyn, C; Oliveira, C I; Barbiéri, C L; Rodrigues, M M

    2007-09-01

    We evaluated whether four recombinant antigens previously used for vaccination against experimental infection with Leishmania (Leishmania) major could also induce protective immunity against a challenge with Leishmania (Viannia) braziliensis, the species responsible for 90% of the 28,712 annual cases of cutaneous and mucocutaneous leishmaniasis recorded in Brazil during the year of 2004. Initially, we isolated the homolog genes encoding four L. (V.) braziliensis antigens: (i) homologue of receptor for activated C kinase, (ii) thiol-specific antioxidant, (iii) Leishmania elongation and initiation factor, and (iv) L. (L.) major stress-inducible protein 1. At the deduced amino acid level, all four open reading frames had a high degree of identity with the previously described genes of L. (L.) major being expressed on promastigotes and amastigotes of L. (V.) braziliensis. These genes were inserted into the vector pcDNA3 or expressed as bacterial recombinant proteins. After immunization with recombinant plasmids or proteins, BALB/c mice generated specific antibody or cell-mediated immune responses (gamma interferon production). After an intradermal challenge with L. (V.) braziliensis infective promastigotes, no significant reduction on the lesions was detected. We conclude that the protective immunity afforded by these four vaccine candidates against experimental cutaneous leishmaniasis caused by L. (L.) major could not be reproduced against a challenge with L. (V.) braziliensis. Although negative, we consider our results important since they suggest that studies aimed at the development of an effective vaccine against L. (V.) braziliensis, the main causative agent of cutaneous leishmaniasis in the New World, should be redirected toward distinct antigens or different vaccination strategies.

  7. Gut-homing conventional plasmablasts and CD27- plasmablasts elicited after a short time exposure to an oral live attenuated Shigella vaccine candidate in humans

    Directory of Open Access Journals (Sweden)

    Franklin R. Toapanta

    2014-08-01

    Full Text Available Currently, there is no licensed Shigella vaccine; however, various promising live attenuated vaccine candidates have emerged, including CVD1208S (ΔguaBA, Δset, Δsen S. flexneri 2a, which was shown to be safe and immunogenic in Phase 1 clinical trials. Here we report the immune responses elicited in an outpatient Phase 2 clinical trial in which subjects were vaccinated with CVD 1208S. Oral immunization with CVD 1208S elicited high anti-S. flexneri 2a LPS and IpaB antibody responses, as well as an acute plasmablast (PB infiltration in peripheral blood 7 days after immunization. PB sorted based on their expression of homing molecules confirmed that cells expressing integrin α4β7 alone or in combination with CD62L were responsible for antibody production (as measured by ELISpot. Furthermore, using high-color flow-cytometry, on day 7 after immunization, we observed the appearance of conventional PB (CPB, CD19dim CD20- CD27+high CD38+high CD3-, as well as a PB population that did not express CD27 (CD27- PB; pre-plasmablasts. The pattern of individual or simultaneous expression of homing markers (integrin α4β7, CD62L, CXCR3 and CXCR4 suggested that CPB cells homed preferentially to the inflamed gut mucosa. In contrast, ~50% CD27- PB cells appear to home to yet to be identified peripheral lymphoid organs or were in a transition state preceding integrin α4β7 upregulation. In sum, these observations demonstrate that strong immune responses, including distinct PB subsets with the potential to home to the gut and other secondary lymphoid organs, can be elicited after a short time of exposure to a shigella oral

  8. Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

    Science.gov (United States)

    Bernard, Marie-Clotilde; Barban, Véronique; Pradezynski, Fabrine; de Montfort, Aymeric; Ryall, Robert; Caillet, Catherine; Londono-Hayes, Patricia

    2015-01-01

    HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine.

  9. Chimeric classical swine fever (CSF)-Japanese encephalitis (JE) viral replicon as a non-transmissible vaccine candidate against CSF and JE infections.

    Science.gov (United States)

    Yang, Zhenhua; Wu, Rui; Li, Robert W; Li, Ling; Xiong, Zhongliang; Zhao, Haizhong; Guo, Deyin; Pan, Zishu

    2012-04-01

    A trans-complemented chimeric CSF-JE virus replicon was constructed using an infectious cDNA clone of the CSF virus (CSFV) Alfort/187 strain. The CSFV E2 gene was deleted, and a fragment containing the region encoding a truncated envelope protein (tE, amino acid 292-402, domain III) of JE virus (JEV) was inserted into the resultant plasmid, pA187delE2, to generate the recombinant cDNA clone pA187delE2/JEV-tE. Porcine kidney 15 (PK15) cells that constitutively express the CSFV E2p7 proteins were then transfected with in vitro-transcribed RNA from pA187delE2/JEV-tE. As a result, the chimeric CSF-JE virus replicon particle (VRP), rv187delE2/JEV-tE, was rescued. In a mouse model, immunization with the chimeric CSF-JE VRP induced strong production of JEV-specific antibody and conferred protection against a lethal JEV challenge. Pigs immunized with CSF-JE VRP displayed strong anti-CSFV and anti-JEV antibody responses and protection against CSFV and JEV challenge infections. Our evidence suggests that E2-complemented CSF-JE VRP not only has potential as a live-attenuated non-transmissible vaccine candidate against CSF and JE but also serves as a potential DIVA (Differentiating Infected from Vaccinated Animals) vaccine for CSF in pigs. Together, our data suggest that the non-transmissible chimeric VRP expressing foreign antigenic proteins may represent a promising strategy for bivalent DIVA vaccine design. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Evaluation of the C-Terminal Fragment of Entamoeba histolytica Gal/GalNAc Lectin Intermediate Subunit as a Vaccine Candidate against Amebic Liver Abscess.

    Science.gov (United States)

    Min, Xiangyang; Feng, Meng; Guan, Yue; Man, Suqin; Fu, Yongfeng; Cheng, Xunjia; Tachibana, Hiroshi

    2016-01-01

    Entamoeba histolytica is an intestinal protozoan parasite that causes amoebiasis, including amebic dysentery and liver abscesses. E. histolytica invades host tissues by adhering onto cells and phagocytosing them depending on the adaptation and expression of pathogenic factors, including Gal/GalNAc lectin. We have previously reported that E. histolytica possesses multiple CXXC sequence motifs, with the intermediate subunit of Gal/GalNAc lectin (i.e., Igl) as a key factor affecting the amoeba's pathogenicity. The present work showed the effect of immunization with recombinant Igl on amebic liver abscess formation and the corresponding immunological properties. A prokaryotic expression system was used to prepare the full-length Igl and the N-terminal, middle, and C-terminal fragments (C-Igl) of Igl. Vaccine efficacy was assessed by challenging hamsters with an intrahepatic injection of E. histolytica trophozoites. Hamsters intramuscularly immunized with full-length Igl and C-Igl were found to be 92% and 96% immune to liver abscess formation, respectively. Immune-response evaluation revealed that C-Igl can generate significant humoral immune responses, with high levels of antibodies in sera from immunized hamsters inhibiting 80% of trophozoites adherence to mammalian cells and inducing 80% more complement-mediated lysis of trophozoites compared with the control. C-Igl was further assessed for its cellular response by cytokine-gene qPCR analysis. The productions of IL-4 (8.4-fold) and IL-10 (2-fold) in the spleen cells of immunized hamsters were enhanced after in vitro stimulation. IL-4 expression was also supported by increased programmed cell death 1 ligand 1 gene. Immunobiochemical characterization strongly suggests the potential of recombinant Igl, especially the C-terminal fragment, as a vaccine candidate against amoebiasis. Moreover, protection through Th2-cell participation enabled effective humoral immunity against amebic liver abscesses.

  11. Subunit vaccine candidate AMM down-regulated the regulatory T cells and enhanced the protective immunity of BCG on a suitable schedule.

    Science.gov (United States)

    Luo, Y; Jiang, W; Da, Z; Wang, B; Hu, L; Zhang, Y; An, R; Yu, H; Sun, H; Tang, K; Tang, Z; Wang, Y; Jing, T; Zhu, B

    2012-03-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) priming and subunit vaccine boosting strategies are urgently needed to improve the protective efficacy of BCG in adult population. However, the schedule of subunit vaccine boosting is not well investigated, especially the optimal immune responses and vaccine immunization schedules are still not clear. We have constructed a novel subunit vaccine candidate consisting of fusion protein Ag85B-Mpt64 (190-198)-Mtb8.4 (AMM) in a complex adjuvant composed of dimo-thylidioctyl ammonium bromide (DDA) and BCG polysaccharide nucleic acid (BCG-PSN). In this study, we compared the effect of different boosting schedules of the subunit vaccine in the prime-boost strategies. C57BL/6 mice were primed with BCG first and then boosted with the AMM vaccine once at 10th week, twice at 8th, 10th week, or thrice at 6th, 8th, 10th week, respectively. The immune responses were evaluated at the 14th and 20th weeks, respectively. Twelve weeks after the last immunization, the mice were challenged with virulent Mycobacterium tuberculosis strain H37Rv, and the protective effect was evaluated. The results showed that BCG priming and the AMM vaccine boosting twice induced the strongest antigen-specific IFN-γ and IL-2 production, down-regulated CD4+ CD25+ FoxP3+ regulatory T cells (Tregs) and had the best protective effect among all groups, while boosting thrice induced the strongest IL-4 production and did not improve BCG-primed protection significantly. Boosting BCG with the AMM vaccine twice instead of once or thrice induced strong Th1-type immunity and down-regulated Tregs significantly, which correlated with the best protection against M. tuberculosis infection in mice. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

  12. Adenovirus-based HIV-1 vaccine candidates tested in efficacy trials elicit CD8+ T cells with limited breadth of HIV-1 inhibition.

    Science.gov (United States)

    Hayes, Peter J; Cox, Josephine H; Coleman, Adam R; Fernandez, Natalia; Bergin, Philip J; Kopycinski, Jakub T; Nitayaphan, Sorachai; Pitisuttihum, Punnee; de Souza, Mark; Duerr, Ann; Morgan, Cecilia; Gilmour, Jill W

    2016-07-17

    The ability of HIV-1 vaccine candidates MRKAd5, VRC DNA/Ad5 and ALVAC/AIDSVAX to elicit CD8 T cells with direct antiviral function was assessed and compared with HIV-1-infected volunteers. Adenovirus serotype 5 (Ad5)-based regimens MRKAd5 and VRC DNA/Ad5, designed to elicit HIV-1-specific T cells, are immunogenic but failed to prevent infection or impact on viral loads in volunteers infected subsequently. Failure may be due in part to a lack of CD8 T cells with effective antiviral functions. An in-vitro viral inhibition assay tested the ability of bispecific antibody expanded CD8 T cells from peripheral blood mononuclear cells to inhibit replication of a multiclade panel of HIV-1 isolates in autologous CD4 T cells. HIV-1 proteins recognized by CD8 T cells were assessed by IFNγ enzyme-linked immunospot assay. Ad5-based regimens elicited CD8 T cells that inhibited replication of HIV-1 IIIB isolate with more limited inhibition of other isolates. IIIB isolate Gag and Pol genes have high sequence identities (>96%) to vector HIV-1 gene inserts, and these were the predominant HIV-1 proteins recognized by CD8 T cells. Virus inhibition breadth was greater in antiretroviral naïve HIV-1-infected volunteers naturally controlling viremia (plasma viral load elicited by the ALVAC/AIDSVAX regimen. The Ad5-based regimens, although immunogenic, elicited CD8 T cells with limited HIV-1-inhibition breadth. Effective T-cell-based vaccines should presumably elicit broader HIV-1-inhibition profiles. The viral inhibition assay can be used in vaccine design and to prioritize promising candidates with greater inhibition breadth for further clinical trials.

  13. Evaluation of a Mycobacterium avium subsp. paratuberculosis leuD Mutant as a Vaccine Candidate against Challenge in a Caprine Model

    Science.gov (United States)

    Faisal, Syed M.; Chen, Jenn-Wei; Yan, Falong; Chen, Tsai-Tzu; Useh, Nicodemus M.; Yan, Weiwei; Guo, Shanguang; Wang, Shih-Jon; Glaser, Amy L.; McDonough, Sean P.; Singh, Bhupinder; Davis, William C.; Akey, Bruce L.

    2013-01-01

    Johne's disease (JD) is prevalent worldwide and has a significant impact on the global agricultural economy. In the present study, we evaluated the protective efficacy of a leuD (Δleud) mutant and gained insight into differential immune responses after challenge with virulent M. avium subsp. paratuberculosis in a caprine colonization model. The immune response and protective efficacy were compared with those of the killed vaccine Mycopar. In vitro stimulation of peripheral blood mononuclear cells with johnin purified protein derivative showed that Mycopar and ΔleuD generated similar levels of gamma interferon (IFN-γ) but significantly higher levels than unvaccinated and challenged phosphate-buffered saline controls. However, only with ΔleuD was the IFN-γ response maintained. Flow cytometric analysis showed that the increase in IFN-γ correlated with proliferation and activation (increased expression of CD25) of CD4, CD8, and γδT cells, but this response was significantly higher in ΔleuD-vaccinated animals at some time points after challenge. Both Mycopar and ΔleuD vaccines upregulated Th1/proinflammatory and Th17 cytokines and downregulated Th2/anti-inflammatory and regulatory cytokines at similar levels at almost all time points. However, significantly higher levels of IFN-γ (at weeks 26 and 30), interleukin-2 (IL-2; week 18), IL-1b (weeks 14 and 22), IL-17 (weeks 18 and 22), and IL-23 (week 18) and a significantly lower level of IL-10 (weeks 14 and 18) and transforming growth factor β (week 18) were detected in the ΔleuD-vaccinated group. Most importantly, ΔleuD elicited an immune response that significantly limited colonization of tissues compared to Mycopar upon challenge with wild-type M. avium subsp. paratuberculosis. In conclusion, the ΔleuD mutant is a promising vaccine candidate for development of a live attenuated vaccine for JD in ruminants. PMID:23408524

  14. Histomorphometric characteristics of immune cells in small intestine of pigs perorally immunized with vaccine candidate F18ac+ nonenterotoxigenic E. coli strain

    Directory of Open Access Journals (Sweden)

    I. Valpotic

    2009-12-01

    Full Text Available Colidiarrhea and colienterotoxemia caused by F4+ and/or F18+ enterotoxigenic E. coli (ETEC strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac+ non-ETEC vaccine candidate strain against challenge infection with F4ac+ ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs. We also evaluated levamisole as an immune response modifier (IRM and its adjuvanticity when given in the combination with the experimental vaccine. The pigs were parenterally immunized with either levamisole (at days -2, -1 and 0 or with levamisole and perorally given F18ac+ non-ETEC strain (at day 0, and challenged with F4ac+ ETEC strain 7 days later. At day 13 the pigs were euthanatized and sampled for immunohistological/histomorphometrical analyses. Lymphoid CD3+, CD45RA+, CD45RC+, CD21+, IgA+ and myeloid SWC3+ cell subsets were identified in jejunal and ileal epithelium, lamina propria and Peyer’s patches using the avidin-biotin complex method, and their numbers were determined by computer-assisted histomorphometry. Quantitative immunophenotypic analyses showed that levamisole treated pigs had highly increased numbers of jejunal CD3+, CD45RC+ and SWC3+ cells (p<0.05 as compared to those recorded in nontreated control pigs. In the ileum of these pigs we have recorded that only CD21+ cells were significantly increased (p<0.01. The pigs that were treated with levamisole adjuvanted experimental vaccine had significantly increased numbers of all tested cell subsets in both segments of the small intestine. It was concluded that levamisole adjuvanted F18ac+ non-ETEC vaccine was a requirement for the elicitation of protective gut immunity in this model; nonspecific immunization with levamisole was less effective, but confirmed its potential as an IRM.

  15. Immunogenicity of a virosomally-formulated Plasmodium falciparum GLURP-MSP3 chimeric protein-based malaria vaccine candidate in comparison to adjuvanted formulations

    Directory of Open Access Journals (Sweden)

    Tamborrini Marco

    2011-12-01

    Full Text Available Abstract Background In clinical trials, immunopotentiating reconstituted influenza virosomes (IRIVs have shown great potential as a versatile antigen delivery platform for synthetic peptides derived from Plasmodium falciparum antigens. This study describes the immunogenicity of a virosomally-formulated recombinant fusion protein comprising domains of the two malaria vaccine candidate antigens MSP3 and GLURP. Methods The highly purified recombinant protein GMZ2 was coupled to phosphatidylethanolamine and the conjugates incorporated into the membrane of IRIVs. The immunogenicity of this adjuvant-free virosomal formulation was compared to GMZ2 formulated with the adjuvants Montanide ISA 720 and Alum in three mouse strains with different genetic backgrounds. Results Intramuscular injections of all three candidate vaccine formulations induced GMZ2-specific antibody responses in all mice tested. In general, the humoral immune response in outbred NMRI mice was stronger than that in inbred BALB/c and C57BL/6 mice. ELISA with the recombinant antigens demonstrated immunodominance of the GLURP component over the MSP3 component. However, compared to the Al(OH3-adjuvanted formulation the two other formulations elicited in NMRI mice a larger proportion of anti-MSP3 antibodies. Analyses of the induced GMZ2-specific IgG subclass profiles showed for all three formulations a predominance of the IgG1 isotype. Immune sera against all three formulations exhibited cross-reactivity with in vitro cultivated blood-stage parasites. Immunofluorescence and immunoblot competition experiments showed that both components of the hybrid protein induced IgG cross-reactive with the corresponding native proteins. Conclusion A virosomal formulation of the chimeric protein GMZ2 induced P. falciparum blood stage parasite cross-reactive IgG responses specific for both MSP3 and GLURP. GMZ2 thus represents a candidate component suitable for inclusion into a multi-valent virosomal

  16. Formalin-Inactivated EV71 Vaccine Candidate Induced Cross-Neutralizing Antibody against Subgenotypes B1, B4, B5 and C4A in Adult Volunteers

    Science.gov (United States)

    Chang, Jui-Yuan; Jiang, Renee; Hsieh, Yi-Chin; Tsao, Amanda; Wu, Chien-Long; Huang, Ju-Lan; Fung, Chang-Phone; Hsieh, Szu-Min; Wang, Ya-Fang; Wang, Jen-Ren; Hu, Mei-Hua; Chiang, Jen-Ron; Su, Ih-Jen; Chong, Pele Choi-Sing

    2013-01-01

    Background Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia. No effective EV71 vaccine is available. A randomized and open-label phase I clinical study registered with ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac) at 5- and 10-µg doses. In this study we report the cross-neutralizing antibody responses from each volunteer against different subgenotypes of EV71 and CVA16. Methods Sixty eligible healthy adults were recruited and vaccinated. Blood samples were obtained on day 0, 21 and 42 and tested against B1, B4, B5, C2, C4A, C4B and CVA16 for cross-neutralizing antibody responses. Results The immunogenicity of both 5- and 10- µg doses were found to be very similar. Approximately 45% of the participants had 4-fold increase in Nt, but there was no further increase in Nt after the second dose. EV71vac induced very strong cross-neutralizing antibody responses in >85% of volunteers without pre-existing Nt against subgenotype B1, B5 and C4A. EV71vac elicited weak cross-neutralizing antibody responses (∼20% of participants) against a C4B and Coxsackie virus A16. Over 90% of vaccinated volunteers did not develop cross-neutralizing antibody responses (Nt<8) against a C2 strain. EV71vac can boost and significantly enhance the neutralizing antibody responses in volunteers who already had pre-vaccination antibodies against EV71 and/or CVA16. Conclusion EV71vac is efficient in eliciting cross-neutralizing antibody responses against EV71 subgenotypes B1, B4, B5, and C4A, and provides the rationale for its evaluation in phase II clinical trials. Trial Registration ClinicalTrials.gov __NCT01268787 PMID:24278177

  17. A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon.

    Directory of Open Access Journals (Sweden)

    Bertrand Lell

    2009-10-01

    Full Text Available The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion--based formulation (AS02 and a formulation based on liposomes (AS01.In this Phase II, double-blind study (NCT00307021, 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01(E or RTS,S/AS02(D, on a 0-1-2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02(D/AS01(E of 0.88 (95% CI: 0.68-1.15 post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.RTS,S/AS01(E proved similarly as well tolerated and immunogenic as RTS,S/AS02(D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.ClinicalTrials.gov. NCT00307021.

  18. Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

    Directory of Open Access Journals (Sweden)

    Marie-Clotilde Bernard

    Full Text Available HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29 has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529 derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a

  19. Evaluation of the antigenicity and reactogenicity of varying formulations of the rhesus rotavirus-based quadrivalent and the M37 rotavirus vaccine candidates.

    Science.gov (United States)

    Perez-Schael, I; Blanco, M; Garcia, D; White, L; Alfonzo, E; Crespo, I; Cunto, W; Pittman, A L; Kapikian, A Z; Flores, J

    1994-04-01

    Three phase I trials of the rhesus rotavirus (RRV)-based quadrivalent vaccine [composed of serotype 3 (RRV), and serotypes 1 (D x RRV), 2 (DS1 x RRV), and 4 (ST3 x RRV) human rotavirus x RRV reassortants] and the M37 (nursery strain) rotavirus vaccine candidates were conducted in an attempt to find a safe and optimally antigenic formulation. Infants 10-20 weeks old received, in trial I, 1) the quadrivalent vaccine as two separate bivalent doses (1 x 10(4) PFU each of D x RRV and RRV, followed 4 weeks later by 1 x 10(4) PFU each of DS1 x RRV and ST3 x RRV) or 2) placebo; in trial II, 1) one dose of quadrivalent vaccine (10(4) PFU of each component), or 2) two doses of quadrivalent vaccine, or 3) a 10(4) PFU dose of M37 vaccine, or 4) M37 vaccine followed by the quadrivalent vaccine, or 5) placebo; in trial III, 1) a dose of a higher-titered quadrivalent vaccine (10(5) PFU of each component), or 2) two doses of higher titered quadrivalent vaccine, or 3) a dose of higher titered M37 vaccine (10(5) PFU) or 4) two doses of M37 vaccine (10(5) PFU), or 5) M37 vaccine (10(5) PFU) followed by the higher titered quadrivalent vaccine, or 6) placebo. A mild, transient fever during the first week postvaccination was associated with the bivalent or quadrivalent vaccines but not with the M37 vaccine. Fourfold or greater serum IgA ELISA responses to rotavirus were observed in 48-92% of the infants receiving quadrivalent vaccine and in 32-50% of those receiving M37 vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Formalin-inactivated EV71 vaccine candidate induced cross-neutralizing antibody against subgenotypes B1, B4, B5 and C4A in adult volunteers.

    Directory of Open Access Journals (Sweden)

    Ai-Hsiang Chou

    Full Text Available Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia. No effective EV71 vaccine is available. A randomized and open-label phase I clinical study registered with ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac at 5- and 10-µg doses. In this study we report the cross-neutralizing antibody responses from each volunteer against different subgenotypes of EV71 and CVA16.Sixty eligible healthy adults were recruited and vaccinated. Blood samples were obtained on day 0, 21 and 42 and tested against B1, B4, B5, C2, C4A, C4B and CVA16 for cross-neutralizing antibody responses.The immunogenicity of both 5- and 10- µg doses were found to be very similar. Approximately 45% of the participants had 4-fold increase in Nt, but there was no further increase in Nt after the second dose. EV71vac induced very strong cross-neutralizing antibody responses in >85% of volunteers without pre-existing Nt against subgenotype B1, B5 and C4A. EV71vac elicited weak cross-neutralizing antibody responses (∼20% of participants against a C4B and Coxsackie virus A16. Over 90% of vaccinated volunteers did not develop cross-neutralizing antibody responses (Nt<8 against a C2 strain. EV71vac can boost and significantly enhance the neutralizing antibody responses in volunteers who already had pre-vaccination antibodies against EV71 and/or CVA16.EV71vac is efficient in eliciting cross-neutralizing antibody responses against EV71 subgenotypes B1, B4, B5, and C4A, and provides the rationale for its evaluation in phase II clinical trials.ClinicalTrials.gov NCT01268787.

  1. Evaluating Vaccine Candidates for Filariasis

    Science.gov (United States)

    2013-04-16

    34hidden" antigens, antigens to which the host does not mount an adaptive immune response during infection, in helminths . We found that the soluble...associated intestinal proteins have shown protection in many models of helminth infection. In order to identify proteins found only within the...23 Immunomodulation

  2. Deficiencies of effectiveness of intervention studies in veterinary medicine: a cross-sectional survey of ten leading veterinary and medical journals

    Science.gov (United States)

    Meursinge Reynders, Reint

    2016-01-01

    The validity of studies that assess the effectiveness of an intervention (EoI) depends on variables such as the type of study design, the quality of their methodology, and the participants enrolled. Five leading veterinary journals and 5 leading human medical journals were hand-searched for EoI studies for the year 2013. We assessed (1) the prevalence of randomized controlled trials (RCTs) among EoI studies, (2) the type of participants enrolled, and (3) the methodological quality of the selected studies. Of 1707 eligible articles, 590 were EoI articles and 435 RCTs. Random allocation to the intervention was performed in 52% (114/219; 95%CI:45.2–58.8%) of veterinary EoI articles, against 87% (321/371; 82.5–89.7%) of human EoI articles (adjusted OR:9.2; 3.4–24.8). Veterinary RCTs were smaller (median: 26 animals versus 465 humans) and less likely to enroll real patients, compared with human RCTs (OR:331; 45–2441). Only 2% of the veterinary RCTs, versus 77% of the human RCTs, reported power calculations, primary outcomes, random sequence generation, allocation concealment and estimation methods. Currently, internal and external validity of veterinary EoI studies is limited compared to human medical ones. To address these issues, veterinary interventional research needs to improve its methodology, increase the number of published RCTs and enroll real clinical patients. PMID:26835187

  3. Deficiencies of effectiveness of intervention studies in veterinary medicine: a cross-sectional survey of ten leading veterinary and medical journals.

    Science.gov (United States)

    Di Girolamo, Nicola; Meursinge Reynders, Reint

    2016-01-01

    The validity of studies that assess the effectiveness of an intervention (EoI) depends on variables such as the type of study design, the quality of their methodology, and the participants enrolled. Five leading veterinary journals and 5 leading human medical journals were hand-searched for EoI studies for the year 2013. We assessed (1) the prevalence of randomized controlled trials (RCTs) among EoI studies, (2) the type of participants enrolled, and (3) the methodological quality of the selected studies. Of 1707 eligible articles, 590 were EoI articles and 435 RCTs. Random allocation to the intervention was performed in 52% (114/219; 95%CI:45.2-58.8%) of veterinary EoI articles, against 87% (321/371; 82.5-89.7%) of human EoI articles (adjusted OR:9.2; 3.4-24.8). Veterinary RCTs were smaller (median: 26 animals versus 465 humans) and less likely to enroll real patients, compared with human RCTs (OR:331; 45-2441). Only 2% of the veterinary RCTs, versus 77% of the human RCTs, reported power calculations, primary outcomes, random sequence generation, allocation concealment and estimation methods. Currently, internal and external validity of veterinary EoI studies is limited compared to human medical ones. To address these issues, veterinary interventional research needs to improve its methodology, increase the number of published RCTs and enroll real clinical patients.

  4. Immunogenic profiling in mice of a HIV/AIDS vaccine candidate (MVA-B expressing four HIV-1 antigens and potentiation by specific gene deletions.

    Directory of Open Access Journals (Sweden)

    Juan García-Arriaza

    Full Text Available BACKGROUND: The immune parameters of HIV/AIDS vaccine candidates that might be relevant in protection against HIV-1 infection are still undefined. The highly attenuated poxvirus strain MVA is one of the most promising vectors to be use as HIV-1 vaccine. We have previously described a recombinant MVA expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B, that induced HIV-1-specific immune responses in different animal models and gene signatures in human dendritic cells (DCs with immunoregulatory function. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to characterize in more detail the immunogenic profile of MVA-B and to improve its immunogenicity we have generated a new vector lacking two genes (A41L and B16R, known to counteract host immune responses by blocking the action of CC-chemokines and of interleukin 1beta, respectively (referred as MVA-B DeltaA41L/DeltaB16R. A DNA prime/MVA boost immunization protocol was used to compare the adaptive and memory HIV-1 specific immune responses induced in mice by the parental MVA-B and by the double deletion mutant MVA-B DeltaA41L/DeltaB16R. Flow cytometry analysis revealed that both vectors triggered HIV-1-specific CD4(+ and CD8(+ T cells, with the CD8(+ T-cell compartment responsible for >91.9% of the total HIV-1 responses in both immunization groups. However, MVA-B DeltaA41L/DeltaB16R enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4(+ and CD8(+ T-cell immune responses. HIV-1-specific CD4(+ T-cell responses were polyfunctional and preferentially Env-specific in both immunization groups. Significantly, while MVA-B induced preferentially Env-specific CD8(+ T-cell responses, MVA-B DeltaA41L/DeltaB16R induced more GPN-specific CD8(+ T-cell responses, with an enhanced polyfunctional pattern. Both vectors were capable of producing similar levels of antibodies against Env. CONCLUSIONS/SIGNIFICANCE: These findings revealed that MVA-B and MVA-B DeltaA41L/DeltaB16R

  5. Molecular characterization and evaluation of Onchocerca volvulus-secreted larval acidic protein 1 (SLAP1) as a putative vaccine candidate on endemic population of lymphatic filariasis.

    Science.gov (United States)

    Mahalakshmi, Natarajan; Aparnaa, Ramanathan; Ansel Vishal, Lawrance; Kaliraj, Perumal

    2013-09-01

    Filarial parasites infected nearly 160 million of the global population with onchocerciasis and lymphatic filariasis, and further, a billion of people are estimated to be at risk of infection, rendering them among the most prevalent infectious agents in the world today. Given the complexity of their life cycle and the immune evasion mechanisms of these organisms, development of a vaccine remains to be a long-term challenge. Though a number of immunodominant antigens have been characterized, the presence of homologous proteins in humans or the allelic variants are some of the major drawbacks. One of the extensively studied vaccine candidates is abundant larval transcripts (ALT) family of proteins for the following properties: highly regulated expression, abundance, excreted-secreted product of infective stage larvae, and essentially for parasite establishment and survival in the host. In the present study, stage-specific expression of secreted larval acidic protein 1 (SLAP1) was identified; an ALT orthologue from Onchocerca volvulus was cloned, expressed, and purified as a recombinant protein. Immunogenicity of OvSLAP1 was demonstrated with sera and peripheral blood mononuclear cells from endemic regions of Brugia malayi and Wuchereria bancrofti. OvSLAP1 antibodies were predominated by IgG1 and IgG2 in endemic normal (EN) and chronic pathology (CP) subjects. It has also induced marked cellular response as observed by lymphoproliferation assay. The study revealed that OvSLAP1 can segregate humoral (EN mean optical density (OD) = 0.87 ± 0.035, CP mean OD = 0.59 ± 0.029) and cellular (EN mean stimulation index (SI) = 5.87 ± 0.167, CP mean SI = 3.5 ± 0.134) immune responses between EN and CP individuals (P < 0.001), signifying its prophylactic ability and vitality for protection from filarial infections in endemic population.

  6. An interferon inducing porcine reproductive and respiratory syndrome virus vaccine candidate elicits protection against challenge with the heterologous virulent type 2 strain VR-2385 in pigs.

    Science.gov (United States)

    Fontanella, Eve; Ma, Zexu; Zhang, Yanjin; de Castro, Alessandra M M G; Shen, Huigang; Halbur, Patrick G; Opriessnig, Tanja

    2017-01-03

    Achieving consistent protection by vaccinating pigs against porcine reproductive and respiratory syndrome virus (PRRSV) remains difficult. Recently, an interferon-inducing PRRSV vaccine candidate strain A2MC2 was demonstrated to be attenuated and induced neutralizing antibodies. The objective of this study was to determine the efficacy of passage 90 of A2MC2 (A2P90) to protect pigs against challenge with moderately virulent PRRSV strain VR-2385 (92.3% nucleic acid identity with A2MC2) and highly virulent atypical PRRSV MN184 (84.5% nucleic acid identity with A2MC2). Forty 3-week old pigs were randomly assigned to five groups including a NEG-CONTROL group (non-vaccinated, non-challenged), VAC-VR2385 (vaccinated, challenged with strain VR-2385), VR2385 (challenged with strain VR-2385), VAC-MN184 (vaccinated, challenged with strain MN184) and a MN184 group (challenged with MN184 virus). Vaccination was done at 3weeks of age followed by challenge at 8weeks of age. No viremia was detectable in any of the vaccinated pigs; however, by the time of challenge, 15/16 vaccinated pigs had seroconverted based on ELISA and had neutralizing antibodies against a homologous strain with titers ranging from 8 to 128. Infection with VR-2385 resulted in mild-to-moderate clinical disease and lesions. For VR-2385 infected pigs, vaccination significantly lowered PRRSV viremia and nasal shedding by 9days post challenge (dpc), significantly reduced macroscopic lung lesions, and significantly increased the average daily weight gain compared to the non-vaccinated pigs. Infection with MN184 resulted in moderate-to-severe clinical disease and lesions regardless of vaccination status; however, vaccinated pigs had significantly less nasal shedding by dpc 5 compared to non-vaccinated pigs. Under the study conditions, the A2P90 vaccine strain was attenuated without detectable shedding, improved weight gain, and offered protection to the pigs challenged with VR-2385 by reduction of virus load and

  7. Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children.

    Directory of Open Access Journals (Sweden)

    John Lusingu

    2010-11-01

    Full Text Available The malaria vaccine candidate, RTS,S/AS01(E, showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind, randomised (1∶1 ratio controlled trial. Three doses of study or control (rabies vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E had fewer SAEs (51/447 than children in the control group (88/447. One SAE episode in a RTS,S/AS01(E recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E will become available from the Phase 3 programme.

  8. Specific memory B cell response and participation of CD4+central and effector memory T cells in mice immunized with liposome encapsulated recombinant NE protein based Hepatitis E vaccine candidate.

    Science.gov (United States)

    Kulkarni, Shruti P; Thanapati, Subrat; Arankalle, Vidya A; Tripathy, Anuradha S

    2016-11-21

    Liposome encapsulated neutralizing epitope protein of Hepatitis E virus (HEV), rNEp, our Hepatitis E vaccine candidate, was shown to be immunogenic and safe in pregnant and non-pregnant mice and yielded sterilizing immunity in rhesus monkeys. The current study in Balb/c mice assessed the levels and persistence of anti-HEV IgG antibodies by ELISA, frequencies of B, memory B, T and memory T cells by flow cytometry and HEV-specific IgG secreting memory B cells by ELISPOT till 420days post immunization (PI) with 5?g rNEp encapsulated in liposome based adjuvant (2 doses, 4weeks apart). Mice immunized with a lower dose (1?g) were assessed only for anamnestic response post booster dose. Vaccine candidate immunized mice (5?g dose) elicited strong anti-HEV IgG response that was estimated to persist for lifetime. At day 120 PI, frequency of memory B cells was higher in immunized mice than those receiving adjuvant alone. Anti-HEV IgG titers were lower in mice immunized with 1?g dose. A booster dose yielded a heightened antibody response in mice with both high (>800GMT, 5?g) and low (?100GMT, 1?g) anti-HEV IgG titers. At day 6th post booster dose, HEV-specific antibody secreting plasma cells (ASCs) were detected in 100% and 50% of mice with high and low anti-HEV IgG titers, respectively, whereas the frequencies of CD4 + central and effector memory T cells were high in mice with high anti-HEV IgG titers only. Taken together, the vaccine candidate effectively generates persistent and anamnestic antibody response, elicits participation of CD4 + memory T cells and triggers memory B cells to differentiate into ASCs upon boosting. This approach of assessing the immunogenicity of vaccine candidate could be useful to explore the longevity of HEV-specific memory response in future HEV vaccine trials in human. Copyright © 2016. Published by Elsevier Ltd.

  9. Ten Leading Causes of Death and Injury

    Science.gov (United States)

    ... PDF 36KB] (color) 2007 [PDF 34KB] (black and white) 2006 [PDF37KB] (color) Charts also available in GIF and JPEG format Causes of Injury Death: Highlighting Unintentional Injury 2015 [PDF 93KB] (color) ...

  10. Clinical testing of an inactivated influenza A/H5N1 vaccine candidate in a double-blinded, placebo-controlled, randomized trial in healthy adults in Vietnam.

    Science.gov (United States)

    Phan, Trong Lan; Ho, Vinh Thang; Vu, Minh Huong; Nguyen, Tuyet Nga; Duong, Huu Thai; Holt, Renee; Wahid, Rahnuma; Donnelly, John; Flores, Jorge

    2016-10-26

    We tested an inactivated egg-grown whole virus influenza A/H5N1 vaccine candidate developed by the Institute of Vaccines and Medical Biologicals (IVAC), a state-run vaccine manufacturer in Vietnam, in a Phase 1, placebo controlled, double blinded, randomized trial. The vaccine was adjuvanted with aluminum hydroxide. The trial enrolled 75 subjects who were randomized to receive two injections of one of the following: low-dose of vaccine (7.5 mcg HA), high-dose of vaccine (15 mcg HA), or placebo. The vaccine candidate was well tolerated with minimal local reactogenicity consisting of mild, short-lived injection site pain and/or tenderness. No systemic reactogenicity was observed other than transient low-grade fever in about 13% of the subjects and no unsolicited adverse events were attributable to product administration. Immune responses were assessed at baseline and after the first and second dose by hemagglutination inhibition (HAI) and microneutralization (MN) assays, with 72% of the high-dose and 68% of the low-dose vaccine recipients presenting a ⩾4-fold response in the HAI assay and 72% of the high-dose and 61% of the low-dose vaccine recipients exhibiting a ⩾4-fold response in the MN assay. These promising results support further development. ClinicalTrials.gov number NCT02171819, June 20, 2014. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Deletion of the vaccinia virus gene A46R, encoding for an inhibitor of TLR signalling, is an effective approach to enhance the immunogenicity in mice of the HIV/AIDS vaccine candidate NYVAC-C.

    Directory of Open Access Journals (Sweden)

    Beatriz Perdiguero

    Full Text Available Viruses have developed strategies to counteract signalling through Toll-like receptors (TLRs that are involved in the detection of viruses and induction of proinflammatory cytokines and IFNs. Vaccinia virus (VACV encodes A46 protein which disrupts TLR signalling by interfering with TLR: adaptor interactions. Since the innate immune response to viruses is critical to induce protective immunity, we studied whether deletion of A46R gene in a NYVAC vector expressing HIV-1 Env, Gag, Pol and Nef antigens (NYVAC-C improves immune responses against HIV-1 antigens. This question was examined in human macrophages and in mice infected with a single A46R deletion mutant of the vaccine candidate NYVAC-C (NYVAC-C-ΔA46R. The viral gene A46R is not required for virus replication in primary chicken embryo fibroblast (CEF cells and its deletion in NYVAC-C markedly increases TNF, IL-6 and IL-8 secretion by human macrophages. Analysis of the immune responses elicited in BALB/c mice after DNA prime/NYVAC boost immunization shows that deletion of A46R improves the magnitude of the HIV-1-specific CD4 and CD8 T cell immune responses during adaptive and memory phases, maintains the functional profile observed with the parental NYVAC-C and enhances anti-gp120 humoral response during the memory phase. These findings establish the immunological role of VACV A46R on innate immune responses of macrophages in vitro and antigen-specific T and B cell immune responses in vivo and suggest that deletion of viral inhibitors of TLR signalling is a useful approach for the improvement of poxvirus-based vaccine candidates.

  12. Genetic Diversity of Polymorphic Vaccine Candidate Antigens (Apical Membrane Antigen-1, Merozoite Surface Protein-3, and Erythrocyte Binding Antigen-175) in Plasmodium falciparum Isolates from Western and Central Africa

    Science.gov (United States)

    Soulama, Issiaka; Bigoga, Jude D.; Ndiaye, Magatte; Bougouma, Edith C.; Quagraine, Josephine; Casimiro, Prisca N.; Stedman, Timothy T.; Sirima, Sodiomon B.

    2011-01-01

    The malaria vaccine candidate antigens erythrocyte binding antigen 175 (EBA-175), merozoite surface protein 3 (MSP-3), and apical membrane antigen (AMA-1) from Plasmodium falciparum isolates from countries in central and west Africa were assessed for allelic diversity. Samples were collected on filter paper from 600 P. falciparum-infected symptomatic patients in Cameroon, Republic of Congo, Burkina Faso, Ghana, and Senegal and screened for class-specific amplification fragments. Genetic diversity, assessed by mean heterozygosity, was comparable among countries. We detected a clinical increase in eba 175 F-allele frequency from west to east across the study region. No statistical difference in msp-3 allele distribution between countries was observed. The ama-1 3D7 alleles were present at a lower frequency in central Africa than in West Africa. We also detected little to no genetic differentiation among sampling locations. This finding indicates that, at least at the level of resolution offered by restriction fragment length polymorphism analysis, these antigens showed remarkable genetic homogeneity throughout the region sampled, perhaps caused by balancing selection to maintain a diverse array of antigen haplotyes. PMID:21292899

  13. Cloning, expression and characterization of recombinant exotoxin A-flagellin fusion protein as a new vaccine candidate against Pseudomonas aeruginosa infections.

    Science.gov (United States)

    Tanomand, Asghar; Farajnia, Safar; Najar Peerayeh, Shahin; Majidi, Jafar

    2013-01-01

    Infections due to Pseudomonas aeruginosa are among the leading causes of morbidity and mortality in patients who suffer from impaired immune responses and chronic diseases such as cystic fibrosis. At present, aggressive antibiotic therapy is the only choice for management of P. aeruginosa infections, but emergence of highly resistant strains necessitated the development of novel alternative therapeutics including an effective vaccine. Several P. aeruginosa antigens have been tested for vaccine development, including lipopolysaccharide alone, polysaccharides alginate, extracellular proteins, exotoxin A (exo A) and killed whole cell. However, none of them are currently available clinically. In this research, recombinant exoA-flagellin (fliC) fusion protein as a cocktail antigen was expressed and purified and its antigenic characteristics were evaluated. Expression of recombinant fusion protein by E. coli using pET22b vector resulted in production of exoA-fliC fusion protein in high concentration. Based on Western-blotting results, recombinant fusion protein showed a good antigenic interaction with sera from patients with various P. aeruginosa infections. These results suggested that recombinant exoA-fliC fusion protein can be produced in the laboratory, and tested as a candidate vaccine in P. aeruginosa infections.

  14. Potentiation of human papilloma vaccine candidate using naloxone/alum mixture as an adjuvant: increasing immunogenicity of HPV-16E7d vaccine.

    Science.gov (United States)

    Yasaghi, Mahsa; Mahdavi, Mehdi

    2016-09-01

    Many types of human papillomaviruses (HPVs) have been identified, with some leading to cancer and others to skin lesions such as anogenital warts. Studies have demonstrated an association between oncogenic HPV and cervical cancer and many researchers have focused on therapeutic vaccines development. At present, the modulatory effect of opioids on the innate and acquired immune system is characterized. Antagonists of opioid receptors such as naloxone (NLX) can contribute to the shifting Th2 response toward Th1. Herein; we studied the adjuvant activity of NLX/Alum mixture for improvement of the immunogenicity of HPV-16E7d vaccine. The mice were administered different regimens of vaccine; E7d, E7d-NLX, E7d-Alum, E7d-NLX-Alum, NLX, alum and PBS via subcutaneous route for three times with two weeks interval. Two weeks after the last immunization, the sera were assessed for total antibody, IgG1 and IgG2a with an optimized ELISA method. The splenocytes culture supernatant was analyzed by ELISA for the presence of IL-4, IFN-γ and IL-17 cytokines and lymphocyte proliferation was evaluated with Brdu method. Immunization of mice with HPV-16 E7d vaccine formulated in NLX/Alum mixture significantly increased lymphocyte proliferation and Th1 and Th17 cytokines responses compared to other experimental groups. Analysis of humoral immune responses revealed that administration of vaccine with NLX/Alum mixture significantly increased specific IgG responses and also isotypes compared to control groups. NLX/Alum mixture as an adjuvant could improve cellular and humoral immune responses and the adjuvant maybe useful for HPV vaccines model for further studies in human clinical trial.

  15. Obtención y evaluación preliminar de un virus canarypox recombinante como candidato a vacuna antirrábica Development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate

    Directory of Open Access Journals (Sweden)

    Flavia Zanetti

    2012-06-01

    Full Text Available En la Argentina, la rabia está circunscripta a algunas provincias del norte. La disponibilidad de nuevas vacunas que eliminen la manipulación del virus rábico y que permitan el control de la enfermedad es de importancia estratégica nacional y regional. Las vacunas basadas en poxvirus recombinantes se han utilizado con éxito como vacunas antirrábicas a nivel mundial. SI bien estos sistemas no están disponibles comercialmente, la plataforma de obtención de virus canarypox (CNPV recombinantes ya ha sido implementada en nuestro laboratorio. El objetivo de este trabajo fue obtener y evaluar un candidato a vacuna antirrábica basado en CNPV recombinantes que expresan la glicoproteína G (RG del virus rábico (RV. Se construyó un virus recombinante que expresa la secuencia codificante de RG (CNPV-RG. La inoculación de ratones con este virus indujo altos títulos de anticuerpos seroneutralizantes de RV (3,58 y 9,76 Ul/ml después de una o dos inmunizaciones, respectivamente y protegió al 78 % de los animales desafiados intracerebralmente con RV. Además, se determinó que el CNPV-RG posee una potencia relativa de 3,5 Ul/ml. Los resultados obtenidos constituyen la primera etapa en la evaluación del CNPV-RG como candidato a vacuna antirrábica. Se requerirán nuevos ensayos para confirmar su utilidad en especies de interés veterinario.In Argentina, rabies is limited to some northern provinces. Availability of new vaccines abolishing the handling of the rabies virus and allowing disease control has regional and national strategic importance. Vaccines based on recombinant poxviruses have been successfully used as antirabic vaccines worldwide. Although these systems are not commercially available, the platform to obtain recombinant canarypox viruses (CNPV has been previously set up in our laboratory. The aim of this work was the development and evaluation of an antirabic vaccine candidate based on recombinant CNPV expressing the rabies virus (RV

  16. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...... to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many...

  17. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many......In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...

  18. Increase in viral yield in eggs and MDCK cells of reassortant H5N1 vaccine candidate viruses caused by insertion of 38 amino acids into the NA stalk.

    Science.gov (United States)

    Zhang, Wenjun; Xue, Tao; Wu, Xiaowei; Zhang, Pinghu; Zhao, Guo; Peng, Daxing; Hu, Shunlin; Wang, Xiaoquan; Liu, Xiaowen; Liu, Wenbo; Liu, Xiufan

    2011-10-19

    The H5N1 subtype of highly pathogenic avian influenza viruses has spread to over 63 countries in Asia, Europe, and Africa and has become endemic in poultry. Since 2004, vaccination against H5N1 influenza has become common in domestic poultry operations in China. Most influenza vaccines have been produced in embryonated chicken eggs. High yield is the essential feature of a good vaccine candidate virus. Therefore, the large-scale manufacture of such a vaccine requires that the viral yield of H5N1 reassortant vaccine viruses in eggs and MDCK cells be increased. We generated two sets of reassortant H5N1 viruses based on backbone viruses A/Chicken/F/98 (H9N2) and A/Puerto Rico/8/34 (H1N1) using reverse genetics. The HAs and NAs of the reassortants were derived from the three epidemic H5N1 strains found in China. We compared the replication properties of these recombinant H5N1 viruses in embryonated chicken eggs and MDCK cells after inserting either 20 or 38 amino acids into their NA stalks. In this study, we demonstrated that inserting 38 amino acids into the NA stalks can significantly increase the viral yield of H5N1 reassortant viruses in both embryonated chicken eggs and MDCK cells, while inserting only 20 amino acids into the same NA stalks does not. Hemagglutinin inhibition testing and protection assays indicated that recombinant H5N1 viruses with 38 aa inserted into their NA stalks had the same antigenicity as the viruses with wt-NA. These results suggest that the generation of an H5N1 recombinant vaccine seed by the insertion of 38 aa into the NA stalk may be a suitable and more economical strategy for the increase in viral yield in both eggs and MDCK cells for the purposes of vaccine production. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Ten Top Tech Trends

    Science.gov (United States)

    McLester, Susan

    2008-01-01

    In this article, the author discusses the major technical issues, products, and practices of the day. The top ten tech trends are listed and discussed. These include: (1) data mining; (2) cyberbullying; (3) 21st century skills; (4) digital content; (5) learning at leisure; (6) personal responders; (7) mobile tools; (8) bandwidth; (9) open-source…

  20. Affordances: Ten Years On

    Science.gov (United States)

    Brown, Jill P.; Stillman, Gloria

    2014-01-01

    Ten years ago the construct, affordance, was rising in prominence in scholarly literature. A proliferation of different uses and meanings was evident. Beginning with its origin in the work of Gibson, we traced its development and use in various scholarly fields. This paper revisits our original question with respect to its utility in mathematics…

  1. Tens bij bevallingen

    NARCIS (Netherlands)

    Tuin-Nuis, F.D.F.

    2000-01-01

    TENS (Transcutane Electrische Neuro Stimulatie) is een pijnverlichtingsmethode die berust op de Gate Control Theory van Melzack en Wall. Door middel van electrische pulsen via de huid zou de geleiding van nociceptieve signalen (pijnprikkels) worden beïnvloed en zou het lichaam endorfinen aanmaken:

  2. Powers of ten

    CERN Multimedia

    Pyramid FILMS

    1977-01-01

    Powers of Ten is a 1977 short documentary film written and directed by Charles Eames and his wife, Ray. The film depicts the relative scale of the Universe in factors of ten (see also logarithmic scale and order of magnitude). The film begins with an aerial image of a man reclining on a blanket; the view is that of one meter across. The viewpoint, accompanied by expository voiceover, then slowly zooms out to a view ten meters across ( or 101 m in standard form), revealing that the man is picnicking in a park with a female companion. The zoom-out continues, to a view of 100 meters (102 m), then 1 kilometer (103 m), and so on, increasing the perspective—the picnic is revealed to be taking place near Soldier Field on Chicago's waterfront—and continuing to zoom out to a field of view of 1024 meters, or the size of the observable universe. The camera then zooms back in to the picnic, and then to views of negative powers of ten—10-1 m (10 centimeters), and so forth, until we are viewing a carbon nucl...

  3. Vaccine candidates for leishmaniasis: a review.

    Science.gov (United States)

    Nagill, Rajeev; Kaur, Sukhbir

    2011-10-01

    Leishmaniasis is a diverse group of clinical syndromes caused by protozoan parasites of the genus Leishmania. The clinical manifestation of the disease varies from self-limiting cutaneous lesions to progressive visceral disease. It is estimated that 350 million people are at risk in 88 countries, with a global incidence of 1-1.5 million cases of cutaneous and 500,000 cases of visceral leishmaniasis. The key control measures mainly rely on early case detection and chemotherapy which has been hampered by the toxicity of drugs, side-effects and by the emergence of drug resistance in parasites. Control of reservoir host and vector is difficult due to operational difficulties and frequent relapses in the host. Therefore, the development of effective and affordable vaccine against leishmaniasis is highly desirable. Although considerable progress has been made over the last decade in understanding immune mechanisms underlying potential candidate antigens, including killed, live attenuated parasites, crude parasites, pure or recombinant Leishmania proteins or DNA encoding leishmanial proteins, as well as immunomodulators from sand fly saliva, very few candidate vaccines have progressed beyond the experimental stage. As such there is no vaccine against any form of human leishmaniasis. In recent years, however, much interest has been stimulated towards vaccination against leishmaniasis focused mainly on cutaneous leishmaniasis with fewer attempts against visceral leishmaniasis. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Ten Utah Painters

    OpenAIRE

    Whitlock, Andrew

    1984-01-01

    Today the art world is rich and diverse with regional as well as national art centers. As in the past, art is alive and well in Utah. The show Ten Utah Painters invites us to see and experiece what some of Utah's best contemporary artists are doing. Their paintings invite us to look and to enjoy but also to learn and open up our visual senses to a broader vista.

  5. A Leishmania-specific hypothetical protein expressed in both promastigote and amastigote stages of Leishmania infantum employed for the serodiagnosis of, and as a vaccine candidate against, visceral leishmaniasis.

    Science.gov (United States)

    Martins, Vivian T; Duarte, Mariana C; Chávez-Fumagalli, Miguel A; Menezes-Souza, Daniel; Coelho, Cecília S P; de Magalhães-Soares, Danielle F; Fernandes, Ana Paula; Soto, Manuel; Tavares, Carlos A P; Coelho, Eduardo A F

    2015-07-11

    HyV protein could be considered as a vaccine candidate against L. infantum infection, as well as a diagnostic marker for CVL.

  6. Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142 administered intramuscularly with adjuvant system AS01

    Directory of Open Access Journals (Sweden)

    Otsyula Nekoye

    2013-01-01

    effector mechanism for blood stage vaccine targets is humoral, the antibody responses demonstrated to this vaccine candidate, both quantitative (total antibody titres and qualitative (functional antibodies inhibiting parasite growth warrant further consideration of its application in endemic settings. Trial registrations Clinical Trials NCT00666380

  7. Rotavirus serotype G9 strains belonging to VP7 gene phylogenetic sequence lineage 1 may be more suitable for serotype G9 vaccine candidates than those belonging to lineage 2 or 3.

    Science.gov (United States)

    Hoshino, Yasutaka; Jones, Ronald W; Ross, Jerri; Honma, Shinjiro; Santos, Norma; Gentsch, Jon R; Kapikian, Albert Z

    2004-07-01

    A safe and effective group A rotavirus vaccine that could prevent severe diarrhea or ameliorate its symptoms in infants and young children is urgently needed in both developing and developed countries. Rotavirus VP7 serotypes G1, G2, G3, and G4 have been well established to be of epidemiologic importance worldwide. Recently, serotype G9 has emerged as the fifth globally common type of rotavirus of clinical importance. Sequence analysis of the VP7 gene of various G9 isolates has demonstrated the existence of at least three phylogenetic lineages. The goal of our study was to determine the relationship of the phylogenetic lineages to the neutralization specificity of various G9 strains. We generated eight single VP7 gene substitution reassortants, each of which bore a single VP7 gene encoding G9 specificity of one of the eight G9 strains (two lineage 1, one lineage 2 and five lineage 3 strains) and the remaining 10 genes of bovine rotavirus strain UK, and two hyperimmune guinea pig antisera to each reassortant, and we then analyzed VP7 neutralization characteristics of the eight G9 strains as well as an additional G9 strain belonging to lineage 1; the nine strains were isolated in five countries. Antisera to lineage 1 viruses neutralized lineage 2 and 3 strains to at least within eightfold of the homotypic lineage viruses. Antisera to lineage 2 virus neutralized lineage 3 viruses to at least twofold of the homotypic lineage 2 virus; however, neutralization of lineage 1 viruses was fourfold (F45 and AU32) to 16- to 64-fold (WI61) less efficient. Antisera to lineage 3 viruses neutralized the lineage 2 strain 16- to 64-fold less efficiently, the lineage 1 strains F45 and AU32 8- to 128-fold less efficiently, and WI61 (prototype G9 strain) 128- to 1024-fold less efficiently than the homotypic lineage 3 viruses. These findings may have important implications for the development of G9 rotavirus vaccine candidates, as the strain with the broadest reactivity (i.e., a prime

  8. The ten thousand Kims

    Science.gov (United States)

    Baek, Seung Ki; Minnhagen, Petter; Kim, Beom Jun

    2011-07-01

    In Korean culture, the names of family members are recorded in special family books. This makes it possible to follow the distribution of Korean family names far back in history. It is shown here that these name distributions are well described by a simple null model, the random group formation (RGF) model. This model makes it possible to predict how the name distributions change and these predictions are shown to be borne out. In particular, the RGF model predicts that for married women entering a collection of family books in a certain year, the occurrence of the most common family name 'Kim' should be directly proportional to the total number of married women with the same proportionality constant for all the years. This prediction is also borne out to a high degree. We speculate that it reflects some inherent social stability in the Korean culture. In addition, we obtain an estimate of the total population of the Korean culture down to the year 500 AD, based on the RGF model, and find about ten thousand Kims.

  9. Daily atmospheric radionuclide observations and health impact estimation before and after the Fukushima-Daiichi nuclear accident: Five-year trends by Canadian monitoring stations - Ten-year trends of atmospheric lead-210 and the correlation to atmospheric mercury in the Canadian Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weihua; Chen, Jing; Ungar, Kurt [Radiation Protection Bureau, Health Canada, 775 Brookfield Rd. Ottawa, K1A 1C1 (Canada)

    2014-07-01

    Mercury is a global threat to human and environmental health. Anthropogenic emissions of mercury have been larger than natural emissions since the start of the industrial age about 200 years ago. In the past decades, many studies have focused on monitoring and controlling anthropogenic emissions of mercury and their transport and transformation in the environment. In October 2013, the Minamata Convention on Mercury was formally adopted as international law. The new treaty aims to further cut mercury emissions and releases; it is the first global convention on environment and health. Coal burning for power generation and industrial use is one of the major sources of anthropogenic mercury emissions to the air. However, coal combustion processes produce significant quantities of dust containing not only mercury but also natural radionuclides that are released into the atmosphere. Like the case of mercury, those radionuclides can be transported over long distances, deposited on soil and oceans and accumulated in Arctic biota. Exposure to elevated levels of radiation is a health concern. This study analyses long-term trends of atmospheric lead-210 from Health Canada's radiological monitoring stations in the Arctic. Results are compared with ten-year records of atmospheric mercury reported by Environment Canada. A discussion is given on the correlation of long-range atmospheric transport of lead-210 and mercury from industrial sources, such as coal burning. It is expected that continuous decline of atmospheric mercury in the Arctic, especially with more and more countries signing the Minamata Convention, will result in a deceasing trend of atmospheric lead-210 from industrial sources as well. (authors)

  10. Construction of four double gene substitution human x bovine rotavirus reassortant vaccine candidates: each bears two outer capsid human rotavirus genes, one encoding P serotype 1A and the other encoding G serotype 1, 2, 3, or 4 specificity.

    Science.gov (United States)

    Hoshino, Y; Jones, R W; Chanock, R M; Kapikian, A Z

    1997-04-01

    Previously, four human x bovine rotavirus reassortant candidate vaccines, each of which derived ten genes from bovine rotavirus UK strain and only the outer capsid protein VP7-gene from human rotavirus strain D (G serotype 1), DS-1 (G serotype 2), P (G serotype 3), or ST3 (G serotype 4), were developed [Midthun et al., (1985): Journal of Virology 53:949-954; (1986): Journal of Clinical Microbiology 24:822-826]. Such human x bovine reassortant vaccines should theoretically provide antigenic coverage for the four epidemiologically most important VP7(G) serotypes 1, 2, 3, and 4. In an attempt to increase the antigenicity of VP7-based human x animal reassortant rotavirus vaccines which derive a single VP7-encoding gene from the human strain and the remaining ten genes from the animal strain, we generated double gene substitution reassortants. This was done by incorporating another protective antigen (VP4) of an epidemiologically important human rotavirus by crossing human rotavirus Wa strain (P serotype 1A), with each of the human x bovine single VP7-gene substitution rotavirus reassortants. In this way four separate double gene substitution rotavirus reassortants were generated. Each of these reassortants bears the VP4-encoding gene from human rotavirus Wa strain, the VP7-encoding gene from human rotavirus strain D, DS-1, P, or ST3, and the remaining nine genes from bovine rotavirus strain UK. The safety, antigenicity, and protective efficacy of individual components as well as combinations of strains are currently under evaluation.

  11. The Top Ten Algorithms in Data Mining

    CERN Document Server

    Wu, Xindong

    2009-01-01

    From classification and clustering to statistical learning, association analysis, and link mining, this book covers the most important topics in data mining research. It presents the ten most influential algorithms used in the data mining community today. Each chapter provides a detailed description of the algorithm, a discussion of available software implementation, advanced topics, and exercises. With a simple data set, examples illustrate how each algorithm works and highlight the overall performance of each algorithm in a real-world application. Featuring contributions from leading researc

  12. Ten-dimensional Supergravity Revisited

    NARCIS (Netherlands)

    Bergshoeff, Eric; Roo, Mees de; Kerstan, Sven; Riccioni, Fabio; Diaz Alonso, J.; Mornas, L.

    2006-01-01

    We show that the exisiting supergravity theories in ten dimensions can be extended with extra gauge fields whose rank is equal to the spacetime dimension. These gauge fields have vanishing field strength but nevertheless play an important role in the coupling of supergravity to spacetime filling

  13. Ten Problems in Experimental Mathematics

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, David H.; Borwein, Jonathan M.; Kapoor, Vishaal; Weisstein, Eric

    2004-09-30

    This article was stimulated by the recent SIAM ''100 DigitChallenge'' of Nick Trefethen, beautifully described in a recent book. Indeed, these ten numeric challenge problems are also listed in a recent book by two of present authors, where they are followed by the ten symbolic/numeric challenge problems that are discussed in this article. Our intent was to present ten problems that are characteristic of the sorts of problems that commonly arise in ''experimental mathematics''. The challenge in each case is to obtain a high precision numeric evaluation of the quantity, and then, if possible, to obtain a symbolic answer, ideally one with proof. Our goal in this article is to provide solutions to these ten problems, and in the process present a concise account of how one combines symbolic and numeric computation, which may be termed ''hybrid computation'', in the process of mathematical discovery.

  14. Understanding Scale: Powers of Ten

    Science.gov (United States)

    Jones, M. Gail; Taylor, Amy; Minogue, James; Broadwell, Bethany; Wiebe, Eric; Carter, Glenda

    2007-01-01

    The classic film "Powers of Ten" is often employed to catalyze the building of more accurate conceptions of scale, yet its effectiveness is largely unknown. This study examines the impact of the film on students' concepts of size and scale. Twenty-two middle school students and six science teachers participated. Students completed pre- and…

  15. A Ten-Year Reflection

    Science.gov (United States)

    Phillip, Cyndi

    2016-01-01

    Five initiatives launched during Cyndi Phillip's term as American Association of School Librarians (AASL) President (2006-2007) continue to have an impact on school librarians ten years later. They include the rewriting of AASL's learning standards, introduction of the SKILLS Act, the presentation of the Crystal Apple Award to Scholastic Library…

  16. Ten Rules of Academic Writing

    NARCIS (Netherlands)

    Donovan, S.K.

    2011-01-01

    Creative writers are well served with 'how to' guides, but just how much do they help? And how might they be relevant to academic authors? A recent survey of writing tips by twenty-eight creative authors has been condensed to the ten most relevant to the academic, supported by some comments on

  17. Ten "Discoveries" About Basic Learning

    Science.gov (United States)

    English, Raymond

    1977-01-01

    Ten conclusions about childrens' learning are presented from 15 years of research by the Educational Research Council of America. These include effectiveness of short textbooks, interest in learning technical words, need for social science curriculum to challenge, and detrimental effect of ingrained teacher attitudes to teach social studies by…

  18. Ten past and ten future GAS/MAUS-payloads

    Science.gov (United States)

    Staniek, S.; Otto, G.; Doepkess, J.

    1988-01-01

    MAUS (materials science autonomous experiments) is one out of a series of flight opportunities which the Space Program of West Germany offers to scientists from the disciplines of materials research and processing for performing materials science investigations under microgravity conditions. Up to now, ten MAUS experiments were flown which were dealing with the following scientific topics: decomposition of binary alloys with miscibility gap in the liquid state, interaction of a solidification front with dispersed particles, critical Marangoni number, investigation of the magnetic compound MnBi, shrinkage of gas bubbles in glass melts and slip casting. The ten future experiments are partly reflights with modification of the scientific objectives as well as new experiments in the fields of chemical reactions, heat transfer, glass technology and Ostwald ripening. Looking to ten flown payloads, the peculiarities of instrument technology in GAS-cans and its evolution is discussed with emphasis on structure, electronics and thermal design. A typical modern payload using 100 percent of the resource is presented.

  19. HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates

    Science.gov (United States)

    García-Arriaza, Juan; Perdiguero, Beatriz; Heeney, Jonathan L.; Seaman, Michael S.; Montefiori, David C.; Yates, Nicole L.; Tomaras, Georgia D.; Ferrari, Guido; Foulds, Kathryn E.; Roederer, Mario; Self, Steven G.; Borate, Bhavesh; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, Jim; Barnett, Susan W.; Burke, Brian; Cristillo, Anthony D.; Weiss, Deborah E.; Lee, Carter; Kibler, Karen V.; Jacobs, Bertram L.; Wagner, Ralf; Ding, Song; Pantaleo, Giuseppe

    2017-01-01

    ABSTRACT The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4+ and CD8+ T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the K1L and C7L vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene B19R, an inhibitor of the type I interferon response (NYVAC-C-KC-ΔB19R). An immunization protocol mimicking that of the RV144 phase III clinical trial was used. Two groups of macaques received two doses of the corresponding NYVAC-C-KC vectors (weeks 0 and 4) and booster doses with NYVAC-C-KC vectors plus the clade C HIV-1 gp120 protein (weeks 12 and 24). The two replicating NYVAC-C-KC vectors induced enhanced and similar HIV-1-specific CD4+ and CD8+ T cell responses, similar levels of binding IgG antibodies, low levels of IgA antibodies, and high levels of antibody-dependent cellular cytotoxicity responses and HIV-1-neutralizing antibodies. Small differences within the NYVAC-C-KC-ΔB19R group were seen in the magnitude of CD4+ and CD8+ T cells, the induction of some cytokines, and the neutralization of some HIV-1 isolates. Thus, replication-competent NYVAC-C-KC vectors acquired relevant immunological properties as vaccine candidates against HIV/AIDS, and the viral B19 molecule exerts some control of immune functions. IMPORTANCE It is of special importance to find a safe and effective HIV/AIDS vaccine that can induce strong and broad T cell and humoral immune responses correlating with HIV-1

  20. HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates.

    Science.gov (United States)

    García-Arriaza, Juan; Perdiguero, Beatriz; Heeney, Jonathan L; Seaman, Michael S; Montefiori, David C; Yates, Nicole L; Tomaras, Georgia D; Ferrari, Guido; Foulds, Kathryn E; Roederer, Mario; Self, Steven G; Borate, Bhavesh; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, Jim; Barnett, Susan W; Burke, Brian; Cristillo, Anthony D; Weiss, Deborah E; Lee, Carter; Kibler, Karen V; Jacobs, Bertram L; Wagner, Ralf; Ding, Song; Pantaleo, Giuseppe; Esteban, Mariano

    2017-05-01

    The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4+ and CD8+ T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the K1L and C7L vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene B19R, an inhibitor of the type I interferon response (NYVAC-C-KC-ΔB19R). An immunization protocol mimicking that of the RV144 phase III clinical trial was used. Two groups of macaques received two doses of the corresponding NYVAC-C-KC vectors (weeks 0 and 4) and booster doses with NYVAC-C-KC vectors plus the clade C HIV-1 gp120 protein (weeks 12 and 24). The two replicating NYVAC-C-KC vectors induced enhanced and similar HIV-1-specific CD4+ and CD8+ T cell responses, similar levels of binding IgG antibodies, low levels of IgA antibodies, and high levels of antibody-dependent cellular cytotoxicity responses and HIV-1-neutralizing antibodies. Small differences within the NYVAC-C-KC-ΔB19R group were seen in the magnitude of CD4+ and CD8+ T cells, the induction of some cytokines, and the neutralization of some HIV-1 isolates. Thus, replication-competent NYVAC-C-KC vectors acquired relevant immunological properties as vaccine candidates against HIV/AIDS, and the viral B19 molecule exerts some control of immune functions.IMPORTANCE It is of special importance to find a safe and effective HIV/AIDS vaccine that can induce strong and broad T cell and humoral immune responses correlating with HIV-1 protection

  1. Ten Blue Links on Mars

    OpenAIRE

    Clarke, Charles L. A.; Cormack, Gordon V.; Lin, Jimmy; Roegiest, Adam

    2016-01-01

    This paper explores a simple question: How would we provide a high-quality search experience on Mars, where the fundamental physical limit is speed-of-light propagation delays on the order of tens of minutes? On Earth, users are accustomed to nearly instantaneous response times from search engines. Is it possible to overcome orders-of-magnitude longer latency to provide a tolerable user experience on Mars? In this paper, we formulate the searching from Mars problem as a tradeoff between "effo...

  2. Ten Thousand Years of Solitude

    Energy Technology Data Exchange (ETDEWEB)

    Benford, G. (Los Alamos National Lab., NM (USA) California Univ., Irvine, CA (USA). Dept. of Physics); Kirkwood, C.W. (Los Alamos National Lab., NM (USA) Arizona State Univ., Tempe, AZ (USA). Coll. of Business Administration); Harry, O. (Los Alamos National Lab., NM (USA)); Pasqualetti, M.J. (Los Alamos National Lab., NM (USA) Arizona State Univ., Tempe, AZ (USA))

    1991-03-01

    This report documents the authors work as an expert team advising the US Department of Energy on modes of inadvertent intrusion over the next 10,000 years into the Waste Isolation Pilot Project (WIPP) nuclear waste repository. Credible types of potential future accidental intrusion into the WIPP are estimated as a basis for creating warning markers to prevent inadvertent intrusion. A six-step process is used to structure possible scenarios for such intrusion, and it is concluded that the probability of inadvertent intrusion into the WIPP repository over the next ten thousand years lies between one and twenty-five percent. 3 figs., 5 tabs.

  3. Differing patterns of selection and geospatial genetic diversity within two leading Plasmodium vivax candidate vaccine antigens.

    Directory of Open Access Journals (Sweden)

    Christian M Parobek

    2014-04-01

    Full Text Available Although Plasmodium vivax is a leading cause of malaria around the world, only a handful of vivax antigens are being studied for vaccine development. Here, we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens--Plasmodium vivax merozoite surface protein 1 (pvmsp-1 and Plasmodium vivax circumsporozoite protein (pvcsp. Using scalable next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of pvmsp-1 (n = 44 and the complete gene of pvcsp (n = 47 from Cambodian isolates. These sequences were then compared with global parasite populations obtained from GenBank. Using a combination of statistical and phylogenetic methods to assess for selection and population structure, we found strong evidence of balancing selection in the 42 kDa region of pvmsp-1, which varied significantly over the length of the gene, consistent with immune-mediated selection. In pvcsp, the highly variable central repeat region also showed patterns consistent with immune selection, which were lacking outside the repeat. The patterns of selection seen in both genes differed from their P. falciparum orthologs. In addition, we found that, similar to merozoite antigens from P. falciparum malaria, genetic diversity of pvmsp-1 sequences showed no geographic clustering, while the non-merozoite antigen, pvcsp, showed strong geographic clustering. These findings suggest that while immune selection may act on both vivax vaccine candidate antigens, the geographic distribution of genetic variability differs greatly between these two genes. The selective forces driving this diversification could lead to antigen escape and vaccine failure. Better understanding the geographic distribution of genetic variability in vaccine candidate antigens will be key to designing and implementing efficacious vaccines.

  4. Lead Test

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Lead Send Us Your Feedback Choose Topic At a ... Related Content View Sources Also Known As Blood Lead Test Blood Lead Level BLL Formal Name Lead, ...

  5. Lead Poisoning

    Science.gov (United States)

    Lead is a metal that occurs naturally in the earth's crust. Lead can be found in all parts of our ... from human activities such as mining and manufacturing. Lead used to be in paint; older houses may ...

  6. Leishmaniasis vaccine candidates for development: a global overview.

    Science.gov (United States)

    Khamesipour, Ali; Rafati, Sima; Davoudi, Noushin; Maboudi, Fereidoun; Modabber, Farrokh

    2006-03-01

    A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and experimental immunology of leishmaniasis, and the availability of vaccines that can protect experimental animals against challenge with different Leishmania species. However, there is no vaccine against any form of leishmaniasis for general human use. One major factor is the lack of a conceived market for human leishmaniasis vaccines. Hence pharmaceutical industries involved in vaccine development are not interested in investing millions of dollars and a decade that is required for developing a new vaccine. Besides, leishmaniasis is a local/regional problem and not a global one. According to the estimates of the World Health Organization, 90 per cent of visceral leishmaniasis occurs in five countries (Bangladesh, Brazil, India, Nepal and Sudan). Those in need are amongst the poorest people in these countries. It should therefore be the objectives of these countries to develop a vaccine. Fortunately, both Brazil and India have designated the control of visceral leishmaniasis as a top priority for their respective Ministries of Health. The purpose of this review is to present only the vaccines in use and those in development for use in dogs or humans. This is not an exhaustive review of vaccine discovery or the principles of clinical immunology underlying vaccine development.

  7. Egg-Independent Influenza Vaccines and Vaccine Candidates.

    Science.gov (United States)

    Manini, Ilaria; Trombetta, Claudia Maria; Lazzeri, Giacomo; Pozzi, Teresa; Rossi, Stefania; Montomoli, Emanuele

    2017-07-18

    Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines.

  8. Egg-Independent Influenza Vaccines and Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Ilaria Manini

    2017-07-01

    Full Text Available Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines.

  9. Reverse Vaccinology: An Approach for Identifying Leptospiral Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Odir A. Dellagostin

    2017-01-01

    Full Text Available Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis.

  10. The Streptococcus pyogenes proteome: maps, virulence factors and vaccine candidates

    OpenAIRE

    Dmitriev, Alexander V.; Chaussee, Michael S.

    2010-01-01

    Streptococcus pyogenes is an important cause of human morbidity and mortality worldwide. A wealth of genomic information related to this pathogen has facilitated exploration of the proteome, particularly in response to environmental conditions thought to mimic various aspects of pathogenesis. Proteomic approaches are also used to identify immunoreactive proteins for vaccine development and to identify proteins that may induce autoimmunity. These studies have revealed new mechanisms involved i...

  11. Characterization of Shigella dysenteriae type 1 hybrid vaccine candidates

    OpenAIRE

    Fält, Inger

    1995-01-01

    Shigellae is endemic in many developing countries in the world and a major cause of childhooddiarrheal morbidity and mortality. Infections caused by Shigella dysenteriae type 1 areparticularly severe. The major virulence factors in Shigella dysenteriae type 1 are the cellenvelope lipopolysaccharide, the invasion peptide antigens and the Shiga toxin. Little is knownof the relative importance of each of the virulence factors and their role in protective immunity.In this study, the expression of...

  12. Vaccines for leishmaniasis: from proteome to vaccine candidates.

    Science.gov (United States)

    Schroeder, Juliane; Aebischer, Toni

    2011-01-01

    Leishmania spp. cause a wide spectrum of tropical diseases which are threatening an estimated 350 million people around the globe. While in most cases non-fatal, the disease is associated with high morbidity, social stigmata and poverty. However, the most severe form visceral leishmaniasis can be fatal if left untreated. Chemotherapeutics are available but show high toxicity, costs and are prone to resistance development due to prolonged treatment periods. Healing is associated with a life-long resistance to re-infection and this argues for the feasibility of vaccination. However, despite much effort, no such vaccine has become available yet. Here, the status of vaccine development in this field is briefly summarized before the focus is set on the promise of reverse vaccinology for anti-Leishmania vaccine development in the post-genomic era. We report on our own experience with this approach using an instructive example of successful candidate vaccine antigen identification.

  13. Development of a VLP-based HCV vaccine candidate

    OpenAIRE

    Fernandes, Marina Isabel Ferreira

    2016-01-01

    Tese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2016 The Hepatitis C Virus (HCV) infects approximately 3% of the world population, being one of the major causes of liver cirrhosis and hepatocellular carcinoma. The development of safe, effective and affordable prophylactic and therapeutic vaccines against HCV has become an important medical priority; however, there are many obstacles to its development. In recent years, strategies of viral ant...

  14. Immunological Evaluation and Comparison of Different EV71 Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Ai-Hsiang Chou

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 and coxsackievirus A16 (CVA16 are major causative agents of hand, foot, and mouth diseases (HFMDs, and EV71 is now recognized as an emerging neurotropic virus in Asia. Effective medications and/or prophylactic vaccines against HFMD are not available. The current results from mouse immunogenicity studies using in-house standardized RD cell virus neutralization assays indicate that (1 VP1 peptide (residues 211–225 formulated with Freund’s adjuvant (CFA/IFA elicited low virus neutralizing antibody response (1/32 titer; (2 recombinant virus-like particles produced from baculovirus formulated with CFA/IFA could elicit good virus neutralization titer (1/160; (3 individual recombinant EV71 antigens (VP1, VP2, and VP3 formulated with CFA/IFA, only VP1 elicited antibody response with 1/128 virus neutralization titer; and (4 the formalin-inactivated EV71 formulated in alum elicited antibodies that cross-neutralized different EV71 genotypes (1/640, but failed to neutralize CVA16. In contrast, rabbits antisera could cross-neutralize strongly against different genotypes of EV71 but weakly against CVA16, with average titers 1/6400 and 1/32, respectively. The VP1 amino acid sequence dissimilarity between CVA16 and EV71 could partially explain why mouse antibodies failed to cross-neutralize CVA16. Therefore, the best formulation for producing cost-effective HFMD vaccine is a combination of formalin-inactivated EV71 and CAV16 virions.

  15. Identification of Novel Vaccine Candidates against Campylobacter through Reverse Vaccinology

    National Research Council Canada - National Science Library

    Meunier, Marine; Guyard-Nicodème, Muriel; Hirchaud, Edouard; Parra, Alberto; Chemaly, Marianne; Dory, Daniel

    2016-01-01

    .... Poultry vaccination is of potential for this purpose. However, despite many studies, there is currently no vaccine available on the market to reduce the intestinal Campylobacter load in chickens...

  16. Production optimisation of a DNA vaccine candidate against ...

    African Journals Online (AJOL)

    Plasmid DNA (pDNA) vaccines are promising means to prevent and treat infectious diseases, such as leishmaniasis, but immunisation protocols require large amounts of supercoiled plasmid DNA (scpDNA). Although pDNA can be produced at a reasonable cost in bioreactors; this scale of production may not be the best ...

  17. Reassortant rotaviruses as potential live rotavirus vaccine candidates.

    Science.gov (United States)

    Midthun, K; Greenberg, H B; Hoshino, Y; Kapikian, A Z; Wyatt, R G; Chanock, R M

    1985-03-01

    A series of reassortants was isolated from coinfection of cell cultures with a wild-type animal rotavirus and a "noncultivatable" human rotavirus. Wild-type bovine rotavirus (UK strain) was reassorted with human rotavirus strains D, DS-1, and P; wild-type rhesus rotavirus was reassorted with human rotavirus strains D and DS-1. The D, DS-1, and P strains represent human rotavirus serotypes 1, 2, and 3, respectively. Monospecific antiserum (to bovine rotavirus, NCDV strain) or a set of monoclonal antibodies to the major outer capsid neutralization glycoprotein, VP7 (of the rhesus rotavirus), was used to select for reassortants with human rotavirus neutralization specificity. This selection technique yielded many reassortants which received only the gene segment coding for the major neutralization protein from the human rotavirus parent, whereas the remaining genes were derived from the animal rotavirus parent. Single human rotavirus gene substitution reassortants of this sort represent potential live vaccine strains.

  18. Reassortant rotaviruses as potential live rotavirus vaccine candidates.

    OpenAIRE

    Midthun, K; Greenberg, H B; Hoshino, Y; Kapikian, A Z; Wyatt, R G; Chanock, R M

    1985-01-01

    A series of reassortants was isolated from coinfection of cell cultures with a wild-type animal rotavirus and a "noncultivatable" human rotavirus. Wild-type bovine rotavirus (UK strain) was reassorted with human rotavirus strains D, DS-1, and P; wild-type rhesus rotavirus was reassorted with human rotavirus strains D and DS-1. The D, DS-1, and P strains represent human rotavirus serotypes 1, 2, and 3, respectively. Monospecific antiserum (to bovine rotavirus, NCDV strain) or a set of monoclon...

  19. Identification Of Protein Vaccine Candidates Using Comprehensive Proteomic Analysis Strategies

    Science.gov (United States)

    2007-12-01

    mice. Infect Immun 70: 3330-3335. 48. Kaufman, L. & P. Standard. 1978. Immuno -identification of cultures of fungi pathogenic to man. Curr Microbiol 1...complex biological systems using micro-column liquid chromatography-electrospray tandem mass spectrometry. Analyst 121: 65R-76R. 88. Washburn, M., D

  20. [Contact dermatitis from polyacrylate in TENS electrode].

    Science.gov (United States)

    Weber-Muller, F; Reichert-Penetrat, S; Schmutz, J-L; Barbaud, A

    2004-05-01

    Transcutaneous electric nerve stimulation (TENS) is useful for many chronic pains. It induces few serious side effects, but skin reactions are not rare. We report on two cases of contact dermatitis due to TENS electrodes by sensitization to the acrylate in TENS conductive gel. A 50 year-old man suffered from post-traumatic lumbar pair. He developed eczematous lesions on the sites where the TENS electrodes were applied. Patch tests were positive with the TENS gel, with ethylene glycol dimethylacrylate (2 p. 100 petrolatum) and ethyl-acrylate (2 p. 100 petrolatum) on day 2 and 4 readings. A 54 Year-old man had a paralysis of the foot elevator following rupture of an aneurysm. After 2 months, he had an eczema on the sites where the TENS electrodes were applied. Patch tests were negative with the TENS electrodes but positive with 2-hydroxyethyl acrylate (0.1 p. 100 petrolatum), triethyleneglycol diacrylate (0.1 p. 100 petrolatum), 2-hydroxyethyl methacrylate (2 p. 100 petrolatum) and 2-hydroxypropyl methacrylate (2 p. 100 petrolatum) on day 2 and 4 readings. TENS transmits small electrical currents through the skin that induce the depolarization of the affected sensory nerve endings. They have few serious side effects but skin reactions such as irritation, burns or allergy to propylene glycol in the electrode gel, to the rubber of the electrodes (mercaptobenzothiazole) or to the metallic part of the electrodes, i.e. nickel, are not uncommon. To our knowledge, only one case of an allergy to the polyacrylates of TENS electrode gel has been previously reported in the literature. We emphasize that acrylate could be the main sensitizer in the more recently commercialized TENS electrodes and will propose alternative ways of treating patients sensitized to acrylate and who require treatment with TENS.

  1. Lead poisoning

    Science.gov (United States)

    ... or dust from lead-based paint. Toys and furniture painted before 1976. Painted toys and decorations made ... by decades of car exhaust or years of house paint scrapings. Lead is more common in soil ...

  2. Lead Poisoning

    Science.gov (United States)

    ... a hard, durable surface. In 1977, federal regulations banned lead from paint for general use. But homes ... OTHERS: Lead has recently been found in some plastic mini-blinds and vertical blinds which were made ...

  3. Clinical experience with TENS and TENS combined with nitrous oxide-oxygen. Report of 371 patients.

    OpenAIRE

    Quarnstrom, F. C.; Milgrom, P.

    1989-01-01

    Transcutaneous electrical nerve stimulation (TENS) alone or TENS combined with nitrous oxide-oxygen (N2O) was administered for restorative dentistry without local anesthesia to 371 adult patients. A total of 55% of TENS alone and 84% of TENS/N2O visits were rated successful. A total of 53% of TENS alone and 82% of TENS/N2O patients reported slight or no pain. In multivariable analyses, pain reports were related to the anesthesia technique and patient fear and unrelated to sex, race, age, toot...

  4. Relational Leading

    DEFF Research Database (Denmark)

    Larsen, Mette Vinther; Rasmussen, Jørgen Gulddahl

    2015-01-01

    This first chapter presents the exploratory and curious approach to leading as relational processes – an approach that pervades the entire book. We explore leading from a perspective that emphasises the unpredictable challenges and triviality of everyday life, which we consider an interesting......, relevant and realistic way to examine leading. The chapter brings up a number of concepts and contexts as formulated by researchers within the field, and in this way seeks to construct a first understanding of relational leading....

  5. Ten new species of Afrotropical Pterophoridae (Lepidoptera)

    NARCIS (Netherlands)

    Gielis, C.

    2008-01-01

    Ten new Afrotropical species of Pterophoridae are described: Agdistis linnaei spec. nov., Agdistis bouyeri spec. nov., Ochyrotica bjoernstadti spec. nov., Platyptilia aarviki spec. nov., Stenoptilia kiitulo spec. nov., Exelastis caroli spec. nov., Eucapperia continentalis spec. nov., Buckleria

  6. Lead Toxicity

    Science.gov (United States)

    ... blue-gray metal that is mined from the earth’s crust. • Lead has been used for many industrial ... including the kidneys, heart, and reproductive system, • Pregnant women should know that the developing fetus is very ...

  7. Lead Poisoning

    Science.gov (United States)

    ... has also been associated with juvenile delinquency and criminal behavior. In adults, lead can increase blood pressure ... and-forth manner, but rather from left to right (or vise-versa), or from the top of ...

  8. Lead Test

    Science.gov (United States)

    ... poison you. Most lead is present as an inorganic compound and does not move well through the ... D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 474. Wu, A. (© ...

  9. Ecotoxicology: Lead

    Science.gov (United States)

    Scheuhammer, A.M.; Beyer, W.N.; Schmitt, C.J.; Jorgensen, Sven Erik; Fath, Brian D.

    2008-01-01

    Lead (Pb) is a naturally occurring metallic element; trace concentrations are found in all environmental media and in all living things. However, certain human activities, especially base metal mining and smelting; combustion of leaded gasoline; the use of Pb in hunting, target shooting, and recreational angling; the use of Pb-based paints; and the uncontrolled disposal of Pb-containing products such as old vehicle batteries and electronic devices have resulted in increased environmental levels of Pb, and have created risks for Pb exposure and toxicity in invertebrates, fish, and wildlife in some ecosystems.

  10. Leading men

    DEFF Research Database (Denmark)

    Bekker-Nielsen, Tønnes

    2016-01-01

    Through a systematic comparison of c. 50 careers leading to the koinarchate or high priesthood of Asia, Bithynia, Galatia, Lycia, Macedonia and coastal Pontus, as described in funeral or honorary inscriptions of individual koinarchs, it is possible to identify common denominators but also disting...

  11. Development and characterization of ten polymorphic microsatellites ...

    Indian Academy of Sciences (India)

    Quililongo C. J., Ríos-Ramírez M. A., Velásquez-Cumplido L., Morales-Muñoz B. and Escobar-Fica J. A. 2012 Development and characterization of ten polymorphic microsatellites isolated from the scallop Argopecten purpuratus. J. Genet.

  12. Ten-year urban forestry action plan

    Science.gov (United States)

    J.W." Jerry" Van Sambeek

    2017-01-01

    The Ten-year Urban Forestry Action Plan: 2016-2026 was published in September, 2015 (see http://www.urbanforestry.subr.edu/FinalActionPlan_Complete_11_17_15.pdf). This 260 page heavily illustrated document was prepared by the National Urban and Community Forestry Advisory Council (NUCFAC) under leadership and funding from the USDA Forest Service. The Plan's...

  13. UTILITY OF THE TEN PER CENT RULE

    African Journals Online (AJOL)

    2001-11-01

    Nov 1, 2001 ... Objective: To measure asymmetry in grip strength between hands in left, right and mixed handers and to test utility of the ten per cent rule. Design: A cross sectional study. Setting: Queen Elizabeth Central Hospital, Blantyre, Malawi. Subjects: One hundred and seventy six healthy volunteers (102 males and ...

  14. Strahlungsfelder und Strahlungsqualitäten

    Science.gov (United States)

    Krieger, Hanno

    Das Kapitel beginnt mit einer Darstellung der wichtigsten Größen zur Beschreibung von Strahlungsfeldern. Diese Größen können sowohl auf die Teilchenzahl als auch auf die Teilchenenergie bezogen sein. Im zweiten Teil werden ausführlich die Verfahren zur Charakterisierung der Strahlungsqualitäten der verschiedenen in der Radiologie verwendeten Strahlungsarten dargestellt.

  15. Ten recommendations for software engineering in research.

    Science.gov (United States)

    Hastings, Janna; Haug, Kenneth; Steinbeck, Christoph

    2014-01-01

    Research in the context of data-driven science requires a backbone of well-written software, but scientific researchers are typically not trained at length in software engineering, the principles for creating better software products. To address this gap, in particular for young researchers new to programming, we give ten recommendations to ensure the usability, sustainability and practicality of research software.

  16. Top-Ten IT Issues, 2008

    Science.gov (United States)

    Allison, Debra H.; DeBlois, Peter B.

    2008-01-01

    EDUCAUSE presents the top-ten IT-related issues in terms of strategic importance to the higher education institution, as revealed by the ninth annual EDUCAUSE Current Issues Survey. This year, "Security" moves back to the top of the list. (Contains 20 notes.)

  17. CRUDE PROTEIN ELECTROPHORESIS OF SEEDS OF TEN

    African Journals Online (AJOL)

    A A Essiett

    Seeds of mature fruits of ten species of Solanum were collected from the gardens near the screen house, Botany. Department, Obafemi Awolowo University, Ile Ife, Osun State, Nigeria. Crude seed proteins were extracted from them and characterised using polyacrylamide gel electrophoresis. Inter and intra specific ...

  18. (CdnTen) and Cadmium Zinc Telluride

    African Journals Online (AJOL)

    Bheema

    solar cells, integrated optics and electro-optics devices. Hence, there are different experimental and theoretical studies on this group using various techniques or methods. A number of theoretical and experimental attempts (Jianguang, 2009) have been made to determine the structure and properties of small CdnTen and ...

  19. Czech, Slovak science ten years after split

    CERN Multimedia

    2003-01-01

    Ten years after the split of Czechoslovakia Czech and Slovak science are facing the same difficulties: shortage of money for research, poor salaries, obsolete equipment and brain drain, especially of the young, according to a feature in the Daily Lidove Noviny (1 page).

  20. Who Leads China's Leading Universities?

    Science.gov (United States)

    Huang, Futao

    2017-01-01

    This study attempts to identify the major characteristics of two different groups of institutional leaders in China's leading universities. The study begins with a review of relevant literature and theory. Then, there is a brief introduction to the selection of party secretaries, deputy secretaries, presidents and vice presidents in leading…

  1. Synchronous ten trigger finger: A case report

    Directory of Open Access Journals (Sweden)

    Gokce Yildiran

    2016-08-01

    Full Text Available Trigger finger is a disorder that presents with a blocking feeling and pain during finger movements. This condition more commonly occurs in the 2nd finger with involvement of multiple digits being extremely rare. There are very few known cases in which trigger finger was developed in all ten fingers. Here, an unusual case of ten-digit finger trigger is presented. A 44-year-old female housewife visited our clinic with painful blocking feeling in her hand. Her examination was compatible with trigger finger. Her hands were operated on in different sessions and A1 pulleys of all fingers were released. After the operations, blocking feeling and pain during flexion disappeared and normal range of motion was obtained. On the occasion of this very rare case, the etiology and approach for multiple trigger fingers is discussed. [Hand Microsurg 2016; 5(2.000: 84-87

  2. Compartmentalized expression of zebrafish ten-m3 and ten-m4, homologues of the Drosophila ten(m)/odd Oz gene, in the central nervous system.

    Science.gov (United States)

    Mieda, M; Kikuchi, Y; Hirate, Y; Aoki, M; Okamoto, H

    1999-09-01

    Zebrafish ten-m3 and ten-m4 encode proteins highly similar to the product of Drosophila pair-rule gene ten(m)/odd Oz (odz). Their products contain eight epidermal growth factor (EGF)-like repeats that resemble mostly those of the extracellular matrix molecule tenascin. During segmentation period, ten-m3 is expressed in the somites, notochord, pharyngeal arches, and the brain, while expression of ten-m4 is mainly restricted to the brain. In the developing brain, ten-m3 and ten-m4 expression delineates several compartments. Interestingly, ten-m3 and ten-m4 show expression patterns complementary to each other in the developing forebrain and midbrain along both rostrocaudal and dorsoventral axes, depending on developmental stages and locations.

  3. EEG Correlates of Ten Positive Emotions

    OpenAIRE

    Hu, Xin; Yu, Jianwen; Song, Mengdi; Yu, Chun; Wang, Fei; Sun, Pei; Wang, Daifa; Zhang, Dan

    2017-01-01

    Compared with the well documented neurophysiological findings on negative emotions, much less is known about positive emotions. In the present study, we explored the EEG correlates of ten different positive emotions (joy, gratitude, serenity, interest, hope, pride, amusement, inspiration, awe, and love). A group of 20 participants were invited to watch 30 short film clips with their EEGs simultaneously recorded. Distinct topographical patterns for different positive emotions were found for th...

  4. EEG Correlates of Ten Positive Emotions.

    Science.gov (United States)

    Hu, Xin; Yu, Jianwen; Song, Mengdi; Yu, Chun; Wang, Fei; Sun, Pei; Wang, Daifa; Zhang, Dan

    2017-01-01

    Compared with the well documented neurophysiological findings on negative emotions, much less is known about positive emotions. In the present study, we explored the EEG correlates of ten different positive emotions (joy, gratitude, serenity, interest, hope, pride, amusement, inspiration, awe, and love). A group of 20 participants were invited to watch 30 short film clips with their EEGs simultaneously recorded. Distinct topographical patterns for different positive emotions were found for the correlation coefficients between the subjective ratings on the ten positive emotions per film clip and the corresponding EEG spectral powers in different frequency bands. Based on the similarities of the participants' ratings on the ten positive emotions, these emotions were further clustered into three representative clusters, as 'encouragement' for awe, gratitude, hope, inspiration, pride, 'playfulness' for amusement, joy, interest, and 'harmony' for love, serenity. Using the EEG spectral powers as features, both the binary classification on the higher and lower ratings on these positive emotions and the binary classification between the three positive emotion clusters, achieved accuracies of approximately 80% and above. To our knowledge, our study provides the first piece of evidence on the EEG correlates of different positive emotions.

  5. EEG Correlates of Ten Positive Emotions

    Science.gov (United States)

    Hu, Xin; Yu, Jianwen; Song, Mengdi; Yu, Chun; Wang, Fei; Sun, Pei; Wang, Daifa; Zhang, Dan

    2017-01-01

    Compared with the well documented neurophysiological findings on negative emotions, much less is known about positive emotions. In the present study, we explored the EEG correlates of ten different positive emotions (joy, gratitude, serenity, interest, hope, pride, amusement, inspiration, awe, and love). A group of 20 participants were invited to watch 30 short film clips with their EEGs simultaneously recorded. Distinct topographical patterns for different positive emotions were found for the correlation coefficients between the subjective ratings on the ten positive emotions per film clip and the corresponding EEG spectral powers in different frequency bands. Based on the similarities of the participants’ ratings on the ten positive emotions, these emotions were further clustered into three representative clusters, as ‘encouragement’ for awe, gratitude, hope, inspiration, pride, ‘playfulness’ for amusement, joy, interest, and ‘harmony’ for love, serenity. Using the EEG spectral powers as features, both the binary classification on the higher and lower ratings on these positive emotions and the binary classification between the three positive emotion clusters, achieved accuracies of approximately 80% and above. To our knowledge, our study provides the first piece of evidence on the EEG correlates of different positive emotions. PMID:28184194

  6. Ten themes of viscous liquid dynamics

    DEFF Research Database (Denmark)

    Dyre, J. C.

    2007-01-01

    simplifies the theory by allowing for an ultra-local Hamiltonian (free energy), but also explains the observed general independence of chemistry. Whereas there are no long-ranged static (i.e., equal-time) correlations in the model, there are important long-ranged dynamic correlations on the alpha timescale.......Ten ‘themes' of viscous liquid physics are discussed with a focus on how they point to a general description of equilibrium viscous liquid dynamics (i.e., fluctuations) at a given temperature. This description is based on standard time-dependent Ginzburg-Landau equations for the density fields...

  7. Water Sustainability Assessment for Ten Army Installations

    Science.gov (United States)

    2011-03-26

    the severity of this scarcity varies by scenario. It seems that natural condi- tions play a bigger part in water availability for the region than does...question lies with: (1) a picture of how short-term water scarcity might play out across the region, which is outside of the scope of this study, and...ER D C/ CE RL T R- 11 -5 Water Sustainability Assessment for Ten Army Installations Co ns tr uc tio n En gi ne er in g R es

  8. Ten Guidelines for Translating Legal Texts

    Directory of Open Access Journals (Sweden)

    Alenka Kocbek

    2017-12-01

    Full Text Available The paper proposes a targeted model for translating legal texts, developed by the author by combining translation science (i.e. functionalist approaches with the findings of comparative law and legal linguistics. It consists of ten guidelines directing the translator from defining the intended function of the target text and selecting the corresponding translation type, through comparing the legal systems involved in the translation and analysing the memetic structure of the source text and parallel texts in the target culture to designing the target text as a cultureme and ensuring its legal security.

  9. Supersymmetric R4-actions in ten dimensions

    OpenAIRE

    de Roo, M.; Suelmann, H.; Wiedemann, A.

    1992-01-01

    We construct supersymmetric R+R4-actions in ten dimensions. Two invariants, of which the bosonic parts are known from string amplitude and sigma model calculations, are obtained. One of these invariants can be generalized to an R+F2+F4-invariant for supersymmetric Yang-Mills theory coupled to supergravity. Supersymmetry requires the presence of B ^ R ^ R ^ R ^ R-terms, (B ^ F ^ F ^ F ^ F for Yang-Mills) which correspond to counterterms in the Green-Schwarz anomaly cancellation.

  10. Ten essential skills for electrical engineers

    CERN Document Server

    Dorr, Barry

    2014-01-01

    Engineers know that, as in any other discipline, getting a good job requires practical, up-to-date skills. An engineering degree provides a broad set of fundamentals. Ten Essential Skills applies those fundamentals to practical tasks required by employers. Written in a user-friendly, no-nonsense format, the book reviews practical skills using the latest tools and techniques, and features a companion website with interview practice problems and advanced material for readers wishing to pursue additional skills. With this book, aspiring and current engineers may approach job interviews confident

  11. TENS (transcutaneous electrical nerve stimulation) for labour pain.

    Science.gov (United States)

    Francis, Richard

    2012-05-01

    Because TENS is applied inconsistently and not always in line with optimal TENS application theory, this may explain why TENS for labour pain appears to be effective in some individuals and not in others. This article reviews TENS theory, advises upon optimal TENS application for labour pain and discusses some of the limitations of TENS research on labour pain. TENS application for labour pain may include TENS applied to either side of the lower spine, set to 200 mus pulse duration and 100 pulses per second. As pain increases, TENS intensity should be increased and as pain decreases, TENS intensity should be reduced to maintain a strong but pain free intensity of stimulation. This application may particularly reduce back pain during labour.

  12. Assessment of hypoallergenicity of ten skincare products.

    Science.gov (United States)

    Brandt, Staci; Lio, Peter

    2014-03-01

    Sensitive skin is a common skin complaint frequently associated with skin diseases or adverse reactions to cosmetic products. Manufacturers have produced numerous products targeted for patients with sensitive skin and frequently label these products as being hypoallergenic. This term implies that the product may be less likely to cause an allergic reaction and be better suited for those with sensitive skin. However, there is no federal regulatory definition of this term and products may not have clinical support of their claim. Patch testing ingredients is frequently done to identify potential irritants; however, patch-testing product formulations may provide more realistic expectations about potential skin sensitivity and help support claims of hypoallergenicity. Ten skincare products were assessed for their sensitizing potential and hypoallergenicity in 14 repeat insult patch test clinical studies, involving over 2,000 subjects. In these studies, the products were deemed to be hypoallergenic if there was no evidence of sensitization or allergic reactions. The results from these trials demonstrated that all ten products were well tolerated, showed no sensitization or allergic reactions, and support claims of hypoallergenicity.

  13. Ten principles of good interdisciplinary team work.

    Science.gov (United States)

    Nancarrow, Susan A; Booth, Andrew; Ariss, Steven; Smith, Tony; Enderby, Pam; Roots, Alison

    2013-05-10

    Interdisciplinary team work is increasingly prevalent, supported by policies and practices that bring care closer to the patient and challenge traditional professional boundaries. To date, there has been a great deal of emphasis on the processes of team work, and in some cases, outcomes. This study draws on two sources of knowledge to identify the attributes of a good interdisciplinary team; a published systematic review of the literature on interdisciplinary team work, and the perceptions of over 253 staff from 11 community rehabilitation and intermediate care teams in the UK. These data sources were merged using qualitative content analysis to arrive at a framework that identifies characteristics and proposes ten competencies that support effective interdisciplinary team work. Ten characteristics underpinning effective interdisciplinary team work were identified: positive leadership and management attributes; communication strategies and structures; personal rewards, training and development; appropriate resources and procedures; appropriate skill mix; supportive team climate; individual characteristics that support interdisciplinary team work; clarity of vision; quality and outcomes of care; and respecting and understanding roles. We propose competency statements that an effective interdisciplinary team functioning at a high level should demonstrate.

  14. Diæten - et andet perspektiv

    DEFF Research Database (Denmark)

    Agerholm, Frank Juul

    2014-01-01

    Temaet for den seneste udgave af vores studenterblad ”Næringsstoffet” er ”Et andet perspektiv”. Ifølge redaktionens oplæg kunne det eksempelvis dreje sig om »artikler om nye kropsidealer, at sundhed ikke kun handler om, hvad man propper i munden, forskellige perspektiver på de nye kostråd, altern......, alternative kostformer (5:2 kuren) osv.«. Det gav mig anledning til et indlæg, hvor jeg har forsøgt at strejfe flere punkter fra listen med et andet perspektiv på diæten. I bloggen gengives det indlæg i en lettere tilrettet version....

  15. Electroanaesthesia--from torpedo fish to TENS.

    Science.gov (United States)

    Francis, J; Dingley, J

    2015-01-01

    In 153 AD, the Roman physician Scribonius Largus identified that electric current had analgesic properties, instructing patients to stand on an electric ray for the treatment of gout. In 2014, transcranial magnetic stimulation was approved by the National Institute for Health and Care Excellence for the treatment of migraine. Although separated by nearly two millennia, these milestones represent the evolution of the utilisation of electric current in medical and anaesthetic practice. Significant advances have been made over the last century in particular, and during the 1960s and 1970s, tens of thousands of patients were reportedly anaesthetised for surgical interventions using electric current as the anaesthetic agent. Many medical interventions, including transcutaneous electrical nerve stimulation and deep brain stimulation, have evolved in the aftermath of investigations into electroanaesthesia; the potential for electric current to be an anaesthetic agent of the future still exists. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

  16. Simultaneous determination of ten preservatives in ten kinds of foods by micellar electrokinetic chromatography.

    Science.gov (United States)

    Ding, Xiao-Jing; Xie, Na; Zhao, Shan; Wu, Yu-Chen; Li, Jiang; Wang, Zhi

    2015-08-15

    An improved micellar electrokinetic capillary chromatography method (MEKC) for the simultaneous determination of ten preservatives in ten different kinds of food samples was reported. An uncoated fused-silica capillary with 50 μm i.d. and 70 cm total length was used. Under the optimized conditions, the linear response was observed in the range of 1.2-200mg/L for the analytes. The limits of detection (LOD, S/N=3) and limits of quantitation (LOQ, S/N=10) ranging from 0.4 to 0.5mg/L and 1.2 to 1.5mg/L, respectively were obtained. The method was used for the determination of sorbic and benzoic acids in two FAPAS® (Food Analysis Performance Assessment Scheme) proficiency test samples (jam and chocolate cake). The results showed that the current method with simple sample pretreatment and small reagent consumption could meet the needs for routine analysis of the ten preservatives in ten types of food products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Successful dexamethasone pulse therapy in a toxic epidermal necrolysis (TEN) patient featuring recurrent TEN to oxazepam

    NARCIS (Netherlands)

    van der Meer, J B; Schuttelaar, M L; Toth, G G; Kardaun, S H; Beerthuizen, G; de Jong, M C; Jonkman, M F; Nieuwenhuis, P

    2001-01-01

    A 62-year-old female patient is described who developed toxic epidermal necrolysis (TEN) after medication with phenytoin and oxazepam. Initially phenytoin was discontinued and dexamethasone pulse therapy (1.5 mg/kg on 3 consecutive days) was initiated on the tenth day of skin disease. This resulted

  18. Humanities and Social Sciences Books of Ten National Disciplinary Associations, 2000-2009

    Science.gov (United States)

    Wiberley, Stephen E., Jr.

    2016-01-01

    Books are the most important medium of communication in the humanities, a major medium in the social sciences, and a central component of academic library collections. This study examined humanities and social sciences books that won prizes from ten leading United States disciplinary associations between 2000 and 2009. The study extends earlier…

  19. Top Ten Environmental Priorities for Africa

    African Journals Online (AJOL)

    LANDA

    disguised as potentially useful “second-hand” products that end up polluting air and water, despite the best intentions of the Basel Convention ... Lead (Pb) poisoning. Smoke pollution. Dust pollution. Pesticide pollution. Drought and deforestation. Petrochemical pollution. Physical injury. 1 World Health Organization. 2007.

  20. Romania: Ten Years of EU Membership

    Directory of Open Access Journals (Sweden)

    Gábor Hunya

    2017-06-01

    Full Text Available By joining the European Union as of 1st of January 2007, Romania made use of a window of opportunity which may not have been open later. In the ten years that followed, advantages and challenges of the membership have in part been overshadowed by the impact of the global financial crisis. The country went through a boom-bust-boom economic cycle. The swing from overheating to depression and back again to overheating has been amplified by pro-cyclical economic policy. Romania has been a selective policy taker in the EU often delaying fiscal and legal actions resulting in lost benefits. By reviewing the current political uncertainties in Europe, the conclusion emerges that more effective governance and more active foreign policy is necessary under the current Europe-wide orientation loss. The country may need to develop a mobilising strategy and policy beyond the direct benefits provided by the EU, one that also contributes to the success of the European integration.

  1. Questioning ten common assumptions about peatlands

    Directory of Open Access Journals (Sweden)

    University of Leeds Peat Club:

    2017-07-01

    Full Text Available Peatlands have been widely studied in terms of their ecohydrology, carbon dynamics, ecosystem services and palaeoenvironmental archives. However, several assumptions are frequently made about peatlands in the academic literature, practitioner reports and the popular media which are either ambiguous or in some cases incorrect. Here we discuss the following ten common assumptions about peatlands: 1. the northern peatland carbon store will shrink under a warming climate; 2. peatlands are fragile ecosystems; 3. wet peatlands have greater rates of net carbon accumulation; 4. different rules apply to tropical peatlands; 5. peat is a single soil type; 6. peatlands behave like sponges; 7. Sphagnum is the main ‘ecosystem engineer’ in peatlands; 8. a single core provides a representative palaeo-archive from a peatland; 9. water-table reconstructions from peatlands provide direct records of past climate change; and 10. restoration of peatlands results in the re-establishment of their carbon sink function. In each case we consider the evidence supporting the assumption and, where appropriate, identify its shortcomings or ways in which it may be misleading.

  2. Ten tips for authors of scientific articles.

    Science.gov (United States)

    Hong, Sung-Tae

    2014-08-01

    Writing a good quality scientific article takes experience and skill. I propose 'Ten Tips' that may help to improve the quality of manuscripts for scholarly journals. It is advisable to draft first version of manuscript and revise it repeatedly for consistency and accuracy of the writing. During the drafting and revising the following tips can be considered: 1) focus on design to have proper content, conclusion, points compliant with scope of the target journal, appropriate authors and contributors list, and relevant references from widely visible sources; 2) format the manuscript in accordance with instructions to authors of the target journal; 3) ensure consistency and logical flow of ideas and scientific facts; 4) provide scientific confidence; 5) make your story interesting for your readers; 6) write up short, simple and attractive sentences; 7) bear in mind that properly composed and reflective titles increase chances of attracting more readers; 8) do not forget that well-structured and readable abstracts improve citability of your publications; 9) when revising adhere to the rule of 'First and Last' - open your text with topic paragraph and close it with resolution paragraph; 10) use connecting words linking sentences within a paragraph by repeating relevant keywords.

  3. Choledochal cysts: our ten year experience.

    LENUS (Irish Health Repository)

    Cianci, F

    2012-04-01

    We present our experience in the management of choledochal cysts from 1999 to 2009. A retrospective review of all charts with a diagnosis of choledochal cysts in our institution in this ten-year period. Data was collated using Excel. A total of 17 patients were diagnosed with choledochal cyst: 9 females and 8 males. The average age at diagnosis was 28 months (range from 0 to 9 years). The most common presenting symptoms were obstructive jaundice 6 (35%) and abdominal pain and vomiting 4 (23%). Ultrasound (US) was the initial diagnostic test in all cases with 4 patients requiring further investigations. All patients underwent Roux-en-Y Hepaticojejunostomy. The average length of stay was 11 days. Patients were followed up with Liver Function Tests (LFTS) and US 4-6 weeks post-operatively. Three patients developed complications including post-op collection, high drain output requiring blood transfusion and adhesive bowel obstruction. Our overall experience with choledochal cyst patients has been a positive one with effective management and low complication rates.

  4. The first ten years of Swift supernovae

    Science.gov (United States)

    Brown, Peter J.; Roming, Peter W. A.; Milne, Peter A.

    2015-09-01

    The Swift Gamma Ray Burst Explorer has proven to be an incredible platform for studying the multiwavelength properties of supernova explosions. In its first ten years, Swift has observed over three hundred supernovae. The ultraviolet observations reveal a complex diversity of behavior across supernova types and classes. Even amongst the standard candle type Ia supernovae, ultraviolet observations reveal distinct groups. When the UVOT data is combined with higher redshift optical data, the relative populations of these groups appear to change with redshift. Among core-collapse supernovae, Swift discovered the shock breakout of two supernovae and the Swift data show a diversity in the cooling phase of the shock breakout of supernovae discovered from the ground and promptly followed up with Swift. Swift observations have resulted in an incredible dataset of UV and X-ray data for comparison with high-redshift supernova observations and theoretical models. Swift's supernova program has the potential to dramatically improve our understanding of stellar life and death as well as the history of our universe.

  5. Comparative Genomics of Ten Solanaceous Plastomes

    Directory of Open Access Journals (Sweden)

    Harpreet Kaur

    2014-01-01

    Full Text Available Availability of complete plastid genomes of ten solanaceous species, Atropa belladonna, Capsicum annuum, Datura stramonium, Nicotiana sylvestris, Nicotiana tabacum, Nicotiana tomentosiformis, Nicotiana undulata, Solanum bulbocastanum, Solanum lycopersicum, and Solanum tuberosum provided us with an opportunity to conduct their in silico comparative analysis in depth. The size of complete chloroplast genomes and LSC and SSC regions of three species of Solanum is comparatively smaller than that of any other species studied till date (exception: SSC region of A. belladonna. AT content of coding regions was found to be less than noncoding regions. A duplicate copy of trnH gene in C. annuum and two alternative tRNA genes for proline in D. stramonium were observed for the first time in this analysis. Further, homology search revealed the presence of rps19 pseudogene and infA genes in A. belladonna and D. stramonium, a region identical to rps19 pseudogene in C. annum and orthologues of sprA gene in another six species. Among the eighteen intron-containing genes, 3 genes have two introns and 15 genes have one intron. The longest insertion was found in accD gene in C. annuum. Phylogenetic analysis using concatenated protein coding sequences gave two clades, one for Nicotiana species and another for Solanum, Capsicum, Atropa, and Datura.

  6. Ten years for the public Web

    CERN Multimedia

    2003-01-01

    Ten years ago, CERN issued a statement declaring that a little known piece of software called the World Wide Web was in the public domain. Nowadays, the Web is an indispensable part of modern communications. The idea for the Web goes back to March 1989 when CERN Computer scientist Tim Berners-Lee wrote a proposal for a 'Distributed Information Management System' for the high-energy physics community. The Web was originaly conceived and developed to meet the demand for information sharing between scientists working all over the world. There were many obstacles in the 1980s to the effective exchange of information. There was, for example a great variety of computer and network systems, with hardly any common features. The main purpose of the web was to allow scientists to access information from any source in a consistent and simple way. By Christmas 1990, Berners-Lee's idea had become the World Wide Web, with its first server and browser running at CERN. Through 1991, the Web spread to other particle physics ...

  7. Role of nanocrystalline silver dressings in the management of toxic epidermal necrolysis (TEN) and TEN/Stevens-Johnson syndrome overlap.

    Science.gov (United States)

    Smith, Saxon D; Dodds, Annabel; Dixit, Shreya; Cooper, Alan

    2015-11-01

    Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe mucocutaneous eruptions. There is currently no defined optimal approach to wound care. The objective of this study was to evaluate silver dressings in the wound-care management of TEN and SJS/TEN syndrome overlap with a retrospective case review of nine patients with TEN and SJS/TEN overlap presenting to our institution. Nanocrystalline silver dressings appear to be useful in the rapid commencement of healing in these patients. TEN and SJS/TEN overlap are rare conditions. This contributed to a relatively small number of cases included in the study. The ease of application, antimicrobial properties and low frequency of change make nanocrystalline silver dressings ideal in TEN/SJS. © 2014 The Australasian College of Dermatologists.

  8. "Take ten minutes": a dedicated ten minute medication review reduces polypharmacy in the elderly.

    LENUS (Irish Health Repository)

    Walsh, E K

    2010-09-01

    Multiple and inappropriate medications are often the cause for poor health status in the elderly. Medication reviews can improve prescribing. This study aimed to determine if a ten minute medication review by a general practitioner could reduce polypharmacy and inappropriate prescribing in elderly patients. A prospective, randomised study was conducted. Patients over the age of 65 (n = 50) underwent a 10-minute medication review. Inappropriate medications, dosage errors, and discrepancies between prescribed versus actual medication being consumed were recorded. A questionnaire to assess satisfaction was completed following review. The mean number of medications taken by patients was reduced (p < 0.001). A medication was stopped in 35 (70%) patients. Inappropriate medications were detected in 27 (54%) patients and reduced (p < 0.001). Dose errors were detected in 16 (32%). A high level of patient satisfaction was reported. A ten minute medication review reduces polypharmacy, improves prescribing and is associated with high levels of patient satisfaction.

  9. "Take ten minutes": a dedicated ten minute medication review reduces polypharmacy in the elderly.

    LENUS (Irish Health Repository)

    Walsh, E K

    2012-02-01

    Multiple and inappropriate medications are often the cause for poor health status in the elderly. Medication reviews can improve prescribing. This study aimed to determine if a ten minute medication review by a general practitioner could reduce polypharmacy and inappropriate prescribing in elderly patients. A prospective, randomised study was conducted. Patients over the age of 65 (n = 50) underwent a 10-minute medication review. Inappropriate medications, dosage errors, and discrepancies between prescribed versus actual medication being consumed were recorded. A questionnaire to assess satisfaction was completed following review. The mean number of medications taken by patients was reduced (p < 0.001). A medication was stopped in 35 (70%) patients. Inappropriate medications were detected in 27 (54%) patients and reduced (p < 0.001). Dose errors were detected in 16 (32%). A high level of patient satisfaction was reported. A ten minute medication review reduces polypharmacy, improves prescribing and is associated with high levels of patient satisfaction.

  10. Evaluation of an aided TEN test for diagnosis of dead regions in the cochlea.

    Science.gov (United States)

    Marriage, Josephine; Moore, Brian C J; Ogg, Vivian; Stone, Michael A

    2008-06-01

    To compare results for the original version of the threshold equalizing noise [TEN(HL)] test for diagnosis of dead regions (DRs) in the cochlea, using stimuli presented via headphones, with results for an aided version of the test, the ATEN test, in which subjects listened to stimuli presented in free field using their own hearing aids. The test tones were warble tones for both the TEN(HL) and the ATEN test. Twenty-five subjects (12 males and 13 females), aged between 12 and 19 yr, with severe or profound sensorineural hearing loss were tested. For each test, two levels of the TEN were used, chosen to fall within the comfortable range of levels for the individual subject. A DR was considered to be present when the TEN(HL) produced at least 10 dB of masking and when the masked threshold was at least 10 dB above the nominal TEN(HL) level. Measurements of the outputs of the hearing aids in response to the TEN(HL) plus the test tones were obtained using a KEMAR acoustic manikin to assess the extent to which distortion or compression might have influenced the outcomes. For the TEN(HL) test, the results were often inconclusive, because the TEN(HL) could not be made sufficiently intense to give at least 10 dB of masking. The incidence of these inconclusive cases was markedly reduced for the ATEN test. There were more positive diagnoses of DRs for the ATEN test than for the TEN(HL) test. The KEMAR measurements indicated that distortion, compression, and/or feedback cancellation probably influenced the outcomes in some cases, leading to a moderate incidence of false positives for the ATEN test, and also some "missed" cases. The ATEN test leads to a lower incidence of inconclusive results than the TEN(HL) test in the diagnosis of DRs in people with severe to profound hearing loss. However, for some hearing aids the gain changed rapidly as a function of frequency, which undermined the validity of the ATEN test. Also, some hearing aids introduced distortion that probably

  11. The TEN-T core network and the Fehmarnbelt region

    DEFF Research Database (Denmark)

    Guasco, Clement Nicolas

    This note is a snapshot picture, taken in early 2014, that places the Green STRING corridor project within the context of the TEN-T strategy and gives a summarized overview on the impact of this strategy in the region. Chapter 1 contains a summary of the TEN-T strategy today, chapter 2 presents...... the sources used for this note, chapter 3 presents all the relevant EU regulations with direct impact on the development of TEN-T corridors, chapter 4 gives practical examples of the challenges for the development of TEN-T corridors, chapter 5 pre-sents the national initiatives related to the TEN-T corridor...

  12. Erkenntnisgewinnn durch Virtuelle Realitäten

    Directory of Open Access Journals (Sweden)

    Breiner, Tobias

    2009-11-01

    Full Text Available Virtual reality will gain a more and more important role in our everyday life. So it is very important to understand fully the impact and influence virtual reality will have on or view of the world. This article reveals that the interdependencies between the real space and the virtual space are much more subtle and profound then on first sight. Especially the value of several mathematical, physical and biological models and simulation methodologies will be reestimated by the use of virtual reality in the long term. As an example the article describes the historical chain from quaternions to quaoaring and how this may lead to a paradigm change in biology.

  13. Tenåringsdrikking i utviklingspsykologisk perspektiv

    Directory of Open Access Journals (Sweden)

    Hilde Pape

    2009-10-01

    Full Text Available  SAMMENDRAGHvorfor er alkohol så populært blant unge mennesker? Dette viktige spørsmålet har vært gjenstand for fåempiriske studier. Forskningsbasert kunnskap om alkoholens positive sider og forsterkende egenskaper erderfor av begrenset omfang. Derimot har tallrike undersøkelser fokusert på ulike skadevirkninger som følgeav tenåringsdrikking. Resultatene av denne forskningen har bidratt til å understreke behovet for en aktivrusforebyggende innsats. Innsikt i alkoholens opplevde goder er imidlertid nødvendig for å kunne utvikleeffektive forebyggingsstrategier. På denne bakgrunn er søkelyset i artikkelen rettet mot psykososiale funksjonerved unge menneskers drikkevaner. Spørsmål knyttet til gruppepress og modell-læring vil også bli berørt.Hensikten er å formidle sentrale funn fra nyere forskning på feltet. Oppsummeringsvis tyder resultatene på atalkohol har en særlig appell til ungdom som er veltilpassede og sosialt anlagte. Samtidig ser det ut til atdrikking kan bidra til å fremme utviklingsprosessen i ungdomstida, men at det primært handler om indirekteeffekter. Hvilke implikasjoner de ulike funnene har mht. forebygging, er skissert i avslutningsdelen.Pape H. Teenage alcohol use from the perspective of psychological development.Nor J EpidemiolEWhy is alcohol so popular among young people? So far, few studies have addressed this important question.The body of scientific research on the positive and reinforcing aspects of drinking is accordingly of limitedextent. Numerous studies have focused on the harmful effects of teenage alcohol use and the findings clearlyunderscore the importance of primary prevention. Knowledge about the perceived advantages of alcohol useis needed to develop effective preventive programs, however. On this background, the article focuses onpsychosocial functions of youthful drinking. Findings from recent research regarding the link between alcoholuse and various indicators of adolescent

  14. Transcutaneous electrical nerve stimulation (TENS) for pain management in labour

    Science.gov (United States)

    Dowswell, Therese; Bedwell, Carol; Lavender, Tina; Neilson, James P

    2014-01-01

    Background Transcutaneous nerve stimulation (TENS) has been proposed as a means of reducing pain in labour. The TENS unit emits low-voltage electrical impulses which vary in frequency and intensity. During labour, TENS electrodes are generally placed on the lower back, although TENS may be used to stimulate acupuncture points or other parts of the body. The physiological mechanisms whereby TENS relieves pain are uncertain. TENS machines are frequently operated by women, which may increase a sense of control in labour. Objectives To assess the effects of TENS on pain in labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 April 2011) and reference lists of retrieved papers. Selection criteria Randomised controlled trials comparing women receiving TENS for pain management in labour versus routine care, alternative non-pharmacological methods of pain relief, or placebo devices. We included all types of TENS machines. Data collection and analysis Two review authors assessed for inclusion all trials identified by the search strategy, carried out data extraction and assessed risk of bias. We have recorded reasons for excluding studies. Main results Seventeen trials with 1466 women contribute data to the review. Thirteen examined TENS applied to the back, two to acupuncture points, and two to the cranium. Overall, there was little difference in pain ratings between TENS and control groups, although women receiving TENS to acupuncture points were less likely to report severe pain (average risk ratio 0.41, 95% confidence interval 0.31 to 0.54; measured in two studies). The majority of women using TENS said they would be willing to use it again in a future labour. Where TENS was used as an adjunct to epidural analgesia there was no evidence that it reduced pain. There was no consistent evidence that TENS had any impact on interventions and outcomes in labour. There was little information on outcomes for mothers and babies. No

  15. Transcutaneous electric nerve stimulation (TENS) in dentistry- A review.

    Science.gov (United States)

    Kasat, Vikrant; Gupta, Aditi; Ladda, Ruchi; Kathariya, Mitesh; Saluja, Harish; Farooqui, Anjum-Ara

    2014-12-01

    Transcutaneous electric nerve stimulation (TENS) is a non-pharmacological method which is widely used by medical and paramedical professionals for the management of acute and chronic pain in a variety of conditions. Similarly, it can be utilized for the management of pain during various dental procedures as well as pain due to various conditions affecting maxillofacial region. This review aims to provide an insight into clinical research evidence available for the analgesic and non analgesic uses of TENS in pediatric as well as adult patients related to the field of dentistry. Also, an attempt is made to briefly discuss history of therapeutic electricity, mechanism of action of TENS, components of TENs equipment, types, techniques of administration, advantages and contradictions of TENS. With this we hope to raise awareness among dental fraternity regarding its dental applications thereby increasing its use in dentistry. Key words:Dentistry, pain, TENS.

  16. The origin of the future ten questions for the next ten years

    CERN Document Server

    Gribbin, John

    2006-01-01

    How did the universe begin? Where do galaxies come from? How do stars and planets form? Where do the material particles we are made of come from? How did life begin? Today we have only provisional answers to such questions. But scientific progress will improve these answers dramatically over the next ten years, predicts John Gribbin in this riveting book. He focuses on what we know—or think we know—about ten controversial, unanswered issues in the physical sciences and explains how current cutting-edge research may yield solutions in the very near future. With his trademark facility for engaging readers with or without a scientific background, the author explores ideas concerning the creation of the universe, the possibility of other forms of life, and the fate of the expanding cosmos. He examines “theories of everything,” including grand unified theories and string theory, and he discusses the Big Bang theory, the origin of structure and patterns of matter in the galaxies, and dark mass and dark ene...

  17. Increasing intensity of TENS prevents analgesic tolerance in rats

    Science.gov (United States)

    Sato, Karina L.; Sanada, Luciana S.; Rakel, Barbara A.; Sluka, Kathleen A.

    2012-01-01

    Transcutaneous electrical nerve stimulation (TENS) reduces hyperalgesia and pain. Both low frequency (LF) and high frequency (HF) TENS, delivered at the same intensity (90% motor threshold (MT)) daily, result in analgesic tolerance with repeated use by the 5th day of treatment. Thecurrentstudytestedif 1) increasingintensityby 10% per daypreventsthedevelopmentoftolerance to repeated TENS, and 2) iflowerintensity TENS (50 % MT) produces an equivalentreduction in hyperalgesia when compared to 90% MT TENS. Sprague-Dawley rats with unilateral knee joint inflammation (3% carrageenan) were separated according to the intensity of TENS used: Sham, 50% LF, 50% HF, 90% LF, 90% HF, and increased intensity by 10% per day (LF and HF). The reduced mechanical withdrawal threshold following the induction of inflammation was reversed by application of TENS applied at 90% MT and increasing intensity for the first 4 days. On the 5th day, the groups that received 90% MT intensity showed tolerance. Nevertheless, the group that received an increased intensity on each day still showed a reversal of the mechanical withdrawal threshold with TENS. These results show that the development of tolerance can be delayed by increasing intensity of TENS. PMID:22858165

  18. ECG monitoring leads and special leads.

    Science.gov (United States)

    Francis, Johnson

    ECG monitoring is common place in the hospital and even pre-hospital setting. The need for different types of lead systems in different settings has been emphasised. Simple three electrode bipolar recording is ubiquitous for monitoring. This can be used to record modified bipolar chest leads as well. Using five leads gives the option of getting a chest lead in addition to bipolar limb leads, enhancing detection of ischemia during procedures. Lead stability is important when the movement of the subject is maximum as in exercise testing. Mason-Likar modification with limb leads shifted to the torso is popular for exercise testing, though the diagnostic value of the ECG is altered. Lund system with leads on proximal part of limbs have both stability and fair diagnostic value. EASI lead system permits derivation of 12 leads from just five electrodes. Lewis lead and the newly devised modified limb lead system are useful in enhancing detection of atrial activity. Fontaine lead has been designed to improve visualization of Epsilon wave in arrhythmogenic right ventricular dysplasia. Copyright © 2016 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

  19. Learn about Lead

    Science.gov (United States)

    ... Protection Agency Search Search Lead Contact Us Share Learn about Lead General Lead Information Read more about ... water, soil, consumer products, food, and occupational settings. Learn more about sources of lead exposure: At home ...

  20. Lead Poisoning Prevention Tips

    Science.gov (United States)

    ... or removed safely. How are children exposed to lead? Lead-based paint and lead contaminated dust are ... What can be done to prevent exposure to lead? It is important to determine the construction year ...

  1. Lead levels - blood

    Science.gov (United States)

    Blood lead levels ... is used to screen people at risk for lead poisoning. This may include industrial workers and children ... also used to measure how well treatment for lead poisoning is working. Lead is common in the ...

  2. Shigella sonnei Vaccine Candidates WRSs2 and WRSs3 Are as Immunogenic as WRSS1, a Clinically Tested Vaccine Candidate, in a Primate Model of Infection

    Science.gov (United States)

    2011-01-01

    Brown AW, Wallace SM, Jones E, Asher LV, Pattarini D, et al. Immune response to and histopathology of Campylobacter jejuni infection in ferrets...WRSs3 a b s t r a c t Shigella causes diarrhea and dysentery through contaminated food and water. Shigella sonnei live vaccine...results in diarrhea , fever, dysentery and considerable gastrointestinal and constitutional symptoms. The low infective dose of 10–100 bacteria, and high

  3. Screening Of Ten Indian Medicinal Plants For Their Antibacterial ...

    African Journals Online (AJOL)

    Screening Of Ten Indian Medicinal Plants For Their Antibacterial Activity Against Shigella sSpecies And Escherichia coli. J Thomas, B Veda. Abstract. Ethanol and Aqueous extracts of ten Indian medicinal plants were tested for their antibacterial properties against Shigella sonei, S. boydi, S. flexeneri, S. dysenteriae and ...

  4. Travels in Tartary : Decoding Ten Export Winter Landscapes

    NARCIS (Netherlands)

    Poel, van der R.H.M.

    2013-01-01

    The Chinese export paintings collection of the National Museum of Ethnology in Leiden includes ten winter views in Tartary painted on canvas. That these ten paintings have never before been studied as a group has inspired the present author to conduct research into their origins, the findings of

  5. Benchmark Dose Software Development and Maintenance Ten Berge Cxt Models

    Science.gov (United States)

    This report is intended to provide an overview of beta version 1.0 of the implementation of a concentration-time (CxT) model originally programmed and provided by Wil ten Berge (referred to hereafter as the ten Berge model). The recoding and development described here represent ...

  6. Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults.

    Science.gov (United States)

    Gibson, William; Wand, Benedict M; O'Connell, Neil E

    2017-09-14

    Neuropathic pain, which is due to nerve disease or damage, represents a significant burden on people and society. It can be particularly unpleasant and achieving adequate symptom control can be difficult. Non-pharmacological methods of treatment are often employed by people with neuropathic pain and may include transcutaneous electrical nerve stimulation (TENS). This review supersedes one Cochrane Review 'Transcutaneous electrical nerve stimulation (TENS) for chronic pain' (Nnoaham 2014) and one withdrawn protocol 'Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults' (Claydon 2014). This review replaces the original protocol for neuropathic pain that was withdrawn. To determine the analgesic effectiveness of TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. We searched CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, Web of Science, PEDro, LILACS (up to September 2016) and various clinical trials registries. We also searched bibliographies of included studies for further relevant studies. We included randomised controlled trials where TENS was evaluated in the treatment of central or peripheral neuropathic pain. We included studies if they investigated the following: TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. Two review authors independently screened all database search results and identified papers requiring full-text assessment. Subsequently, two review authors independently applied inclusion/exclusion criteria to these studies. The same review authors then independently extracted data, assessed for risk of bias using the Cochrane standard tool and rated the quality of evidence using GRADE. We included 15 studies with 724 participants. We found a

  7. Ten Things Every Professor Should Know about Assessment

    Science.gov (United States)

    Wolf, Kenneth; Dunlap, Joanna; Stevens, Ellen

    2012-01-01

    This article describes ten key assessment practices for advancing student learning that all professors should be familiar with and strategically incorporate in their classrooms and programs. Each practice or concept is explained with examples and guidance for putting it into practice. The ten are: learning outcomes, performance assessments,…

  8. TRANSCUTANEOUS ELECTRICAL NERVE-STIMULATION (TENS) IN RAYNAUDS-PHENOMENON

    NARCIS (Netherlands)

    MULDER, P; DOMPELING, EC; VANSLOCHTERENVANDERBOOR, JC; KUIPERS, WD; SMIT, AJ

    Transcutaneous nerve stimulation (TENS) has been described as resulting in vasodilatation. The effect of 2 Hz TENS of the right hand during forty-five minutes on skin temperature and plethysmography of the third digit of both hands and feet and on transcutaneous oxygen tension (TcpO2) of the right

  9. Epidemiological analysis of tuberculosis in Ethiopia: A ten-year ...

    African Journals Online (AJOL)

    A time-series study design was applied to analyze the ten-year trends of Tuberculosis in Ethiopia. Data on ten-key indicators for the period of 2000-2009 was obtained from the Ministry of Health public documents. Five stratifying variables were used to analyze the trends in the key TB indicators. The data on the indicators ...

  10. Using TENS for pain control: the state of the evidence

    Science.gov (United States)

    Vance, Carol GT; Dailey, Dana L; Rakel, Barbara A; Sluka, Kathleen A

    2014-01-01

    Summary Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that activates a complex neuronal network to reduce pain by activating descending inhibitory systems in the central nervous system to reduce hyperalgesia. The evidence for TENS efficacy is conflicting and requires not only description but also critique. Population-specific systemic reviews and meta-analyses are emerging, indicating both HF and LF TENS being shown to provide analgesia, specifically when applied at a strong, nonpainful intensity. The purpose of this article is to provide a critical review of the latest basic science and clinical evidence for TENS. Additional research is necessary to determine if TENS has effects specific to mechanical stimuli and/or beyond reduction of pain and will improve activity levels, function and quality of life. PMID:24953072

  11. Transcutaneous electrical nerve stimulation (TENS) for fibromyalgia in adults.

    Science.gov (United States)

    Johnson, Mark I; Claydon, Leica S; Herbison, G Peter; Jones, Gareth; Paley, Carole A

    2017-10-09

    Fibromyalgia is characterised by persistent, widespread pain; sleep problems; and fatigue. Transcutaneous electrical nerve stimulation (TENS) is the delivery of pulsed electrical currents across the intact surface of the skin to stimulate peripheral nerves and is used extensively to manage painful conditions. TENS is inexpensive, safe, and can be self-administered. TENS reduces pain during movement in some people so it may be a useful adjunct to assist participation in exercise and activities of daily living. To date, there has been only one systematic review in 2012 which included TENS, amongst other treatments, for fibromyalgia, and the authors concluded that TENS was not effective. To assess the analgesic efficacy and adverse events of TENS alone or added to usual care (including exercise) compared with placebo (sham) TENS; no treatment; exercise alone; or other treatment including medication, electroacupuncture, warmth therapy, or hydrotherapy for fibromyalgia in adults. We searched the following electronic databases up to 18 January 2017: CENTRAL (CRSO); MEDLINE (Ovid); Embase (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS; PEDRO; Web of Science (ISI); AMED (Ovid); and SPORTDiscus (EBSCO). We also searched three trial registries. There were no language restrictions. We included randomised controlled trials (RCTs) or quasi-randomised trials of TENS treatment for pain associated with fibromyalgia in adults. We included cross-over and parallel-group trial designs. We included studies that evaluated TENS administered using non-invasive techniques at intensities that produced perceptible TENS sensations during stimulation at either the site of pain or over nerve bundles proximal (or near) to the site of pain. We included TENS administered as a sole treatment or TENS in combination with other treatments, and TENS given as a single treatment or as a course of treatments. Two review authors independently determined study eligibility by assessing each record and

  12. Effect of burst TENS and conventional TENS combined with cryotherapy on pressure pain threshold: randomised, controlled, clinical trial.

    Science.gov (United States)

    Macedo, L B; Josué, A M; Maia, P H B; Câmara, A E; Brasileiro, J S

    2015-06-01

    To assess the immediate effect of conventional and burst transcutaneous electrical nerve stimulation (TENS) in combination with cryotherapy on pain threshold and tolerance in healthy individuals. Randomised, controlled trial. University laboratory. One hundred and twelve healthy women. Volunteers were allocated at random to seven groups (n=16): (1) control, (2) placebo TENS, (3) conventional TENS, (4) burst TENS, (5) cryotherapy, (6) cryotherapy in combination with burst TENS, and (7) cryotherapy in combination with conventional TENS. Pain threshold and tolerance were measured by applying a pressure algometer at the lateral epicondyle of the humerus, before and after each intervention. The primary outcome measure was pressure pain threshold. A significant increase in pain threshold and tolerance at the 5% level of significance was recorded as follows: burst TENS {pain threshold: mean difference 1.3 [95% confidence interval (CI) 1.4 to 1.2]; pain tolerance: mean difference 3.8 (95% CI 3.9 to 3.7)}, cryotherapy [pain threshold: mean difference 1.3 (95% CI 1.4 to 1.2); pain tolerance: mean difference 1.9 (95% CI 1.8 to 2.0)] and cryotherapy in combination with burst TENS [pain threshold: mean difference 2.6 (95% CI 2.4 to 2.8); pain tolerance: mean difference 4.9 (95% CI 5.0 to 4.8)]. Cryotherapy in combination with burst TENS provided greater analgesia compared with the other groups (Pcryotherapy in combination with burst TENS to reduce induced pain, and suggest a potentiating effect when these techniques are combined. No such association was found between cryotherapy and conventional TENS. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  13. Revision Surgery of Deep Brain Stimulation Leads.

    Science.gov (United States)

    Falowski, Steven M; Bakay, Roy A E

    2016-07-01

    Deep brain stimulation (DBS) is widely used for various movement disorders. DBS lead revisions are becoming more common as the indications and number of cases increases. Patients undergoing DBS lead revisions at a single institution were retrospectively analyzed based on diagnosis, reason for revision, where the lead was relocated, and surgical technique. We reviewed 497 consecutive DBS lead placements and found that there was need for 25 DBS lead revisions with at least six months of follow-up. Loss of efficacy and development of adverse effects over time were the most common reasons for lead revision across all diagnosis. Lead malfunction was the least common. Ten patients requiring 19 DBS lead revisions that underwent their original surgery at another institution were also analyzed. Surgical technique dictated replacing with a new lead while maintaining brain position and tract with the old lead until final placement. Methods to seal exposed wire were developed. Surgical technique, as well as variable options are important in lead revision and can be dictated based on reason for revision. Over time patients who have had adequate relief with DBS placement may experience loss of efficacy and development of adverse effects requiring revision of the DBS lead to maintain its effects. © 2016 International Neuromodulation Society.

  14. Brauchen die Universitäten noch dezentral strukturierte Bibliothekssysteme?

    Directory of Open Access Journals (Sweden)

    Wilfried Sühl-Strohmenger

    2014-12-01

    Full Text Available Dieser Artikel stellt provokativ die Frage, ob es nicht konsequenter wäre, angesichts des Wandels der Informations- und Wissenschaftsstrukturen in den Hochschulen gänzlich auf dezentrale Bibliotheken in den Fakultäten, Fachbereichen und Instituten zu verzichten – beispielsweise zugunsten von Kommunikations- und Lernräumen. Die Überlegungen konzentrieren sich auf Hochschulbibliothekssysteme in Deutschland, Österreich und der Schweiz, beleuchten – auch im Licht der Anforderungen aufgrund überregionaler wissenschafts- bzw. hochschulpolitischer Empfehlungen und Gutachten – das Für und Wider dezentral organisierter Bibliothekssysteme und münden in dem Versuch einer Perspektive zukunftsgerichteter Hochschulbibliothekssysteme. In view of the changes in the information and scientific structures of the universities, this paper raises the provocative question, whether, it wouldn’t be more consistent to dispense entirely with decentralized libraries in the faculties, departments and institutes, and, for example, set up communication and learning spaces instead. The authors discuss pros and cons of decentrally structured library systems (taking also into account science and higher education policy advice and expertise for the requirements of the scientific system and the tertiary education in Germany, leading to an attempt to describe a perspective for forward-looking university library systems. Der Text ist die überarbeitete Fassung des gleichnamigen Vortrags, gehalten auf dem 103. Deutschen Bibliothekartag in Bremen 2014. Nicht wenige Erkenntnisse basieren auf dem von uns herausgegebenen „Handbuch Hochschulbibliothekssysteme. Leistungsfähige Informationsinfrastrukturen für Wissenschaft und Studium“ (Berlin, Boston: de Gruyter Saur, 2014. Wir danken allen Autorinnen und Autoren auch an dieser Stelle noch einmal für ihre hervorragenden Textbeiträge.

  15. Lead and the Romans

    Science.gov (United States)

    Reddy, Aravind; Braun, Charles L.

    2010-01-01

    Lead poisoning has been a problem since early history and continues into modern times. An appealing characteristic of lead is that many lead salts are sweet. In the absence of cane and beet sugars, early Romans used "sugar of lead" (lead acetate) to sweeten desserts, fruits, and sour wine. People most at risk would have been those who…

  16. Lead (Pb) Air Pollution

    Science.gov (United States)

    ... Environmental Protection Agency Search Search Lead (Pb) Air Pollution Contact Us Share As a result of EPA's ... protect aquatic and terrestrial ecosystems. Lead (Pb) Air Pollution Basic Information How does lead get in the ...

  17. Litter decomposition and nutrient dynamics of ten selected tree ...

    African Journals Online (AJOL)

    Litter decomposition processes in tropical rainforests are still poorly understood. Leaf litter decomposition and nutrient dynamics of ten contrasting tree species, Entandraphragma utile, Guibourtia tessmannii, Klainedoxa gabonensis, Musanga cecropioides, Panda oleosa, Plagiostyles africana, Pterocarpus soyauxii, ...

  18. Ten new species of Daidalotarsonemus (Prostigmata: Tarsonemidae) from Costa Rica

    Science.gov (United States)

    Ten new tarsonemid species of the genus Daidalotarsonemus found on native plants in Costa Rica are described herein: Daidalotarsonemus alas sp. n. Ochoa, Rezende & Lofego; Daidalotarsonemus azofeifai sp. n. Ochoa, Rezende & Lofego; Daidalotarsonemus bauchani sp. n. Rezende, Ochoa & Lofego; Daidalota...

  19. Ten Thousand Islands National Wildlife Refuge: Comprehensive Conservation Plan

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This Comprehensive Conservation Plan (CCP) was written to guide management on Ten Thousand Islands NWR for the next 15 years. This plan outlines the Refuge vision...

  20. The Trail Inventory of Ten Thousand Islands NWR [Cycle 2

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of this report is to create a baseline inventory of all non-motorized trails on Ten Thousand Islands National Wildlife Refuge. Trails in this inventory...

  1. Ten-Competence: Life-Long Competence Development and Learning

    NARCIS (Netherlands)

    Koper, Rob; Specht, Marcus

    2006-01-01

    Koper, R., & Specht, M. (2008). Ten-Competence: Life-Long Competence Development and Learning. In M-A. Cicilia (Ed.), Competencies in Organizational e-learning: concepts and tools (pp. 234-252). Hershey: IGI-Global.

  2. Managing mountain hardwoods - a ten-year appraisal

    Science.gov (United States)

    George R., Jr. Trimble

    1961-01-01

    Ten years ago - in 1949 - four 5-acre plots were established on the Fernow Experimental Forest near Parsons, West Virginia, to show the effects upon mountain hardwoods of each of four management treatments.

  3. Webometric Analysis of Top Ten Asian and Indian Universities

    OpenAIRE

    Jalal, Samir Kumar; Sutradhar, B; Mukhopadhyay, Parthasarathi

    2016-01-01

    The paper tries to assess all the existing ranking systems which are used to rank higher educational institutions. The aim of the paper is to provide sufficient background to design and develop a new ranking system for a country. An attempt has been taken to find out the reasons of low ranking of Indian universities with respect to the world university ranking through webometric analysis of top ten Indian and Asian universities. A comparative study of top Ten Indian Universities and Asian uni...

  4. How repeatable are the physiological effects of TENS?

    Science.gov (United States)

    Fernandez-Del-Olmo, Miguel; Alvarez-Sauco, Maria; Koch, Giacomo; Franca, Michele; Marquez, Gonzalo; Sanchez, Jose A; Acero, Rafael M; Rothwell, John C

    2008-08-01

    Several studies suggest that transcutaneous electrical stimulation (TENS) can have a variety of effects on the central nervous system (CNS). In this study, we tried to replicate the physiological effects of TENS and to explore its effects on intracortical circuits. We used transcranial magnetic stimulation (TMS) and spinal reflex testing to examine excitability of intracortical and spinal cord circuits before and after a 30-min period of TENS over the flexor carpi radialis (FCR) muscle. We measured the amplitude of TMS-evoked muscle responses (MEP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical antagonist inhibition (CAI) in flexor and extensor carpial radialis (FCR, ECR) muscles as well as spinal reciprocal inhibition (RI) and presynaptic inhibition (PI) from ECR to FCR. TENS had no significant effect on any of these measures apart from a reduction in median nerve induced facilitation of FCR when testing CAI. When compared with previous studies, our results suggest that the effects of TENS are highly variable and unreliable, likely by the difficulty in defining precise parameters of stimulation in individual subjects. Care should be taken in assuming that effects after TENS observed in small populations of subjects will apply equally to a wider population.

  5. Generation and characterization of six single VP4 gene substitution reassortant rotavirus vaccine candidates: each bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] and the remaining 10 genes of rhesus monkey rotavirus MMU18006 or bovine rotavirus UK.

    Science.gov (United States)

    Hoshino, Yasutaka; Jones, Ronald W; Chanock, Robert M; Kapikian, Albert Z

    2002-10-04

    The global disease burden of rotavirus diarrhea in infants and young children has stimulated interest in the biological and clinical characteristics of these agents, leading to intensive efforts to develop a vaccine. A rhesus rotavirus (RRV)-based quadrivalent vaccine ("RotaShield") was licensed and administered to about 1 million infants and found to be highly effective. However, it was withdrawn because of a link with intussusception. This vaccine was developed according to a modified "Jennerian" approach in which one of the two major outer capsid proteins (VP7) shares neutralization specificity with one of the four epidemiologically important human rotavirus serotypes. The other outer capsid protein (VP4) is derived solely from RRV and is distinct from the VP4 of the four human rotavirus serotypes of epidemiologic importance. In an effort to further increase the immunogenicity of the existing VP7-based RRV quadrivalent vaccine, we generated three single VP4 gene substitution reassortant rotavirus candidate vaccines, each of which bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] specificity while the remaining 10 genes are derived from the rhesus rotavirus. By incorporating one or two of these strains into the quadrivalent vaccine, a pentavalent or hexavalent RRV-based vaccine could be formulated thus providing antigenic coverage not only for VP7 serotype 1, 2, 3 and 4 but also for VP4 serotype 1A[8] or 1B[4], thus possibly augmenting its immunogenicity. Similarly, three single VP4 gene (P1A[8] or P1B[4]) substitution reassortants have also been generated in a background of 10 bovine (UK) rotavirus genes for addition to a second generation UK-based quadrivalent vaccine.

  6. Cryogenic current leads

    Energy Technology Data Exchange (ETDEWEB)

    Zizek, F.

    1982-01-01

    Theoretical, technical and design questions are examined of cryogenic current leads for SP of magnetic systems. Simplified mathematical models are presented for the current leads. To illustrate modeling, the calculation is made of the real current leads for 500 A and three variants of current leads for 1500 A for the enterprise ''Shkoda.''

  7. Avoid costly litigation: ten steps to implementing lawful hiring practices.

    Science.gov (United States)

    Holmes, Judith H

    2004-01-01

    employment-related disputes that lead to costly litigation would never have arisen if the employer had implemented more effective employment practices. Hiring mistakes in particular cause many costly legal battles. This article identifies legal issues that precipitate litigation and suggests ten steps physicians can take to implement lawful hiring practices that will reduce the risk of costly employment suits while improving office efficiency, morale, and productivity. NOTE: This article is intended as an overview of lawful hiring strategies, and is not a substitute for legal advice from experienced employment counsel. Applicable laws vary from state to state and appropriate procedures may depend on specific factual situations. This article is not, and should not be construed as, legal advice.

  8. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN): Could Retinoids Play a Causative Role?

    Science.gov (United States)

    Mawson, Anthony R.; Eriator, Ike; Karre, Sridhar

    2015-01-01

    Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are overlapping manifestations on a spectrum of acute drug-induced conditions associated with severe blistering, skin peeling, and multi-organ damage. TEN is an eruption resembling severe scalding, with ≥30% skin detachment. SJS is a mild form of TEN, characterized histologically by epidermal keratinocyte apoptosis with dermo-epidermal separation and extensive small blisters with syndrome can be induced by numerous medications and typically occurs 1–4 weeks after the initiation of therapy. Granulysin is found in the lesions of patients with SJS/TEN and plays a significant pathogenic role in the condition, but the overall mechanisms linking medications, granulysin, and disease manifestations remain obscure. This paper reviews evidence suggesting that the different medications implicated in SJS/TEN have the common property of interacting and synergizing with endogenous retinoids (vitamin A and its congeners), in many instances causing the latter to accumulate in and damage the liver, the main storage organ for vitamin A. It is hypothesized that liver damage leads to the spillage of toxic retinoid compounds into the circulation, resulting in an endogenous form of hypervitaminosis A and cytotoxicity with widespread apoptosis, mediated by granulysin and recognized as SJS/TEN. Subject to testing, the model suggests that symptom worsening could be arrested at onset by lowering the concentration of circulating retinoids and/or granulysin via phlebotomy or plasmapheresis or by pharmacological measures to limit their expression. PMID:25579087

  9. Nonresponse Error in Mail Surveys: Top Ten Problems

    Directory of Open Access Journals (Sweden)

    Jeanette M. Daly

    2011-01-01

    Full Text Available Conducting mail surveys can result in nonresponse error, which occurs when the potential participant is unwilling to participate or impossible to contact. Nonresponse can result in a reduction in precision of the study and may bias results. The purpose of this paper is to describe and make readers aware of a top ten list of mailed survey problems affecting the response rate encountered over time with different research projects, while utilizing the Dillman Total Design Method. Ten nonresponse error problems were identified, such as inserter machine gets sequence out of order, capitalization in databases, and mailing discarded by postal service. These ten mishaps can potentiate nonresponse errors, but there are ways to minimize their frequency. Suggestions offered stem from our own experiences during research projects. Our goal is to increase researchers' knowledge of nonresponse error problems and to offer solutions which can decrease nonresponse error in future projects.

  10. Delaktighet i avstämningsmöten

    OpenAIRE

    Pia H. Bülow; Wilinska, Monika

    2014-01-01

    Den här rapporten handlar om de lagstadgade möten som kallas avstämningsmöten. Det är Försäkringskassan som kallar olika aktörer till dessa flerpartssamtal, för att utreda arbetsförmågan hos en sjukskriven person (här: försäkrad), och eventuella behov av rehabilitering för att denne ska kunna återgå till arbete. Syftet med det här redovisade forskningsprojektet var att studera den kommunikativa processen i sådana möten avseende främst de försäkrades delaktighet och upplevelse av mötet. Studie...

  11. Lead content of foodstuffs.

    Science.gov (United States)

    Mitchell, D G; Aldous, K M

    1974-05-01

    The lead content of a number of foodstuffs, particularly baby fruit juices and milk, is reported. Samples were analyzed in quadruplicate by using an automated Delves cup atomic absorption procedure. A large proportion of the products examined contained significant amounts of lead. Of 256 metal can examined, the contents of 62% contained a lead level of 100 mug/l. or more, 37% contained 200 mug/l. or more and 12% contained 400 mug/l. lead or more. Of products in glass and aluminum containers, only 1% had lead levels in excess of 200 mug/l. Lead levels of contents also correlate with the seam length/volume ratio of the leaded seam can. A survey of bulk milk showed a mean lead level of 40 mug/l. for 270 samples; for canned evaporated milk the mean level was 202 mug/l. These data indicate a potential health hazard.

  12. Lead and tap water

    Science.gov (United States)

    Water contaminated with lead ... The Environmental Protection Agency (EPA) monitors drinking water in the United States. It requires water suppliers to produce annual water quality reports. These reports include information about lead amounts, and they ...

  13. Time in powers of ten natural phenomena and their timescales

    CERN Document Server

    't Hooft, Gerard

    2014-01-01

    In this richly illustrated book, Nobel Laureate Gerard 't Hooft and Theoretical Physicist Stefan Vandoren describe the enormous diversity of natural phenomena that take place at different time scales. In the tradition of the bestseller Powers of Ten , the authors zoom in and out in time, each step with a factor of ten. Starting from one second, time scales are enlarged until processes are reached that take much longer than the age of the universe. After the largest possible eternities, the reader is treated to the shortest and fastest phenomena known. Then the authors increase with powers of t

  14. NA49: lead-lead collision

    CERN Multimedia

    1996-01-01

    This is an image of an actual lead ion collision taken from tracking detectors on the NA49 experiment, part of the heavy ion project at CERN. These collisions produce a very complicated array of hadrons as the heavy ions break up. It is hoped that one of these collisions will eventually create a new state of matter known as quark-gluon plasma.

  15. Lead Poisoning (For Parents)

    Science.gov (United States)

    ... Needs a Kidney Transplant Vision Facts and Myths Lead Poisoning KidsHealth > For Parents > Lead Poisoning Print A ... Family en español La intoxicación por plomo About Lead Poisoning If you have young kids, it's important ...

  16. Lead Poisoning in Childhood.

    Science.gov (United States)

    Pueschel, Siegfried M., Ed.; Linakis, James G., Ed.; Anderson, Angela C., Ed.

    The magnitude of childhood lead poisoning has been inexplicably neglected by modern medicine and by legislators. However, since the 1970s, increased attention has been focused on lead poisoning, and advances have been made in several areas, including understanding of the neurodevelopmental and behavioral ramifications of lead poisoning, and…

  17. Lead poisoning: An overview

    Science.gov (United States)

    Gendel, Neil

    1993-01-01

    A problem that should be of great concern to all of us is the lead poisoning of children. First, I would like to present a short overview concerning the reasons everyone should care about lead poisoning, then discuss the history of lead poisoning, what is happening today across the country, and the future.

  18. Lead Poisoning in Children.

    Science.gov (United States)

    Drummond, A. H., Jr.

    1981-01-01

    Early symptoms of lead poisoning in children are often overlooked. Lead poisoning has its greatest effects on the brain and nervous system. The obvious long-term solution to the lead poisoning problem is removal of harmful forms of the metal from the environment. (JN)

  19. Lead encephalopathy in adults

    Directory of Open Access Journals (Sweden)

    Janapareddy Vijaya Bhaskara Rao

    2014-01-01

    Full Text Available Lead poisoning is a common occupational health hazard in developing countries. We report the varied clinical presentation, diagnostic and management issues in two adult patients with lead encephalopathy. Both patients worked in a battery manufacturing unit. Both patients presented with seizures and one patient also complained of abdominal colic and vomiting. Both were anemic and a lead line was present. Blood lead level in both the patients was greater than 25 µg/dl. Magnetic resonance imaging of brain revealed bilateral symmetric involvement of the thalamus, lentiform nucleus in both patients and also the external capsules, sub-cortical white matter in one patient. All these changes, seen as hyperintensities in T2-weighted images suggested demyelination. They were advised avoidance of further exposure to lead and were treated with anti-epileptics; one patient also received D-penicillamine. They improved well on follow-up. Lead encephalopathy is an uncommon but important manifestation of lead toxicity in adults.

  20. Lead in the environment

    Science.gov (United States)

    Pattee, Oliver H.; Pain, Deborah J.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

    2003-01-01

    Anthropogenic uses of lead have probably altered its availability and environmental distribution more than any other toxic element. Consequently, lead concentrations in many living organisms may be approaching thresholds of toxicity for the adverse effects of lead. Such thresholds are difficult to define, as they vary with the chemical and physical form of lead, exposure regime, other elements present and also vary both within and between species. The technological capability to accurately quantify low lead concentrations has increased over the last decade, and physiological and behavioral effects have been measured in wildlife with tissue lead concentrations below those previously considered safe for humans.s.236 Consequently. lead criteria for the protection of wildlife and human health are frequently under review, and 'thresholds' of lead toxicity are being reconsidered. Proposed lead criteria for the protection of natural resources have been reviewed by Eisler. Uptake of lead by plants is limited by its generally low availability in soils and sediments, and toxicity may be limited by storage mechanisms and its apparently limited translocation within most plants. Lead does not generally accumulate within the foliar parts of plants, which limits its transfer to higher trophic levels. Although lead may concentrate in plant and animal tissues, no evidence of biomagnification exists. Acid deposition onto surface waters and soils with low buffering capacity may influence the availability of lead for uptake by plants and animals, and this may merit investigation at susceptible sites. The biological significance of chronic low-level lead exposure to wildlife is sometimes difficult to quantify. Animals living in urban environments or near point sources of lead emission are inevitably subject to greater exposure to lead and enhanced risk of lead poisoning. Increasingly strict controls on lead emissions in many countries have reduced exposure to lead from some sources

  1. Strategic evaluation of vaccine candidate antigens for the prevention of Visceral Leishmaniasis.

    Science.gov (United States)

    Duthie, Malcolm S; Favila, Michelle; Hofmeyer, Kimberley A; Tutterrow, Yeung L; Reed, Steven J; Laurance, John D; Picone, Alessandro; Guderian, Jeffrey; Bailor, H Remy; Vallur, Aarthy C; Liang, Hong; Mohamath, Raodoh; Vergara, Julie; Howard, Randall F; Coler, Rhea N; Reed, Steven G

    2016-05-27

    Infection with Leishmania parasites results in a range of clinical manifestations and outcomes, the most severe of which is visceral leishmaniasis (VL). Vaccination will likely provide the most effective long-term control strategy, as the large number of vectors and potential infectious reservoirs renders sustained interruption of Leishmania parasite transmission extremely difficult. Selection of the best vaccine is complicated because, although several vaccine antigen candidates have been proposed, they have emerged following production in different platforms. To consolidate the information that has been generated into a single vaccine platform, we expressed seven candidates as recombinant proteins in E. coli. After verifying that each recombinant protein could be recognized by VL patients, we evaluated their protective efficacy against experimental L. donovani infection of mice. Administration in formulation with the Th1-potentiating adjuvant GLA-SE indicated that each antigen could elicit antigen-specific Th1 responses that were protective. Considering the ability to reduce parasite burden along with additional factors such as sequence identity across Leishmania species, we then generated a chimeric fusion protein comprising a combination of the 8E, p21 and SMT proteins. This E. coli -expressed fusion protein was also demonstrated to protect against L. donovani infection. These data indicate a novel recombinant vaccine antigen with the potential for use in VL control programs. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. Optimizing expression of the pregnancy malaria vaccine candidate, VAR2CSA in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Narum David L

    2009-06-01

    Full Text Available Abstract Background VAR2CSA is the main candidate for a vaccine against pregnancy-associated malaria, but vaccine development is complicated by the large size and complex disulfide bonding pattern of the protein. Recent X-ray crystallographic information suggests that domain boundaries of VAR2CSA Duffy binding-like (DBL domains may be larger than previously predicted and include two additional cysteine residues. This study investigated whether longer constructs would improve VAR2CSA recombinant protein secretion from Pichia pastoris and if domain boundaries were applicable across different VAR2CSA alleles. Methods VAR2CSA sequences were bioinformatically analysed to identify the predicted C11 and C12 cysteine residues at the C-termini of DBL domains and revised N- and C-termimal domain boundaries were predicted in VAR2CSA. Multiple construct boundaries were systematically evaluated for protein secretion in P. pastoris and secreted proteins were tested as immunogens. Results From a total of 42 different VAR2CSA constructs, 15 proteins (36% were secreted. Longer construct boundaries, including the predicted C11 and C12 cysteine residues, generally improved expression of poorly or non-secreted domains and permitted expression of all six VAR2CSA DBL domains. However, protein secretion was still highly empiric and affected by subtle differences in domain boundaries and allelic variation between VAR2CSA sequences. Eleven of the secreted proteins were used to immunize rabbits. Antibodies reacted with CSA-binding infected erythrocytes, indicating that P. pastoris recombinant proteins possessed native protein epitopes. Conclusion These findings strengthen emerging data for a revision of DBL domain boundaries in var-encoded proteins and may facilitate pregnancy malaria vaccine development.

  3. Evaluation of novel oral vaccine candidates and validation of a caprine model of Johne's disease

    Science.gov (United States)

    A Mycobacterium avium subspecies paratuberculosis (MAP) vaccine that reduced the incidence of clinical disease and/or reduced fecal shedding of MAP would aid control of Johne’s disease (JD). The objectives of this study were 1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candi...

  4. Identification of conserved surface proteins as novel antigenic vaccine candidates of Actinobacillus pleuropneumoniae.

    Science.gov (United States)

    Chen, Xiabing; Xu, Zhuofei; Li, Lu; Chen, Huanchun; Zhou, Rui

    2012-12-01

    Actinobacillus pleuropneumoniae is an important swine respiratory pathogen causing great economic losses worldwide. Identification of conserved surface antigenic proteins is helpful for developing effective vaccines. In this study, a genome-wide strategy combined with bioinformatic and experimental approaches, was applied to discover and characterize surface-associated immunogenic proteins of A. pleuropneumoniae. Thirty nine genes encoding outer membrane proteins (OMPs) and lipoproteins were identified by comparative genomics and gene expression profiling as being-highly conserved and stably transcribed in the different serotypes of A. pleuropneumoniae reference strains. Twelve of these conserved proteins were successfully expressed in Escherichia coli and their immunogenicity was estimated by homologous challenge in the mouse model, and then three of these proteins (APJL_0126, HbpA and OmpW) were further tested in the natural host (swine) by homologous and heterologous challenges. The results showed that these proteins could induce high titers of antibodies, but vaccination with each protein individually elicited low protective immunity against A. pleuropneumoniae. This study gives novel insights into immunogenicity of the conserved OMPs and lipoproteins of A. pleuropneumoniae. Although none of the surface proteins characterized in this study could individually induce effective protective immunity against A. pleuropneumoniae, they are potential candidates for subunit vaccines in combination with Apx toxins.

  5. Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease.

    Directory of Open Access Journals (Sweden)

    Shivali Gupta

    Full Text Available Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and an emerging infectious disease in the US and Europe. We have shown TcG1, TcG2, and TcG4 antigens elicit protective immunity to T. cruzi in mice and dogs. Herein, we investigated antigenicity of the recombinant proteins in humans to determine their potential utility for the development of next generation diagnostics for screening of T. cruzi infection and Chagas disease.Sera samples from inhabitants of the endemic areas of Argentina-Bolivia and Mexico-Guatemala were analyzed in 1(st-phase for anti-T. cruzi antibody response by traditional serology tests; and in 2(nd-phase for antibody response to the recombinant antigens (individually or mixed by an ELISA. We noted similar antibody response to candidate antigens in sera samples from inhabitants of Argentina and Mexico (n=175. The IgG antibodies to TcG1, TcG2, and TcG4 (individually and TcG(mix were present in 62-71%, 65-78% and 72-82%, and 89-93% of the subjects, respectively, identified to be seropositive by traditional serology. Recombinant TcG1- (93.6%, TcG2- (96%, TcG4- (94.6% and TcG(mix- (98% based ELISA exhibited significantly higher specificity compared to that noted for T. cruzi trypomastigote-based ELISA (77.8% in diagnosing T. cruzi-infection and avoiding cross-reactivity to Leishmania spp. No significant correlation was noted in the sera levels of antibody response and clinical severity of Chagas disease in seropositive subjects.Three candidate antigens were recognized by antibody response in chagasic patients from two distinct study sites and expressed in diverse strains of the circulating parasites. A multiplex ELISA detecting antibody response to three antigens was highly sensitive and specific in diagnosing T. cruzi infection in humans, suggesting that a diagnostic kit based on TcG1, TcG2 and TcG4 recombinant proteins will be useful in diverse situations.

  6. Conservation analysis of dengue virust-cell epitope-based vaccine candidates using peptide block entropy

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Zhang, Guang Lan; Keskin, Derin B.

    2011-01-01

    residues. The block entropy analysis provides broad coverage of variant antigens. We applied the block entropy analysis method to the proteomes of the four serotypes of dengue virus (DENV) and found 1,551 blocks of 9-mer peptides, which cover 99% of available sequences with five or fewer unique peptides...

  7. Limited Transmission Potential of Takeda's Tetravalent Dengue Vaccine Candidate byAedes albopictus.

    Science.gov (United States)

    Dietrich, Elizabeth A; Ong, Yee Tsuey; Stovall, Janae L; Dean, Hansi; Huang, Claire Y-H

    2017-11-01

    Recombinant live-attenuated chimeric tetravalent dengue vaccine viruses, TDV-1, -2, -3, and -4, contain the premembrane and envelope genes of dengue virus serotypes 1-4 in the replicative background of the attenuated dengue virus type-2 (DENV-2) PDK-53 vaccine strain. Previous results have shown that these recombinant vaccine viruses demonstrate limited infection and dissemination in Aedes aegypti and are unlikely to be transmitted by the primary mosquito vector of DENVs. In this report, we expand this analysis by assessing vector competence of all four serotypes of the TDV virus in Aedes albopictus , the secondary mosquito vector of DENVs. Our results indicate that these vaccine viruses demonstrate incompetence or defective infection and dissemination in these mosquitoes and will likely not be transmissible.

  8. Construction and Characterization of Human Rotavirus Recombinant VP8* Subunit Parenteral Vaccine Candidates

    Science.gov (United States)

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W.; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka

    2012-01-01

    Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P[8], DS-1 P[4] or 1076 P[6] expressed in E. coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., (P[8], P[4] or P[6]) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines. PMID:22885016

  9. Synthesis and Characterization of Lipooligosaccharide-Based Conjugates as Vaccine Candidates for Moraxella (Branhamella) catarrhalis

    Science.gov (United States)

    Gu, Xin-Xing; Chen, Jing; Barenkamp, Stephen J.; Robbins, John B.; Tsai, Chao-Ming; Lim, David J.; Battey, James

    1998-01-01

    Moraxella (Branhamella) catarrhalis is an important cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits bactericidal antibodies. Treatment of the LOS from strain ATCC 25238 with anhydrous hydrazine reduced its toxicity 20,000-fold, as assayed in the Limulus amebocyte lysate (LAL) test. The detoxified LOS (dLOS) was coupled to tetanus toxoid (TT) or high-molecular-weight proteins (HMP) from nontypeable Haemophilus influenzae through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratios of dLOS to TT and HMP conjugates were 19:1 and 31:1, respectively. The antigenicity of the two conjugates was similar to that of the LOS, as determined by double immunodiffusion. Subcutaneous or intramuscular injection of both conjugates elicited a 50- to 100-fold rise in the geometric mean of immunoglobulin G (IgG) to the homologous LOS in mice after three injections and a 350- to 700-fold rise of anti-LOS IgG in rabbits after two injections. The immunogenicity of the conjugate was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced antisera had complement-mediated bactericidal activity against the homologous strain and heterologous strains of M. catarrhalis. These results indicate that a detoxified LOS-protein conjugate is a candidate for immunization against M. catarrhalis diseases. PMID:9573066

  10. Malaria Vaccine Candidate Diversity Offers Challenges and Opportunities for Effective Vaccine Development

    OpenAIRE

    Chowdhury, Kamal; Kantor, Mihail; Sestras, Radu E.

    2009-01-01

    Malaria is one of the most deadly diseases caused by protozoan parasites of genus Plasmodium. It affects 300-500 million people annually, of which more than a million lives are lost; among them majority under 5 years of age. By conventional wisdom, the immune mechanisms responsible for protection against malaria will require a multiple of 10-15 antigen targets for proper protection against various stages of malarial infection. Such large number of targets cannot be delivered to humans, by thi...

  11. Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate.

    Science.gov (United States)

    McKenzie, Robin; Venkatesan, Malabi M; Wolf, Marcia K; Islam, Dilara; Grahek, Shannon; Jones, Andrea M; Bloom, Arlene; Taylor, David N; Hale, Thomas L; Bourgeois, A Louis

    2008-06-19

    Among Shigella serotypes Shigella dysenteriae type 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a live S. dysenteriae 1 strain attenuated by deletion of the virG(icsA) gene, which encodes a protein that mediates intercellular spread, and stxA and stxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects ingested escalating doses of WRSd1 ranging from 10(3) to 10(7)CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuated Shigella vaccine must colonize well.

  12. Assessment of vaccine candidates for persons aged 50 and older : a review

    NARCIS (Netherlands)

    Eilers, Renske; Krabbe, Paul F. M.; van Essen, Ted G. A.; Suijkerbuijk, Anita; van Lier, Alies; de Melker, Hester E.

    2013-01-01

    Background: The increasing life expectancy in most European countries has resulted in growth of the population 50 and older. This population is more susceptible to infectious diseases because of immunosenescence, comorbidity and general frailty. Thus, to promote healthy aging, vaccination against

  13. Proteome-wide antigen discovery of novel protective vaccine candidates against Staphylococcus aureus infection

    DEFF Research Database (Denmark)

    Rasmussen, Karina Juhl; Mattsson, Andreas Holm; Pilely, Katrine

    2016-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly growing problem, especially in hospitals where MRSA cause increased morbidity and mortality and a significant rise in health expenditures. As many strains of MRSA are resistant to other antimicrobials in addition to methicillin, ther...

  14. Algorithmic Assessment of Vaccine-Induced Selective Pressure and Its Implications on Future Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Mones S. Abu-Asab

    2010-01-01

    Full Text Available Posttrial assessment of a vaccine's selective pressure on infecting strains may be realized through a bioinformatic tool such as parsimony phylogenetic analysis. Following a failed gonococcal pilus vaccine trial of Neisseria gonorrhoeae, we conducted a phylogenetic analysis of pilin DNA and predicted peptide sequences from clinical isolates to assess the extent of the vaccine's effect on the type of field strains that the volunteers contracted. Amplified pilin DNA sequences from infected vaccinees, placebo recipients, and vaccine specimens were phylogenetically analyzed. Cladograms show that the vaccine peptides have diverged substantially from their paternal isolate by clustering distantly from each other. Pilin genes of the field clinical isolates were heterogeneous, and their peptides produced clades comprised of vaccinated and placebo recipients' strains indicating that the pilus vaccine did not exert any significant selective pressure on gonorrhea field strains. Furthermore, sequences of the semivariable and hypervariable regions pointed out heterotachous rates of mutation and substitution.

  15. Identification of novel vaccine candidates against multidrug-resistant Acinetobacter baumannii.

    Directory of Open Access Journals (Sweden)

    Danilo G Moriel

    Full Text Available Acinetobacter baumannii is an emerging opportunistic bacterium associated with nosocomial infections in intensive care units. The alarming increase in infections caused by A. baumannii is strongly associated with enhanced resistance to antibiotics, in particular carbapenems. This, together with the lack of a licensed vaccine, has translated into significant economic, logistic and health impacts to health care facilities. In this study, we combined reverse vaccinology and proteomics to identify surface-exposed and secreted antigens from A. baumannii. Using in silico prediction tools and comparative genome analysis in combination with in vitro proteomic approaches, we identified 42 antigens that could be used as potential vaccine targets. Considering the paucity of effective antibiotics available to treat multidrug-resistant A. baumannii infections, these vaccine targets may serve as a framework for the development of a broadly protective multi-component vaccine, an outcome that would have a major impact on the burden of A. baumannii infections in intensive care units across the globe.

  16. A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

    DEFF Research Database (Denmark)

    Bélard, Sabine; Issifou, Saadou; Hounkpatin, Aurore B

    2011-01-01

    GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese ...... adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials....

  17. Toxoplasma gondii protease inhibitor-1 (TgPI-1) is a novel vaccine candidate against toxoplasmosis.

    Science.gov (United States)

    Cuppari, Anahi Fernandez; Sanchez, Vanesa; Ledesma, Bibiana; Frank, Fernanda M; Goldman, Alejandra; Angel, Sergio O; Martin, Valentina

    2008-09-15

    The Toxoplasma gondii serin protease inhibitor-1 (TgPI-1) is a dense granule antigen that showed to specifically inhibit trypsin, chymotrypsin and neutrophil elastase, suggesting a possible modulatory role during the parasite invasion process and on the development of the innate immune response. To study the immune-protective value of TgPI-1, C3H/HeN mice were immunized with a recombinant form of the antigen rTgPI-1 combined with alum. All immunized mice produced specific anti-rTgPI-1 immunoglobulins, with high IgG antibody titers and a mixed IgG(1)/IgG(2a) response, with predominance of IgG(1) production. The cellular immune response was associated with the production of IFN-gamma and IL-10 cytokines. Vaccinated mice displayed significant protection against an oral challenge either after a lethal infection with Me49 cysts (90% survival vs. 50%) and also after a non-lethal infection (58% reduction in brain parasite load) compared to the non-vaccinated control group. In conclusion, rTgPI-1 elicits a strong specific immune response providing partial protection against both T. gondii acute and chronic infection, so it would be a good candidate in a vaccine against toxoplasmosis, which could be combined with other relevant parasite antigens.

  18. Efficacy assessment of an inactivated Tembusu virus vaccine candidate in ducks.

    Science.gov (United States)

    Zhang, Lijiao; Li, Zhanhong; Zhang, Qingshui; Sun, Mengxu; Li, Shuang; Su, Wenliang; Hu, Xueying; He, Weiyong; Su, Jingliang

    2017-02-01

    Duck Tembusu virus (TMUV) is a recently identified pathogen that causes severe egg drop and neurological disease in domestic duck and goose flocks. The infection has spread across the China mainland since its outbreak in 2010. Effective vaccines are needed to fight the disease. In this work, we describe the development and laboratory assessment of a cell culture-derived, inactivated duck TMUV vaccine. The TMUV-JXSP strain was successfully propagated on a baby hamster kidney cell line (BHK-21), inactivated with beta-propiolactone (BPL) and emulsified with mineral oil. The efficacy of different vaccination schedules was assessed in laying ducks and table ducks using virus challenge experiments. Two doses of vaccine provided efficient protection against the virus challenge to avoid the egg production drop in laying ducks. An ELISA demonstrated that 97% (39/40) of ducks seroconverted on day 21 after one dose of the inactivated vaccine and that significant increases in antibody titers against the virus were induced after the second immunization. For table ducks, a single dose of vaccine immunization resulted in a protection index of 87% and significant reduction of viral loads in tissues. Sterilizing immunity can be attained after second immunization. Our results demonstrate that BHK-21 cell culture is suitable for duck TMUV propagation and that BPL-inactivated TMUV vaccine can provide a high level of protection from virus challenge in laying ducks and table ducks. These data provide a scientific basis for the development of an inactivated vaccine for the prevention of duck TMUV infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Nielsen, M; Lamberth, K

    2004-01-01

    % of all individuals of all major human populations (Sette & Sidney, Immunogenetics 1999: 50: 201-12). For each HLA supertype, we have selected the 15 top candidates for test in biochemical binding assays. At this time (approximately 6 months after the genome was established), we have tested the majority...

  20. SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C.; Nielsen, Morten; Lamberth, K.

    2004-01-01

    % of all individuals of all major human populations (Sette & Sidney, Immunogenetics 1999: 50: 201-12). For each HLA supertype, we have selected the 15 top candidates for test in biochemical binding assays. At this time (approximately 2 6 months after the genome was established), we have tested the majority...

  1. Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate.

    Science.gov (United States)

    Batzloff, Michael R; Fane, Anne; Gorton, Davina; Pandey, Manisha; Rivera-Hernandez, Tania; Calcutt, Ainslie; Yeung, Grace; Hartas, Jon; Johnson, Linda; Rush, Catherine M; McCarthy, James; Ketheesan, Natkunam; Good, Michael F

    2016-12-01

    Streptococcus pyogenes (group A streptococcus, GAS) causes a wide range of clinical manifestations ranging from mild self-limiting pyoderma to invasive diseases such as sepsis. Also of concern are the post-infectious immune-mediated diseases including rheumatic heart disease. The development of a vaccine against GAS would have a large health impact on populations at risk of these diseases. However, there is a lack of suitable models for the safety evaluation of vaccines with respect to post-infectious complications. We have utilized the Lewis Rat model for cardiac valvulitis to evaluate the safety of the J8-DT vaccine formulation in parallel with a rabbit toxicology study. These studies demonstrated that the vaccine did not induce abnormal pathology. We also show that in mice the vaccine is highly immunogenic but that 3 doses are required to induce protection from a GAS skin challenge even though 2 doses are sufficient to induce a high antibody titer.

  2. A synthetic carbohydrate-protein conjugate vaccine candidate against Shigella flexneri 2a infection.

    Science.gov (United States)

    Phalipon, Armelle; Tanguy, Myriam; Grandjean, Cyrille; Guerreiro, Catherine; Bélot, Frédéric; Cohen, Dani; Sansonetti, Philippe J; Mulard, Laurence A

    2009-02-15

    The protective Ag of Shigella, the Gram-negative enteroinvasive bacterium causing bacillary dysentery, or shigellosis, is its O-specific polysaccharide (O-SP) domain of the LPS, the major bacterial surface component. As an alternative to the development of detoxified LPS-based conjugate vaccines, recent effort was put into the investigation of neoglycoproteins encompassing synthetic oligosaccharides mimicking the protective Ags of the O-SP. We previously reported that when coupled to tetanus toxoid via single point attachment, a synthetic pentadecasaccharide representing three biological repeating units of the O-SP of Shigella flexneri 2a (SF2a), one of the most common Shigella serotypes, elicits a better serum anti-LPS 2a Ab response in mice than shorter synthetic O-SP sequences. In this study, we show that the pentadecasaccharide-induced anti-LPS 2a Abs protect passively administered naive mice from Shigella infection. Therefore, this three repeating units sequence, which is recognized by anti-SF2a sera from infected patients, acts as a functional mimic of the native polysaccharide Ag. Analyses of parameters influencing immunogenicity revealed that an investigational SF2a vaccine displaying a pentadecasaccharide:tetanus toxoid molar loading of 14:1 triggers a high and sustained anti-LPS Ab response, without inducing anti-linker Ab, when administered four times at a dose corresponding to 1 mug of carbohydrate. In addition, the profile of the anti-LPS Ab response, dominated by IgG1 production (Th2-type response), mimics that observed in human upon natural SF2a infection. This synthetic carbohydrate-based conjugate may be a candidate for a SF2a vaccine.

  3. Targeted modifications of foot-and-mouth disease virus; towards improved vaccine candidates

    DEFF Research Database (Denmark)

    Gullberg, Maria; Polacek, Charlotta; Bøtner, Anette

    these into susceptible cells it is possible to rescue specifically altered FMDVs. We have used this approach to generate modified viruses that have particular properties; these studies can assist in the development of improved and safer vaccines to protect against FMDV. For example, we have made changes to the leader (L...

  4. Construction and Characterization of Human Rotavirus Recombinant VP8* Subunit Parenteral Vaccine Candidates

    OpenAIRE

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W.; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka

    2012-01-01

    Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effec...

  5. Construction and characterization of human rotavirus recombinant VP8* subunit parenteral vaccine candidates.

    Science.gov (United States)

    Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka

    2012-09-21

    Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P[8], DS-1 P[4] or 1076 P[6] expressed in Escherichia coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., P[8], P[4] or P[6]) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines. Published by Elsevier Ltd.

  6. In silico identification of genetically attenuated vaccine candidate genes for Plasmodium liver stage.

    Science.gov (United States)

    Kumar, Hirdesh; Frischknecht, Friedrich; Mair, Gunnar R; Gomes, James

    2015-12-01

    Genetically attenuated parasites (GAPs) that lack genes essential for the liver stage of the malaria parasite, and therefore cause developmental arrest, have been developed as live vaccines in rodent malaria models and recently been tested in humans. The genes targeted for deletion were often identified by trial and error. Here we present a systematic gene - protein and transcript - expression analyses of several Plasmodium species with the aim to identify candidate genes for the generation of novel GAPs. With a lack of liver stage expression data for human malaria parasites, we used data available for liver stage development of Plasmodium yoelii, a rodent malaria model, to identify proteins expressed in the liver stage but absent from blood stage parasites. An orthology-based search was then employed to identify orthologous proteins in the human malaria parasite Plasmodium falciparum resulting in a total of 310 genes expressed in the liver stage but lacking evidence of protein expression in blood stage parasites. Among these 310 possible GAP candidates, we further studied Plasmodium liver stage proteins by phyletic distribution and functional domain analyses and shortlisted twenty GAP-candidates; these are: fabB/F, fabI, arp, 3 genes encoding subunits of the PDH complex, dnaJ, urm1, rS5, ancp, mcp, arh, gk, lisp2, valS, palm, and four conserved Plasmodium proteins of unknown function. Parasites lacking one or several of these genes might yield new attenuated malaria parasites for experimental vaccination studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing

    NARCIS (Netherlands)

    Pizza, M; Scarlato, [No Value; Masignani, [No Value; Giuliani, MM; Arico, B; Comanducci, M; Jennings, GT; Baldi, L; Bartolini, E; Capecchi, B; Galeotti, CL; Luzzi, E; Manetti, R; Marchetti, E; Mora, M; Nuti, S; Ratti, G; Santini, L; Savino, S; Scarselli, M; Storni, E; Zuo, PJ; Broeker, M; Hundt, E; Knapp, B; Blair, E; Mason, T; Tettelin, H; Hood, DW; Jeffries, AC; Saunders, NJ; Granoff, DM; Venter, JC; Moxon, ER; Grandi, G; Rappuoli, R

    2000-01-01

    Neisseria meningitidis is a major cause of bacterial septicemia and meningitis. Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the

  8. Closer to zero: Reflections on ten years of ART rollout

    African Journals Online (AJOL)

    To reflect upon ten years of antiretroviral therapy. (ART) rollout, one really should set the clock back a little further to see the massive impact of ART on our lives – for clinicians and patients alike. My own journey with HIV began in 1999 when, as a young doctor, I decided to venture into private practice with a local general ...

  9. WISE Albedos for Tens of Thousands of Main Belt Asteroids

    NARCIS (Netherlands)

    Masiero, Joseph R.; Mainzer, A. K.; Bauer, J.; Cutri, R.; Dailey, J.; Delbo, M.; Grav, T.; McMillan, R. S.; Mueller, M.; Walker, R.; Wright, E.; WISE Science Team, [No Value

    2010-01-01

    Using thermal IR data from the Wide-field Infrared Survey Explorer (WISE) mission we have calculated diameters for tens of thousands of previously known Main Belt asteroids. Using archival optical observations we have also determined albedos for each object. We present our results from this

  10. Ten Indicators of Vitality in Smaller Academic Libraries

    Science.gov (United States)

    Pappas, David

    2009-01-01

    This paper provides a means of quickly ascertaining the relative health of smaller academic libraries by presenting a top ten list of vitality indicators. The list is based on an observational convenience sampling of thirty smaller academic libraries across the United States. The indicators making the list were those which appeared most often in…

  11. A ten-year histopathological study of generalised lymphadenopathy ...

    African Journals Online (AJOL)

    2010-07-31

    Jul 31, 2010 ... Original Research: A ten-year histopathological study of generalised lymphadenopathy in India. 267. Vol 53 No 3. S Afr Fam Pract 2011. Introduction. The body contains approximately 600 lymph nodes, but only those in the submandibular, axillary and inguinal regions may be palpable in healthy people.

  12. DIE APOSTOLAAT VAN DIE KERK IN HIERDIE TYD TEN OPSIGTE ...

    African Journals Online (AJOL)

    Test

    Hierdie verkondiging het net een doel en net een inhoud. Die doel ... is die vlees- geworde Woord, Christus. Die apostalaat is nie een funksie van die kerk tussen ander nie. Die kerk is apostel in alles wat hy is en doen. Die doel van die. 239 ... skawing, nie vir uitbreiding van politieke magssfere nie, ens. Selfs ten koste van ...

  13. Ten-year-olds' reflections on their life in preschool

    DEFF Research Database (Denmark)

    Broström, Stig

    2016-01-01

    What do children think of their time in preschool? In the present study, twelve ten-year-old children collected data from their classmates. The children tend to remember their friends, and reflect on what games they played and with whom. Only about one in three respondents even mentioned the day...

  14. A Design Taxonomy Utilizing Ten Major Evaluation Strategies.

    Science.gov (United States)

    Willis, Barry

    This paper discusses ten evaluation strategies selected on the basis of their general acceptance and their relatively unique approach to the field: (1) State, "Countenance of Evaluation"; (2) Stufflebeam, "Decision Centered Evaluation (CIPP)"; (3) Provus, "Discrepancy Evaluation"; (4) Scriven, "Goal Free Evaluation"; (5) Scriven, "Formative and…

  15. Technical descriptions of ten irrigation technologies for conserving energy

    Energy Technology Data Exchange (ETDEWEB)

    Harrer, B.J.; Wilfert, G.L.

    1983-05-01

    Technical description of ten technologies which were researched to save energy in irrigated agriculture are presented. These technologies are: well design and development ground water supply system optimization, column and pump redesign, variable-speed pumping, pipe network optimization, reduced-pressure center-pivot systems, low-energy precision application, automated gated-pipe system, computerized irrigation scheduling, and instrumented irrigation scheduling. (MHR)

  16. Effects of TENS and methylphenidate in tuberculous meningo-encephalistis

    NARCIS (Netherlands)

    Scherder, E.J.A.; Deursen, S.; Manen, S.R.; Ferenschild, K.C.M.P.

    2001-01-01

    Primary objective: Beneficial effects of transcutaneous electrical nerve stimulation (TENS) on cognition and behaviour were observed in a child with probable Herpes Simplex Encephalitis. Based on these positive findings, it was examined in the present case study whether a child who had been

  17. Ten Strengths of How Teachers Do Cooperative Learning

    Science.gov (United States)

    Jaocbs, George M.

    2016-01-01

    Cooperative learning involves students in working together with peers to learn, to develop learning skills and to enjoy the learning process. This paper examines ten areas in which the author believes he and other teachers do cooperative learning well. These areas are: (1) keeping group size small, usually four or fewer; (2) encouraging students…

  18. Ten Helpful Ideas for Teaching English to Young Learners

    Science.gov (United States)

    Shin, Joan Kang

    2006-01-01

    This article offers ten suggestions for teaching young learners between the age of 7 and 12 based on language-teaching principles. They include supplementing activities with visuals, realia and movement; involving students in making visuals and realia; moving from activity to activity; teaching in themes; using stories and contexts familiar to…

  19. Ten statistics commandments that almost never should be broken.

    Science.gov (United States)

    Knapp, Thomas R; Brown, Jean K

    2014-08-01

    Quantitative researchers must choose among a variety of statistical methods when analyzing their data. In this article, the authors identify ten common errors in how statistical techniques are used and reported in clinical research and recommend stronger alternatives. Useful references to the methodological research literature in which such matters are discussed are provided. © 2014 Wiley Periodicals, Inc.

  20. Mid-term evaluation of ten National Research schools

    DEFF Research Database (Denmark)

    Gustafsson, Göran; Dahl, Hanne Marlene; Gustafsson, Christina

    grant applications, monitoring the progress of the FORSKERSKOLER scheme and serving as the evaluation panel for the mid-term evaluation in 2013 and in 2016/2017. The task of the evaluation panel has been to: 1) evaluate the quality of and progress achieved by the ten research schools which were awarded...

  1. Ten years into the marshes – Hapalemur alaotrensis conservation ...

    African Journals Online (AJOL)

    This article describes the approach that Madagascar Wildlife Conservation has been implementing during the past ten years at Lake Alaotra, discussing the plan of action and challenges for environmental education, ecotourism and alternative livelihoods. Les problèmes de gestion des ressources naturelles impliquent ...

  2. Changes in users' Web search performance after ten years ...

    African Journals Online (AJOL)

    The changes in users' Web search performance using search engines over ten years was investigated in this study. Matched data obtained from samples in 2000 and 2010 were used for the comparative analysis. The patterns of Web search engine use suggested a dominance in using a particular search engine. Statistical ...

  3. A Survey of Ten Money and Banking Textbooks.

    Science.gov (United States)

    Amsler, Christine E.

    1985-01-01

    Ten college-level money and banking textbooks were arrayed along six continua representing professors' major preferences when choosing a text. The continua topics are theoretical approach, complexity of presentation, theory/institution mix, nuts and bolts explanations, organizational approach, and writing style. (RM)

  4. Phytochemical and Anticancer Studies on Ten Medicinal Plants ...

    African Journals Online (AJOL)

    Ten medicinal plants used in Nigerian ethno medicine were subjected to phytochemical and anticancer studies using established standard procedures. The result of the study revealed the presence of phytochemical constituents such as alkaloids, saponins, tannins and flavonoids. Anona muricata, Andrographis paniculata ...

  5. Does the Russian Economy Need Human Capital? Ten Doubts

    Science.gov (United States)

    Gimpelson, V. E.

    2016-01-01

    It is generally accepted that human capital is an important factor in economic growth, but its impact on growth depends on the demand for education and skills on the labor market. Demand for human capital is largely determined by the institutional environment that governs the basic conditions for economic activity. The author expresses ten doubts…

  6. Ten Challenges of the Amyloid Hypothesis of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2017-01-01

    The inability to effectively halt or cure Alzheimer's disease (AD), exacerbated by the recent failures of high-profile clinical trials, emphasizes the urgent need to understand the complex biochemistry of this major neurodegenerative disease. In this paper, ten central, current challenges...

  7. Ten questions about radiant heating and cooling systems

    DEFF Research Database (Denmark)

    Rhee, Kyu-Nam; Olesen, Bjarne W.; Kim, Kwang Woo

    2017-01-01

    to extend the applicability of the RHC system are providing the continuous impetus for research on RHC systems. This paper summarizes the important issues involved in the research on RHC system, whereby ten questions and answers concerning the RHC system are discussed, which will help researchers to conduct...

  8. Molecular characterization of ten mango cultivars using simple ...

    African Journals Online (AJOL)

    DEAN

    2013-11-20

    Nov 20, 2013 ... Molecular characterization of ten mango cultivars using simple sequences repeat (SSR) markers. M. Kumar1*, V. Ponnuswami1, P. Nagarajan2, P. Jeyakumar3 and N. Senthil2. 1Horticultural College and Research Institute, Periyakulam, Tamil Nadu, 625604, India. 2Centre for Plant Molecular Biology, ...

  9. Ten Years after Columbine: The Tragedy of Youth Deepens

    Science.gov (United States)

    Giroux, Henry A.

    2009-01-01

    For young people it just gets worse. Ten years after the Columbine tragedy, the debate over school safety has clearly shown that educators, parents, politicians, and the mainstream media have created the conditions in which young people have increasingly become the victims of adult mistreatment, indifference, neglect, even violence. The tragic…

  10. ALICE: Simulated lead-lead collision

    CERN Document Server

    2003-01-01

    This track is an example of simulated data modelled for the ALICE detector on the Large Hadron Collider (LHC) at CERN, which will begin taking data in 2008. ALICE will focus on the study of collisions between nuclei of lead, a heavy element that produces many different particles when collided. It is hoped that these collisions will produce a new state of matter known as the quark-gluon plasma, which existed billionths of a second after the Big Bang.

  11. Organic Lead Toxicology

    Directory of Open Access Journals (Sweden)

    Jiří Patočka

    2008-01-01

    Full Text Available Lead is one of the oldest known and most widely studied occupational and environmental poison. Despite intensive study, there is still debate about the toxic effects of lead, both from low-level exposure in the general population owing to environmental pollution and historic use of lead in paint and plumbing and from exposure in the occupational setting. Significant position have organic lead compounds used more than 60 years as antiknock additives in gasoline. Chemical and toxicological characteristics of main tetraalkyl leads used as gasoline additives are discussed in this article. The majority of industries historically associated with high lead exposure have made dramatic advances in their control of occupational exposure. However, cases of unacceptably high exposure and even of frank lead poisoning are still seen, predominantly in the demolition and tank cleaning industries. Nevertheless, in most industries blood lead levels have declined below levels at which signs or symptoms are seen and the current focus of attention is on the subclinical effects of exposure. The significance of some of these effects for the overt health of the workers is often the subject of debate. Inevitably there is pressure to reduce lead exposure in the general population and in working environments, because current studies show that no level of lead exposure appears to be a ‘safe’ and even the current ‘low’ levels of exposure, especially in children, are associated with neurodevelopmental deficits.

  12. Lead-Free Piezoelectrics

    CERN Document Server

    Nahm, Sahn

    2012-01-01

    Ecological restrictions in many parts of the world are demanding the elimination of Pb from all consumer items. At this moment in the piezoelectric ceramics industry, there is no issue of more importance than the transition to lead-free materials. The goal of Lead-Free Piezoelectrics is to provide a comprehensive overview of the fundamentals and developments in the field of lead-free materials and products to leading researchers in the world. The text presents chapters on demonstrated applications of the lead-free materials, which will allow readers to conceptualize the present possibilities and will be useful for both students and professionals conducting research on ferroelectrics, piezoelectrics, smart materials, lead-free materials, and a variety of applications including sensors, actuators, ultrasonic transducers and energy harvesters.

  13. Zastosowanie elektroterapii TENS w łagodzeniu bólu porodowego / Application of TENS electrotherapy in alleviating labour pain

    Directory of Open Access Journals (Sweden)

    Sowa Magdalena

    2016-06-01

    Full Text Available Introduction. Easing labour pain is an extremely important issue in obstetric practice. Various physiotherapy methods are increasingly often applied in obstetric practice. Transcutaneous electric nerve stimulation (TENS aiming at central and peripheral modulation of pain sensation is one of them.

  14. Transcutaneous electric nerve stimulation (TENS) for cancer pain in adults.

    Science.gov (United States)

    Hurlow, Adam; Bennett, Michael I; Robb, Karen A; Johnson, Mark I; Simpson, Karen H; Oxberry, Stephen G

    2012-03-14

    Cancer-related pain is complex and multi-dimensional but the mainstay of cancer pain management has predominantly used a biomedical approach. There is a need for non-pharmacological and innovative approaches. Transcutaneous Electric Nerve Stimulation (TENS) may have a role in pain management but the effectiveness of TENS is currently unknown. This is an update of the original review published in Issue 3, 2008. The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. The initial review searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED and PEDRO databases in April 2008. We performed an updated search of CENTRAL, MEDLINE, EMBASE, CINAHL and PEDRO databases in November 2011. We included only randomised controlled trials (RCTS) investigating the use of TENS for the management of cancer-related pain in adults. The search strategy identified a further two studies for possible inclusion. One of the review authors screened each abstract using a study eligibility tool. Where eligibility could not be determined, a second author assessed the full paper. One author used a standardised data extraction sheet to collect information on the studies and independently assess the quality of the studies using the validated five-point Oxford Quality Scale. The small sample sizes and differences in patient study populations of the three included studies (two from the original review and a third included in this update) prevented meta-analysis. For the original review the search strategy identified 37 possible published studies; we divided these between two pairs of review authors who decided on study selection; all four review authors discussed and agreed final scores. Only one additional RCT met the eligibility criteria (24 participants) for this updated review. Although this was a feasibility study, not designed to investigate intervention effect, it suggested that TENS may improve bone pain on movement in a

  15. Lead and the skin

    Energy Technology Data Exchange (ETDEWEB)

    Allen, B.R.; Moore, M.R.; Hunter, J.A.A.

    1975-01-01

    The increasing use of lead will continue to give rise to problems of toxicity. Protective measures have resulted in florid lead poisoning becoming rare. Attention has recently turned to the possibility of prolonged exposure to low doses of lead causing morbidity in the absence of the classical clinical features of poisoning. Lead is absorbed mostly through the lungs and gastrointestinal tract. Some is also absorbed through the skin but with inorganic compounds the amount is small. Shortly after the most widely used compound, tetraethyl lead, was first manufactured, cases of toxicity began to occur. Manufacture was forbidden until plant design produced greater safety. Significant absorption can occur through the skin. The hazard to those handling leaded gasoline in a normal manner is probably small, mainly because 95 percent of a dose applied to the open skin surface evaporates. Hair has been used as a biopsy material to assess lead exposure. The biological effects of lead poisoning are discussed, including the synergistic effects of lead and agents provoking porphyria.

  16. A version of the TEN Test for use with ER-3A insert earphones.

    Science.gov (United States)

    Moore, Brian C J; Creeke, Sarah; Glasberg, Brian R; Stone, Michael A; Sek, Aleksander

    2012-01-01

    The aim of this study was to develop a version of the threshold-equalizing noise (TEN) test for the diagnosis of dead regions for use with Etymotic ER-3A insert earphones. The use of such earphones is helpful when testing clients with asymmetric hearing loss or clients whose ear canals tend to collapse under the pressure of supra-aural headphones. It can also be useful when ambient noise levels are problematic. The spectral shape of the noise required to give equal masked thresholds at all frequencies, when expressed in dB HL, was derived by empirical measurements of the electrical output of audiometers using ER-3A earphones. To reduce the loudness of the noise and to minimize distortion generated in the audiometer or earphone, the noise was band-limited between 354 and 6500 Hz. In addition, the noise was synthesized using a method that leads to a low crest factor (ratio of peak to root mean square value). This further reduced audiometer/earphone distortion, and allowed higher levels per ERBN; ERBN is the equivalent rectangular bandwidth of the auditory filter at 1 kHz, as determined using young normally hearing subjects. The test tone frequencies were limited to the range 500 to 4000 Hz. Subjects with normal or near-normal hearing were tested using a noise level of 60 dB HL/ERBN, to assess whether the noise did lead to equal masked thresholds in dB HL for all audiometric frequencies from 500 to 4000 Hz. Thresholds in the TEN were measured using manual audiometry with a 2 dB final step size. The mean-masked thresholds varied by 1.3 dB across frequency when expressed in dB HL, and were close to the noise level per ERBN. This version of the TEN test can be used with ER-3A insert earphones.

  17. Increasing lead burden correlates with externalized cables during systematic fluoroscopic screening of Riata leads.

    Science.gov (United States)

    Moorman, Liza P; Moorman, J Randall; DiMarco, John P; Malhotra, Rohit; Darby, Andrew; Bilchick, Kenneth; Ferguson, John D; Mangrum, J Michael; Kamath, Sandeep; Mason, Pamela K

    2013-06-01

    Riata and Riata ST defibrillator leads (St. Jude Medical, Sylmar, CA, USA) have been recalled due to increased risk of insulation failure leading to externalized cables. As this mechanical failure does not necessarily correlate with electrical failure, it can be difficult to diagnose. Fluoroscopic screening can identify insulation failure. Studies have suggested that insulation failure is predominantly seen in 8-Fr, single-coil models. Our patients have exclusively dual-coil leads and a high proportion of 7-Fr leads. Fluoroscopic screening was performed in 48 patients with recalled Riata leads. Twenty-three patients had 8-Fr Riata leads and 25 patients had 7-Fr Riata ST leads. Images were recorded in at least three projections and studies were reviewed by seven attending electrophysiologists. Externalized cables were seen in ten patients (21 %), and another five patients (10 %) had abnormal cable spacing. All device interrogations showed normal parameters. Patients with abnormal leads had more leads in situ (2.5 ± 0.7 vs. 1.6 ± 0.8 leads; P = 0.002) and a higher rate of nonischemic cardiomyopathy (80 vs. 24 %; P = 0.03). There were no differences between the groups with regards to patient age, body mass index, lead age, lead parameters, or vascular access site. There was no difference with regard to lead size (P = 0.76). The Riata family of leads has a high incidence of mechanical failure, as demonstrated on fluoroscopic screening. In this study, the 7-Fr models were just as likely to mechanically fail as the 8-Fr models. Increasing lead burden and a diagnosis of nonischemic cardiomyopathy correlated with insulation failure.

  18. Soil Lead and Children's Blood Lead Disparities in Pre- and Post-Hurricane Katrina New Orleans (USA).

    Science.gov (United States)

    Mielke, Howard W; Gonzales, Christopher R; Powell, Eric T

    2017-04-12

    This study appraises New Orleans soil lead and children's lead exposure before and ten years after Hurricane Katrina flooded the city. Introduction : Early childhood exposure to lead is associated with lifelong and multiple health, learning, and behavioral disorders. Lead exposure is an important factor hindering the long-term resilience and sustainability of communities. Lead exposure disproportionately affects low socioeconomic status of communities. No safe lead exposure is known and the common intervention is not effective. An essential responsibility of health practitioners is to develop an effective primary intervention. Methods : Pre- and post-Hurricane soil lead and children's blood lead data were matched by census tract communities. Soil lead and blood lead data were described, mapped, blood lead graphed as a function of soil lead, and Multi-Response Permutation Procedures statistics established disparities. Results : Simultaneous decreases occurred in soil lead accompanied by an especially large decline in children's blood lead 10 years after Hurricane Katrina. Exposure disparities still exist between children living in the interior and outer areas of the city. Conclusions : At the scale of a city, this study demonstrates that decreasing soil lead effectively reduces children's blood lead. Primary prevention of lead exposure can be accomplished by reducing soil lead in the urban environment.

  19. EFFECT OF LEAD ACETATE

    African Journals Online (AJOL)

    MICROSOFT

    The project was conducted to evaluate the effect of lead administered as lead acetate at different dosage levels via drinking water in broiler chicks. Thirty-five healthy chicks were divided into seven groups (five chicks each) and one group was kept as un-medicated control. Groups A, B, C, D, E and F were medicated with ...

  20. Leading Acquisition Reform

    Science.gov (United States)

    2011-03-22

    Army and Undersecretary of Defense for Acquisition, for a reduction of the Excalibur and Accelerated Precision Mortar initiative rounds.25...Can’t Dance? Leading a Great Enterprise Through Dramatic Change, (New York: HarperCollins Publishers, 2003), 235. 13 John P. Kotter , Leading Change

  1. Developmental immunotoxicology of lead.

    Science.gov (United States)

    Dietert, Rodney R; Lee, Ji-Eun; Hussain, Irshad; Piepenbrink, Michael

    2004-07-15

    The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered.

  2. Lead - nutritional considerations

    Science.gov (United States)

    ... lead soldered cans goes into effect. If imported wine containers have a lead foil wrapper, wipe the rim and neck of the bottle with a towel moistened with lemon juice, vinegar, or wine before using. DO NOT store wine, spirits, or ...

  3. [THE TEN MOST CITED ARTICLES OF THE JOURNAL "NUTRICION HOSPITALARIA"].

    Science.gov (United States)

    Franco-López, Ángeles; González-Gallego, Javier; Sanz-Valero, Javier; Tuñón, María Jesús; García-De-Lorenzo, Abelardo; Culebras, Jesús M

    2015-12-01

    After 36 years of continued publication of the journal Nutrición Hospitalaria, a list with the ten most cited articles published in it is elaborated. The top ten most cited articles in the world literature and stratification according to language, English or Spanish, subject, or period of time published are also analyzed. Nutr Hosp is the most important Ibero latin American nutrition journal. Nutr Hosp published 369 items in 2014 gaining the fourth position among all the world's journals devoted to nutrition. Article publication in English, or simultaneously in Spanish and English and Open Access policy probably benefit the number of citations. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  4. Childhood herpes zoster: A clustering of ten cases

    Directory of Open Access Journals (Sweden)

    Prabhu Smitha

    2009-01-01

    Full Text Available Herpes zoster occurs due to reactivation of the latent varicella zoster virus and is usually a disease of the elderly. Childhood herpes zoster is believed to be rare, though recent studies suggest increasing incidence in children. Here we report ten cases of childhood herpes zoster, seven of which occurred within a short span of six months, at a tertiary care level hospital in Pokhara, Nepal. Only three of the ten children reported previous history of varicella infection and none was immunized against varicella. Though childhood herpes zoster accounted for less than 1% of the total zoster cases in the past, recent reports show an increase in the number of cases in apparently healthy children. So far, no studies have been done linking childhood herpes zoster with HIV, though there are many studies linking it with other immunocompromised conditions.

  5. Clinical alarm hazards: a "top ten" health technology safety concern.

    Science.gov (United States)

    Keller, James P

    2012-01-01

    For the past several years ECRI Institute has published a list of Top Ten Health Technology Hazards. This list is based on ECRI's extensive research in health technology safety and on data provided to its problemreporting systems. For every year that the Top Ten list has been published, Alarm Hazards have been at or near the top of the list. Improving alarm safety requires a systematic review of a hospital's alarm-based technologies and analysis of alarm management policies like alarm escalation strategies and staffing patterns. It also requires careful selection of alarm setting criteria for each clinical care area. This article will overview the clinical alarm problems that have been identified through ECRI Institute's research and analysis of various problem reporting databases, including those operated by ECRI Institute. It will also highlight suggestions for improvement, particularly from a technology design and technology management perspective. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. The Ten Commandments tra Vecchio e Nuovo Testamento

    Directory of Open Access Journals (Sweden)

    De Berti Raffaele

    2011-06-01

    Full Text Available Cecil B. DeMille adapted for the screen the biblical text of Exodus twice, and in both cases he devised sophisticated strategies for intersemiotic translation with the aim to create a great show for a popular Christian audience. This is the reason why The Ten Commandments cannot be considered a mere illustration of the biblical story but instead a complex fiction film, which uses the Bible only as a starting point.

  7. The Ten Commandments tra Vecchio e Nuovo Testamento

    OpenAIRE

    De Berti Raffaele; Tomaso Subini

    2011-01-01

    Cecil B. DeMille adapted for the screen the biblical text of Exodus twice, and in both cases he devised sophisticated strategies for intersemiotic translation with the aim to create a great show for a popular Christian audience. This is the reason why The Ten Commandments cannot be considered a mere illustration of the biblical story but instead a complex fiction film, which uses the Bible only as a starting point.

  8. TEN KEY CONCEPTS AND THE SUCCESS OF ROMANIAN ORGANIZATIONS

    Directory of Open Access Journals (Sweden)

    Ada Mirela TOMESCU

    2006-01-01

    Full Text Available This paper is focused on ten key concepts which influence the success of theorganizations at the beginning of XXI century. The great changes generatedby globalization determine firms to be more competitive. This means that wehave to focus on: mission, leadership, emotional intelligence, innovation,organizational culture, human resources, total quality management, ethics,conflict management, brand, and the value offered to the clients.

  9. Ten inherited disorders in purebred dogs by functional breed groupings

    OpenAIRE

    Oberbauer, A. M.; Belanger, J. M.; Bellumori, T.; BANNASCH, D. L.; Famula, T R

    2015-01-01

    Background Analysis of 88,635 dogs seen at the University of California, Davis Veterinary Medical Teaching Hospital from 1995 to 2010 identified ten inherited conditions having greater prevalence within the purebred dog population as compared to the mixed-breed dog population: aortic stenosis, atopy/allergic dermatitis, gastric dilatation volvulus (GDV), early onset cataracts, dilated cardiomyopathy, elbow dysplasia, epilepsy, hypothyroidism, intervertebral disk disease (IVDD), and hepatic po...

  10. Fundamental Field Theory in Ten Dimensions and The Early Universe

    OpenAIRE

    Patwardhan, Ajay

    2006-01-01

    A unified field theory in ten dimensions, of all interactions, can describe high energy processes occuring in the early universe. In such a theory transitions that give properties of the universe can occur due to the presence of algebraic and geometric structures. A correspondence between theory and observations of the universe is made, to obtain a new interpretation and properties. This paper consists of a field theory and cosmological model of dark and normal energy and matter, cosmological...

  11. The African Association for Lexicography: After Ten Years

    OpenAIRE

    Mariëtta Alberts

    2011-01-01

    ABSTRACT: This year it has been ten years since the establishment of AFRILEX. After an expla-nation of what led to its forming, this article gives a short overview of its composition and activi-ties.


    Keywords: AFRICAN ASSOCIATION FOR LEXICOGRAPHY (AFRILEX), AFRICAN LAN-GUAGES ASSOCIATION OF SOUTH AFRICA (ALASA), BUREAU OF THE WOORDEBOEK VAN DIE AFRIKAANSE TAAL (WAT), DICTIONARY OF SOUTH AFRICAN ENGLISH (DSAE), LINGUISTIC ASSOCIATION OF SOUTHERN AFRICA (L...

  12. Quantitation of Ten Flavor Compounds in Unburned Tobacco Products†

    OpenAIRE

    Lisko, Joseph G.; Stanfill, Stephen B.; Watson, Clifford H.

    2014-01-01

    Most research on unburned tobacco has focused on the harmful chemicals associated with the tobacco itself. However, certain flavor additives in tobacco products can pose additional health risks. Flavors like camphor, coumarin, pulegone, eugenol, methyl salicylate, menthol and diphenyl ether have exhibited biological activity and/or toxicity in both lab animals and humans. This publication presents a new GC/MS method for the quantitation of ten flavor compounds (eucalyptol, camphor, menthol, p...

  13. AHP 28: Review: Scripture of the Ten Kings

    Directory of Open Access Journals (Sweden)

    Paul K. Nietupski

    2013-11-01

    Full Text Available This book is a study of the various influences on the complex Tibetan visions of the afterlife. It is based on new text-critical research and includes an introduction and translation of a rare Tibetan manuscript entitled Scripture on the Ten Kings, housed in the National Gallery, Prague. The book includes extensive references to secondary scholarship, as well as collaborative work by competent scholars and an appended study of the text illustrations by Luboš Bělka.

  14. Modification of the 'ten-day rule'

    Energy Technology Data Exchange (ETDEWEB)

    Klempfner, G.

    1985-02-01

    In a 1964 decision the National Health and Medical Research Council recommended that radiological examinations of the lower abdomen and pelvis of women of childbearing age should be confined to the 10-day interval following the onset of menstruation. Recent evidence suggests that the first four weeks from the first day of the last menstrual period is not a critically radiosensitive period and consequently strict adherence to the ten-day rule is no longer indicated.

  15. Lead toxicity: Current concerns

    Energy Technology Data Exchange (ETDEWEB)

    Goyer, R.A. (Univ. of Western Ontario, London (Canada))

    1993-04-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has been the demonstration that blood lead (PbB) levels of 10-15 micrograms/dL in newborn and very young infants result in cognitive and behavioral deficits. Further support for this observation is being obtained by prospective or longitudinal studies presently in progress. The mechanism(s) for the central nervous system effects of lead is unclear but involve lead interactions within calcium-mediated intracellular messenger systems and neurotransmission. Effects of low-level lead exposure on blood pressure, particularly in adult men, may be related to the effect of lead on calcium-mediated control of vascular smooth muscle contraction and on the renin-angiotensin system. Reproductive effects of lead have long been suspected, but low-level effects have not been well studied. Whether lead is a carcinogen or its association with renal adenocarcinoma is a consequence of cystic nephropathy is uncertain. Major risk factors for lead toxicity in children in the United States include nutrition, particularly deficiencies of essential metals, calcium, iron, and zinc, and housing and socioeconomic status. A goal for the year 2000 is to reduce prevalence of blood lead levels exceeding 15 micrograms/dL. 97 refs.

  16. Mathematics and Liberature: Fajfer’s Ten Letters

    Directory of Open Access Journals (Sweden)

    Matuszyk Łukasz

    2016-05-01

    Full Text Available The article discusses liberature in the context of its mathematical qualities. In this trend which inextricably connects the textual and physical layer of the work, each element in the book is expected to be created according to a certain formula which should bring a holistic piece of literature. After 1999, a great number of mathematically-oriented works have appeared which are strictly liberary. In the presentation, I base on the theoretical idea behind liberature when discussing Zenon Fajfer’s liberary work Ten Letters (Pol. Dwadzieścia jeden liter. This innovative piece is analysed mainly from the point of view of geometry and play with numbers, which is visible already in the title: the ten-letter phrase “ten letters.” Mathematical qualities are indicated on various layers of the piece: the physical, the textual, and the visual, but especially in its form. The game of numbers is found not only where it is obviously visible and essential to understand the message, but also in places which might not have been intended. Liberature is analysed as literature but at the same time, it is shown not to be literature, and in this respect, to be mathematical at the core.

  17. Frictional amyloidosis in Oman - A study of ten cases

    Directory of Open Access Journals (Sweden)

    Mysore Venkataram

    2002-01-01

    Full Text Available Macular amyloidosis is an important cause for cutaneous pigmentation, the aetiology of which is poorly understood. Friction has recently been implicated the causation of early lesions, referred to as frictional amyloidosis. Confirmation of diagnosis by the detect on of amyloid using histochemical stains is inconsistent. Ten patients with pigmentation suggestive of macular amyloidosis were studied with detailed history, clinical examination, biopsy for histochemistry and electron microscopy. Nine out of ten patients had a history of prolonged friction with various objects such as bath sponges, brushes, towels, plant sticks and leaves. Amyloid was demonstrated by histochemical staining in only six out of ten cases. In the remaining four cases, amyloid was detected by electron microscopy. These consisted of aggregates of non-branching, extracellular, intertwining fibres measuring between 200-500 nm in length and between 20-25 nm in diameter. The study confirms the role of friction in the causation of this condition. Histochemical stains are not always successful in the detection of amyloid and electron microscopy is helpful for confirming its presence. The term frictional amyloidosis aptly describes the condition.

  18. Six to Ten Digits Multiplication Fun Learning Using Puppet Prototype

    Science.gov (United States)

    Islamiah Rosli, D.'oria; Ali, Azita; Peng, Lim Soo; Sujardi, Imam; Usodo, Budi; Adie Perdana, Fengky

    2017-01-01

    Logic and technical subjects require students to understand basic knowledge in mathematic. For instance, addition, minus, division and multiplication operations need to be mastered by students due to mathematic complexity as the learning mathematic grows higher. Weak foundation in mathematic also contribute to high failure rate in mathematic subjects in schools. In fact, students in primary schools are struggling to learn mathematic because they need to memorize formulas, multiplication or division operations. To date, this study will develop a puppet prototyping for learning mathematic for six to ten digits multiplication. Ten participants involved in the process of developing the prototype in this study. Students involved in the study were those from the intermediate class students whilst teachers were selected based on their vast knowledge and experiences and have more than five years of experience in teaching mathematic. Close participatory analysis will be used in the prototyping process as to fulfil the requirements of the students and teachers whom will use the puppet in learning six to ten digit multiplication in mathematic. Findings showed that, the students had a great time and fun learning experience in learning multiplication and they able to understand the concept of multiplication using puppet. Colour and materials of the puppet also help to attract student attention during learning. Additionally, students able to visualized and able to calculate accurate multiplication value and the puppet help them to recall in multiplying and adding the digits accordingly.

  19. Perseptuele verskille tussen bestuurders en ondergeskiktes ten opsigte van prestasiebeoordeling

    Directory of Open Access Journals (Sweden)

    C. W. le Roux

    1991-06-01

    Full Text Available Perceptual differences between managers and subordinates regarding performance appraisal. In order to determine the degree of similarity or disparity in perceptions of subordinates and managers regarding the administrative and developmental dimensions of performance appraisal a subsection (Satisfaction with the Performance and Developmental Appraisal of the Leadership Analysis Questionnaire (LAQ(Mount, 1983 was administered to 92 managers, 142 successful subordinates and 67 unsuccessful subordinates. The research reveals that no significant differences exist between the perceptions of successful and unsuccessful subordinates, and between subordinates and managers regarding the administrative and developmental dimensions of performance appraisal. Opsomming Ten einde die mate van ooreenstemming of die verskil in persepsies van ondergeskiktes en toesighouers ten opsigte van die administratiewe- en ontwikkelingsdimensies van prestasiebeoordeling te ondersoek is 'n onderafdeling ("Satisfaction with the Performance and Developmental Appraisal" van die "Leadership Analysis Questionnaire" (LAQ (Mount, 1983 aan 92 bestuurders, 142 suksesvolle ondergeskiktes en 67 onsuksesvolle ondergeskiktes geadministreer. Dit blyk uit die ondersoek dat daar geen beduidende verskille tussen die persepsies van suksesvole en onsuksesvolle ondergeskiktes, en tussen ondergeskiktes en bestuurders ten opsigte van die administratiewe- en ontwikkelingsdimensies van prestasiebeoordeling bestaan nie.

  20. Hypoalgesia in response to transcutaneous electrical nerve stimulation (TENS) depends on stimulation intensity.

    Science.gov (United States)

    Moran, Fidelma; Leonard, Tracey; Hawthorne, Stephanie; Hughes, Ciara M; McCrum-Gardner, Evie; Johnson, Mark I; Rakel, Barbara A; Sluka, Kathleen A; Walsh, Deirdre M

    2011-08-01

    Transcutaneous electrical nerve stimulation (TENS) is an electrophysical modality used for pain management. This study investigated the dose response of different TENS intensities on experimentally induced pressure pain. One hundred and thirty TENS naïve healthy individuals (18-64 years old; 65 males, 65 females) were randomly allocated to 5 groups (n = 26 per group): Strong Non Painful TENS; Sensory Threshold TENS; Below Sensory Threshold TENS; No Current Placebo TENS; and Transient Placebo TENS. Active TENS (80 Hz) was applied to the forearm for 30 minutes. Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds (PPT) were recorded from 2 points on the hand and forearm before and after TENS to measure hypoalgesia. There were significant differences between groups at both the hand and forearm (ANOVA; P = .005 and .002). At 30 minutes, there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to: Below Sensory Threshold TENS, No Current Placebo TENS and Transient Placebo TENS groups (P TENS and No Current Placebo TENS groups at the hand (P = .001). There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups. The area under the curve for the changes in PPT significantly correlated with the current amplitude (r(2) = .33, P = .003). These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes. This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect; thus, we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  1. Lead User Innovation

    DEFF Research Database (Denmark)

    Brem, Alexander; Larsen, Henry

    2015-01-01

    User innovation and especially the integration of lead users is a key topic in the innovation management literature of recent years. This paper contributes by providing a rare perspective into what easily could be seen as innovation failure, shown from two perspectives. We show how a lack of shared...... imagination hampers participation and kills innovation between interdependent stakeholders at the threshold between invention and innovation in practice. We present a first case in the fun-sport industry where an external lead user and diverse firm representatives in different functions fail to create......, deliver and capture the value of an innovatively new device together. From the perspective of the lead user, we show antecedents and effects of social interaction between organizational actors and the lead user on the development of social capital, especially trust and shared imagination. The second case...

  2. Research on Activators for Lead-Acid Batteries

    OpenAIRE

    Sugawara, Michio; Kozawa, Akiya

    2008-01-01

    Abstract : The ITE Battery Research group has developed a new organic battery activator for new and used lead-acid batteries. Ten years of investigation have established the validity of the ITE activator that prolongs the useful life of lead-acid batteries. It has been shown that the specific gravity of spent batteries can be restored to the original level in automotive, motive power; uninterruptible power supplies (UPS) and stationary energy storage batteries. Our results show that the disca...

  3. Magnesium Diboride Current Leads

    Science.gov (United States)

    Panek, John

    2010-01-01

    A recently discovered superconductor, magnesium diboride (MgB2), can be used to fabricate conducting leads used in cryogenic applications. Dis covered to be superconducting in 2001, MgB2 has the advantage of remaining superconducting at higher temperatures than the previously used material, NbTi. The purpose of these leads is to provide 2 A of electricity to motors located in a 1.3 K environment. The providing environment is a relatively warm 17 K. Requirements for these leads are to survive temperature fluctuations in the 5 K and 11 K heat sinks, and not conduct excessive heat into the 1.3 K environment. Test data showed that each lead in the assembly could conduct 5 A at 4 K, which, when scaled to 17 K, still provided more than the required 2 A. The lead assembly consists of 12 steelclad MgB2 wires, a tensioned Kevlar support, a thermal heat sink interface at 4 K, and base plates. The wires are soldered to heavy copper leads at the 17 K end, and to thin copper-clad NbTi leads at the 1.3 K end. The leads were designed, fabricated, and tested at the Forschungszentrum Karlsruhe - Institut foer Technische Physik before inclusion in Goddard's XRS (X-Ray Spectrometer) instrument onboard the Astro-E2 spacecraft. A key factor is that MgB2 remains superconducting up to 30 K, which means that it does not introduce joule heating as a resistive wire would. Because the required temperature ranges are 1.3-17 K, this provides a large margin of safety. Previous designs lost superconductivity at around 8 K. The disadvantage to MgB2 is that it is a brittle ceramic, and making thin wires from it is challenging. The solution was to encase the leads in thin steel tubes for strength. Previous designs were so brittle as to risk instrument survival. MgB2 leads can be used in any cryogenic application where small currents need to be conducted at below 30 K. Because previous designs would superconduct only at up to 8 K, this new design would be ideal for the 8-30 K range.

  4. How green are the TEN-T core network corridors?

    DEFF Research Database (Denmark)

    Panagakos, George; Psaraftis, Harilaos N.

    "Green corridors‟ is a concept introduced by the European Commission to enhance the provision of sustainable freight transport logistics services by concentrating freight traffic between major hubs and by relatively long distances. SuperGreen, a Coordination and Support Action aiming at further...... defining this concept, identified the characteristics that distinguish a green corridor from an otherwise efficient one. The main thesis of this paper is that the „core network corridors‟ of the new TEN-T guidelines exhibit all these qualities and the vision of a green corridor network in Europe is close...

  5. Ten years of multidisciplinary mental health guidelines in the Netherlands.

    Science.gov (United States)

    Franx, Gerdien; Niesink, Peter; Swinkels, Jan; Burgers, Jako; Wensing, Michel; Grol, Richard

    2011-08-01

    From 1999 until 2009 the National Steering Group for Multidisciplinary Guideline Development in Mental Health led a national guideline programme in the Netherlands. Ten service user and carer groups and 30 professional organizations were involved. Within the programme 13 practice guidelines and a range of other deliverables, such as patient versions, checklists and implementation materials, were produced. Lessons learned included the methodology of developing guidelines, service user and carer involvement, and the dissemination and implementation of the guidelines. There are important future challenges such as following a strict and transparent methodology, adhering to process management, improving integration of the service user and professional perspectives, and bridging the gap between guideline and practice.

  6. Ten PM Note of Organophosphae Poisoning- Successful outcome of a Medical Audit with complete seven steps

    Directory of Open Access Journals (Sweden)

    M D Bhattarai

    2010-03-01

    Full Text Available Medical audit in general consists of seven steps like choosing topic, setting criterion and standard, collecting first data, comparing data with standard, introducing change, collecting second data and reflecting. Its three basic premise are improvement of patient care by using existing knowledge, team work with ongoing educational process and change management and promotion of blame-free culture maintaining confidentiality. Audit mostly relates to a particular practice and is therefore not generalisable. An audit of residents' late evening routine notes of organophosphate poisoning patients is reported here, as the change introduced appears relevant to the situation of developing countries. Organophosphate poisoning patients should be managed in intensive care unit with close monitoring, as inadvertent stoppage or slowing of atropine infusion may occur, particularly at night, leading to reappearance of poisoning manifestations, which may cause respiratory failure and death. If they are managed in wards, residents-on-duty can check the clinical and intravenous drip status in the late evening and communicate with nurses and relatives to be particularly vigilant. In the audit done, such regular ten pm notes of organophosphate poisoning about the clinical and drip status and communication by residents were increased from 15.5% in the first to 81.7% in the second data collection (p < 0.01 after the introduction of the change. The ten pm note is being continued for about two years now. Implementation of ten pm note of organophosphate poisoning patients admitted in medical wards is feasible and appears useful to improve the quality of health care delivery and learning of residents. Keywords: atrophine, audit, audit steps, organophosphate mortality, organophosphate poisoning.

  7. Causative drugs and clinical outcome in Stevens Johnson Syndrome (SJS, Toxic Epidermal Necrolysis (TEN, and SJS-TEN overlap in children

    Directory of Open Access Journals (Sweden)

    Gomathy Sethuraman

    2012-01-01

    Full Text Available Background : Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are the most severe adverse drug reactions in children. Objectives : The objective was to study the causative drugs and outcome in children with SJS, SJS-TEN overlap, and TEN. Materials and Methods : Retrospective analysis of all the in-patient records of children below 18 years of age with the diagnosis of SJS, SJS-TEN overlap, and TEN was carried out. Results and Conclusions : Twenty children were identified, eight patients each were diagnosed as SJS and TEN and four as SJS-TEN overlap. Multiple drugs were implicated in 15 cases while single drug was responsible in 5 cases. Antibiotics (40.7% were implicated as the commonest cause followed by NSAIDS (25.9% and anticonvulsants (7.4%. Seventeen patients recovered completely and three patients died.

  8. Keys to success: Ten case studies of effective weatherization programs

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.A.; Berry, L.G.; Kolb, J.O.; White, D.L. [Oak Ridge National Lab., TN (United States); Kinney, L.F.; Wilson, T. [Synertech Systems Corp., Syracuse, NY (United States)

    1993-11-01

    In 1990, DOE initiated a nationwide evaluation of its Weatherization Program, with assistance from Oak Ridge National Laboratory and an advisory group of 40 weatherization professionals, program managers, and researchers. The evaluation is comprised of three impact studies covering the Program`s major market segments: Single-family homes, mobile homes, and dwellings in small (2 to 4-unit) multifamily buildings (the Single-Family Study), Single-family homes heated primarily with fuel oil (the Fuel-Oil Study), and Dwellings in buildings with five or more units (the Multifamily Study). The Single-Family Study, the subject of this report, is a critical part of this coordinated evaluation effort. Its focus on single-family dwellings, mobile homes, and dwellings in small multifamily buildings covers 83% of the income-eligible population and 96% of the dwellings weatherized during Program Year 1989. The first phase of the Single-Family Study involved the analysis of a massive data base of information collected from 368 local weatherization agencies and 543 electric and gas utilities. This analysis resulted in energy-saving and cost-effectiveness estimates for the Weatherization Program and the identification of a set of ten high-performing agencies located throughout the country. The second phase, which is the subject of this report, involves a ``process`` evaluation of these ten high performers, aimed at identifying those weatherization practices that explain their documented success.

  9. Ten-day observation of live rabies suspected dogs.

    Science.gov (United States)

    Tepsumethanon, V; Wilde, H; Sitprija, V

    2008-01-01

    This study aimed at analyzing a ten-day observation period of rabies suspected dogs and cats according to six criteria. Dogs and cats suspected of being rabid were brought for observation when they had either bitten a person or another animal or when abnormal behaviour or unusual illness was observed. Between 1985 and 2005, retrospective and prospective data from 1,222 dogs and 303 cats was collected during the ten-day observation period. If an animal had died, brain examination using fluorescent antibody testing was routinely performed. If an animal had survived for > or =10 days, it was released to its owner or transferred to the municipal dog shelter. A total of 644 dogs and 58 cats found rabid died within 10 days of observation. In addition, for 208 dogs confirmed rabid with laboratory tests between 1997 and 2005, six criteria were analysed from the day of submission. This experience with the implemented 10-day observation period confirms the WHO recommendation on identifying suspected rabid dogs or cats under veterinary supervision following a human exposure.

  10. The next ten years in neonatology: new directions in research

    Directory of Open Access Journals (Sweden)

    Vassilios Fanos

    2014-06-01

    Full Text Available This paper is a prelude to proceedings of the 10th International Workshop on Neonatology to be held in Cagliari, Italy from October 21st to 25th, 2014. These proceedings will be a significant milestone, highlighting the new frontiers of perinatal and neonatal research. Over the five days of this meeting, we aim to (1 examine the roots of the new directions in perinatal and neonatal research; (2 predict the trajectories of advancement in medical technologies, research, clinical care and teaching that will be the future of perinatology and neonatology. The discussion will be in four sections:back to the future: the placenta and perinatal programming;paradigm shift: the revolution of metabolomics in perinatalogy and neonatology;brave new world: the microbiome and microbiomics from perinatal to adult life;new inhabitants on the planet earth: adults who were born with extremely low birth weight. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  11. Extraskeletal mesenchymal chondrosarcoma: an imaging review of ten new patients

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, N.; Joyama, S.; Araki, N. [Osaka Medical Center for Cancer and Cardiovascular Disease, Department of Orthopedic Surgery, Osaka (Japan); Ueda, T.; Yoshikawa, H. [Osaka University Graduate School of Medicine, Department of Orthopedic Surgery, Osaka (Japan); Beppu, Y. [National Cancer Center Hospital, Department of Orthopedic Surgery, Tokyo (Japan); Tatezaki, S. [Chiba Cancer Center Hospital, Department of Orthopedic Surgery, Chiba (Japan); Matsumoto, S. [Cancer Institute Hospital, Japanese Foundation for Cancer Research Hospital, Department of Orthopedic Surgery, Tokyo (Japan); Nakanishi, K. [Osaka Seamen' s Insurance Hospital, Department of Radiology, Osaka (Japan); Tomita, Y. [Osaka University Graduate School of Medicine, Department of Pathology, Osaka (Japan)

    2005-12-01

    Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare soft-tissue tumor that most arises in young adults. Because of its rarity, few imaging studies have been reported to date. The purpose of this study was to elucidate the imaging features of this tumor. We conducted a multi-institutional study in cooperation with five referral cancer centers in Japan. Imaging findings of ten new EMC cases, including conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI), performed at each institute, were reviewed along with clinical features. Ten patients with EMC, who had been treated at each hospital from 1990 to 2001, participated in this study. Soft-tissue masses with well-demarcated, dense and granular calcification were most frequently observed on plain radiographs and CT scans. T2-weighted MR images most clearly depicted a two-component structure composed of calcified and uncalcified areas, and enhanced MRI showed inhomogeneous enhancement in both areas. Although the sensitivity and specificity of these findings are unknown, they might be characteristic and have diagnostic value for this rare tumor. (orig.)

  12. Skovflåten spreder Borrelia fra mus til menneske

    DEFF Research Database (Denmark)

    Thostrup, Lykke

    2005-01-01

    Mødet med en skovflåt bliver for nogle mennesker en alvorlig sag. Flåten kan nemlig være inficeret med bakterien Borrelia, der kan resultere i sygdommen borreliose. Borrelia-bakterien stammer fra mus, og små flåtlarver får bakterien i sig, når de første gang snupper sig et blodmåltid. Bakterien kan...... overleve i flåten op til et helt år, og kan så videregives til for eksempel fasaner, rådyr, hunde eller mennesker. På KVL – Den Kgl. Veterinær- og Landbohøjskole forsøger en forsker at få et billede af samspillet mellem flåt og Borrelia-bakterie. Hendes jagt har ført hende forbi blodproteiner i slagtekvæg...... der er nogle dyr, der er hovedansvarlige for spredningen af Borrelia-bakterien. Udgivelsesdato: November...

  13. Assessment of clinical residents' needs for ten educational subjects

    Directory of Open Access Journals (Sweden)

    Mansour Razavi

    2002-04-01

    Full Text Available Background Fulfilling the learners' "real needs" will improve medical education. There are subjects that are necessary for any clinical residents not considering their field of specialty. Among the subjects ten seems to be the most important: research methodology and data analysis, computer-based programs, medical recording, cardiopulmonary and cerebral resuscitation, clinical teaching programs, communication skills, clinical ethics, laboratory examinations, reporting special diseases and death certification, and prescription. Purpose This cross-sectional study assessed educational needs of clinical residents for ten educational subjects. Methods A questionnaire prepared by board faculty members consisted of 10 close-ended questions, and one open­ ended question was distributed among 1307 residents from 22 clinical disciplines, who registered for preboard or promotion exam in June 2000. Results Among the subjects three were the most needed: computer-based programs 149 (60%, data collecting system 606 (49%, and clinical ethics 643 (46%. The prescription standard was the least required 177(13%. Conclusion Complementary training courses on these subjects can be an answer to the clinical residents needs. Keywords : research methodology, computer in medicine, cpr, clinical teaching methods, communication in medicine, medical ethics, laboratory ordering, disease coding system, death certificate, prescription writing

  14. Metateoretiese vertrekpunte ten opsigte van wetenskaplike navorsing in gemeentebediening

    Directory of Open Access Journals (Sweden)

    Gert Breed

    2013-11-01

    Full Text Available Hierdie artikel is deel van ’n reeks oor die verrekening van die metateoretiese vertrekpunte in die wetenskap van Praktiese Teologie. Die eerste fase van die reeks bied die teoretiese onderbou vir die werklikheids-, hermeneuties- en wetenskapsteoretiese beskouing van die vak. Die tweede fase fokus op die invloed wat hierdie vertrekpunte op die wetenskaplike navorsing van die verskillende vakgroepe in die Praktiese Teologie het. Hierdie artikel handel oor die wetenskaplike benaderingswyse tot die navorsingsveld van gemeentebediening. In hierdie artikel word die persoonlike metateoretiese perspektief waarmee die vakgebied van gemeentebediening benader word, uitgespel en verantwoord ten opsigte van die volgende: die werklikheidsbeskouing waarmee daar op die navorsingsveld van gemeentebou gefokus word; die onderbou van die hermeneutiese beskouing wat nodig is om tot ’n verstaan te kom en tot ’n verantwoordbare verhouding tussen die elemente wat in die gemeentebouproses ter sprake kom; en ten slotte om die wetenskapsteoretiese benadering waarmee die navorsingsveld van gemeentebou op ’n wetenskaplik-verantwoorde wyse ondersoek kan word, te beskryf.

  15. Lead toxicity in plants

    OpenAIRE

    Sharma, Pallavi; Dubey, Rama Shanker

    2005-01-01

    Contamination of soils by heavy metals is of widespread occurrence as a result of human, agricultural and industrial activities. Among heavy metals, lead is a potential pollutant that readily accumulates in soils and sediments. Although lead is not an essential element for plants, it gets easily absorbed and accumulated in different plant parts. Uptake of Pb in plants is regulated by pH, particle size and cation exchange capacity of the soils as well as by root exudation and other physico-che...

  16. Flexibility in faculty work-life policies at medical schools in the Big Ten conference.

    Science.gov (United States)

    Welch, Julie L; Wiehe, Sarah E; Palmer-Smith, Victoria; Dankoski, Mary E

    2011-05-01

    Women lag behind men in several key academic indicators, such as advancement, retention, and securing leadership positions. Although reasons for these disparities are multifactorial, policies that do not support work-life integration contribute to the problem. The objective of this descriptive study was to compare the faculty work-life policies among medical schools in the Big Ten conference. Each institution's website was accessed in order to assess its work-life policies in the following areas: maternity leave, paternity leave, adoption leave, extension of probationary period, part-time appointments, part-time benefits (specifically health insurance), child care options, and lactation policy. Institutions were sent requests to validate the online data and supply additional information if needed. Each institution received an overall score and subscale scores for family leave policies and part-time issues. Data were verified by the human resources office at 8 of the 10 schools. Work-life policies varied among Big Ten schools, with total scores between 9.25 and 13.5 (possible score: 0-21; higher scores indicate greater flexibility). Subscores were not consistently high or low within schools. Comparing the flexibility of faculty work-life policies in relation to other schools will help raise awareness of these issues and promote more progressive policies among less progressive schools. Ultimately, flexible policies will lead to greater equity and institutional cultures that are conducive to recruiting, retaining, and advancing diverse faculty.

  17. Leading through Conflict

    Science.gov (United States)

    Gerzon, Mark

    2006-01-01

    This article talks about leading significant learning opportunities through conflict of ideas in a school system. Catalyzing school change can turn emotional differences of opinion into learning opportunities. Leaders who want to deal effectively with these challenging, often tense situations need to be more than good managers. They need to be…

  18. Turning lead into gold

    DEFF Research Database (Denmark)

    Jensen, Steffen Moltrup Ernø

    For years the field of entrepreneurship has been blinded by the alchemical promise of turning lead into gold, of finding the ones most likely to become the next Branson, Zuckerberg or Gates. The promise has been created in the midst of political and scientific agendas where certain individuals...

  19. Relational Perspectives on Leading

    DEFF Research Database (Denmark)

    Relational Perspectives on Leading discusses leadership from a relational and social constructionism perspective as practiced on an everyday basis between people. The book pursues a fast growing, practice-based approach - particularly within the Anglo-Saxon parts of the world - to organization...

  20. Relational Perspectives on Leading

    DEFF Research Database (Denmark)

    Larsen, Mette Vinther; Rasmussen, Jørgen Gulddahl

    2015-01-01

    Relational Perspectives on Leading discusses leadership from a relational and social constructionism perspective as practiced on an everyday basis between people. The book pursues a fast growing, practice-based approach - particularly within the Anglo-Saxon parts of the world - to organization...

  1. The Vixen Star Book user guide how to use the star book ten and the original star book

    CERN Document Server

    Chen, James

    2016-01-01

    This book is for anyone who owns, or is thinking of owning, a Vixen Star Book Ten telescope mount or its predecessor. A revolution in amateur astronomy has occurred in the past decade with the wide availability of high tech, computer-driven, Go-To telescopes. Vixen Optics is leading the way by offering the Star Book Ten system, with its unique star map graphics software. The Star Book Ten is the latest version of computer telescope control using star map graphics as a user interface, first introduced in the original Star Book first offered in 2003. The increasingly complicated nature of this software means that learning to optimize this program is not straightforward, and yet the resulting views when all features are correctly deployed can be phenomenal. After a short history of computerized Go-To telescopes for the consumer amateur astronomer market, Chen offers a treasury of technical information. His advice, tips, and solutions aid the user in getting the most out of the Star Book Ten system in observing s...

  2. Comparison of the refractive error changes among young children in ten years interval

    Directory of Open Access Journals (Sweden)

    Hai-Yan Li

    2013-07-01

    Full Text Available AIM: To compare the optometric examination results of myopic young children between those diagnosed in the period from 1998 to 2000 and those diagnosed in the period from 2008 to 2010; and to find out the causes of myopia and factors that worsen the condition, and suggest methods of its prevention and treatment.METHODS: This study was a retrospective case study. We randomly selected sample from out-patient department register of cases and divided them into two main groups, ‘ten year before group'(TYBG(1998/2000 year casesand ‘ten years later group'(2008/2010 year cases(TYLG. Each group was further subdivided into three sub-groups by age: under-six years old children group(CG, seven-twelve years old primary-school group(PSGand thirteen-eighteen years old middle-school group(MSG. The optometric examination results were statistically analyzed.RESULTS: The difference of the mean dioptre between the TYBG and TYLG was strongly statistically significant, also forward-lead trend of age when children suffered from myopia was found(P0.01. There was a significant increase of dioptre among PSG and MSG in TYLG compared to TYBG(PCONCLUSION: Our study shows that the age of getting myopia was forward lead, the dioptre increases by 1.00 degree and the prevalence of myopia is increasing gradually. This situation may due to the modern life style and changes of living standard of the population. Therefore, prevention of myopia should concentrate more on younger children at kindergarten and primary school stage students.

  3. In vitro fermentation of ten cultivars of barley silage

    Directory of Open Access Journals (Sweden)

    Federico Infascelli

    2010-01-01

    Full Text Available The fermentation characteristics of whole-crop barley silages from ten different cultivars were evaluated by the in vitro gas production technique. The organic matter degradability of barley silage (62.9% in average was comparable to those reported in our previous trials for oat (59.7% and sorghum silages (65.5%; while the maximum gas production rate (5.38 ml/h in average was slightly lower respect to oat (6.71 ml/h and sorghum silage (6.74 ml/h. The mean nutritive value (4.00 MJ/kg DM calculated on the basis of both chemical composition and in vitro fermentation data was comparable to that (4.16 MJ/kg DM obtained in our previous research performed on corn silage, from crop sowed in the same area.

  4. Breast Cancer in Transgender Veterans: A Ten-Case Series.

    Science.gov (United States)

    Brown, George R

    2015-03-01

    All known cases of breast cancer in patients with a diagnosis consistent with transgender identification were identified in the Veterans Health Administration (1996-2013). Ten cases were confirmed: seven birth sex females and three birth sex males. Of the three birth sex males, two identified as gender dysphoric male-to-female and one identified as transgender with transvestic fetishism. The birth sex males all presented with late-stage disease that proved fatal, whereas most of the birth sex female transgender veterans presented with earlier stage disease that could be treated. These cases support the importance of screening for breast cancer using standard guidelines in birth sex males and females. Family history of breast cancer should be obtained from transgender people as part of routine care. This report expands the known cases of breast cancer in transgender persons from 5 to 12 (female-to-male) and from 10 to 13 (male-to-female).

  5. Instability Rules: The Ten Most Amazing Ideas of Modern Science

    Science.gov (United States)

    Flowers, Charles

    2002-03-01

    World-altering discoveries that reveal a universe of uncertainty and constant change Whether probing the farthest reaches of the vast universe or exploring the microscopic world of genetics and the subatomic world of quantum mechanics, Instability Rules is a remarkably informative and engaging look at ten milestone discoveries and their discoverers-a wide range of very human personalities whose insights have dramatically altered our most basic assumptions about human existence during the last century. The stories include Edwin Hubble and the expanding universe, Alfred Wegener and continental drift, Neils Bohr and quantum mechanics, Alan Turing and artificial intelligence, and James Watson and Francis Crick and DNA. Also covering discoveries of the twenty-first century that are already refining these and other ideas, Instability Rules is an exhilarating, sometimes amusing encounter with the defining scientific discoveries of our age.

  6. Eight to ten years follow-up after carotid endarterectomy

    DEFF Research Database (Denmark)

    Knudsen Rathenborg, Lisbet; Sillesen, H; Schroeder, T

    1990-01-01

    Follow-up information was obtained on 185 patients who consecutively underwent carotid endarterectomy eight to ten years previously. Doppler ultrasound examination was performed in 59 patients who were still alive and living within 100 miles of the hospital. Using lifetable analysis, the annual...... of restenosis and the development of symptoms, perhaps with the exception of internal carotid artery occlusion, which is not an accepted indication for carotid endarterectomy. Together with recent data from the literature, these observations challenge the indication for reoperative carotid surgery....... rate of focal strokes was estimated to be 2% and 1.5% on the operated and the contralateral, non-operated carotid artery, respectively. Doppler examination revealed 48% re-stenoses, including 14% occlusion and 15% greater than 50% stenosis. However, there was no association between the occurrence...

  7. Top ten list of user-hostile interface design

    Energy Technology Data Exchange (ETDEWEB)

    Miller, D.P.

    1994-10-01

    This report describes ten of the most frequent ergonomic problems found in human-computer interfaces (HCIs) associated with complex industrial machines. In contrast with being thought of as ``user friendly,`` many of these machines are seen as exhibiting ``user-hostile`` attributes by the author. The historical lack of consistent application of ergonomic principles in the HCIs has led to a breed of very sophisticated, complex manufacturing equipment that few people can operate without extensive orientation, training, or experience. This design oversight has produced the need for extensive training programs and help documentation, unnecessary machine downtime, and reduced productivity resulting from operator stress and confusion. Ergonomic considerations affect industrial machines in at least three important areas: (1) the physical package including CRT and keyboard, maintenance access areas, and dedicated hardware selection, layout, and labeling; (2) the software by which the user interacts with the computer that controls the equipment; and (3) the supporting documentation.

  8. The Last Ten Years in the Bristish Education System

    OpenAIRE

    Rodriguez Rico, Juan Antonio

    2016-01-01

    Después de la Segunda Guerra mundial, Gran Bretaña se encontró con una escasez de trabajadores cualificados sin precedente. El problema más importante era como animar a la población más joven a continuar su educación ya que cada uno de ellos era una pieza imprescindible en la reconstrucción nacional y en la imagen internacional del país. La discriminación racial y la filosofía de Charles Darwin ayudó a elaborar la idea que el británico blanco tenía la superioridad económica , moral e inte...

  9. Antioxidant capacities of ten edible North American plants.

    Science.gov (United States)

    Acuña, Ulyana Muñoz; Atha, Daniel E; Ma, Jun; Nee, Michael H; Kennelly, Edward J

    2002-02-01

    The EtOAc extract obtained from ten edible North American plants, Acorus calamus, Clintonia borealis, Gaultheria shallon, Juniperus osteosperma, Opuntia polyacantha, Prunus americana, Prunus virginiana, Sambucus cerulea, Sorbus americana and Vaccinium parvifolium, were tested in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical assay. High antioxidant activity was obtained from the extracts of three fruits, Gaultheria shallon, Sambucus cerulea and Prunus americana and one extracted rhizome, Acorus calamus. Catechin and epicatechin, potent polyphenolic antioxidants, were identified in the EtOAc extracts of Gaultheria shallon and Sambucus cerulea by reversed-phase thin-layer chromatography (TLC) and reversed-phase high-performance liquid chromatography (HPLC). Copyright 2002 John Wiley & Sons, Ltd.

  10. Managing information resources: a study of ten healthcare organizations.

    Science.gov (United States)

    Austin, C J; Hornberger, K D; Shmerling, J E

    2000-01-01

    This article presents the results of information technology management audits conducted by senior executives at ten healthcare organizations. The audits evaluated how well the following seven information technology management responsibilities were carried out: (1) strategic information systems planning; (2) employment of a user focus in system development; (3) recruiting of competent personnel; (4) information systems integration; (5) protection of information security and confidentiality; (6) employment of effective project management in system development; and (7) post-implementation evaluation of information systems. The audit results suggest that most of these responsibilities are being met to a considerable extent by a majority of the organizations studied. However, substantial variation across organizations was noted. Executives participating in the study were able to define areas in which the management of information resources in their organizations was in need of attention. The audit process encourages senior management to provide the leadership required to ensure that information technology is used to maximum advantage.

  11. Mobile and Social: Ten Best Practices for Designing Mobile Applications

    Directory of Open Access Journals (Sweden)

    Liviu LICA

    2010-01-01

    Full Text Available This paper gives ten best practices for designing mobile applications that have social-networking functions. The need for such an approach is given by the rapid growth in impor-tance of both social networks and mobile applications. In order to make it easy to follow where the best practices come from, the paper starts with a look at why social networks are more than just a buzz word and at how the field of mobile applications is evolving. It also shows how and why the two fields go together so well. To further make the point, there is a case study of four interesting mobile applications that are textbooks examples of successful applications. The best practices are based on research done for this article and on the extensive knowledge of the author.

  12. Ten Years of Support for Basic Scientific Research by CONACYT

    Directory of Open Access Journals (Sweden)

    Luis Humberto Fabila Castillo

    2014-01-01

    Full Text Available This paper reviews the results of ten years of support for basic scientific research by the CONACYT. The paper identifies the strongest areas of knowledge in basic science in Mexico and concludes that the institutions where basic science is done are mainly public higher education institutions, followed by also public research centers, while private institutions of higher education and companies carry out almost no research in basic science. Findings show that research on basic science in state universities has grown impressively in recent years, reaching the level of the institutions of higher education of the Federal District. Finally, the implications of these findings as well as the public policies through which support has been granted are discussed.

  13. Systems Analysis of Ten Supply Chains for Whole Tree Chips

    Directory of Open Access Journals (Sweden)

    Helmer Belbo

    2014-09-01

    Full Text Available Whole trees from energy thinnings constitute one of many forest fuel sources, yet ten widely applied supply chains could be defined for this feedstock alone. These ten represent only a subset of the real possibilities, as felling method was held constant and only a single market (combustion of whole tree chips was considered. Stages included in-field, roadside landing, terminal, and conversion plant, and biomass states at each of these included loose whole trees, bundled whole trees or chipped material. Assumptions on prices, performances, and conversion rates were based on field trials and published literature in similar boreal forest conditions. The economic outcome was calculated on the basis of production, handling, treatment and storage costs and losses. Outcomes were tested for robustness on a range of object volumes (50–350 m3solid, extraction distances (50–550 m and transport distances (10–70 km using simulation across a set of discrete values. Transport was calculated for both a standard 19.5 m and an extended 24 m timber truck. Results showed that the most expensive chain (roadside bundling, roadside storage, terminal storage and delivery using a 19.5 m timber truck at 158 € td−1 was 23% more costly than the cheapest chain (roadside chipping and direct transport to conversion plant with container truck, at 128 € td−1. Outcomes vary at specific object volumes and transport distances, highlighting the need to verify assumptions, although standard deviations around mean supply costs for each chain were small (6%–9%. Losses at all stages were modelled, with the largest losses (23 € td−1 occurring in the chains including bundles. The study makes all methods and assumptions explicit and can assist the procurement manager in understanding the mechanisms at work.

  14. Ten good reasons to practice ultrasound in critical care.

    Science.gov (United States)

    Lichtenstein, Daniel; van Hooland, Simon; Elbers, Paul; Malbrain, Manu L N G

    2014-01-01

    Over the past decade, critical care ultrasound has gained its place in the armamentarium of monitoring tools. A greater understanding of lung, abdominal, and vascular ultrasound plus easier access to portable machines have revolutionised the bedside assessment of our ICU patients. Because ultrasound is not only a diagnostic test, but can also be seen as a component of the physical exam, it has the potential to become the stethoscope of the 21st century. Critical care ultrasound is a combination of simple protocols, with lung ultrasound being a basic application, allowing assessment of urgent diagnoses in combination with therapeutic decisions. The LUCI (Lung Ultrasound in the Critically Ill) consists of the identification of ten signs: the bat sign (pleural line); lung sliding (seashore sign); the A-lines (horizontal artefact); the quad sign and sinusoid sign indicating pleural effusion; the fractal and tissue-like sign indicating lung consolidation; the B-lines and lung rockets indicating interstitial syndromes; abolished lung sliding with the stratosphere sign suggesting pneumothorax; and the lung point indicating pneumothorax. Two more signs, the lung pulse and the dynamic air bronchogram, are used to distinguish atelectasis from pneumonia. The BLUE protocol (Bedside Lung Ultrasound in Emergency) is a fast protocol (advantage of lung ultrasound is that the patient is not exposed to radiation, and so the LUCI-FLR project (LUCI favouring limitation of radiation) can be unfolded in trauma patients. Although it has been practiced for 25 years, critical care ultrasound is a relatively young but expanding discipline and can be seen as the stethoscope of the modern intensivist. In this review, the usefulness and advantages of ultrasound in the critical care setting are discussed in ten points. The emphasis is on a holistic approach, with a central role for lung ultrasound.

  15. Fatty Acid Composition and Antioxidant Potential of Ten Cephalaria Species

    Directory of Open Access Journals (Sweden)

    Nazli Boke Sarikahya

    2015-01-01

    Full Text Available This paper focused on the assessment of fatty acid composition and antioxidant properties of ten Cephalaria (C. aytachii, C. taurica, C. tuteliana, C. procera, C. speciosa, C. tchihatchewii, C. hirsuta, C. elazigensis var. elazigensis,C. anatolica and C. aristata species. The principal fatty acids in all species were oleic acid (10.28-31.65%, linoleic acid (17.81–37.67% and palmitic acid (10.54–23.81%. L inolenic acid was also the most abundant fatty acid component in C. tuteliana (24.42% and in C. speciosa (36.65% . Invitro antioxidant capacity of the hexane extracts of ten Cephalaria species was investigated by CUPRAC and DPPH methods. Total phenolic content of hexane extracts was also examined. The results showed that all species of Cephalaria have antioxidant properties with the highest trolox equivalent antioxidant capacity (1.005 ± 0.13 mmol trolox equivalent per gram extact in C. aristata and the highest radical scavenging activity (IC 50 value 3.768 ± 0.67 mg/mL in C. tchihatchewii . It was found that reducing power of C. aristata and radical scavenging potential of C. tchihatchewii were mainly due to highest phenolic contents of these species (2.907 ± 0.146 and 3.037 ± 0.156 mg gallic acid equivalent per gram extract, respectively. These findings suggest that the Cephalaria species might be used as a potential source of unsaturated fatty acids as well as phenolic constituents possessing antioxidant activity in food, cosmetics and pharmaceutical industries

  16. Ten major trends now emerging in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Naisbitt, J.

    1978-01-01

    Using a special analytical procedure for tracking and assessing events reported in the nation's newspapers, the Center for Policy Process has identified ten emerging trends in the United States that are having a major impact on all our lives and on all businesses and industries--and especially on the electric utility industry. Although the trends may move in contradictory directions and have different degrees of significance, all have been carefully monitored for a considerable length of time. All are firmly established--and are not to be viewed as the momentary interests of certain radical elements of the population. The ten trends are: the fast-emerging clash between nuclear fuel and coal as an environmental health issue; displacement of racism and sexism by ''ageism'' as society's most prominent anti-discrimination preoccupation, and the complete elimination soon of mandatory retirement; in government and technology, the phenomenon of ''appropriate scale'' replacing economies of scale, emergence of single-issue political organizations; coming-of-age of the recycling ethic; emergence of ''access to capital'' as the new equity issue--the new rights issue; continuing shift from centralization to decentralization; movement of society in the dual directions of high technology/high touch; business' increasing involvement with the well-established accountability trend; and shift from a representative democracy to a participatory democracy--this profound change in American democracy actually began about a decade or so ago.

  17. Managing, Leading, and Bossing

    Science.gov (United States)

    2011-08-01

    Defense AT&L: July–August 2011 76 Managing , Leading, and Bossing Stan Emelander Boss Manager Leader Emelander is a project manager in the Army’s...and management . He is level II certified in program management and level I in systems engineering. Leaders fascinate us. From the smallest shop to...me about your boss” will work. Another great question is, “What’s the difference between a leader and a manager ?” Early in my career, I thought there

  18. Lead tungstate scintillation material

    CERN Document Server

    Annenkov, A N; Lecoq, P

    2002-01-01

    In this paper we summarize the results of a research programme on lead-tungstate (PWO) crystals performed by the CMS Collaboration at CERN, as well as by other groups who promoted the progress of the PWO scintillation crystal technology. Crystal properties, mass production technology, scintillation mechanism, origin of colouring, defects in crystal and radiation induced phenomena, light yield improvement and results of beam tests are described. (96 refs).

  19. Problem of lead in petrol: The effect of triethyl lead

    Energy Technology Data Exchange (ETDEWEB)

    Roederer, G.

    1985-10-01

    Triethyl lead is a highly toxic derivate of the anti-knock agent tetraethyl lead. Contrary to anorganic lead compounds triethyl lead causes serious disorders in the central nervous system of poisoned mammals leading to dramatic mental changes. Triethyl lead destroys microtubuli in the cells of plants and animals. It is assumed that the neurotoxic effect of triethyl lead is caused by its interacting with the microtubuli of the nerves (neurotubuli) and their subsequent destruction.

  20. lead glass brick

    CERN Multimedia

    When you look through the glass at a picture behind, the picture appears raised up because light is slowed down in the dense glass. It is this density (4.06 gcm-3) that makes lead glass attractive to physicists. The refractive index of the glass is 1.708 at 400nm (violet light), meaning that light travels in the glass at about 58% its normal speed. At CERN, the OPAL detector uses some 12000 blocks of glass like this to measure particle energies.

  1. Leading change: 2--planning.

    Science.gov (United States)

    Kerridge, Joanna

    National initiatives have outlined the importance of involving frontline staff in service improvement, and the ability to influence and manage change has been identified as an essential skill for delivering new models of care. Nurses often have to take the lead in managing change in clinical practice. The second in a three-part series is designed to help nurses at all levels develop the knowledge and skills to function as change agents within their organisations. This article focuses on planning the change and dealing with resistance.

  2. The influence of transcutaneous electrical neurostimulation (TENS) on human cerebral blood flow velocities

    NARCIS (Netherlands)

    ter Laan, Mark; van Dijk, J. Marc C.; Elting, Jan-Willem J.; Fidler, Vaclav; Staal, Michiel J.

    It has been shown that transcutaneous electrical neurostimulation (TENS) reduces sympathetic tone. Spinal cord stimulation (SCS) has proven qualities to improve coronary, peripheral, and cerebral blood circulation. Therefore, we postulate that TENS and SCS affect the autonomic nervous system in

  3. Sexism and Ten Techniques to Combat It through Children's Books.

    Science.gov (United States)

    Snee, Beth

    A summary of studies on sexism in books leads to the conclusion that nonsexist books should be included in the elementary curriculum so that children can be exposed to a variety of lifestyles and career options. Various checklists and guidelines for evaluating the sex fairness of reading materials are available. Activities that can be used to…

  4. Maternal depression and filicide-case study of ten mothers.

    Science.gov (United States)

    Kauppi, Anne; Kumpulainen, Kirsti; Vanamo, Tuija; Merikanto, Juhani; Karkola, Kari

    2008-07-01

    This study describes ten cases of filicides committed by mothers who intentionally killed one or more of their children within 12 months after delivery. The data were collected from police and court records, forensic psychiatric records, autopsy reports, and other medical records. The mean age of the mothers was 28.5 years and of the victims 4 months. The symptoms of depression were clear: an irritable, severely depressed mood with crying spells, insomnia, fatigue, anxiety, preoccupation with worries about the baby's well-being and the mother's caring abilities, suicidal ideation, or even psychotic thoughts. Most mothers had had house calls from the public health nurse or psychologist. The mothers' conditions deteriorated rapidly, and the filicide was committed when the mother was left alone with the baby against her will. The babies were well taken care of, not neglected or abused. The majority of the mothers had felt that their own parents, especially their mothers, were very demanding, rejecting, and emotionally unsupportive. All the mothers had also had traumatic experiences in their childhood or in adulthood.

  5. Ten years of integrated care for the older in France

    Directory of Open Access Journals (Sweden)

    Dominique Somme

    2011-12-01

    Full Text Available Background: This paper analyzes progress made toward the integration of the French health care system for the older and chronically ill population.Policies: Over the last ten years, the French health care system has been principally influenced by two competing linkage models that failed to integrate social and health care services: local information and coordination centers, governed by the social field, and the gerontological health networks governed by the health field. In response to this fragmentation, Homes for the Integration and Autonomy for Alzheimer patients (MAIAs is currently being implemented at experimental sites in the French national Alzheimer plan, using an evidence-based model of integrated care. In addition, the state's reforms recently created regional health agencies (ARSs by merging seven strategic institutions to manage the overall delivery of care.Conclusion: The French health care system is moving from a linkage-based model to a more integrated care system. We draw some early lessons from these changes, including the importance of national leadership and governance and a change management strategy that uses both top-down and bottom-up approaches to implement these reforms.

  6. Angioleiomyoma: magnetic resonance imaging features in ten cases

    Energy Technology Data Exchange (ETDEWEB)

    Gupte, Cynthia; Butt, Sajid H.; Saifuddin, Asif [Royal National Orthopaedic Hospital, Department of Radiology, Middlesex (United Kingdom); Tirabosco, Roberto [Royal National Orthopaedic Hospital, Department of Histopathology, Middlesex (United Kingdom)

    2008-11-15

    Angioleiomyoma is a rare, benign smooth muscle tumour arising from the tunica media of small veins and arteries and can occur anywhere in the body. The histological appearances are well documented, but there are relatively few descriptions of the magnetic resonance imaging (MRI) findings. A retrospective study of the clinical presentation, MRI appearances and histological findings of ten angioleiomyomas presenting as extremity soft tissue masses. MRI typically demonstrated a well-defined, oval mass located superficial to the fascia with the commonest sites being the hand (three cases) and ankle/foot (five cases). The lesion was isointense to muscle on T1-weighted spin echo images with heterogeneous increased internal T2W/short tau inversion recovery (STIR) signal intensity, which commonly appeared as multiple linear or branching areas of hyperintensity. Enhancement after IV gadolinium ranged from diffuse to heterogeneous. In a single case, central fat signal intensity was seen, while a further case showed marked T2W/STIR hypointensity due to diffuse hyalinisation within the lesion. This is the largest reported MRI series of extremity musculoskeletal angioleiomyoma. Angioleiomyoma should be considered in the differential diagnosis of a superficial mass in the hand or foot, particularly when characteristic linear or branching hyperintensity is seen on T2W or STIR images. (orig.)

  7. Distinct fatty acid profile of ten brown macroalgae

    Directory of Open Access Journals (Sweden)

    Graça Silva

    2013-08-01

    Full Text Available It is widely accepted that the consumption of ω-3 polyunsaturated fatty acids has beneficial effects on human health. In this work, ten brown macroalgae species collected along the Portuguese west coast were studied for their fatty acids composition by GC-MS after alkaline hydrolysis and derivatization. The results of this survey showed that different macroalgae from the same region display distinct fatty acids profile. Concerning ω-3 polyunsaturated fatty acids, eicosapentaenoic acid was found in all but one species. Additionally, some species contained docosahexaenoic acid. Linoleic acid, an essential fatty acid of the ω-6 series, was present in all studied macroalgae. Fucus spiralis L. exhibited the highest amounts of monounsaturated fatty acids and of polyunsaturated fatty acids of the ω-3 and ω-6 series. The ω-6/ω-3 ratio in half of the studied species was lower than 1. This information reinforces the potential application of some brown macroalgae as dietary sources of polyunsaturated fatty acids.

  8. A critical comparison of ten disposable cup LCAs

    Energy Technology Data Exchange (ETDEWEB)

    Harst, Eugenie van der, E-mail: eugenie.vanderharst@wur.nl [Environmental Systems Analysis Group, Wageningen University, P.O. Box 47, NL-6700 AA Wageningen (Netherlands); Potting, José, E-mail: jose.potting@wur.nl [Environmental Systems Analysis Group, Wageningen University, P.O. Box 47, NL-6700 AA Wageningen (Netherlands); Environmental Strategies Research (fms), KTH Royal Institute of Technology, SE-110 44 Stockholm (Sweden)

    2013-11-15

    Disposable cups can be made from conventional petro-plastics, bioplastics, or paperboard (coated with petro-plastics or bioplastics). This study compared ten life cycle assessment (LCA) studies of disposable cups with the aim to evaluate the robustness of their results. The selected studies have only one impact category in common, namely climate change with global warming potential (GWP) as its category indicator. Quantitative GWP results of the studies were closer examined. GWPs within and across each study show none of the cup materials to be consistently better than the others. Comparison of the absolute GWPs (after correction for the cup volume) also shows no consistent better or worse cup material. An evaluation of the methodological choices and the data sets used in the studies revealed their influence on the GWP. The differences in GWP can be attributed to a multitude of factors, i.e., cup material and weight, production processes, waste processes, allocation options, and data used. These factors basically represent different types of uncertainty. Sensitivity and scenario analyses provided only the influence of one factor at once. A systematic and simultaneous use of sensitivity and scenario analyses could, in a next research, result in more robust outcomes. -- Highlights: • Conflicting results from life cycle assessment (LCA) on disposable cups • GWP results of LCAs did not point to a best or worst cup material. • Differences in GWP results are due to methodological choices and data sets used. • Standardized LCA: transparency of LCA studies, but still different in approaches.

  9. Ten new and emerging trends in residential group living environments.

    Science.gov (United States)

    Regnier, Victor; Denton, Alexis

    2009-01-01

    Residential styled environments for physically challenged people with neuro disabilities are rapidly replacing the standard institutional skilled nursing home. Ten trends are described that utilize residential design approaches to the physical environment while relying on home-care style methods for service delivery. Combined these two forces create powerful differentiators which make group residential settings more friendly and humane. Northern European, as well as, US best practices and prototypes are described that combine housing with services in a range of contexts. The success of northern Europeans in promulgating models of aging-in-place that keep those at risk more independent in the community or within family settings are remarkable. Topics like the impact of small group living clusters, interior design treatments, access to landscape gardens, life skill management methods, movement systems for circulation and exercise, shared space priorities, unit design trends and innovative care giving techniques are introduced. The focus of the article is on specific practices gleaned from cultures and exemplars that appear to increase autonomy, independence and privacy for those who are threatened because of their disabilities with the loss of these lifestyle attributes. Promising concepts of service organization and community outreach are combined with detailed recommendations that address the need for lift technology and safety features in bathrooms and kitchens.

  10. Ten new species of Telipogon (Orchidaceae, Oncidiinae from southern Peru

    Directory of Open Access Journals (Sweden)

    Galán de Mera, Antonio

    2008-06-01

    Full Text Available Ten new species of Telipogon, T. antisuyuensis, T. austroperuvianus, T. casadevalliae, T. farfanii, T. javiercastroviejoi, T. kosnipatensis, T. marleneae, T. mesotropicalis, T. santiagocastroviejoi, and T. tupayachii are described and illustrated. These are terrestrial or epiphytes of the montane humid forests from Andean valleys of southern Peru. Diagnostic morphological characters are discussed for each species. A key is provided for the species of the genus found in southern Peru. The number of Telipogon species currently recognized for the Peruvian flora is 46.Se describen e ilustran diez especies nuevas de Telipogon –T. antisuyuensis, T. austroperuvianus, T. casadevalliae, T. farfanii, T. javiercastroviejoi, T. kosnipatensis, T. marleneae, T. mesotropicalis, T. santiagocastroviejoi y T. tupayachii. Éstas son plantas terrestres o epífitas de los bosques húmedos montanos de los valles andinos del sur de Perú. Se discuten sus caracteres morfológicos diagnósticos y se propone una clave dicotómica para diferenciar las especies que crecen en el sur del país. El número de especies de Telipogon actualmente reconocidas para la flora peruana es de 46.

  11. Ten-year retrospective: OPEC and the world oil market

    Energy Technology Data Exchange (ETDEWEB)

    Gately, D.

    1984-09-01

    This paper reviews the main events in the world oil market since 1973 and some major explanations as to what happened and why (Section I). Then there is a discussion of some projections for the next two decades and of some implications of various theories about OPEC's decisionmaking process (Section II). Section III summarizes what we have learned about modeling OPEC and the world oil market. This includes: the dominant theoretical approach based on the wealth-maximization model of Harold Hotelling (1931); the simulation approach most common in the applied literature, which envisages target-capacity-utilization pricing by OPEC; and the difficult problem of modeling price behavior during disruptions. Finally, Section IV discusses some important unresolved issues, both theoretical and empirical. A variety of contributions to the literature are considered, but the discussion pays special attention to two important recent works. One is the book OPEC Behavior and World Oil Prices (1982) (EAPA 9:3899) edited by James Griffin and David Teece, an important collection of papers on OPEC and world oil, prepared for a 1981 conference at the University of Houston. The other is the 1980 to 1981 world oil study by the Energy Modeling Forum of Stanford Univesity, which involved ten prominent models of the world oil market. 31 references.

  12. Foothills Model Forest: a ten-year review

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, R.

    2002-04-01

    The first ten years of the Foothills Model Forest, established in 1992, is reviewed. The model forest has been established to develop sustainable forest management within the broader concept of sustainable development and integrated resource management. The project focuses on issues such as wildlife habits and habitats; biodiversity monitoring; natural disturbance trends and patterns; and socio-economic studies. In Phase One of the Canadian Model Forest Network the Foothills Model Forest focused primarily on conducting world class research to advance the concept of sustainable forest management. Phase Two was devoted to communicating the results of that research, with a strong emphasis on generating baseline awareness of the concept of sustainable forest management and creating public awareness of the project's mandate in Alberta. Work during the next five years is expected to focus on demonstration and implementation of research results to forest managers and practitioners and others with a stake in the continued sustainability of Alberta's forests. The Sustainable Forest Management project shares a common objective with the Alberta Chamber of Resources' Integrated Landscape Management project; both projects recognise that reducing the industrial footprint is key to sustainable development. The emphasis on demonstration and implementation in the third phase of the Foothills Model Forest is expected to ensure continued sustainability of forests, ecosystems, communities and resources, with full recognition of the fact that the goal of sustainable development can be achieved only by full cooperation and integrated action of all stakeholders.

  13. Ten years of integrated care for the older in France

    Directory of Open Access Journals (Sweden)

    Dominique Somme

    2011-12-01

    Full Text Available Background: This paper analyzes progress made toward the integration of the French health care system for the older and chronically ill population. Policies: Over the last ten years, the French health care system has been principally influenced by two competing linkage models that failed to integrate social and health care services: local information and coordination centers, governed by the social field, and the gerontological health networks governed by the health field. In response to this fragmentation, Homes for the Integration and Autonomy for Alzheimer patients (MAIAs is currently being implemented at experimental sites in the French national Alzheimer plan, using an evidence-based model of integrated care. In addition, the state's reforms recently created regional health agencies (ARSs by merging seven strategic institutions to manage the overall delivery of care. Conclusion: The French health care system is moving from a linkage-based model to a more integrated care system. We draw some early lessons from these changes, including the importance of national leadership and governance and a change management strategy that uses both top-down and bottom-up approaches to implement these reforms.

  14. 42 CFR 414.232 - Special payment rules for transcutaneous electrical nerve stimulators (TENS).

    Science.gov (United States)

    2010-10-01

    ... nerve stimulators (TENS). 414.232 Section 414.232 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Special payment rules for transcutaneous electrical nerve stimulators (TENS). (a) General payment rule. Except as provided in paragraph (b) of this section, payment for TENS is made on a purchase basis with...

  15. Blockade of NMDA receptors prevents analgesic tolerance to repeated transcutaneous electrical nerve stimulation (TENS) in rats

    Science.gov (United States)

    Hingne, Priyanka M.; Sluka, Kathleen A.

    2008-01-01

    Repeated daily application transcutaneous electrical nerve stimulation (TENS) results in tolerance, at spinal opioid receptors, to the anti-hyperalgesia produced by TENS. Since N-Methyl-D-Aspartate (NMDA) receptor antagonists prevent analgesic tolerance to opioid agonists we hypothesized that blockade of NMDA receptors will prevent tolerance to TENS. In rats with knee joint inflammation, TENS was applied for 20 minute daily at high frequency (100 Hz), low frequency (4 Hz), or sham TENS. Rats were treated with the NMDA antagonist MK-801 (0.01 mg/kg-0.1 mg/kg) or vehicle daily before TENS. Paw withdrawal thresholds were tested before and after inflammation, and before and after TENS treatment for 4 days. On day 1 TENS reversed the decreased mechanical withdrawal threshold induced by joint inflammation. On day 4 TENS had no effect on the decreased withdrawal threshold in the group treated with vehicle demonstrating development of tolerance. However, in the group treated with 0.1 mg/kg MK-801, TENS significantly reversed the mechanical withdrawal thresholds on day 4 demonstrating that tolerance did not develop. Vehicle treated animals developed cross-tolerance at spinal opioid receptors. Treatment with MK-801 reversed this cross-tolerance at spinal opioid receptors. In summary, blockade of NMDA receptors prevents analgesic tolerance to daily TENS by preventing tolerance at spinal opioid receptors. Perspective Tolerance observed to the clinical treatment of TENS could be prevented by administration of pharmaceutical agents with NMDA receptors activity such as ketamine or dextromethorphan. PMID:18061543

  16. Testing for lead in toys at day care centers.

    Science.gov (United States)

    Sanders, Martha; Stolz, Julie; Chacon-Baker, Ashley

    2013-01-01

    Exposure to lead-based paint or material has been found to impact children's cognitive and behavioral development at blood lead levels far below current standards. The purpose of the project was to screen for lead in toy items in daycare centers in order to raise awareness of inside environmental lead exposures and minimize lead-based exposures for children. Occupational therapy students in a service learning class tested for lead in ten daycare or public centers using the XRF Thermo Scientific Niton XL3t, a method accepted by the Consumer Product Safety Commission (CPSC). A total of 460 items were tested over a two-month period for an average of 66 toys per setting. Fifty six (56) items tested > 100 ppm, which represented 12% of the entire sample. Items with high lead levels included selected toys constructed with lead-based paint, lead metals, plastics using lead as a color enhancer, and decorative objects. While the actual number of lead-based products is small, the cumulative exposure or habitual use may pose an unnecessary risk to children. Indoor exposures occurred for all day care centers regardless of socio-economic levels. Recommendations to minimize exposures are provided.

  17. Lead and lead-based alloys as waste matrix materials

    Energy Technology Data Exchange (ETDEWEB)

    Arustamov, A.E.; Ojovan, M.I.; Kachalov, M.B.

    1999-07-01

    Metals and alloys with relatively low melting temperatures such as lead and lead-based alloys are considered in Russia as prospective matrices for encapsulation of spent nuclear fuel in containers in preparation for final disposal in underground repositories. Now lead and lead-based alloys are being used for conditioning spent sealed radioactive sources at radioactive waste disposal facilities.

  18. Differences in climbing-specific strength between boulder and lead rock climbers.

    Science.gov (United States)

    Fanchini, Maurizio; Violette, Frédéric; Impellizzeri, Franco M; Maffiuletti, Nicola A

    2013-02-01

    The purpose of this study was to compare maximal muscle strength and rapid force capacity of finger flexors between boulder and lead climbers of national-international level. Ten boulder (mean ± SD, age 27 ± 8 years) and 10 lead climbers (age 27 ± 6 years) volunteered for the study. Ten nonclimbers (age 25 ± 4 years) were also tested. Isometric maximal voluntary contraction (MVC) force and rate of force development (RFD) produced in "crimp" and "open-crimp" hand positions were evaluated on an instrumented hold. Climbers were stronger than nonclimbers. More interestingly, MVC force and RFD were significantly greater in boulder compared with lead climbers (p rock climbers.

  19. The Turkish Adaptation of the Ten-Item Personality Inventory.

    Science.gov (United States)

    Atak, Hasan

    2013-12-01

    Personality is one of the important domains of psychology, and it is an integration of emotional, cognitive, social and physical properties. In this study, we aimed to assess the applicability of the "Ten-Item Personality Inventory (TIPI)" which measures five basic personality traits in Turkish young people. Data from a total of 420 participants - 208 male (49.1%) and 212 female (50.9%) - were employed for the validity and reliability analyses. Of the participants, 230 (54,8%; mean age: 23.2 years; sd=1.6) were university students and the rest were not (n=190; 45.2%; mean age: 23.4 years; df=1.7). The mean age of the participants was 22.1 years (df=1.3), ranging from 18 to 25 years. Language validity (correlations between 0.92 and 0.97), exploratory factor analysis yielded 10 items and five-factor model explaining 65.21% of the variance. Confirmatory factor analyses (χ2/df: 2.20, GFI=0.95, AGFI=0.92, CFI=0.93, NNFI=0.91, RMR=0.04, and RMSEA=0.03), item analysis, and convergent validity results indicated that a five-factor solution with 10 items met the criteria standards for adequacy of fit among Turkish young people. The internal consistency (Openness to Experiences 0.83, Agreeableness 0.81, Emotional Stability 0.83, Conscientiousness 0.84, and Extraversion 0.86) and test-retest stability (=54; Openness to Experiences 0.89, Agreeableness 0.87, Emotional Stability 0.89, Conscientiousness 0.87, and Extraversion 0.88) revealed a moderate to acceptable reliabilities. The results demonstrated that the TIPI could be used in studies that evaluate personality in Turkish young people.

  20. In vitro activity of ten essential oils against Sarcoptes scabiei

    Directory of Open Access Journals (Sweden)

    Fang Fang

    2016-11-01

    Full Text Available Abstract Background The development of alternative approaches in ectoparasite management is currently required. Essential oils have been demonstrated to exhibit fumigant and topical toxicity to a number of arthropods. The aim of the present study was to assess the potential efficacy of ten essential oils against Sarcoptes scabiei. Methods The major chemical components of the oils were identified by GC-MS analysis. Contact and fumigation bioassays were performed on Sarcoptes mites collected from experimentally infected pigs. For contact bioassays, essential oils were diluted with paraffin to get concentrations at 10, 5, and even 1% for the most efficient ones. The mites were inspected under a stereomicroscope 10, 20, 30, 40, 50, 60, 90, 120, 150, and 180min after contact. For fumigation bioassay, a filter paper was treated with 100 μL of the pure essential oil. The mites were inspected under a stereomicroscope for the first 5min, and then every 5min until 1h. Results Using contact bioassays, 1% clove and palmarosa oil killed all the mites within 20 and 50min, respectively. The oils efficacy order was: clove > palmarosa > geranium > tea tree > lavender > manuka > bitter orange > eucalyptus > Japanese cedar. In fumigation bioassays, the efficacy order was: tea tree > clove > eucalyptus > lavender > palmarosa > geranium > Japanese cedar > bitter orange > manuka. In both bioassays, cade oil showed no activity. Conclusion Essential oils, especially tea tree, clove, palmarosa, and eucalyptus oils, are potential complementary or alternative products to treat S. scabiei infections in humans or animals, as well as to control the mites in the environment.