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  1. Improved NYVAC-based vaccine vectors.

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    Karen V Kibler

    Full Text Available While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144 have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.

  2. An Adenoviral Vector Based Vaccine for Rhodococcus equi.

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    Carla Giles

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

  3. Construction and Application of Newcastle Disease Virus-Based Vector Vaccines.

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    Wichgers Schreur, Paul J

    2016-01-01

    Paramyxoviruses are able to stably express a wide-variety of heterologous antigens at relatively high levels in various species and are consequently considered as potent gene delivery vehicles. A single vaccination is frequently sufficient for the induction of robust humoral and cellular immune responses. Here we provide detailed methods for the construction and application of Newcastle disease virus (NDV)-based vector vaccines. The in silico design and in vitro rescue as well as the in vivo evaluation of NDV based vectors are described in this chapter.

  4. Flagellin Encoded in Gene-Based Vector Vaccines Is a Route-Dependent Immune Adjuvant.

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    Rady, Hamada F; Dai, Guixiang; Huang, Weitao; Shellito, Judd E; Ramsay, Alistair J

    2016-01-01

    Flagellin has been tested as a protein-based vaccine adjuvant, with the majority of studies focused on antibody responses. Here, we evaluated the adjuvant activity of flagellin for both cellular and humoral immune responses in BALB/c mice in the setting of gene-based immunization, and have made several novel observations. DNA vaccines and adenovirus (Ad) vectors were engineered to encode mycobacterial protein Ag85B, with or without flagellin of Salmonella typhimurium (FliC). DNA-encoded flagellin given IM enhanced splenic CD4+ and CD8+ T cell responses to co-expressed vaccine antigen, including memory responses. Boosting either IM or intranasally with Ad vectors expressing Ag85B without flagellin led to durable enhancement of Ag85B-specific antibody and CD4+ and CD8+ T cell responses in both spleen and pulmonary tissues, correlating with significantly improved protection against challenge with pathogenic aerosolized M. tuberculosis. However, inclusion of flagellin in both DNA prime and Ad booster vaccines induced localized pulmonary inflammation and transient weight loss, with route-dependent effects on vaccine-induced T cell immunity. The latter included marked reductions in levels of mucosal CD4+ and CD8+ T cell responses following IM DNA/IN Ad mucosal prime-boosting, although antibody responses were not diminished. These findings indicate that flagellin has differential and route-dependent adjuvant activity when included as a component of systemic or mucosally-delivered gene-based prime-boost immunization. Clear adjuvant activity for both T and B cell responses was observed when flagellin was included in the DNA priming vaccine, but side effects occurred when given in an Ad boosting vector, particularly via the pulmonary route. PMID:26844553

  5. Flagellin Encoded in Gene-Based Vector Vaccines Is a Route-Dependent Immune Adjuvant.

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    Hamada F Rady

    Full Text Available Flagellin has been tested as a protein-based vaccine adjuvant, with the majority of studies focused on antibody responses. Here, we evaluated the adjuvant activity of flagellin for both cellular and humoral immune responses in BALB/c mice in the setting of gene-based immunization, and have made several novel observations. DNA vaccines and adenovirus (Ad vectors were engineered to encode mycobacterial protein Ag85B, with or without flagellin of Salmonella typhimurium (FliC. DNA-encoded flagellin given IM enhanced splenic CD4+ and CD8+ T cell responses to co-expressed vaccine antigen, including memory responses. Boosting either IM or intranasally with Ad vectors expressing Ag85B without flagellin led to durable enhancement of Ag85B-specific antibody and CD4+ and CD8+ T cell responses in both spleen and pulmonary tissues, correlating with significantly improved protection against challenge with pathogenic aerosolized M. tuberculosis. However, inclusion of flagellin in both DNA prime and Ad booster vaccines induced localized pulmonary inflammation and transient weight loss, with route-dependent effects on vaccine-induced T cell immunity. The latter included marked reductions in levels of mucosal CD4+ and CD8+ T cell responses following IM DNA/IN Ad mucosal prime-boosting, although antibody responses were not diminished. These findings indicate that flagellin has differential and route-dependent adjuvant activity when included as a component of systemic or mucosally-delivered gene-based prime-boost immunization. Clear adjuvant activity for both T and B cell responses was observed when flagellin was included in the DNA priming vaccine, but side effects occurred when given in an Ad boosting vector, particularly via the pulmonary route.

  6. Flagellin Encoded in Gene-Based Vector Vaccines Is a Route-Dependent Immune Adjuvant.

    Science.gov (United States)

    Rady, Hamada F; Dai, Guixiang; Huang, Weitao; Shellito, Judd E; Ramsay, Alistair J

    2016-01-01

    Flagellin has been tested as a protein-based vaccine adjuvant, with the majority of studies focused on antibody responses. Here, we evaluated the adjuvant activity of flagellin for both cellular and humoral immune responses in BALB/c mice in the setting of gene-based immunization, and have made several novel observations. DNA vaccines and adenovirus (Ad) vectors were engineered to encode mycobacterial protein Ag85B, with or without flagellin of Salmonella typhimurium (FliC). DNA-encoded flagellin given IM enhanced splenic CD4+ and CD8+ T cell responses to co-expressed vaccine antigen, including memory responses. Boosting either IM or intranasally with Ad vectors expressing Ag85B without flagellin led to durable enhancement of Ag85B-specific antibody and CD4+ and CD8+ T cell responses in both spleen and pulmonary tissues, correlating with significantly improved protection against challenge with pathogenic aerosolized M. tuberculosis. However, inclusion of flagellin in both DNA prime and Ad booster vaccines induced localized pulmonary inflammation and transient weight loss, with route-dependent effects on vaccine-induced T cell immunity. The latter included marked reductions in levels of mucosal CD4+ and CD8+ T cell responses following IM DNA/IN Ad mucosal prime-boosting, although antibody responses were not diminished. These findings indicate that flagellin has differential and route-dependent adjuvant activity when included as a component of systemic or mucosally-delivered gene-based prime-boost immunization. Clear adjuvant activity for both T and B cell responses was observed when flagellin was included in the DNA priming vaccine, but side effects occurred when given in an Ad boosting vector, particularly via the pulmonary route.

  7. Expanding the repertoire of Modified Vaccinia Ankara-based vaccine vectors via genetic complementation strategies.

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    David A Garber

    Full Text Available BACKGROUND: Modified Vaccinia virus Ankara (MVA is a safe, highly attenuated orthopoxvirus that is being developed as a recombinant vaccine vector for immunization against a number of infectious diseases and cancers. However, the expression by MVA vectors of large numbers of poxvirus antigens, which display immunodominance over vectored antigens-of-interest for the priming of T cell responses, and the induction of vector-neutralizing antibodies, which curtail the efficacy of subsequent booster immunizations, remain as significant impediments to the overall utility of such vaccines. Thus, genetic approaches that enable the derivation of MVA vectors that are antigenically less complex may allow for rational improvement of MVA-based vaccines. PRINCIPAL FINDINGS: We have developed a genetic complementation system that enables the deletion of essential viral genes from the MVA genome, thereby allowing us to generate MVA vaccine vectors that are antigenically less complex. Using this system, we deleted the essential uracil-DNA-glycosylase (udg gene from MVA and propagated this otherwise replication-defective variant on a complementing cell line that constitutively expresses the poxvirus udg gene and that was derived from a newly identified continuous cell line that is permissive for growth of wild type MVA. The resulting virus, MVADeltaudg, does not replicate its DNA genome or express late viral gene products during infection of non-complementing cells in culture. As proof-of-concept for immunological 'focusing', we demonstrate that immunization of mice with MVADeltaudg elicits CD8+ T cell responses that are directed against a restricted repertoire of vector antigens, as compared to immunization with parental MVA. Immunization of rhesus macaques with MVADeltaudg-gag, a udg(- recombinant virus that expresses an HIV subtype-B consensus gag transgene, elicited significantly higher frequencies of Gag-specific CD8 and CD4 T cells following both primary (2

  8. A nonintegrative lentiviral vector-based vaccine provides long-term sterile protection against malaria.

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    Frédéric Coutant

    Full Text Available Trials testing the RTS,S candidate malaria vaccine and radiation-attenuated sporozoites (RAS have shown that protective immunity against malaria can be induced and that an effective vaccine is not out of reach. However, longer-term protection and higher protection rates are required to eradicate malaria from the endemic regions. It implies that there is still a need to explore new vaccine strategies. Lentiviral vectors are very potent at inducing strong immunological memory. However their integrative status challenges their safety profile. Eliminating the integration step obviates the risk of insertional oncogenesis. Providing they confer sterile immunity, nonintegrative lentiviral vectors (NILV hold promise as mass pediatric vaccine by meeting high safety standards. In this study, we have assessed the protective efficacy of NILV against malaria in a robust pre-clinical model. Mice were immunized with NILV encoding Plasmodium yoelii Circumsporozoite Protein (Py CSP and challenged with sporozoites one month later. In two independent protective efficacy studies, 50% (37.5-62.5 of the animals were fully protected (p = 0.0072 and p = 0.0008 respectively when compared to naive mice. The remaining mice with detectable parasitized red blood cells exhibited a prolonged patency and reduced parasitemia. Moreover, protection was long-lasting with 42.8% sterile protection six months after the last immunization (p = 0.0042. Post-challenge CD8+ T cells to CSP, in contrast to anti-CSP antibodies, were associated with protection (r = -0.6615 and p = 0.0004 between the frequency of IFN-g secreting specific T cells in spleen and parasitemia. However, while NILV and RAS immunizations elicited comparable immunity to CSP, only RAS conferred 100% of sterile protection. Given that a better protection can be anticipated from a multi-antigen vaccine and an optimized vector design, NILV appear as a promising malaria vaccine.

  9. Vaccine Design: Replication-Defective Adenovirus Vectors.

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    Zhou, Xiangyang; Xiang, Zhiquan; Ertl, Hildegund C J

    2016-01-01

    Replication-defective adenovirus (Ad) vectors were initially developed for gene transfer for correction of genetic diseases. Although Ad vectors achieved high levels of transgene product expression in a variety of target cells, expression of therapeutic proteins was found to be transient as vigorous T cell responses directed to components of the vector as well as the transgene product rapidly eliminate Ad vector-transduced cells. This opened the use of Ad vectors as vaccine carriers and by now a multitude of preclinical as well as clinical studies has shown that Ad vectors induce very potent and sustained transgene product-specific T and B cell responses. This chapter provides guidance on developing E1-deleted Ad vectors based on available viral molecular clones. Specifically, it describes methods for cloning, viral rescue and purification as well as quality control studies. PMID:27076309

  10. A Novel Immunogenic Spore Coat-Associated Protein in Bacillus Anthracis: Characterization via Proteomics Approaches and a Vector-Based Vaccine System

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    Liu, Yu-Tsueng; Lin, Shwu-Bin; Huang, Cheng-Po; Huang, Chun-Ming

    2007-01-01

    New generation anthrax vaccines have been actively explored with the aim of enhancing efficacies and decreasing undesirable side effects that could be caused by licensed vaccines. Targeting novel antigens and/or eliminating the requirements for multiple needle injections and adjuvants are major objectives in the development of new anthrax vaccines. Using proteomics approaches, we identified a spore coat-associated protein (SCAP) in Bacillus anthracis. An E. coli vector-based vaccine system wa...

  11. Architectural insight into inovirus-associated vectors (IAVs) and development of IAV-based vaccines inducing humoral and cellular responses: implications in HIV-1 vaccines.

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    Hassapis, Kyriakos A; Stylianou, Dora C; Kostrikis, Leondios G

    2014-12-01

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

  12. Prime-boost bacillus Calmette-Guérin vaccination with lentivirus-vectored and DNA-based vaccines expressing antigens Ag85B and Rv3425 improves protective efficacy against Mycobacterium tuberculosis in mice.

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    Xu, Ying; Yang, Enzhuo; Wang, Jianguang; Li, Rui; Li, Guanghua; Liu, Guoyuan; Song, Na; Huang, Qi; Kong, Cong; Wang, Honghai

    2014-10-01

    To prevent the global spread of tuberculosis (TB), more effective vaccines and vaccination strategies are urgently needed. As a result of the success of bacillus Calmette-Guérin (BCG) in protecting children against miliary and meningeal TB, the majority of individuals will have been vaccinated with BCG; hence, boosting BCG-primed immunity will probably be a key component of future vaccine strategies. In this study, we compared the ability of DNA-, protein- and lentiviral vector-based vaccines that express the antigens Ag85B and Rv3425 to boost the effects of BCG in the context of immunity and protection against Mycobacterium tuberculosis in C57BL/6 mice. Our results demonstrated that prime-boost BCG vaccination with a lentiviral vector expressing the antigens Ag85B and Rv3425 significantly enhanced immune responses, including T helper type 1 and CD8(+) cytotoxic T lymphocyte responses, compared with DNA- and protein-based vaccines. However, lentivirus-vectored and DNA-based vaccines greatly improved the protective efficacy of BCG against M. tuberculosis, as indicated by a lack of weight loss and significantly reduced bacterial loads and histological damage in the lung. Our study suggests that the use of lentiviral or DNA vaccines containing the antigens Ag85B and Rv3425 to boost BCG is a good choice for the rational design of an efficient vaccination strategy against TB.

  13. Vector Design for Improved DNA Vaccine Efficacy, Safety and Production

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    James A. Williams

    2013-06-01

    Full Text Available DNA vaccination is a disruptive technology that offers the promise of a new rapidly deployed vaccination platform to treat human and animal disease with gene-based materials. Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through more effective gene delivery. This review summarizes complementary vector design innovations that, when combined with leading delivery platforms, further enhance DNA vaccine performance. These next generation vectors also address potential safety issues such as antibiotic selection, and increase plasmid manufacturing quality and yield in exemplary fermentation production processes. Application of optimized constructs in combination with improved delivery platforms tangibly improves the prospect of successful application of DNA vaccination as prophylactic vaccines for diverse human infectious disease targets or as therapeutic vaccines for cancer and allergy.

  14. Alphavirus-Based Vaccines

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    Kenneth Lundstrom

    2014-06-01

    Full Text Available Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans.

  15. Geminiviral vectors based on bean yellow dwarf virus for production of vaccine antigens and monoclonal antibodies in plants

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    Chen, Qiang; He, Junyun; Phoolcharoen, Waranyoo; Mason, Hugh S.

    2011-01-01

    Expression of recombinant vaccine antigens and monoclonal antibodies using plant viral vectors has developed extensively during the past several years. The approach benefits from high yields of recombinant protein obtained within days after transient delivery of viral vectors to leaves of Nicotiana benthamiana, a tobacco relative. Modified viral genomes of both RNA and DNA viruses have been created. Geminiviruses such as bean yellow dwarf virus (BeYDV) have a small, single stranded DNA genome...

  16. Improving DNA vaccine performance through vector design.

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    Williams, James A

    2014-01-01

    DNA vaccines are a rapidly deployed next generation vaccination platform for treatment of human and animal disease. DNA delivery devices, such as electroporation and needle free jet injectors, are used to increase gene transfer. This results in higher antigen expression which correlates with improved humoral and cellular immunity in humans and animals. This review highlights recent vector and transgene design innovations that improve DNA vaccine performance. These new vectors improve antigen expression, increase plasmid manufacturing yield and quality in bioreactors, and eliminate antibiotic selection and other potential safety issues. A flowchart for designing synthetic antigen transgenes, combining antigen targeting, codon-optimization and bioinformatics, is presented. Application of improved vectors, of antibiotic free plasmid production, and cost effective manufacturing technologies will be critical to ensure safety, efficacy, and economically viable manufacturing of DNA vaccines currently under development for infectious disease, cancer, autoimmunity, immunotolerance and allergy indications.

  17. Virus-Like Vesicle-Based Therapeutic Vaccine Vectors for Chronic Hepatitis B Virus Infection

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    Tracy D Reynolds; Buonocore, Linda; Rose, Nina F.; Rose, John K.; Robek, Michael D.

    2015-01-01

    More than 500,000 people die each year from the liver diseases that result from chronic hepatitis B virus (HBV) infection. Therapeutic vaccines, which aim to elicit an immune response capable of controlling the virus, offer a potential new treatment strategy for chronic hepatitis B. Recently, an evolved, high-titer vaccine platform consisting of Semliki Forest virus RNA replicons that express the vesicular stomatitis virus glycoprotein (VSV G) has been described. This platform generates virus...

  18. Chimeric avian paramyxovirus-based vector immunization against highly pathogenic avian influenza followed by conventional Newcastle disease vaccination eliminates lack of protection from virulent ND virus

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    C. Steglich

    2014-01-01

    Full Text Available Recently, we described a chimeric, hemagglutinin of highly pathogenic avian influenza virus (HPAIV H5 expressing Newcastle disease virus (NDV-based vector vaccine (chNDVFHNPMV8H5 in which NDV envelope glycoproteins were replaced by those of avian paramyxovirus-8 (APMV-8. This chimeric vaccine induced solid protection against lethal HPAIV H5N1 even in chickens with maternal antibodies against NDV (MDA+. However, due to the absence of the major NDV immunogens it failed to induce protection against Newcastle disease (ND. Here, we report on protection of MDA+ chickens against HPAI H5N1 and ND, by vaccination with chNDVFHNPMV8H5 either on day 1 or day seven after hatch, and subsequent immunization with live attenuated NDV seven days later. Vaccination was well tolerated and three weeks after immunization, challenge infections with highly pathogenic NDV as well as HPAIV H5N1 were carried out. All animals remained healthy without exhibiting any clinical signs, whereas non-vaccinated animals showed morbidity and mortality. Therefore, vaccination with chNDVFHNPMV8H5 can be followed by NDV vaccination to protect chickens from HPAIV as well as NDV, indicating that the antibody response against chNDVFHNPMV8H5 does not interfere with live ND vaccination.

  19. A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target.

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    Daniel M Appledorn

    Full Text Available BACKGROUND: Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals. METHODOLOGY/PRINCIPAL FINDINGS: In this study we designed a novel vaccine strategy utilizing an Ad-based vector expressing a potent TLR agonist derived from Eimeria tenella as an adjuvant to improve immune responses from a [E1-]Ad-based HIV-Gag vaccine. Our results confirm that expression of rEA elicits significantly increased TLR mediated innate immune responses as measured by the influx of plasma cytokines and chemokines, and activation of innate immune responding cells. Furthermore, our data show that the quantity and quality of HIV-Gag specific CD8(+ and CD8(- T-cell responses were significantly improved when coupled with rEA expression. These responses also correlated with a significantly increased number of HIV-Gag derived epitopes being recognized by host T cells. Finally, functional assays confirmed that rEA expression significantly improved antigen specific CTL responses, in vivo. Moreover, we show that these improved responses were dependent upon improved TLR pathway interactions. CONCLUSION/SIGNIFICANCE: The data presented in this study illustrate the potential utility of Ad-based vectors expressing TLR agonists to improve clinical outcomes dependent upon induction of robust, antigen specific immune responses.

  20. Characterization of the immune responses elicited by baculovirus-based vector vaccines against influenza virus hemagglutinin

    Institute of Scientific and Technical Information of China (English)

    Zhi-peng HU; Juan YIN; Yuan-yuan ZHANG; Shu-ya JIA; Zuo-jia CHEN; Jiang ZHONG

    2012-01-01

    Aim:To compare the specific immune responses elicited by different baculovirus vectors in immunized mice.Methods:We constructed and characterized two recombinant baculoviruses carrying the expression cassette for the H5N1 influenza virus hemagglutinin (HA) gene driven by either an insect cell promoter (vAc-HA) or a dual-promoter active both in insect and mammalian cells (vAc-HA-DUAL).Virus without the HA gene (vAc-EGFP) was used as a control.These viruses were used to immunize mice subcutaneously and intraperitoneally.The production of total and specific antibodies was determined by ELISA and competitive ELISA.Cytokine production by the spleen cells of immunized mice was studied using the ELISPOT assay.Results:Both the vAc-HA and vAc-HA-DUAL vectors expressed HA proteins in insect Sf9 cells,and HA antigen was present in progeny virions.The vAc-HA-DUAL vector also mediated HA expression in virus-transduced mammalian cell lines (BHK and A547).Both vAo-HA and vAc-HA-DUAL exhibited higher transduction efficiencies than vAc-EGFP in mammalian cells,as shown by the expression of the reporter gene egfp.Additionally,both vAc-HA and vAc-HA-DUAL induced high levels of HA-specific antibody production in immunized mice; vAc-HA-DUAL was more efficient in inducing IFN-Y and IL-2 upon stimulation with specific antigen,whereas vAc-HA was more efficient in inducing IL-4 and IL-6.Conclusion:Baculovirus vectors elicited efficient,specific immune responses in immunized mice.The vector displaying the HA antigen on the virion surface (vAc-HA) elicited a Th2-biased immune response,whereas the vector displaying HA and mediating HA expression in the cell (vAc-HA-DUAL) elicited a Th1-biased immune response.

  1. A Human Vaccine Strategy Based On Chimpanzee Adenoviral and MVA Vectors That Primes, Boosts and Sustains Functional HCV Specific T-Cell Memory*

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    Swadling, Leo; Capone, Stefania; Antrobus, Richard D.; Brown, Anthony; Richardson, Rachel; Newell, Evan W.; Halliday, John; Kelly, Christabel; Bowen, Dan; Fergusson, Joannah; Kurioka, Ayako; Ammendola, Virginia; Sorbo, Mariarosaria Del; Grazioli, Fabiana; Esposito, Maria Luisa; Siani, Loredana; Traboni, Cinzia; Hill, Adrian; Colloca, Stefano; Davis, Mark; Nicosia, Alfredo; Cortese, Riccardo; Folgori, Antonella; Klenerman, Paul; Barnes, Eleanor

    2015-01-01

    A protective vaccine against hepatitis C virus (HCV) remains an unmet clinical need. HCV infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular cancer. Animal challenge experiments, immunogenetics studies and assessment of host immunity during acute infection highlight the critical role that effective T-cell immunity plays in viral control. In this first-in-man study we have induced antiviral immunity with functional characteristics analogous to those associated with viral control in natural infection, and improved upon a vaccine based on adenoviral vectors alone. We assessed a heterologous prime-boost vaccination strategy based on a replicative defective simian adenoviral vector (ChAd3) and modified vaccinia Ankara (MVA) vector encoding the NS3, NS4, NS5A and NS5B proteins of HCV genotype-1b. Analysis employed single cell mass cytometry (CyTOF), and HLA class-I peptide tetramer technology in healthy human volunteers. We show that HCV specific T-cells induced by ChAd3 are optimally boosted with MVA, and generate very high levels of both CD8+ and CD4+ HCV specific T-cells targeting multiple HCV antigens. Sustained memory and effector T-cell populations are generated and T-cell memory evolved over time with improvement of quality (proliferation and polyfunctionality) following heterologous MVA boost. We have developed a HCV vaccine strategy, with durable, broad, sustained and balanced T-cell responses, characteristic of those associated with viral control, paving the way for the first efficacy studies of a prophylactic HCV vaccine. PMID:25378645

  2. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    International Nuclear Information System (INIS)

    Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost

  3. Emerging Cancer Vaccines: The Promise of Genetic Vectors

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    Gennaro Ciliberto

    2011-09-01

    Full Text Available Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.

  4. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    Energy Technology Data Exchange (ETDEWEB)

    Aurisicchio, Luigi, E-mail: aurisicchio@takis-it.it [Takis, via di Castel Romano 100, 00128 Rome (Italy); BIOGEM scarl, via Camporeale, 83031 Ariano Irpino (AV) (Italy); Ciliberto, Gennaro [Takis, via di Castel Romano 100, 00128 Rome (Italy); Dipartimento di Medicina Sperimentale e Clinica, Università degli studi di Catanzaro “Magna Graecia”, 88100 Catanzaro (Italy)

    2011-09-22

    Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.

  5. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    OpenAIRE

    Wold, William S.M.; Toth, Karoly

    2013-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  6. Simultaneous subcutaneous and conjunctival administration of the influenza viral vector based Brucella abortus vaccine to pregnant heifers provides better protection against B. abortus 544 infection than the commercial B. abortus S19 vaccine.

    Science.gov (United States)

    Tabynov, Kaissar; Orynbayev, Mukhit; Renukaradhya, Gourapura J; Sansyzbay, Abylai

    2016-09-30

    In this study, we explored possibility of increasing the protective efficacy of our novel influenza viral vector based B. abortus vaccine (Flu-BA) in pregnant heifers by adapting an innovative method of vaccine delivery. We administered the vaccine concurrently via the conjunctival and subcutaneous routes to pregnant heifers, and these routes were previously tested individually. The Flu-BA vaccination of pregnant heifers (n=9) against a challenge B. abortus 544 infection provided protection from abortion, infection of heifers and fetuses/calves by 88.8%, 100% and 100%, respectively (alpha=0.004-0.0007 vs. negative control; n=7). Our candidate vaccine using this delivery method provided slightly better protection than the commercial B. abortus S19 vaccine in pregnant heifers (n=8), which provided protection from abortion, infection of heifers and fetuses/calves by 87.5%, 75% and 87.5%, respectively. This improved method of the Flu-BA vaccine administration is highly recommended for the recovery of farms which has high prevalence of brucellosis. PMID:27595898

  7. Aerosolized adenovirus-vectored vaccine as an alternative vaccine delivery method

    Directory of Open Access Journals (Sweden)

    Roy Chad J

    2011-11-01

    Full Text Available Abstract Conventional parenteral injection of vaccines is limited in its ability to induce locally-produced immune responses in the respiratory tract, and has logistical disadvantages in widespread vaccine administration. Recent studies suggest that intranasal delivery or vaccination in the respiratory tract with recombinant viral vectors can enhance immunogenicity and protection against respiratory diseases such as influenza and tuberculosis, and can offer more broad-based generalized protection by eliciting durable mucosal immune responses. Controlled aerosolization is a method to minimize vaccine particle size and ensure delivery to the lower respiratory tract. Here, we characterize the dynamics of aerosolization and show the effects of vaccine concentration on particle size, vector viability, and the actual delivered dose of an aerosolized adenoviral vector. In addition, we demonstrate that aerosol delivery of a recombinant adenoviral vaccine encoding H1N1 hemagglutinin is immunogenic and protects ferrets against homologous viral challenge. Overall, aerosol delivery offers comparable protection to intramuscular injection, and represents an attractive vaccine delivery method for broad-based immunization campaigns.

  8. Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

    Directory of Open Access Journals (Sweden)

    Joan Joseph

    2010-01-01

    Full Text Available Mycobacterium bovis Bacillus Calmette-Guérin (BCG as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261 and Mycobacteria spp. α-antigen promoter (in plasmid pJH222. Among 14 rBCG:HIV-1gp120 (pMV261 colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222 colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

  9. Adenoviral-based foot-and-mouth disease virus vaccine: evaluation of new vectors expressing serotype O in bovines

    Science.gov (United States)

    Foot-and-mouth disease virus (FMDV), an antigenically variable virus, is considered the most important infectious disease of cloven-hoofed animals. Recently serotypes A and O have been the cause of major outbreaks. We previously demonstrated that an adenovirus-based FMDV serotype A24 subunit vaccine...

  10. Adjuvants and vector systems for allergy vaccines.

    Science.gov (United States)

    Moingeon, Philippe; Lombardi, Vincent; Saint-Lu, Nathalie; Tourdot, Sophie; Bodo, Véronique; Mascarell, Laurent

    2011-05-01

    Allergen-specific immunotherapy represents a curative treatment of type I allergies. Subcutaneous immunotherapy is conducted with allergens adsorbed on aluminum hydroxide or calcium phosphate particles, whereas sublingual immunotherapy relies on high doses of soluble allergen without any immunopotentiator. There is a potential benefit of adjuvants enhancing regulatory and Th1 CD4+T cell responses during specific immunotherapy. Molecules affecting dendritic cells favor the induction of T regulatory cell and Th1 responses and represent valid candidate adjuvants for allergy vaccines. Furthermore, the interest in viruslike particles and mucoadhesive particulate vector systems, which may better address the allergen(s) to tolerogenic antigen-presenting cells, is documented.

  11. Functional Human Immunodeficiency Virus Type 1 (HIV-1) Gag-Pol or HIV-1 Gag-Pol and Env Expressed from a Single Rhabdovirus-Based Vaccine Vector Genome

    OpenAIRE

    McGettigan, James P.; Naper, Kristin; Orenstein, Jan; Koser, Martin; McKenna, Philip M.; Schnell, Matthias J.

    2003-01-01

    Recombinant rabies virus (RV) vaccine strain-based vectors have been successfully developed as vaccines against other viral diseases (J. P. McGettigan et al., J. Virol. 75:4430-4434, 2001; McGettigan et al., J. Virol. 75:8724-8732, 2001; C. A. Siler et al., Virology 292:24-34, 2002), and safety concerns have recently been addressed (McGettigan et al., J. Virol. 77:237-244, 2003). However, size limitations of the vectors may restrict their use for development of vaccine applications that requi...

  12. Co-expression of the C-terminal domain of Yersinia enterocolitica invasin enhances the efficacy of classical swine-fever-vectored vaccine based on human adenovirus

    Indian Academy of Sciences (India)

    Helin Li; Pengbo Ning; Zhi Lin; Wulong Liang; Kai Kang; Lei He; Yanming Zhang

    2015-03-01

    The use of adenovirus vector-based vaccines is a promising approach for generating antigen-specific immune responses. Improving vaccine potency is necessary in other approaches to address their inadequate protection for the majority of infectious diseases. This study is the first to reconstruct a recombinant replication-defective human adenovirus co-expressing E2 and invasin C-terminal (InvC) glycoproteins (rAd-E2-InvC). rAd-E2-InvC with 2×106 TCID50 was intramuscularly administered two times to CSFV-free pigs at 14 day intervals. No adverse clinical reactions were observed in any of the pigs after the vaccination. The CSFV E2-specific antibody titer was significantly higher in the rAd-E2-InvC group than that in the rAdV-E2 group as measured by NPLA and blocking ELISA. Pigs immunized with rAd-E2-InvC were completely protected against lethal challenge. Neither CSFV RNA nor pathological changes were detected in the tissues after CSFV challenge. These results demonstrate that rAd-E2-InvC could be an alternative to the existing CSF vaccine. Moreover, InvC that acts as an adjuvant could enhance the immunogenicity of rAdV-E2 and induce high CSFV E2-specific antibody titer and protection level.

  13. VectorBase

    Data.gov (United States)

    U.S. Department of Health & Human Services — VectorBase is a Bioinformatics Resource Center for invertebrate vectors. It is one of four Bioinformatics Resource Centers funded by NIAID to provide web-based...

  14. Combination recombinant simian or chimpanzee adenoviral vectors for vaccine development.

    Science.gov (United States)

    Cheng, Cheng; Wang, Lingshu; Ko, Sung-Youl; Kong, Wing-Pui; Schmidt, Stephen D; Gall, Jason G D; Colloca, Stefano; Seder, Robert A; Mascola, John R; Nabel, Gary J

    2015-12-16

    Recombinant adenoviral vector (rAd)-based vaccines are currently being developed for several infectious diseases and cancer therapy, but pre-existing seroprevalence to such vectors may prevent their use in broad human populations. In this study, we investigated the potential of low seroprevalence non-human primate rAd vectors to stimulate cellular and humoral responses using HIV/SIV Env glycoprotein (gp) as the representative antigen. Mice were immunized with novel simian or chimpanzee rAd (rSAV or rChAd) vectors encoding HIV gp or SIV gp by single immunization or in heterologous prime/boost combinations (DNA/rAd; rAd/rAd; rAd/NYVAC or rAd/rLCM), and adaptive immunity was assessed. Among the rSAV and rChAd tested, rSAV16 or rChAd3 vector alone generated the most potent immune responses. The DNA/rSAV regimen also generated immune responses similar to the DNA/rAd5 regimen. rChAd63/rChAd3 and rChAd3 /NYVAC induced similar or even higher levels of CD4+ and CD8+ T-cell and IgG responses as compared to rAd28/rAd5, one of the most potent combinations of human rAds. The optimized vaccine regimen stimulated improved cellular immune responses and neutralizing antibodies against HIV compared to the DNA/rAd5 regimen. Based on these results, this type of novel rAd vector and its prime/boost combination regimens represent promising candidates for vaccine development. PMID:26514419

  15. Novel vector vaccine against Brucella abortus based on influenza A viruses expressing Brucella L7/L12 or Omp16 proteins: evaluation of protection in pregnant heifers.

    Science.gov (United States)

    Tabynov, Kaissar; Yespembetov, Bolat; Sansyzbay, Abylai

    2014-10-14

    The present study provides the first information about the protection of a novel influenza viral vector vaccine expressing the Brucella proteins ribosomal L7/L12 or Omp16 containing the adjuvant Montanide Gel01 in pregnant heifers. Immunization of pregnant heifers was conducted via the conjunctival (n=10) or subcutaneous (n=10) route using cross prime and booster vaccination schedules at an interval of 28 days. The vector vaccine was evaluated in comparison with positive control groups vaccinated with Brucella abortus S19 (n=10) or B. abortus RB51 (n=10) and a negative (PBS+Montanide Gel01; n=10) control group. Via both the conjunctival or subcutaneous route, evaluation of protectiveness against abortion, effectiveness of vaccination and index of infection (in heifers and their fetuses or calves) demonstrated the vector vaccine provided good protection against B. abortus 544 infection compared to the negative control group (PBS+Montanide Gel01) and comparable protection to commercial vaccines B. abortus S19 or B. abortus RB51. PMID:25218295

  16. 人乳头瘤病毒治疗性活载体疫苗的研究进展%Research progress of human papillonmavirus live vector-based vaccines

    Institute of Scientific and Technical Information of China (English)

    吴小红; 陈科达; 吴洁; 庄昉

    2011-01-01

    The high-risk types of human papillomavirus (HPV-16 and HPV-18) play essential roles in the pathogenesis of cervical cancers. Despite recent advances in preventive HPV vaccine development, preventive HPV vaccines are costly and may not be capable of treating established HPV infections and HPV-associated esions. Various forms of therapeutic HPV vaccines targeting E6/E7 antigens have been tested in preclinical models and clinical trials, including live vector-based vaccines, peptide-based vaccines, protein-based vaccines, nucleic acid-based vaccines, and whole cellbased vaccines. Live-based therapeutic HPV vaccines are reviewed in the article.%高危型人乳头瘤病毒(HPV)-16和HPV-18在宫颈癌的致病过程中起着重要作用.近年来,HPV预防性疫苗已成功上市,但其费用较高,且不能治疗已感染的患者及相关的损伤.多种靶向E6/E7抗原的HPV治疗性疫苗已进入临床前模型和临床试验,包括活载体疫苗,多肽、蛋白疫苗,核酸疫苗及细胞疫苗.此文就HPV治疗性活载体疫苗进行了综述.

  17. New approaches and omics tools for mining of vaccine candidates against vector-borne diseases.

    Science.gov (United States)

    Kuleš, Josipa; Horvatić, Anita; Guillemin, Nicolas; Galan, Asier; Mrljak, Vladimir; Bhide, Mangesh

    2016-08-16

    Vector-borne diseases (VBDs) present a major threat to human and animal health, as well as place a substantial burden on livestock production. As a way of sustainable VBD control, focus is set on vaccine development. Advances in genomics and other "omics" over the past two decades have given rise to a "third generation" of vaccines based on technologies such as reverse vaccinology, functional genomics, immunomics, structural vaccinology and the systems biology approach. The application of omics approaches is shortening the time required to develop the vaccines and increasing the probability of discovery of potential vaccine candidates. Herein, we review the development of new generation vaccines for VBDs, and discuss technological advancement and overall challenges in the vaccine development pipeline. Special emphasis is placed on the development of anti-tick vaccines that can quell both vectors and pathogens.

  18. A role for vector control in dengue vaccine programs.

    Science.gov (United States)

    Christofferson, Rebecca C; Mores, Christopher N

    2015-12-10

    Development and deployment of a successful dengue virus (DENV) vaccine has confounded research and pharmaceutical entities owing to the complex nature of DENV immunity and concerns over exacerbating the risk of DENV hemorrhagic fever (DHF) as a consequence of vaccination. Thus, consensus is growing that a combination of mitigation strategies will be needed for DENV to be successfully controlled, likely involving some form of vector control to enhance a vaccine program. We present here a deterministic compartmental model to illustrate that vector control may enhance vaccination campaigns with imperfect coverage and efficacy. Though we recognize the costs and challenges associated with continuous control programs, simultaneous application of vector control methods coincident with vaccine roll out can have a positive effect by further reducing the number of human cases. The success of such an integrative strategy is predicated on closing gaps in our understanding of the DENV transmission cycle in hyperedemic locations.

  19. A role for vector control in dengue vaccine programs.

    Science.gov (United States)

    Christofferson, Rebecca C; Mores, Christopher N

    2015-12-10

    Development and deployment of a successful dengue virus (DENV) vaccine has confounded research and pharmaceutical entities owing to the complex nature of DENV immunity and concerns over exacerbating the risk of DENV hemorrhagic fever (DHF) as a consequence of vaccination. Thus, consensus is growing that a combination of mitigation strategies will be needed for DENV to be successfully controlled, likely involving some form of vector control to enhance a vaccine program. We present here a deterministic compartmental model to illustrate that vector control may enhance vaccination campaigns with imperfect coverage and efficacy. Though we recognize the costs and challenges associated with continuous control programs, simultaneous application of vector control methods coincident with vaccine roll out can have a positive effect by further reducing the number of human cases. The success of such an integrative strategy is predicated on closing gaps in our understanding of the DENV transmission cycle in hyperedemic locations. PMID:26478199

  20. Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Chad E Mire

    Full Text Available The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV that expresses an individual filovirus glycoprotein (GP in place of the VSV glycoprotein (G. The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV GP; three animals received rVSV-wild type (wt vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.

  1. Recombinant Mycobacterium bovis BCG as an HIV Vaccine Vector

    OpenAIRE

    Chapman, Rosamund; Chege, Gerald; Shephard, Enid; Stutz, Helen; Williamson, Anna-Lise

    2010-01-01

    HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addi...

  2. A Vesicular Stomatitis Virus-Based Hepatitis B Virus Vaccine Vector Provides Protection against Challenge in a Single Dose ▿

    OpenAIRE

    Cobleigh, Melissa A.; Buonocore, Linda; Uprichard, Susan L; Rose, John K.; Robek, Michael D.

    2010-01-01

    As one of the world's most common infectious diseases, hepatitis B virus (HBV) is a serious worldwide public health problem, with HBV-associated liver disease accounting for more than half a million deaths each year. Although there is an effective prophylactic vaccine currently available to prevent infection, it has a number of characteristics that are suboptimal: multiple doses are needed to induce long-lasting immunity, immunity declines over time, it does not elicit protection in some indi...

  3. Progress of Influenza Virus Like Particles Vaccine Based on Baculovirus Expression Vector System%昆虫杆状病毒表达系统生产流感疫苗的研究进展

    Institute of Scientific and Technical Information of China (English)

    李晶梅; 靖志强; 秦红刚; 薛霜; 漆世华; 谢红玲; 吴玉石

    2012-01-01

    Influenza virus -like particles (VLPs) based on baculovirus expression vector system (BEVS) was a new platform for influenza vaccines. Its research progress was reviewed so as to provide reference for development of animal influenza VLPs vaccine. Influenza VLPs derived from BEVS may be promising vaccine candidate for influenza. Furthermore, influenza VLPs derived from BEVS may be used as animal vaccines.%综述了昆虫杆状病毒表达系统生产流感疫苗的研究进展,同时分析了昆虫杆状病毒表达系统表达流感病毒样颗粒用于流感疫苗的优势和前景,以期为兽用流感病毒VLPs疫苗研发提供参考。

  4. Optimal vaccination scenarios against vector-borne diseases

    DEFF Research Database (Denmark)

    Græsbøll, Kaare; Enøe, Claes; Bødker, Rene;

    Using a process oriented semi-agent based model we simulated the spread of Bluetongue virus in Denmark. We evaluated the efficiency and minimum vaccination cover for eight different preventive vaccination strategies in Denmark. The simulation model replicates both passive and active flight...... of Culicoides between hosts on pasture and stables in Denmark. Seasonal abundance of midges and temperature dependence on biological processes were included in the model. The eight vaccination scenarios comprised of: All holdings vaccinated to a given percentage, random holdings selected for vaccination, two...... scenarios based on the size of holdings, mosaic vaccination of nearest neighbor farms, vaccination of hosts on pasture, regional vaccination, and trench vaccination from the border to Germany. These eight scenarios were investigated under normal grazing conditions and under a forced housing scenario...

  5. Attenuated Measles Virus as a Vaccine Vector

    OpenAIRE

    Zuniga, Armando; Wang, Zili; Liniger, Matthias; Hangartner, Lars; Caballero, Michael; Pavlovic, Jovan; Wild, Peter; Viret, Jean Francois; Glueck, Reinhard; Billeter, Martin A.; Naim, Hussein Y.

    2007-01-01

    Live attenuated measles virus (MV) vaccines have an impressive record of safety, efficacy and ability to induce life-long immunity against measles infection. Using reverse genetics technology, such negative-strand RNA viruses can now be rescued from cloned DNA. This technology allows the insertion of exogenous genes encoding foreign antigens into the MV genome in such a way that they can be expressed by the MV vaccine strain, without affecting virus structure, propagation and cell targeting. ...

  6. Dendritic cell-based vaccination with lentiviral vectors encoding ubiquitinated hepatitis B core antigen enhances hepatitis B virus-specific immune responses in vivo.

    Science.gov (United States)

    Dai, Shenglan; Zhuo, Meng; Song, Linlin; Chen, Xiaohua; Yu, Yongsheng; Tang, Zhenghao; Zang, Guoqing

    2015-11-01

    The activity of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) plays a predominant role in the clearance of HBV. Dendritic cells (DCs) are key antigen-presenting cells and play an important role in the initiation of immune responses. We previously verified that lentiviral vector encoding ubiquitinated hepatitis B core antigen (LV-Ub-HBcAg) effectively transduced DCs to induce maturation, and the mature DCs efficiently induced T cell polarization to Th1 and generated HBcAg-specific CTLs ex vivo. In this study, HBV-specific immune responses of LV-Ub-HBcAg in BALB/c mice (H-2Kd) were evaluated. It was shown that direct injection of LV-Ub-HBcAg increased the production of cytokines IL-2 and IFN-γ, elicited strong antibody responses, and remarkably generated a high percentage of IFN-γ+CD8+ T cells with HBV-specific CTL responses in BALB/c mice. In addition, direct injection of LV-Ub-HBcAg induced potent anti-HBV immune responses, similar to those elicited by in vitro-transduced DCs. In conclusion, the DC-based therapeutic vaccine LV-Ub-HBcAg elicited specific antibody immune responses and induced robust specific CTL activity in vivo. PMID:26373843

  7. Recombinant Mycobacterium bovis BCG as an HIV vaccine vector.

    Science.gov (United States)

    Chapman, Rosamund; Chege, Gerald; Shephard, Enid; Stutz, Helen; Williamson, Anna-Lise

    2010-06-01

    HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable, a necessary consideration for developing countries. In this review we discuss the numerous factors that influence generation of a genetically stable recombinant BCG vaccine for HIV. PMID:20353397

  8. Vector transmission of leishmania abrogates vaccine-induced protective immunity.

    Directory of Open Access Journals (Sweden)

    Nathan C Peters

    2009-06-01

    Full Text Available Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand fly bite. The only immunization strategy known to protect humans against natural exposure is "leishmanization," in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand fly bite within 24 hours, and these mice were highly resistant to sand fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania.

  9. Bovine adenoviral vector-based H5N1 influenza vaccine overcomes exceptionally high levels of pre-existing immunity against human adenovirus.

    Science.gov (United States)

    Singh, Neetu; Pandey, Aseem; Jayashankar, Lakshmi; Mittal, Suresh K

    2008-05-01

    Because of the high prevalence of adenovirus (Ad) infections in humans, it is believed that pre-existing Ad-neutralizing antibodies (vector immunity) may negatively impact the immune response to vaccine antigens when delivered by human Ad (HAd) vectors. In order to evaluate whether bovine Ad subtype 3 (BAd3), a non-HAd vector, can effectively elude high levels of pre-existing vector immunity, naïve and HAd serotype 5 (HAd)-primed mice were immunized with BAd-H5HA [BAd3 vector expressing the hemagglutinin (HA) gene from H5N1 influenza virus]. Even in the presence of very high levels of HAd-specific neutralizing antibody, no significant reductions in HA-specific humoral and cell-mediated immune (CMI) responses were observed in HAd-primed mice immunized with BAd-H5HA. In naïve mice immunized with HAd-H5HA (HAd5 vector expressing H5N1 HA) and boosted with BAd-H5HA, the humoral responses elicited were significantly higher (P BAd-H5HA alone, while the CMI responses were comparable in the groups. This finding underlines the importance of a heterologous prime-boost approach for achieving an enhanced immune response. The immunization of naïve or HAd-primed mice with BAd-H5HA bestowed full protection from morbidity and mortality following a potentially lethal challenge with A/Hong Kong/483/97. These results demonstrate the importance of BAd vectors as an alternate or supplement to HAd vectors for influenza pandemic preparedness.

  10. Adenovirus-Vectored Vaccine as a Rapid-Response Tool Against Avian Influenza Pandemic

    International Nuclear Information System (INIS)

    Influenza viruses in nature undergo genetic mutation and reassortment. Three pandemics of avian influenza in man were recorded in the twentieth century. Highly pathogenic avian influenza (HPAI) viruses currently in circulation pose a threat for another world-wide pandemic, if they become transmissible from man to man. Manufacturing protective vaccines using current egg-based technology is often difficult due to the virulence of the virus and its adverse effects on the embryonating egg substrate. New technologies allow the creation of safe and protective pandemic influenza vaccines without the need for egg based substrates. These technologies allow new vaccines to be created in less than one month. Manufacturing is in tissue culture, not eggs. Vaccine can be administered to man non-invasively, without adjuvants, eliciting a rapid and protective immune response. Protective immunity against avian influenza (AI) virus was elicited in chickens by single-dose in ovo vaccination with a replication-competent adenovirus (RCA)-free human adenovirus serotype 5 (Ad5)-derived vector encoding an H5N9 avian influenza virus hemagglutinin. Vaccinated chickens were protected against both H5N1 and H5N2 HPAI virus challenges. Mass-administration of this bird flu vaccine can be streamlined with available robotic in ovo injectors. Vaccination using this vaccine could protect the the largest host reservoir (chickens) and greatly reduce the exposure of man to avian influenza. In addition, Ad5-vectored vaccines can be produced rapidly and the safety margin of a non-replicating vector is superior to that of a replicating counterpart. Furthermore, this mode of vaccination is compatible with epidemiological surveys of natural AI virus infections. In addition to mass immunization of poultry, both animals and humans have been effectively immunized by intranasal administration of Ad5-vectored influenza vaccines without any appreciable side effects, even in mice and human volunteers with

  11. Non-Replicating Adenovirus-Vectored Anthrax Vaccine

    International Nuclear Information System (INIS)

    As bioterrorism is emerging as a national threat, it is urgent to develop a new generation of anthrax vaccines that can be rapidly produced and mass administered in an emergency setting. We have demonstrated that protective immunity against anthrax spores could be elicited in mice by intranasal administration of a non-replicating human adenovirus serotype 5 (Ad5)-derived vector encoding Bacillus anthracis protective antigen (PA) in a single-dose regimen. The potency of an Ad5 vector encoding PA was remarkably enhanced by codon optimization of the PA gene to match the tRNA pool found in human cells. This nasal vaccine can be mass-administered by non-medical personnel during a bioterrorist attack. In addition, replication-competent adenovirus (RCA)-free Ad5-vectored anthrax vaccines can be mass produced in PER.C6 cells in serum-free wave bioreactors and purified by column chromatography to meet a surge in demand. The non-replicating nature of this new generation of anthrax vaccine ensures an excellent safety profile for vaccines and the environment.(author)

  12. Dengue in Cape Verde: vector control and vaccination

    CERN Document Server

    Rodrigues, Helena Sofia; Torres, Delfim F M

    2012-01-01

    In 2009, for the first time in Cape Verde, an outbreak of dengue was reported and over twenty thousand people were infected. Only a few prophylactic measures were taken. The effects of vector control on disease spreading, such as insecticide (larvicide and adulticide) and mechanical control, as well as an hypothetical vaccine, are estimated through simulations with the Cape Verde data.

  13. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M;

    2012-01-01

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

  14. Avipoxviruses: infection biology and their use as vaccine vectors

    Directory of Open Access Journals (Sweden)

    Tryland Morten

    2011-02-01

    Full Text Available Abstract Avipoxviruses (APVs belong to the Chordopoxvirinae subfamily of the Poxviridae family. APVs are distributed worldwide and cause disease in domestic, pet and wild birds of many species. APVs are transmitted by aerosols and biting insects, particularly mosquitoes and arthropods and are usually named after the bird species from which they were originally isolated. The virus species Fowlpox virus (FWPV causes disease in poultry and associated mortality is usually low, but in flocks under stress (other diseases, high production mortality can reach up to 50%. APVs are also major players in viral vaccine vector development for diseases in human and veterinary medicine. Abortive infection in mammalian cells (no production of progeny viruses and their ability to accommodate multiple gene inserts are some of the characteristics that make APVs promising vaccine vectors. Although abortive infection in mammalian cells conceivably represents a major vaccine bio-safety advantage, molecular mechanisms restricting APVs to certain hosts are not yet fully understood. This review summarizes the current knowledge relating to APVs, including classification, morphogenesis, host-virus interactions, diagnostics and disease, and also highlights the use of APVs as recombinant vaccine vectors.

  15. Optimal vaccination strategies against vector-borne diseases

    DEFF Research Database (Denmark)

    Græsbøll, Kaare; Enøe, Claes; Bødker, Rene;

    2014-01-01

    Using a process oriented semi-agent based model, we simulated the spread of Bluetongue virus by Culicoides, biting midges, between cattle in Denmark. We evaluated the minimum vaccination cover and minimum cost for eight different preventive vaccination strategies in Denmark. The simulation model...... replicates both a passive and active flight of midges between cattle distributed on pastures and cattle farms in Denmark. A seasonal abundance of midges and temperature dependence of biological processes were included in the model. The eight vaccination strategies were investigated under four different...... grazing conditions. Furthermore, scenarios were tested with three different index locations stratified for cattle density. The cheapest way to vaccinate cattle with a medium risk profile (less than 1000 total affected cattle) was to vaccinate cattle on pasture. Regional vaccination displayed better...

  16. Venezuelan Equine Encephalitis Virus-Vectored Vaccines Protect Mice against Anthrax Spore Challenge

    OpenAIRE

    Lee, John S.; Hadjipanayis, Angela G.; Welkos, Susan L.

    2003-01-01

    Anthrax, a disease usually associated with herbivores, is caused by the bacterium Bacillus anthracis. The current vaccine licensed for human use requires a six-dose primary series and yearly boosters and causes reactogenicity in up to 30% of vaccine recipients. A minimally reactogenic vaccine requiring fewer inoculations is warranted. Venezuelan equine encephalitis (VEE) virus has been configured for use as a vaccine vector for a wide variety of immunogens. The VEE vaccine vector is composed ...

  17. Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

    Directory of Open Access Journals (Sweden)

    Clement A Meseda

    Full Text Available The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification. The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1 elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that

  18. Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

    Science.gov (United States)

    Meseda, Clement A; Atukorale, Vajini; Kuhn, Jordan; Schmeisser, Falko; Weir, Jerry P

    2016-01-01

    The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored

  19. Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine.

    Science.gov (United States)

    Gupta, Gaurav; Giannino, Viviana; Rishi, Narayan; Glueck, Reinhard

    2016-09-01

    Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver. The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world. We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV. The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1. PMID:27523740

  20. Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine.

    Science.gov (United States)

    Gupta, Gaurav; Giannino, Viviana; Rishi, Narayan; Glueck, Reinhard

    2016-09-01

    Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver. The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world. We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV. The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1.

  1. DNA Virus Vectors for Vaccine Production in Plants: Spotlight on Geminiviruses

    Directory of Open Access Journals (Sweden)

    Kathleen L. Hefferon

    2014-08-01

    Full Text Available Plants represent a safe, efficacious and inexpensive production platform by which to provide vaccines and other therapeutic proteins to the world’s poor. Plant virus expression vector technology has rapidly become one of the most popular methods to express pharmaceutical proteins in plants. This review discusses several of the state-of-the-art plant expression systems based upon geminiviruses that have been engineered for vaccine production. An overview of the advantages of these small, single-stranded DNA viruses is provided and comparisons are made with other virus expression systems. Advances in the design of several different geminivirus vectors are presented in this review, and examples of vaccines and other biologics generated from each are described.

  2. Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    2014-10-01

    Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

  3. Salmonella Typhi: from a Human Pathogen to a Vaccine Vector

    Institute of Scientific and Technical Information of China (English)

    Xiao-Lian Zhang; Victor Tunje Jeza; Qin Pan

    2008-01-01

    Salmonella (S.) typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. Typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. Typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. Typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector.

  4. A pilot study comparing the development of EIAV Env-specific antibodies induced by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine.

    Science.gov (United States)

    Meng, Qinglai; Lin, Yuezhi; Ma, Jian; Ma, Yan; Zhao, Liping; Li, Shenwei; Yang, Kai; Zhou, Jianhua; Shen, Rongxian; Zhang, Xiaoyan; Shao, Yiming

    2012-12-01

    Data from successful attenuated lentiviral vaccine studies indicate that fully mature Env-specific antibodies characterized by high titer, high avidity, and the predominant recognition of conformational epitopes are associated with protective efficacy. Although vaccination with a DNA prime/recombinant vaccinia-vectored vaccine boost strategy has been found to be effective in some trials with non-human primate/simian/human immunodeficiency virus (SHIV) models, it remains unclear whether this vaccination strategy could elicit mature equine infectious anemia virus (EIAV) Env-specific antibodies, thus protecting vaccinated horses against EIAV infection. Therefore, in this pilot study we vaccinated horses using a strategy based on DNA prime/recombinant Tiantan vaccinia (rTTV)-vectored vaccines encoding EIAV env and gag genes, and observed the development of Env-specific antibodies, neutralizing antibodies, and p26-specific antibodies. Vaccination with DNA induced low titer, low avidity, and the predominant recognition of linear epitopes by Env-specific antibodies, which was enhanced by boosting vaccinations with rTTV vaccines. However, the maturation levels of Env-specific antibodies induced by the DNA/rTTV vaccines were significantly lower than those induced by the attenuated vaccine EIAV(FDDV). Additionally, DNA/rTTV vaccines did not elicit broadly neutralizing antibodies. After challenge with a virulent EIAV strain, all of the vaccinees and control horses died from EIAV disease. These data indicate that the regimen of DNA prime/rTTV vaccine boost did not induce mature Env-specific antibodies, which might have contributed to immune protection failure. PMID:23171359

  5. Increased efficacy of an adenovirus-vectored foot-and-mouth disease capsid subunit vaccine expressing nonstructural protein 2B is associated with a specific T cell response

    Science.gov (United States)

    We previously demonstrated that an adenovirus-based FMDV serotype A24 subunit vaccine, Ad5-A24, expressed under the control of a cytomegalovirus promoter (CMV) can protect swine and bovines against homologous challenge, but swine vaccinated with an Ad5-vectored FMDV O1 Campos vaccine, Ad5-O1Campos (...

  6. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG).

    Science.gov (United States)

    Chen, Robert T; Carbery, Baevin; Mac, Lisa; Berns, Kenneth I; Chapman, Louisa; Condit, Richard C; Excler, Jean-Louis; Gurwith, Marc; Hendry, Michael; Khan, Arifa S; Khuri-Bulos, Najwa; Klug, Bettina; Robertson, James S; Seligman, Stephen J; Sheets, Rebecca; Williamson, Anna-Lise

    2015-01-01

    Recombinant viral vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines against human pathogens from Ebola to tuberculosis. An increasing number of candidate viral vector vaccines are entering human clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to improve our ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when licensed. PMID:25305565

  7. A CD46-binding chimpanzee adenovirus vector as a vaccine carrier.

    Science.gov (United States)

    Tatsis, Nia; Blejer, Ariella; Lasaro, Marcio O; Hensley, Scott E; Cun, Ann; Tesema, Lello; Li, Yan; Gao, Guang-Ping; Xiang, Zhi Q; Zhou, Dongming; Wilson, James M; Ertl, Hildegund C J

    2007-03-01

    A replication-defective chimeric vector based on the chimpanzee adenovirus serotype C1 was developed and tested as a vaccine carrier in mice. The AdC1 virus is closely related to human adenoviruses of subgroup B2 and uses CD46 for cell attachment. To overcome poor growth of E1-deleted AdC1 vectors on cell lines that provide the E1 of adenovirus of the human serotype 5 (AdHu5) virus in trans, the inverted terminal repeats and some of the early genes of AdC1 were replaced with those from AdC5, a chimpanzee origin adenovirus of subfamily E. The chimeric AdC1/C5 vector efficiently transduces CD46-expressing mouse dendritic cells (DCs) in vitro and initiates their maturation. Transduction of DCs in vivo is inefficient in CD46 transgenic mice. The AdC1/C5 vector induces transgene product-specific B- and CD8(+) T-cell responses in mice. Responses are slightly higher in wild-type mice than in CD46 transgenic mice. Transgene product-specific T-cell responses elicited by the AdC1/C5 vector can be increased by priming or boosting with a heterologous adenovirus vector. Pre-existing immunity to adenovirus of the common human serotype 5 does not affect induction of cell-mediated immune responses by the AdC1/C5 vector. This vector provides an additional tool in a repertoire of adenovirus-based vaccine vectors. PMID:17228314

  8. Characterization of recombinant Raccoonpox Vaccine Vectors in Chickens

    Science.gov (United States)

    Hwa, S.-H.; Iams, K.P.; Hall, J.S.; Kingstad, B.A.; Osorio, J.E.

    2010-01-01

    Raccoonpox virus (RCN) has been used as a recombinant vector against several mammalian pathogens but has not been tested in birds. The replication of RCN in chick embryo fibroblasts (CEFs) and chickens was studied with the use of highly pathogenic avian influenza virus H5N1 hemagglutinin (HA) as a model antigen and luciferase (luc) as a reporter gene. Although RCN replicated to low levels in CEFs, it efficiently expressed recombinant proteins and, in vivo, elicited anti-HA immunoglobulin yolk (IgY) antibody responses comparable to inactivated influenza virus. Biophotonic in vivo imaging of 1-wk-old chicks with RCN-luc showed strong expression of the luc reporter gene lasting up to 3 days postinfection. These studies demonstrate the potential of RCN as a vaccine vector for avian influenza and other poultry pathogens. ?? American Association of Avian Pathologists 2010.

  9. Infectivity of attenuated poxvirus vaccine vectors and immunogenicity of a raccoonpox vectored rabies vaccine in the Brazilian Free-tailed bat (Tadarida brasiliensis)

    Science.gov (United States)

    Stading, Benjamin; Osorio, Jorge E.; Velasco-Villa, Andres; Smotherman, Michael; Kingstad-Bakke, Brock; Rocke, Tonie E.

    2016-01-01

    Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat (Tadarida brasiliensis), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA-luc, RCN-luc) through oronasal (ON) or intramuscular (IM) routes and subsequently monitored for bioluminescent signal indicative of viral infection. No clinical illness was noted after exposure to any of the vectors, and limited luciferase expression was observed. Higher and longer levels of expression were observed with the RCN-luc construct. When given IM, luciferase expression was limited to the site of injection, while ON exposure led to initial expression in the oral cavity, often followed by secondary replication at another location, likely the gastric mucosa or gastric associated lymphatic tissue. Viral DNA was detected in oral swabs up to 7 and 9 days post infection (dpi) for MVA and RCN, respectively. While no live virus was detected in oral swabs from MVA-infected bats, titers up to 3.88 x 104 PFU/ml were recovered from oral swabs of RCN-infected bats. Viral DNA was also detected in fecal samples from two bats inoculated IM with RCN, but no live virus was recovered. Finally, we examined the immunogenicity of a RCN based rabies vaccine (RCN-G) following ON administration. Significant rabies neutralizing antibody titers were detected in the serum of immunized bats using the rapid fluorescence focus inhibition test (RFFIT). These studies highlight the safety and immunogenicity of attenuated poxviruses and their potential use as vaccine vectors in bats.

  10. Biodistribution and Toxicological Safety of Adenovirus Type 5 and Type 35 Vectored Vaccines Against Human Immunodeficiency Virus-1 (HIV-1), Ebola, or Marburg Are Similar Despite Differing Adenovirus Serotype Vector, Manufacturer's Construct, or Gene Inserts

    OpenAIRE

    Sheets, Rebecca L.; Stein, Judith; Bailer, Robert T.; Koup, Richard A.; Andrews, Charla; Nason, Martha; He, Bin; Koo, Edward; Trotter, Holly; Duffy, Chris; Manetz, T. Scott; Gomez, Phillip

    2008-01-01

    The Vaccine Research Center has developed vaccine candidates for different diseases/infectious agents (including HIV-1, Ebola, and Marburg viruses) built on an adenovirus vector platform, based on adenovirus type 5 or 35. To support clinical development of each vaccine candidate, pre-clinical studies were performed in rabbits to determine where in the body they biodistribute and how rapidly they clear, and to screen for potential toxicities (intrinsic and immunotoxicities). The vaccines biodi...

  11. A Tetravalent Dengue Vaccine Based on a Complex Adenovirus Vector Provides Significant Protection in Rhesus Monkeys against All Four Serotypes of Dengue Virus▿

    OpenAIRE

    Raviprakash, Kanakatte; Wang, Danher; Ewing, Dan; Holman, David H.; Block, Karla; Woraratanadharm, Jan; Chen, Lan; Hayes, Curtis; Dong., John Y.; Porter, Kevin

    2008-01-01

    Nearly a third of the human population is at risk of infection with the four serotypes of dengue viruses, and it is estimated that more than 100 million infections occur each year. A licensed vaccine for dengue viruses has become a global health priority. A major challenge to developing a dengue vaccine is the necessity to produce fairly uniform protective immune responses to all four dengue virus serotypes. We have developed two bivalent dengue virus vaccines, using a complex adenovirus vect...

  12. Safety of the novel influenza viral vector Brucella abortus vaccine in pregnant heifers

    OpenAIRE

    Kaissar Tabynov; Sholpan Ryskeldinova; Zhailaubay Kydyrbayev; Abylai Sansyzbay

    2016-01-01

    ABSTRACT: The present study provides the first information about the safety of a new influenza viral vector vaccine expressing the Brucella ribosomal protein L7/L12 or Omp16 containing the adjuvant Montanide Gel01 in pregnant heifers. Immunization of pregnant heifers was conducted via the conjunctival (n=10) or subcutaneous (n=10) route using cross prime and booster vaccination schedules at an interval of 28 days. The vector vaccine was evaluated in comparison with positive control groups vac...

  13. Advances in host and vector development for the production of plasmid DNA vaccines.

    Science.gov (United States)

    Mairhofer, Juergen; Lara, Alvaro R

    2014-01-01

    Recent developments in DNA vaccine research provide a new momentum for this rather young and potentially disruptive technology. Gene-based vaccines are capable of eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria, and tuberculosis, for which the conventional vaccine technologies have failed so far. The recent identification and characterization of genes coding for tumor antigens has stimulated the development of DNA-based antigen-specific cancer vaccines. Although most academic researchers consider the production of reasonable amounts of plasmid DNA (pDNA) for immunological studies relatively easy to solve, problems often arise during this first phase of production. In this chapter we review the current state of the art of pDNA production at small (shake flasks) and mid-scales (lab-scale bioreactor fermentations) and address new trends in vector design and strain engineering. We will guide the reader through the different stages of process design starting from choosing the most appropriate plasmid backbone, choosing the right Escherichia coli (E. coli) strain for production, and cultivation media and scale-up issues. In addition, we will address some points concerning the safety and potency of the produced plasmids, with special focus on producing antibiotic resistance-free plasmids. The main goal of this chapter is to make immunologists aware of the fact that production of the pDNA vaccine has to be performed with as much as attention and care as the rest of their research.

  14. Mucin-Based Vaccines

    Science.gov (United States)

    Richardson, Jonathan P.; MacMillan, Derek

    Mucins are heavily O-glycosylated cell surface and secreted glycoproteins . In addition to orchestrating cell-extracellular matrix and cell-cell interactions in healthy organisms mucins are also the major carriers of altered glycosylation in carcinomas. Tumor-associated antigens displayed by cancer cells comprise oligosaccharide and glycopeptide motifs not encountered in the same locale or at the same frequency in healthy cells, and potentially confer a selective advantage to the tumor. Frequently tumor-associated antigens are under-glycosylated and prematurely sialylated, and it is these relatively simple saccharide and glycopeptide structures that have been targeted to serve as drug candidates in most cases. A major goal is to assemble glycopeptide vaccine candidates based on partial mucin sequences and displaying tumor-associated antigens that can mount a potent immunological tumor-specific response when, in reality, the tumor has already coerced the immune system into a state of co-existence.

  15. Construction of a trivalent candidate Shigella vaccine strain with host-vector balanced-lethal system

    Institute of Scientific and Technical Information of China (English)

    芮贤良; 徐永强; 吴旭东; 苏国富; 黄翠芬

    1997-01-01

    A trivalent live Shigella vaccine candidate FSD01 against S. flexneri 2a, S. sonnei and S. dysen-teriae I was constructed. This candidate strain was based on the S. flexneri 2a vaccine T32. By homologous recombi-nation exchange, the chromosomal asd gene of T32 was site-specifically inactivated, resulting in the strain unable to grow normally in LB broth, while another asd gene of S. mutans was employed to construct an Asd complementary vector. This combination of asd ’host/ Asd+ vector formed a balanced-lethal expression system in T32 strain. By use of this system, two important protective antigen genes coding for S. sonnei Form I antigen and Shiga toxin B subunit were cloned and expressed in T32, which led to the construction of trivalent candidate vaccine FSD01. Experimental results showed that this strain was genetically stable, but its recombinant plasmid was non-resistant. Moreover, it was able to effectively express trivalent antigens in one host and induce protective responses in mice against the

  16. On the efficacy of malaria DNA vaccination with magnetic gene vectors.

    Science.gov (United States)

    Nawwab Al-Deen, Fatin; Ma, Charles; Xiang, Sue D; Selomulya, Cordelia; Plebanski, Magdalena; Coppel, Ross L

    2013-05-28

    We investigated the efficacy and types of immune responses from plasmid malaria DNA vaccine encoding VR1020-PyMSP119 condensed on the surface of polyethyleneimine (PEI)-coated SPIONs. In vivo mouse studies were done firstly to determine the optimum magnetic vector composition, and then to observe immune responses elicited when magnetic vectors were introduced via different administration routes. Higher serum antibody titers against PyMSP119 were observed with intraperitoneal and intramuscular injections than subcutaneous and intradermal injections. Robust IgG2a and IgG1 responses were observed for intraperitoneal administration, which could be due to the physiology of peritoneum as a major reservoir of macrophages and dendritic cells. Heterologous DNA prime followed by single protein boost vaccination regime also enhanced IgG2a, IgG1, and IgG2b responses, indicating the induction of appropriate memory immunity that can be elicited by protein on recall. These outcomes support the possibility to design superparamagnetic nanoparticle-based DNA vaccines to optimally evoke desired antibody responses, useful for a variety of diseases including malaria.

  17. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using direct homologous challenge

    Science.gov (United States)

    The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularl...

  18. Sequence and immunogenicity of a clinically approved novel measles virus vaccine vector

    OpenAIRE

    Zuniga, Amando; Liniger, Mathias; Morin, Teldja Neige Azzouz; Marty, René R.; Wiegand, Marian; Ilter, Orhan; Weibel, Sara; Billeter, Martin A.; Knuchel, Marlyse C.; Naim, Hussein Y

    2013-01-01

    The measles virus vaccine (MVbv) is a clinically certified and well-tolerated vaccine strain that has been given both parenterally and mucosally. It has been extensively used in children and has proven to be safe and effective in eliciting protective immunity. This specific strain was therefore chosen to generate a measles viral vector. The genome of the commercial MVbv vaccine strain was isolated, sequenced and a plasmid, p(+)MVb, enabling transcription of the viral antigenome and rescue of ...

  19. Vaccines for viral and parasitic diseases produced with baculovirus vectors

    NARCIS (Netherlands)

    Oers, van M.M.

    2006-01-01

    The baculovirus¿insect cell expression system is an approved system for the production of viral antigens with vaccine potential for humans and animals and has been used for production of subunit vaccines against parasitic diseases as well. Many candidate subunit vaccines have been expressed in this

  20. Lactococcus lactis-based vaccines from laboratory bench to human use: an overview.

    Science.gov (United States)

    Bahey-El-Din, Mohammed

    2012-01-17

    Developing effective vaccines is an important weapon in the battle against potential pathogens and their evolving antibiotic resistance trends. Several vaccine delivery vectors have been investigated among which the generally regarded as safe (GRAS) Lactococcus lactis has a distinguished position. In this review, different factors affecting the efficacy of L. lactis-based vaccines are discussed. In addition, the issues of biological containment and pharmaceutical quality assurance of L. lactis vaccines are highlighted. These issues are critical for the success of medical translation of L. lactis-based vaccines from research laboratories to clinical use by ensuring consistent manufacturing of safe and efficacious vaccines.

  1. Plant viral vectors based on tobamoviruses.

    Science.gov (United States)

    Yusibov, V; Shivprasad, S; Turpen, T H; Dawson, W; Koprowski, H

    1999-01-01

    The potential of plant virus-based transient expression vectors is substantial. One objective is the production of large quantities of foreign peptides or proteins. At least one commercial group (Biosource Technologies) is producing large quantities of product in the field, has built factories to process truck-loads of material and soon expects to market virus-generated products. In the laboratory, large amounts of protein have been produced for structural or biochemical analyses. An important aspect of producing large amounts of a protein or peptide is to make the product easily purifiable. This has been done by attaching peptides or proteins to easily purified units such as virion particles or by exporting proteins to the apoplast so that purification begins with a highly enriched product. For plant molecular biology, virus-based vectors have been useful in identifying previously unknown genes by overexpression or silencing or by expression in different genotypes. Also, foreign peptides fused to virions are being used as immunogens for development of antisera for experimental use or as injected or edible vaccines for medical use. As with liposomes and microcapsules, plant cells and plant viruses are also expected to provide natural protection for the passage of antigen through the gastrointestinal tract. Perhaps the greatest advantage of plant virus-based transient expression vectors is their host, plants. For the production of large amounts of commercial products, plants are one of the most economical and productive sources of biomass. They also present the advantages of lack of contamination with animal pathogens, relative ease of genetic manipulation and the presence eukaryotic protein modification machinery.

  2. Plant viral vectors based on tobamoviruses.

    Science.gov (United States)

    Yusibov, V; Shivprasad, S; Turpen, T H; Dawson, W; Koprowski, H

    1999-01-01

    The potential of plant virus-based transient expression vectors is substantial. One objective is the production of large quantities of foreign peptides or proteins. At least one commercial group (Biosource Technologies) is producing large quantities of product in the field, has built factories to process truck-loads of material and soon expects to market virus-generated products. In the laboratory, large amounts of protein have been produced for structural or biochemical analyses. An important aspect of producing large amounts of a protein or peptide is to make the product easily purifiable. This has been done by attaching peptides or proteins to easily purified units such as virion particles or by exporting proteins to the apoplast so that purification begins with a highly enriched product. For plant molecular biology, virus-based vectors have been useful in identifying previously unknown genes by overexpression or silencing or by expression in different genotypes. Also, foreign peptides fused to virions are being used as immunogens for development of antisera for experimental use or as injected or edible vaccines for medical use. As with liposomes and microcapsules, plant cells and plant viruses are also expected to provide natural protection for the passage of antigen through the gastrointestinal tract. Perhaps the greatest advantage of plant virus-based transient expression vectors is their host, plants. For the production of large amounts of commercial products, plants are one of the most economical and productive sources of biomass. They also present the advantages of lack of contamination with animal pathogens, relative ease of genetic manipulation and the presence eukaryotic protein modification machinery. PMID:10394716

  3. Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors.

    Science.gov (United States)

    Wang, Hai-Chao; An, Huai-Jie; Yu, Yun-Zhou; Xu, Qing

    2015-02-01

    DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax. PMID:25102364

  4. RECOMBINANT INFLUENZA VACCINES

    OpenAIRE

    Sedova, E.; Shcherbinin, D.; Migunov, A.; Smirnov, Iu; Logunov, D.; Shmarov, M.; Tsybalova, L.; Naroditskiĭ, B.; O. Kiselev; Gintsburg, A.

    2012-01-01

    This review covers the problems encountered in the construction and production of new recombinant influenza vaccines. New approaches to the development of influenza vaccines are investigated; they include reverse genetics methods, production of virus-like particles, and DNA- and viral vector-based vaccines. Such approaches as the delivery of foreign genes by DNA- and viral vector-based vaccines can preserve the native structure of antigens. Adenoviral vectors are a promising gene-delivery pla...

  5. Cationic lipid-formulated DNA vaccine against hepatitis B virus: immunogenicity of MIDGE-Th1 vectors encoding small and large surface antigen in comparison to a licensed protein vaccine.

    Directory of Open Access Journals (Sweden)

    Anne Endmann

    Full Text Available Currently marketed vaccines against hepatitis B virus (HBV based on the small (S hepatitis B surface antigen (HBsAg fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals.

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

    Directory of Open Access Journals (Sweden)

    Chad E Mire

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

  7. Feline Foamy Virus-Based Vectors: Advantages of an Authentic Animal Model

    Directory of Open Access Journals (Sweden)

    Martin Löchelt

    2013-07-01

    Full Text Available New-generation retroviral vectors have potential applications in vaccination and gene therapy. Foamy viruses are particularly interesting as vectors, because they are not associated to any disease. Vector research is mainly based on primate foamy viruses (PFV, but cats are an alternative animal model, due to their smaller size and the existence of a cognate feline foamy virus (FFV. The potential of replication-competent (RC FFV vectors for vaccination and replication-deficient (RD FFV-based vectors for gene delivery purposes has been studied over the past years. In this review, the key achievements and functional evaluation of the existing vectors from in vitro cell culture systems to out-bred cats will be described. The data presented here demonstrate the broad application spectrum of FFV-based vectors, especially in pathogen-specific prophylactic and therapeutic vaccination using RD vectors in cats and in classical gene delivery. In the cat-based system, FFV-based vectors provide an advantageous platform to evaluate and optimize the applicability, efficacy and safety of foamy virus (FV vectors, especially the understudied aspect of FV cell and organ tropism.

  8. Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges

    International Nuclear Information System (INIS)

    The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guinea pigs. Significantly, guinea pigs vaccinated with at least 5 x 107 pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV

  9. Main features of DNA-based immunization vectors

    Directory of Open Access Journals (Sweden)

    V. Azevedo

    1999-02-01

    Full Text Available DNA-based immunization has initiated a new era of vaccine research. One of the main goals of gene vaccine development is the control of the levels of expression in vivo for efficient immunization. Modifying the vector to modulate expression or immunogenicity is of critical importance for the improvement of DNA vaccines. The most frequently used vectors for genetic immunization are plasmids. In this article, we review some of the main elements relevant to their design such as strong promoter/enhancer region, introns, genes encoding antigens of interest from the pathogen (how to choose and modify them, polyadenylation termination sequence, origin of replication for plasmid production in Escherichia coli, antibiotic resistance gene as selectable marker, convenient cloning sites, and the presence of immunostimulatory sequences (ISS that can be added to the plasmid to enhance adjuvanticity and to activate the immune system. In this review, the specific modifications that can increase overall expression as well as the potential of DNA-based vaccination are also discussed.

  10. Safety of the novel influenza viral vector Brucella abortus vaccine in pregnant heifers

    Directory of Open Access Journals (Sweden)

    Kaissar Tabynov

    2016-01-01

    Full Text Available ABSTRACT: The present study provides the first information about the safety of a new influenza viral vector vaccine expressing the Brucella ribosomal protein L7/L12 or Omp16 containing the adjuvant Montanide Gel01 in pregnant heifers. Immunization of pregnant heifers was conducted via the conjunctival (n=10 or subcutaneous (n=10 route using cross prime and booster vaccination schedules at an interval of 28 days. The vector vaccine was evaluated in comparison with positive control groups vaccinated with B. abortus S19 (n=10 or B. abortus RB51 (n=10 and a negative (PBS+Montanide Gel01; n=10 control group. Clinical studies, thermometry, assessment of local reactogenicity and observation of abortion showed that the vector vaccine via the conjunctival or subcutaneous route was completely safe for pregnant heifers compared to the commercial vaccines B. abortus S19 or B. abortus RB51. The only single adverse event was the formation of infiltration at the site of subcutaneous injection; this reaction was not observed for the conjunctival route.

  11. An antivector vaccine protects against a lethal vector-borne pathogen.

    Directory of Open Access Journals (Sweden)

    Milan Labuda

    2006-04-01

    Full Text Available Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks, have the potential to protect against the many diseases caused by vector-borne pathogens. We tested the ability of an anti-tick vaccine derived from a tick cement protein (64TRP of Rhipicephalus appendiculatus to protect mice against tick-borne encephalitis virus (TBEV transmitted by infected Ixodes ricinus ticks. The vaccine has a "dual action" in immunized animals: when infested with ticks, the inflammatory and immune responses first disrupt the skin feeding site, resulting in impaired blood feeding, and then specific anti-64TRP antibodies cross-react with midgut antigenic epitopes, causing rupture of the tick midgut and death of engorged ticks. Three parameters were measured: "transmission," number of uninfected nymphal ticks that became infected when cofeeding with an infected adult female tick; "support," number of mice supporting virus transmission from the infected tick to cofeeding uninfected nymphs; and "survival," number of mice that survived infection by tick bite and subsequent challenge by intraperitoneal inoculation of a lethal dose of TBEV. We show that one dose of the 64TRP vaccine protects mice against lethal challenge by infected ticks; control animals developed a fatal viral encephalitis. The protective effect of the 64TRP vaccine was comparable to that of a single dose of a commercial TBEV vaccine, while the transmission-blocking effect of 64TRP was better than that of the antiviral vaccine in reducing the number of animals supporting virus transmission. By contrast, the commercial antitick vaccine (TickGARD that targets only the tick's midgut showed transmission-blocking activity but was not protective. The 64TRP vaccine demonstrates the potential to control vector-borne disease by interfering with pathogen transmission, apparently by mediating a local cutaneous inflammatory immune response at the tick-feeding site.

  12. An Antivector Vaccine Protects against a Lethal Vector-Borne Pathogen.

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks, have the potential to protect against the many diseases caused by vector-borne pathogens. We tested the ability of an anti-tick vaccine derived from a tick cement protein (64TRP of Rhipicephalus appendiculatus to protect mice against tick-borne encephalitis virus (TBEV transmitted by infected Ixodes ricinus ticks. The vaccine has a "dual action" in immunized animals: when infested with ticks, the inflammatory and immune responses first disrupt the skin feeding site, resulting in impaired blood feeding, and then specific anti-64TRP antibodies cross-react with midgut antigenic epitopes, causing rupture of the tick midgut and death of engorged ticks. Three parameters were measured: "transmission," number of uninfected nymphal ticks that became infected when cofeeding with an infected adult female tick; "support," number of mice supporting virus transmission from the infected tick to cofeeding uninfected nymphs; and "survival," number of mice that survived infection by tick bite and subsequent challenge by intraperitoneal inoculation of a lethal dose of TBEV. We show that one dose of the 64TRP vaccine protects mice against lethal challenge by infected ticks; control animals developed a fatal viral encephalitis. The protective effect of the 64TRP vaccine was comparable to that of a single dose of a commercial TBEV vaccine, while the transmission-blocking effect of 64TRP was better than that of the antiviral vaccine in reducing the number of animals supporting virus transmission. By contrast, the commercial antitick vaccine (TickGARD that targets only the tick's midgut showed transmission-blocking activity but was not protective. The 64TRP vaccine demonstrates the potential to control vector-borne disease by interfering with pathogen transmission, apparently by mediating a local cutaneous inflammatory immune response at the tick-feeding site.

  13. [The vaccines based on the replicon of the venezuelan equine encephalomyelitis virus against viral hemorrhagic fevers].

    Science.gov (United States)

    Petrov, A A; Plekhanova, T M; Sidorova, O N; Borisevich, S V; Makhlay, A A

    2015-01-01

    The status of the various recombinant DNA and RNA-derived candidate vaccines, as well as the Venezuelan equine encephalomyelitis virus (VEEV) replicon vaccine system against extremely hazardous viral hemorrhagic fevers, were reviewed. The VEEV-based replication-incompetent vectors offer attractive features in terms of safety, high expression levels of the heterologous viral antigen, tropism to dendritic cells, robust immune responses, protection efficacy, low potential for pre-existing anti-vector immunity and possibility of engineering multivalent vaccines were tested. These features of the VEEV replicon system hold much promise for the development of new generation vaccine candidates against viral hemorrhagic fevers.

  14. General Considerations on the Biosafety of Virus-derived Vectors Used in Gene Therapy and Vaccination

    OpenAIRE

    Baldo, Aline; van den Akker, Eric; Bergmans, Hans E.; Lim, Filip; Pauwels, Katia

    2013-01-01

    This introductory paper gathers general considerations on the biosafety of virus-derived vectors that are used in human gene therapy and/or vaccination. The importance to assess the potential risks for human health and the environment related to the use of genetically modified organisms (GMO) in this case genetically modified viral vectors is highlighted by several examples. This environmental risk assessment is one of the requirements within the European regulatory framework covering the con...

  15. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge.

    Science.gov (United States)

    Schutta, Christopher; Barrera, José; Pisano, Melia; Zsak, Laszlo; Grubman, Marvin J; Mayr, Gregory A; Moraes, Mauro P; Kamicker, Barbara J; Brake, David A; Ettyreddy, Damodar; Brough, Douglas E; Butman, Bryan T; Neilan, John G

    2016-06-01

    The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0×10(8) to 2.1×10(11) particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R(2)=0.97) and viremia (R(2)=0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R(2)=0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge. PMID:26707216

  16. Algae-based oral recombinant vaccines

    OpenAIRE

    Specht, Elizabeth A.; Mayfield, Stephen P

    2014-01-01

    Recombinant subunit vaccines are some of the safest and most effective vaccines available, but their high cost and the requirement of advanced medical infrastructure for administration make them impractical for many developing world diseases. Plant-based vaccines have shifted that paradigm by paving the way for recombinant vaccine production at agricultural scale using an edible host. However, enthusiasm for “molecular pharming” in food crops has waned in the last decade due to difficulty in ...

  17. VaccineDA: Prediction, design and genome-wide screening of oligodeoxynucleotide-based vaccine adjuvants.

    Science.gov (United States)

    Nagpal, Gandharva; Gupta, Sudheer; Chaudhary, Kumardeep; Dhanda, Sandeep Kumar; Prakash, Satya; Raghava, Gajendra P S

    2015-01-01

    Immunomodulatory oligodeoxynucleotides (IMODNs) are the short DNA sequences that activate the innate immune system via toll-like receptor 9. These sequences predominantly contain unmethylated CpG motifs. In this work, we describe VaccineDA (Vaccine DNA adjuvants), a web-based resource developed to design IMODN-based vaccine adjuvants. We collected and analyzed 2193 experimentally validated IMODNs obtained from the literature. Certain types of nucleotides (e.g., T, GT, TC, TT, CGT, TCG, TTT) are dominant in IMODNs. Based on these observations, we developed support vector machine-based models to predict IMODNs using various compositions. The developed models achieved the maximum Matthews Correlation Coefficient (MCC) of 0.75 with an accuracy of 87.57% using the pentanucleotide composition. The integration of motif information further improved the performance of our model from the MCC of 0.75 to 0.77. Similarly, models were developed to predict palindromic IMODNs and attained a maximum MCC of 0.84 with the accuracy of 91.94%. These models were evaluated using a five-fold cross-validation technique as well as validated on an independent dataset. The models developed in this study were integrated into VaccineDA to provide a wide range of services that facilitate the design of DNA-based vaccine adjuvants (http://crdd.osdd.net/raghava/vaccineda/). PMID:26212482

  18. Utilizing poxviral vectored vaccines for antibody induction-progress and prospects.

    Science.gov (United States)

    Draper, Simon J; Cottingham, Matthew G; Gilbert, Sarah C

    2013-09-01

    Over the last decade, poxviral vectors emerged as a mainstay approach for the induction of T cell-mediated immunity by vaccination, and their suitability for human use has led to widespread clinical testing of candidate vectors against infectious intracellular pathogens and cancer. In contrast, poxviruses have been widely perceived in the vaccine field as a poor choice of vector for the induction of humoral immunity. However, a growing body of data, from both animal models and recent clinical trials, now suggests that these vectors can be successfully utilized to prime and boost B cells and effective antibody responses. Significant progress has been made in the context of heterologous prime-boost immunization regimes, whereby poxviruses are able to boost responses primed by other vectors, leading to the induction of high-titre antigen-specific antibody responses. In other cases, poxviral vectors have been shown to stimulate humoral immunity against both themselves and encoded transgenes, in particular viral surface proteins such as influenza haemagglutinin. In the veterinary field, recombinant poxviral vectors have made a significant impact with numerous vectors licensed for use against a variety of animal viruses. On-going studies continue to explore the potential of poxviral vectors to modulate qualitative aspects of the humoral response, as well as their amenability to adjuvantation seeking to improve quantitative antibody immunogenicity. Nevertheless, the underlying mechanisms of B cell induction by recombinant poxviruses remain poorly defined, and further work is necessary to help guide the rational optimization of future poxviral vaccine candidates aiming to induce antibodies. PMID:23746455

  19. Enhanced protective immunity of the chimeric vector-based vaccine rAdV-SFV-E2 against classical swine fever in pigs by a Salmonella bacterial ghost adjuvant.

    Science.gov (United States)

    Xia, Shui-Li; Lei, Jian-Lin; Du, Mingliang; Wang, Yimin; Cong, Xin; Xiang, Guang-Tao; Li, Lian-Feng; Yu, Shenye; Du, Enqi; Liu, Siguo; Sun, Yuan; Qiu, Hua-Ji

    2016-01-01

    Classical swine fever (CSF) is a highly contagious swine disease caused by classical swine fever virus (CSFV). Previously, we demonstrated that rAdV-SFV-E2, an adenovirus-delivered, Semliki Forest virus replicon-vectored marker vaccine against CSF, is able to protect pigs against lethal CSFV challenge. From an economical point of view, it will be beneficial to reduce the minimum effective dose of the vaccine. This study was designed to test the adjuvant effects of Salmonella enteritidis-derived bacterial ghosts (BG) to enhance the protective immunity of rAdV-SFV-E2 in pigs. Groups of 5-week-old pigs (n = 4) were immunized intramuscularly twice with 10(5) median tissue culture infective doses (TCID50) rAdV-SFV-E2 combined with 10(10) colony forming units (CFU) BG, 10(6) or 10(5) TCID50 rAdV-SFV-E2 alone or 10(10) CFU BG alone at an interval of 3 weeks, and challenged with the highly virulent CSFV Shimen strain at 1 week post-booster immunization. The results show that the pigs inoculated with 10(5) TCID50 rAdV-SFV-E2 plus BG or 10(6) TCID50 rAdV-SFV-E2 alone were completely protected from lethal CSFV challenge, in contrast with the pigs vaccinated with 10(5) TCID50 rAdV-SFV-E2 or BG alone, which displayed partial or no protection following virulent challenge. The data indicate that BG are a promising adjuvant to enhance the efficacy of rAdV-SFV-E2 and possibly other vaccines. PMID:27301745

  20. The interplay of vaccination and vector control on small dengue networks.

    Science.gov (United States)

    Hendron, Ross-William S; Bonsall, Michael B

    2016-10-21

    Dengue fever is a major public health issue affecting billions of people in over 100 countries across the globe. This challenge is growing as the invasive mosquito vectors, Aedes aegypti and Aedes albopictus, expand their distributions and increase their population sizes. Hence there is an increasing need to devise effective control methods that can contain dengue outbreaks. Here we construct an epidemiological model for virus transmission between vectors and hosts on a network of host populations distributed among city and town patches, and investigate disease control through vaccination and vector control using variants of the sterile insect technique (SIT). Analysis of the basic reproductive number and simulations indicate that host movement across this small network influences the severity of epidemics. Both vaccination and vector control strategies are investigated as methods of disease containment and our results indicate that these controls can be made more effective with mixed strategy solutions. We predict that reduced lethality through poor SIT methods or imperfectly efficacious vaccines will impact efforts to control disease spread. In particular, weakly efficacious vaccination strategies against multiple virus serotype diversity may be counter productive to disease control efforts. Even so, failings of one method may be mitigated by supplementing it with an alternative control strategy. Generally, our network approach encourages decision making to consider connected populations, to emphasise that successful control methods must effectively suppress dengue epidemics at this landscape scale. PMID:27457093

  1. General considerations on the biosafety of virus-derived vectors used in gene therapy and vaccination.

    Science.gov (United States)

    Baldo, Aline; van den Akker, Eric; Bergmans, Hans E; Lim, Filip; Pauwels, Katia

    2013-12-01

    This introductory paper gathers general considerations on the biosafety of virus-derived vectors that are used in human gene therapy and/or vaccination. The importance to assess the potential risks for human health and the environment related to the use of genetically modified organisms (GMO) in this case genetically modified viral vectors is highlighted by several examples. This environmental risk assessment is one of the requirements within the European regulatory framework covering the conduct of clinical trials using GMO. Risk assessment methodologies for the environmental risk assessment of genetically modified virus-derived vectors have been developed. PMID:24195604

  2. Antigen design enhances the immunogenicity of Semliki Forest virus-based therapeutic human papillomavirus vaccines

    NARCIS (Netherlands)

    Ip, P. P.; Boerma, A.; Walczak, M.; Oosterhuis, K.; Haanen, J. B.; Schumacher, T. N.; Nijman, H. W.; Daemen, T.

    2015-01-01

    Cellular immunity against cancer can be achieved with viral vector-and DNA-based immunizations. In preclinical studies, cancer vaccines are very potent, but in clinical trials these potencies are not achieved yet. Thus, a rational approach to improve cancer vaccines is warranted. We previously demon

  3. Vector prime/protein boost vaccine that overcomes defects acquired during aging and cancer

    DEFF Research Database (Denmark)

    Tang, Y.; Akbulut, H.; Maynard, J.;

    2006-01-01

    decrement of negative regulatory CD4CD25FOXP3-T cells in the tumor tissue of 18-mo-old mice. These results suggest that the Ad-sig-TAA/ecdCD40L vector prime-TAA/ecdCD40L protein boost vaccine platform may be valuable in reducing postsurgery recurrence in a variety of epithelial neoplasms....... following the Ad-sig-TAA/ecdCD40L vector, the levels of the TAA-specific CD8 T cells and Abs increase dramatically over that seen with vector alone, in young (2-mo-old) as well as old (18-mo-old) mice. The Abs induced against hMUC-1 react with human breast cancer. This vaccine also induces a 4-fold...

  4. Adenoviral Vector Vaccination Induces a Conserved Program of CD8+ T Cell Memory Differentiation in Mouse and Man

    Directory of Open Access Journals (Sweden)

    Beatrice Bolinger

    2015-11-01

    Full Text Available Following exposure to vaccines, antigen-specific CD8+ T cell responses develop as long-term memory pools. Vaccine strategies based on adenoviral vectors, e.g., those developed for HCV, are able to induce and sustain substantial CD8+ T cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T cell memory pools induced by an adenovector encoding a model antigen (beta-galactosidase. We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV. Key transcriptional hallmarks include upregulation of homing receptors and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet. In humans, an adenovirus vaccine induced similar CMV-like phenotypes and transcription factor regulation. These data clarify the core features of CD8+ T cell memory following vaccination with adenovectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.

  5. Liposome-Based Adjuvants for Subunit Vaccines

    DEFF Research Database (Denmark)

    Tandrup Schmidt, Signe; Foged, Camilla; Rades, Thomas

    2016-01-01

    The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens...... for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce...... been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI). Adjuvants constitute a heterogeneous group of compounds, which can broadly...

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

    Science.gov (United States)

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

    2012-10-01

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

  7. Enhanced and sustained CD8+ T cell responses with an adenoviral vector-based hepatitis C virus vaccine encoding NS3 linked to the MHC class II chaperone protein invariant chain

    DEFF Research Database (Denmark)

    Mikkelsen, Marianne; Holst, Peter Johannes; Bukh, Jens;

    2011-01-01

    Potent and broad cellular immune responses against the nonstructural (NS) proteins of hepatitis C virus (HCV) are associated with spontaneous viral clearance. In this study, we have improved the immunogenicity of an adenovirus (Ad)-based HCV vaccine by fusing NS3 from HCV (Strain J4; Genotype 1b...... memory. Functionally, the AdIiNS3-vaccinated mice had a significantly increased cytotoxic capacity compared with the AdNS3 group. The AdIiNS3-induced CD8(+) T cells protected mice from infection with recombinant vaccinia virus expressing HCV NS3 of heterologous 1b strains, and studies in knockout mice......) to the MHC class II chaperone protein invariant chain (Ii). We found that, after a single vaccination of C57BL/6 or BALB/c mice with Ad-IiNS3, the HCV NS3-specific CD8(+) T cell responses were significantly enhanced, accelerated, and prolonged compared with the vaccine encoding NS3 alone. The AdIiNS3...

  8. Development and Applications of VSV Vectors Based on Cell Tropism

    OpenAIRE

    HidekiTani; YoshiharuMatsuura

    2012-01-01

    Viral vectors have been available in various fields such as medical and biological research or gene therapy applications. Targeting vectors pseudotyped with distinct viral envelope proteins that influence cell tropism and transfection efficiency is a useful tool not only for examining entry mechanisms or cell tropisms but also for vaccine vector development. Vesicular stomatitis virus (VSV) is an excellent candidate for development as a pseudotype vector. A recombinant VSV lacking its own env...

  9. Development of a Canine Adenovirus Type 1 Vaccine Strain E3-deleted Based Expression Vector%犬腺病毒1型疫苗株E3缺失表达载体的构建

    Institute of Scientific and Technical Information of China (English)

    黎皓; 唐七义; 张云; 王树蕙; 郭彩云

    2001-01-01

    Objective To evaluate canine adenovirus type 1 vaccine strain (Cannaught Laboratory Limited,CLL) as recombinant vaccine and gene transfer vector. Methods Recombinant virus CLLEGFP which contains enhanced green fluorescent protein(EGFP) reporter gene was constructed. CLLEGFP was used to infect various human derived cell lines (293, Hela, CO, SW, Hep-2 and CAM) by inoculating intraperitoneally(IP), intravenously(IV)and intramuscularly (IM)to Kunming mice other than oral administration. Various tissue samples of the mice were collected at multitime point for observing EGFP green fluorescence. Anti-EGFP antibodies were detected by Western blot analysis in the sera after 4 weeks. Results CLLEGFP can infect various human derived cell lines and express EGFP. EGFP green fluorescence were observed in liver tissue cells after IP transducing 3 days. All immune inoculation ways above could induce Kunming mice producing anti-EGFP antibodies which were identified by Western blot analysis. Conclusions These resluts indicate that CLL possess powerful potential as recombinant vaccine and gene transfer vector.%探索以犬腺病毒1型疫苗株(Cannaught Laboratory Limited.CLL)作为病毒重组疫苗和基因转移载体的可行性。方法构建带增强型绿色荧光蛋白(enhanced green fluorescent protein,EGFP)报告基因的E3缺失重组病毒CLLEGFP。将CLLEGFP感染各种人源细胞,并以灌胃、腹腔注射、尾静脉注射和肌肉注射等不同途径接种昆明小鼠。多时间点取小鼠组织标本,冷冻干燥切片,观察EGFP的表达。4周后采集小鼠血清,以Western blot分析抗EGFP 抗体的产生。结果 CLLEGFP能够感染各种人源细胞并表达EGFP。在腹腔接种CLLEGFP 3 d的小鼠肝组织细胞中可见转导的EGFP。Western blot分析显示,以各种途径免疫接种重组病毒4周后的小鼠血清中均存在抗EGFP特异抗体。结论 CLL具有开发成为病毒重组疫苗和基因转移载体的潜力。

  10. HIV-1 vaccine-specific responses induced by Listeria vector vaccines are maintained in mice subsequently infected with a model helminth parasite, Schistosoma mansoni.

    Science.gov (United States)

    Shollenberger, Lisa M; Bui, Cac T; Paterson, Yvonne; Nyhoff, Lindsay; Harn, Donald A

    2013-11-19

    In areas co-endemic for helminth parasites and HIV/AIDS, infants are often administered vaccines prior to infection with immune modulatory helminth parasites. Systemic Th2 biasing and immune suppression caused by helminth infection reduces cell-mediated responses to vaccines such as tetanus toxoid and BCG. Therefore, we asked if infection with helminthes post-vaccination, alters already established vaccine induced immune responses. In our model, mice are vaccinated against HIV-1 Gag using a Listeria vaccine vector (Lm-Gag) in a prime-boost manner, then infected with the human helminth parasite Schistosoma mansoni. This allows us to determine if established vaccine responses are maintained or altered after helminth infection. Our second objective asked if helminth infection post-vaccination alters the recipient's ability to respond to a second boost. Here we compared responses between uninfected mice, schistosome infected mice, and infected mice that were given an anthelminthic, which occurred coincident with the boost or four weeks prior, as well as comparing to un-boosted mice. We report that HIV-1 vaccine-specific responses generated by Listeria vector HIV-1 vaccines are maintained following subsequent chronic schistosome infection, providing further evidence that Listeria vector vaccines induce potent vaccine-specific responses that can withstand helminth infection. We also were able to demonstrate that administration of a second Listeria boost, which markedly enhanced the immune response, was minimally impacted by schistosome infection, or anthelminthic therapy. Surprisingly, we also observed enhanced antibody responses to HIV Gag in vaccinated mice subsequently infected with schistosomes.

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

    Science.gov (United States)

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

    2011-01-01

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

  12. Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle

    Science.gov (United States)

    Medina, Gisselle N.; Montiel, Nestor; Diaz-San Segundo, Fayna; Sturza, Diego; Ramirez-Medina, Elizabeth; Grubman, Marvin J.

    2015-01-01

    Novel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4+ and CD8+ gamma interferon (IFN-γ)+ cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle. PMID:26607309

  13. Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle.

    Science.gov (United States)

    Medina, Gisselle N; Montiel, Nestor; Diaz-San Segundo, Fayna; Sturza, Diego; Ramirez-Medina, Elizabeth; Grubman, Marvin J; de los Santos, Teresa

    2015-11-25

    Novel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4(+) and CD8(+) gamma interferon (IFN-γ)(+) cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle.

  14. [Construction of recombinant yellow fever virus 17D containing 2A fragment as a vaccine vector].

    Science.gov (United States)

    Xiaowu, Pang; Fu, Wen-Chuan; Guo, Yin-Han; Zhang, Li-Shu; Xie, Tian-Pei; Xinbin, Gu

    2006-05-01

    The Yellow Fever (YF) vaccine, an attenuated yellow fever 17D (YF-17D) live vaccine, is one of the most effective and safest vaccines in the world and is regarded as one of the best candidates for viral expression vector. We here first reported in China the construction and characterization of the recombinant expression vector of yellow fever 17D which contained the proteinase 2A fragment of foot-and-mouth disease virus (FMDV). Three cDNA fragments representing the full-length YF-17D genome, named 5'-end cDNA (A), 3'-end cDNA (B) and middle cDNA (C), were obtained by reverse transcription polymerase chain reaction (RT-PCR), together with the introduction of SP6 enhancer, necessary restriction sites and overlaps for homologous recombination in yeast. Fragment A and B were then introduced into pRS424 in turn by DNA recombination, followed by transfection of fragment C and the recombinant pRS424 containing A and B (pRS-A-B) into yeast. A recombinant vector containing full length cDNA of YF-17D (pRS-YF) was obtained by screening on medium lack of tryptophan and uracil. A recombinant YF-17D expression vector containing FMDV-2A gene fragment (pRS-YF-2A1) was then constructed by methods of DNA recombination and homologous recombination in yeast described above. In vitro transcription of the recombinant vector pRS-YF-2A1 was then carried out and introduced into BHK-21 cells by electroporation. Results of indirect immunofluorescence assay (IFA) and titer determination showed a stable infectious recombinant virus was gotten, whose features such as growth curve were similar to those of the parental YF-17D. The results suggest that the recombinant vector pRS-YF-2A1, by introduction of heterogenous genes via 2A region, is potential to be an effective live vaccine expression vector. PMID:16755933

  15. Evaluation of fiber-modified adenovirus vector-vaccine against foot-and-mouth diseaes in cattle

    Science.gov (United States)

    Novel vaccination approaches against foot-and-mouth-disease (FMD) include the use of a replication-defective human adenovirus type 5 vector (Ad5) that contains the capsid encoding regions of FMD virus (FMDV). An Ad5.A24 has proven effective as a vaccine against FMD in swine and cattle. However, ther...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Particulate based vaccines for cancer immunotherapy

    NARCIS (Netherlands)

    Rosalia, Rodney Alexander

    2014-01-01

    In this thesis we describe our studies aimed at optimizing the efficacy of synthetic long peptide (SLP) vaccines via the encapsulation in Poly-(lactic-co-glycolic acid) (PLGA)particles. Immunotherapy based on SLP-vaccines has resulted in strong tumor specific immune response and importantly, impro

  19. Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free-ranging prairie dogs (Cynomys spp.), Colorado, USA

    Science.gov (United States)

    Tripp, Daniel W.; Rocke, Tonie E.; Streich, Sean P.; Abbott, Rachel C.; Osorio, Jorge E.; Miller, Michael W.

    2015-01-01

    Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.

  20. Apple latent spherical virus vector as vaccine for the prevention and treatment of mosaic diseases in pea, broad bean, and eustoma plants by bean yellow mosaic virus.

    Science.gov (United States)

    Satoh, Nozomi; Kon, Tatsuya; Yamagishi, Noriko; Takahashi, Tsubasa; Natsuaki, Tomohide; Yoshikawa, Nobuyuki

    2014-11-01

    We investigated the protective effects of a viral vector based on an Apple latent spherical virus (ALSV) harboring a segment of the Bean yellow mosaic virus (BYMV) genome against mosaic diseases in pea, broad bean, and eustoma plants caused by BYMV infection. In pea plants pre-inoculated with the ALSV vaccine and challenge inoculated with BYMV expressing green fluorescence protein, BYMV multiplication occurred in inoculated leaves, but was markedly inhibited in the upper leaves. No mosaic symptoms due to BYMV infection were observed in the challenged plants pre-inoculated with the ALSV vaccine. Simultaneous inoculation with the ALSV vaccine and BYMV also prevented mosaic symptoms in broad bean and eustoma plants, and BYMV accumulation was strongly inhibited in the upper leaves of plants treated with the ALSV vaccine. Pea and eustoma plants were pre-inoculated with BYMV followed by inoculation with the ALSV vaccine to investigate the curative effects of the ALSV vaccine. In both plant species, recovery from mosaic symptoms was observed in upper leaves and BYMV accumulation was inhibited in leaves developing post-ALSV vaccination. These results show that ALSV vaccination not only prevents mosaic diseases in pea, broad bean, and eustoma, but that it is also effective in curing these diseases. PMID:25386843

  1. Apple Latent Spherical Virus Vector as Vaccine for the Prevention and Treatment of Mosaic Diseases in Pea, Broad Bean, and Eustoma Plants by Bean Yellow Mosaic Virus

    Directory of Open Access Journals (Sweden)

    Nozomi Satoh

    2014-11-01

    Full Text Available We investigated the protective effects of a viral vector based on an Apple latent spherical virus (ALSV harboring a segment of the Bean yellow mosaic virus (BYMV genome against mosaic diseases in pea, broad bean, and eustoma plants caused by BYMV infection. In pea plants pre-inoculated with the ALSV vaccine and challenge inoculated with BYMV expressing green fluorescence protein, BYMV multiplication occurred in inoculated leaves, but was markedly inhibited in the upper leaves. No mosaic symptoms due to BYMV infection were observed in the challenged plants pre-inoculated with the ALSV vaccine. Simultaneous inoculation with the ALSV vaccine and BYMV also prevented mosaic symptoms in broad bean and eustoma plants, and BYMV accumulation was strongly inhibited in the upper leaves of plants treated with the ALSV vaccine. Pea and eustoma plants were pre-inoculated with BYMV followed by inoculation with the ALSV vaccine to investigate the curative effects of the ALSV vaccine. In both plant species, recovery from mosaic symptoms was observed in upper leaves and BYMV accumulation was inhibited in leaves developing post-ALSV vaccination. These results show that ALSV vaccination not only prevents mosaic diseases in pea, broad bean, and eustoma, but that it is also effective in curing these diseases.

  2. Oral Delivery of a Novel Recombinant Streptococcus mitis Vector Elicits Robust Vaccine Antigen-Specific Oral Mucosal and Systemic Antibody Responses and T Cell Tolerance.

    Directory of Open Access Journals (Sweden)

    Emily Xie

    Full Text Available The pioneer human oral commensal bacterium Streptococcus mitis has unique biologic features that make it an attractive mucosal vaccine or therapeutic delivery vector. S. mitis is safe as a natural persistent colonizer of the mouth, throat and nasopharynx and the oral commensal bacterium is capable of inducing mucosal antibody responses. A recombinant S. mitis (rS. mitis that stably expresses HIV envelope protein was generated and tested in the germ-free mouse model to evaluate the potential usefulness of this vector as a mucosal vaccine against HIV. Oral vaccination led to the efficient and persistent bacterial colonization of the mouth and the induction of both salivary and systemic antibody responses. Interestingly, persistently colonized animals developed antigen-specific systemic T cell tolerance. Based on these findings we propose the use of rS. mitis vaccine vector for the induction of mucosal antibodies that will prevent the penetration of the mucosa by pathogens such as HIV. Moreover, the first demonstration of rS. mitis having the ability to elicit T cell tolerance suggest the potential use of rS. mitis as an immunotherapeutic vector to treat inflammatory, allergic and autoimmune diseases.

  3. Combining viral vectored and protein-in-adjuvant vaccines against the blood-stage malaria antigen AMA1: report on a phase 1a clinical trial.

    Science.gov (United States)

    Hodgson, Susanne H; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Rampling, Thomas W; Biswas, Sumi; Poulton, Ian D; Miura, Kazutoyo; Douglas, Alexander D; Alanine, Daniel Gw; Illingworth, Joseph J; de Cassan, Simone C; Zhu, Daming; Nicosia, Alfredo; Long, Carole A; Moyle, Sarah; Berrie, Eleanor; Lawrie, Alison M; Wu, Yimin; Ellis, Ruth D; Hill, Adrian V S; Draper, Simon J

    2014-12-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines--chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising "mixed-modality" regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8- or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible. PMID:25156127

  4. Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

    Directory of Open Access Journals (Sweden)

    Ivan Y. C. Lin

    2015-11-01

    Full Text Available Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined.

  5. Algae-based oral recombinant vaccines.

    Science.gov (United States)

    Specht, Elizabeth A; Mayfield, Stephen P

    2014-01-01

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

  6. Algae-based oral recombinant vaccines.

    Science.gov (United States)

    Specht, Elizabeth A; Mayfield, Stephen P

    2014-01-01

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

  7. Algae-based oral recombinant vaccines

    Directory of Open Access Journals (Sweden)

    Elizabeth A Specht

    2014-02-01

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

  8. A Prime-Boost Vaccination Strategy in Cattle to Prevent Foot-and-Mouth Disease Using a "Single-Cycle" Alphavirus Vector and Empty Capsid Particles

    DEFF Research Database (Denmark)

    Gullberg, Maria; Lohse, Louise; Bøtner, Anette;

    2016-01-01

    Foot-and-mouth disease (FMD) remains one of the most economically important infectious diseases of production animals globally. Vaccination can successfully control this disease, however, current vaccines are imperfect. They are made using chemically inactivated FMD virus (FMDV) that is produced...... in large-scale mammalian cell culture under high containment conditions. Here, we have expressed the FMDV capsid protein precursor (P1-2A) of strain O1 Manisa alone or with the FMDV 3C protease (3Cpro) using a "single cycle" packaged alphavirus self-replicating RNA based on Semliki Forest virus (SFV). When...... observed was decreased in level and duration. In subsequent experiments, cattle were sequentially vaccinated with a rSFV-FMDV followed by recombinant FMDV empty capsid particles, or vice versa, prior to challenge. Animals given a primary vaccination with the rSFV-FMDV vector and then boosted with FMDV...

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

    OpenAIRE

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

    2014-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for mark...

  10. Glycoprotein Exchange Vectors Based on Vesicular Stomatitis Virus Allow Effective Boosting and Generation of Neutralizing Antibodies to a Primary Isolate of Human Immunodeficiency Virus Type 1

    OpenAIRE

    Rose, Nina F.; Roberts, Anjeanette; Buonocore, Linda; Rose, John K.

    2000-01-01

    Live recombinant vesicular stomatitis viruses (VSVs) expressing foreign antigens are highly effective vaccine vectors. However, these vectors induce high-titer neutralizing antibody directed at the single VSV glycoprotein (G), and this antibody alone can prevent reinfection and boosting with the same vector. To determine if efficient boosting could be achieved by changing the G protein of the vector, we have developed two new recombinant VSV vectors based on the VSV Indiana serotype but with ...

  11. Plant-Based Vaccines: Production and Challenges

    Directory of Open Access Journals (Sweden)

    Erna Laere

    2016-01-01

    Full Text Available Plant-based vaccine technologies involve the integration of the desired genes encoding the antigen protein for specific disease into the genome of plant tissues by various methods. Agrobacterium-mediated gene transfer and transformation via genetically modified plant virus are the common methods that have been used to produce effective vaccines. Nevertheless, with the advancement of science and technology, new approaches have been developed to increase the efficiency of former methods such as biolistic, electroporation, agroinfiltration, sonication, and polyethylene glycol treatment. Even though plant-based vaccines provide many benefits to the vaccine industry, there are still challenges that limit the rate of successful production of these third-generation vaccines. Even with all the limitations, continuous efforts are still ongoing in order to produce efficient vaccine for many human and animals related diseases owing to its great potentials. This paper reviews the existing conventional methods as well as the development efforts by researchers in order to improve the production of plant-based vaccines. Several challenges encountered during and after the production process were also discussed.

  12. Different Levels of Immunogenicity of Two Strains of Fowlpox Virus as Recombinant Vaccine Vectors Eliciting T-Cell Responses in Heterologous Prime-Boost Vaccination Strategies

    OpenAIRE

    Cottingham, Matthew G; van Maurik, Andre; Zago, Manola; Newton, Angela T.; Anderson, Richard J.; Howard, M. Keith; Schneider, Jörg; Skinner, Michael A.

    2006-01-01

    The FP9 strain of Fowlpox virus has been described as a more immunogenic recombinant vaccine vector than the Webster FPV-M (FPW) strain (R. J. Anderson et al., J. Immunol. 172:3094-3100, 2004). This study expands the comparison to include two separate recombinant antigens and multiple, rather than single, independent viral clones derived from the two strains. Dual-poxvirus heterologous prime-boost vaccination regimens using individual clones of recombinant FP9 or FPW in combination with recom...

  13. Vector Development for the Expression of Foreign Proteins in the Vaccine Strain Brucella abortus S19

    OpenAIRE

    Diego J Comerci; Pollevick, Guido D.; Vigliocco, Ana M.; Frasch, Alberto C. C.; Ugalde, Rodolfo A.

    1998-01-01

    A vector for the expression of foreign antigens in the vaccine strain Brucella abortus S19 was developed by using a DNA fragment containing the regulatory sequences and the signal peptide of the Brucella bcsp31 gene. This fragment was cloned in broad-host-range plasmid pBBR4MCS, resulting in plasmid pBEV. As a reporter protein, a repetitive antigen of Trypanosoma cruzi was used. The recombinant fusion protein is stably expressed and secreted into the Brucella periplasmic space, inducing a goo...

  14. Vaccination with lentiviral vector expressing the nfa1 gene confers a protective immune response to mice infected with Naegleria fowleri.

    Science.gov (United States)

    Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Jinyoung; Yang, Hee-Jong; Chwae, Yong-Joon; Kim, Kyongmin; Park, Sun; Shin, Ho-Joon

    2013-07-01

    Naegleria fowleri, a pathogenic free-living amoeba, causes fatal primary amoebic meningoencephalitis (PAM) in humans and animals. The nfa1 gene (360 bp), cloned from a cDNA library of N. fowleri, produces a 13.1-kDa recombinant protein which is located on pseudopodia, particularly the food cup structure. The nfa1 gene plays an important role in the pathogenesis of N. fowleri infection. To examine the effect of nfa1 DNA vaccination against N. fowleri infection, we constructed a lentiviral vector (pCDH) expressing the nfa1 gene. For the in vivo mouse study, BALB/c mice were intranasally vaccinated with viral particles of a viral vector expressing the nfa1 gene. To evaluate the effect of vaccination and immune responses of mice, we analyzed the IgG levels (IgG, IgG1, and IgG2a), cytokine induction (interleukin-4 [IL-4] and gamma interferon [IFN-γ]), and survival rates of mice that developed PAM. The levels of both IgG and IgG subclasses (IgG1 and IgG2a) in vaccinated mice were significantly increased. The cytokine analysis showed that vaccinated mice exhibited greater IL-4 and IFN-γ production than the other control groups, suggesting a Th1/Th2 mixed-type immune response. In vaccinated mice, high levels of Nfa1-specific IgG antibodies continued until 12 weeks postvaccination. The mice vaccinated with viral vector expressing the nfa1 gene also exhibited significantly higher survival rates (90%) after challenge with N. fowleri trophozoites. Finally, the nfa1 vaccination effectively induced protective immunity by humoral and cellular immune responses in N. fowleri-infected mice. These results suggest that DNA vaccination using a viral vector may be a potential tool against N. fowleri infection.

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

    OpenAIRE

    Xiang Zuoshuang; Hur Junguk; Feldman Eva L; He Yongqun

    2011-01-01

    Abstract Background Vaccine literature indexing is poorly performed in PubMed due to limited hierarchy of Medical Subject Headings (MeSH) annotation in the vaccine field. Vaccine Ontology (VO) is a community-based biomedical ontology that represents various vaccines and their relations. SciMiner is an in-house literature mining system that supports literature indexing and gene name tagging. We hypothesize that application of VO in SciMiner will aid vaccine literature indexing and mining of va...

  16. An equine herpesvirus 1 (EHV-1) vectored H1 vaccine protects against challenge with swine-origin influenza virus H1N1.

    Science.gov (United States)

    Said, Abdelrahman; Damiani, Armando; Ma, Guanggang; Kalthoff, Donata; Beer, Martin; Osterrieder, Nikolaus

    2011-12-29

    In 2009, a novel swine-origin H1N1 influenza A virus (S-OIV), antigenically and genetically divergent from seasonal H1N1, caused a flu pandemic in humans. Development of an effective vaccine to limit transmission of S-OIV in animal reservoir hosts and from reservoir hosts to humans and animals is necessary. In the present study, we constructed and evaluated a vectored vaccine expressing the H1 hemagglutinin of a recent S-OIV isolate using equine herpesvirus 1 (EHV-1) as the delivery vehicle. Expression of the recombinant protein was demonstrated by immunofluorescence and western blotting and the in vitro growth properties of the modified live vector were found to be comparable to those of the parental virus. The EHV-1-H1 vaccine induced an influenza virus-specific antibody response when inoculated into mice by both the intranasal and subcutaneous routes. Upon challenge infection, protection of vaccinated mice could be demonstrated by reduction of clinical signs and faster virus clearance. Our study shows that an EHV-1-based influenza H1N1 vaccine may be a promising alternative for protection against S-OIV infection.

  17. Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

    OpenAIRE

    Ru Wen; Umeano, Afoma C.; Lily Francis; Nivita Sharma; Smanla Tundup; Shanta Dhar

    2016-01-01

    Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death ...

  18. Evaluation of the Protection Efficacy of a Serotype 1 Marek's Disease Virus-Vectored Bivalent Vaccine Against Infectious Laryngotracheitis and Marek's Disease.

    Science.gov (United States)

    Gimeno, Isabel M; Cortes, Aneg L; Faiz, Nik M; Hernandez-Ortiz, Byron A; Guy, James S; Hunt, Henry D; Silva, Robert F

    2015-06-01

    Laryngotracheitis (LT) is a highly contagious respiratory disease of chickens that produces significant economic losses to the poultry industry. Traditionally, LT has been controlled by administration of modified live vaccines. In recent years, the use of recombinant DNA-derived vaccines using turkey herpesvirus (HVT) and fowlpox virus has expanded, as they protect not only against the vector used but also against LT. However, HVT-based vaccines confer limited protection against challenge, with emergent very virulent plus Marek's disease virus (vv+MDV). Serotype 1 vaccines have been proven to be the most efficient against vv+MDV. In particular, deletion of oncogene MEQ from the oncogenic vvMDV strain Md5 (BACδMEQ) resulted in a very efficient vaccine against vv+MDV. In this work, we have developed two recombinant vaccines against MD and LT by using BACδMEQ as a vector that carries either the LT virus (LTV) gene glycoprotein B (gB; BACΔMEQ-gB) or LTV gene glycoprotein J (gJ; BACδMEQ-gJ). We have evaluated the protection that these recombinant vaccines confer against MD and LT challenge when administered alone or in combination. Our results demonstrated that both bivalent vaccines (BACΔMEQ-gB and BACδMEQ-gJ) replicated in chickens and were safe to use in commercial meat-type chickens bearing maternal antibodies against MDV. BACΔMEQ-gB protected as well as a commercial recombinant (r)HVT-LT vaccine against challenge with LTV. However, BACδMEQ-gJ did not protect adequately against LT challenge or increase protection conferred by BACΔMEQ-gB when administered in combination. On the other hand, both BACΔMEQ-gB and BACδMEQ-gJ, administered alone or in combination, protected better against an early challenge with vv+MDV strain 648A than commercial strains of rHVT-LT or CVI988. Our results open a new avenue in the development of recombinant vaccines by using serotype 1 MDV as vectors.

  19. Plant-based vaccines: novel and low-cost possible route for Mediterranean innovative vaccination strategies.

    Science.gov (United States)

    Aboul-Ata, Aboul-Ata E; Vitti, Antonella; Nuzzaci, Maria; El-Attar, Ahmad K; Piazzolla, Giuseppina; Tortorella, Cosimo; Harandi, Ali M; Olson, Olof; Wright, Sandra A; Piazzolla, Pasquale

    2014-01-01

    A plant bioreactor has enormous capability as a system that supports many biological activities, that is, production of plant bodies, virus-like particles (VLPs), and vaccines. Foreign gene expression is an efficient mechanism for getting protein vaccines against different human viral and nonviral diseases. Plants make it easy to deal with safe, inexpensive, and provide trouble-free storage. The broad spectrum of safe gene promoters is being used to avoid risk assessments. Engineered virus-based vectors have no side effect. The process can be manipulated as follows: (a) retrieve and select gene encoding, use an antigenic protein from GenBank and/or from a viral-genome sequence, (b) design and construct hybrid-virus vectors (viral vector with a gene of interest) eventually flanked by plant-specific genetic regulatory elements for constitutive expression for obtaining chimeric virus, (c) gene transformation and/or transfection, for transient expression, into a plant-host model, that is, tobacco, to get protocols processed positively, and then moving into edible host plants, (d) confirmation of protein expression by bioassay, PCR-associated tests (RT-PCR), Northern and Western blotting analysis, and serological assay (ELISA), (e) expression for adjuvant recombinant protein seeking better antigenicity, (f) extraction and purification of expressed protein for identification and dosing, (g) antigenicity capability evaluated using parental or oral delivery in animal models (mice and/or rabbit immunization), and (h) growing of construct-treated edible crops in protective green houses. Some successful cases of heterologous gene-expressed protein, as edible vaccine, are being discussed, that is, hepatitis C virus (HCV). R9 mimotope, also named hypervariable region 1 (HVR1), was derived from the HVR1 of HCV. It was used as a potential neutralizing epitope of HCV. The mimotope was expressed using cucumber mosaic virus coat protein (CP), alfalfa mosaic virus CP P3/RNA3, and

  20. Influence of HEK293 metabolism on the production of viral vectors and vaccine.

    Science.gov (United States)

    Petiot, Emma; Cuperlovic-Culf, Miroslava; Shen, Chun Fang; Kamen, Amine

    2015-11-01

    Mammalian cell cultures are increasingly used for the production of complex biopharmaceuticals including viral vectors and vaccines. HEK293 is the predominant cell line used for the transient expression of recombinant proteins and a well-established system for the production of viral vectors. Understanding metabolic requirements for high productivity in HEK293 cells remains an important area of investigation. Many authors have presented approaches for increased productivity through optimization of cellular metabolism from two distinct perspectives. One is a non-targeted approach, which is directed to improving feeding strategies by addition of exhausted or critical substrates and eventually removal of toxic metabolites. Alternatively, a targeted approach has attempted to identify specific targets for optimization through better understanding of the cellular metabolism under different operating conditions. This review will present both approaches and their successes with regards to improvement of viral production in HEK293 cells outlining the key relations between HEK293 cell metabolism and viral vector productivity. Also, we will summarize the current knowledge on HEK293 metabolism indicating remaining issues to address and problems to resolve to maximize the productivity of viral vectors in HEK293 cells.

  1. In situ tumor vaccination with adenovirus vectors encoding measles virus fusogenic membrane proteins and cytokines

    Institute of Scientific and Technical Information of China (English)

    Dennis Hoffmann; Wibke Bayer; Oliver Wildner

    2007-01-01

    AIM: To evaluate whether intratumoral expression of measles virus fusogenic membrane glycoproteins H and "F (MV-FMG), encoded by an adenovirus vector Ad.MV-H/ F, alone or in combination with local coexpression of cytokines (IL-2, IL-12, IL-18, IL-21 or GM-CSF), can serve as a platform for inducing tumor-specific immune responses in colon cancer.METHODS: We used confocal laser scanning microscopy and flow cytometry to analyze cell-cell fusion after expression of MV-FMG by dye colocalization. In a syngeneic bilateral subcutaneous MC38 and Colon26 colon cancer model in C57BL/6 and BALB/c mice, we assessed the effect on both the directly vector-treated tumor as well as the contralateral, not directly vector-treated tumor. We assessed the induction of a tumor-specific cytotoxic T lymphocyte (CTL) response with a lactate dehydrogenase (LDH) release assay.RESULTS: We demonstrated in vitro that transduction of MC38 and Colon26 cells with Ad.MV-H/F resulted in dye colocalization, indicative of cell-cell fusion. In addition, in the syngeneic bilateral tumor model we demonstrated a significant regression of the directly vector-inoculated tumor upon intratumoral expression of MV-FMG alone or in combination with the tested cytokines. We observed the highest anti-neoplastic efficacy with MV-FMG and IL-21 coexpression. The degree of tumor regression of the not directly vector-treated tumor correlated with the anti-neoplastic response of the directly vector-treated tumor. This regression was mediated by a tumor-specific CTL response.CONCLUSION: Our data indicate that intratumoral expression of measles virus fusogenic membrane glycoproteins is a promising tool both for direct tumor treatment as well as for tumor vaccination approaches that can be further enhanced by cytokine coexpression.

  2. Nonlinear Growth of Singular Vector Based Perturbations

    Science.gov (United States)

    Reynolds, C. A.

    2002-12-01

    The nonlinearity of singular vector-based perturbation growth is examined within the context of a global atmospheric forecast model. The characteristics of these nonlinearities and their impact on the utility of SV-based diagnostics are assessed both qualitatively and quantitatively. Nonlinearities are quantified by examining the symmetry of evolving positive and negative "twin" perturbations. Perturbations initially scaled to be consistent with estimates of analysis uncertainty become significantly nonlinear by 12 hours. However, the relative magnitude of the nonlinearities is a strong function of scale and metric. Small scales become nonlinear very quickly while synoptic scales can remain significantly linear out to three day. Small shifts between positive and negative perturbations can result in significant nonlinearities even when the basic anomaly patterns are quite similar. Thus, singular vectors may be qualitatively useful even when nonlinearities are large. Post-time pseudo-inverse experiments show that despite significant nonlinear perturbation growth, the nonlinear forecast corrections are similar to the expected linear corrections, even at 72 hours. When the nonlinear correction does differ significantly from the expected linear correction, the nonlinear correction is usually better, indicating that in some cases the pseudo-inverse correction effectively suppresses error growth outside the subspace defined by the leading (dry) singular vectors. Because a significant portion of the nonlinear growth occurs outside of the dry singular vector subspace, an a priori nonlinearity index based on the full perturbations is not a good predictor of when pseudo-inverse based corrections will be ineffective. However, one can construct a reasonable predictor of pseudo-inverse ineffectiveness by focusing on nonlinearities in the synoptic scales or in the singular vector subspace only.

  3. Apple Latent Spherical Virus Vector as Vaccine for the Prevention and Treatment of Mosaic Diseases in Pea, Broad Bean, and Eustoma Plants by Bean Yellow Mosaic Virus

    OpenAIRE

    Nozomi Satoh; Tatsuya Kon; Noriko Yamagishi; Tsubasa Takahashi; Tomohide Natsuaki; Nobuyuki Yoshikawa

    2014-01-01

    We investigated the protective effects of a viral vector based on an Apple latent spherical virus (ALSV) harboring a segment of the Bean yellow mosaic virus (BYMV) genome against mosaic diseases in pea, broad bean, and eustoma plants caused by BYMV infection. In pea plants pre-inoculated with the ALSV vaccine and challenge inoculated with BYMV expressing green fluorescence protein, BYMV multiplication occurred in inoculated leaves, but was markedly inhibited in the upper leaves. No mosaic sym...

  4. Cost-Based Vectorization of Instance-Based Integration Processes

    Science.gov (United States)

    Boehm, Matthias; Habich, Dirk; Preissler, Steffen; Lehner, Wolfgang; Wloka, Uwe

    The inefficiency of integration processes—as an abstraction of workflow-based integration tasks—is often reasoned by low resource utilization and significant waiting times for external systems. With the aim to overcome these problems, we proposed the concept of process vectorization. There, instance-based integration processes are transparently executed with the pipes-and-filters execution model. Here, the term vectorization is used in the sense of processing a sequence (vector) of messages by one standing process. Although it has been shown that process vectorization achieves a significant throughput improvement, this concept has two major drawbacks. First, the theoretical performance of a vectorized integration process mainly depends on the performance of the most cost-intensive operator. Second, the practical performance strongly depends on the number of available threads. In this paper, we present an advanced optimization approach that addresses the mentioned problems. Therefore, we generalize the vectorization problem and explain how to vectorize process plans in a cost-based manner. Due to the exponential complexity, we provide a heuristic computation approach and formally analyze its optimality. In conclusion of our evaluation, the message throughput can be significantly increased compared to both the instance-based execution as well as the rule-based process vectorization.

  5. Topology based methods for vector field comparisons

    Science.gov (United States)

    Batra, Rajesh Kumar

    Vector fields are commonly found in almost all branches of the physical sciences. Aerodynamics, dynamical systems, electromagnetism, and global climate modeling are a few examples. These multivariate data fields are often large, and no general, automated method exists for comparing these fields. Existing methods require either subjective visual judgments, or data interface compatibility, or domain specific knowledge. A topology based method intrinsically eliminates all of the above limitations and has the additional advantage of significantly compressing the vector field by representing only key features of the flow. Therefore, large databases are compactly represented and quickly searched. Topology is a natural framework for the study of many vector fields. It provides rules of an organizing principle, a flow grammar, that can describe and connect together the properties common to flows. Helman and Hesselink first introduced automated methods to extract and visualize this grammar. This work extends their method by introducing automated methods for vector topology comparison. Basic two-dimensional flows are first compared. The theory is extended to compare three-dimensional flow fields and the topology on no-slip surfaces. Concepts from graph theory and linear programming are utilized to solve these problems. Finally, the first automated method for higher order singularity comparisons is introduced using mathematical theories from geometric (Clifford) algebra.

  6. Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

    OpenAIRE

    Wee, Sunmee; Hicks, Martin J.; De, Bishnu P.; Rosenberg, Jonathan B; Moreno, Amira Y.; KaMinSky, Stephen M.; Kim D. Janda; Crystal, Ronald G.; Koob, George F.

    2011-01-01

    Immunotherapy is a promising treatment for drug addiction. However, insufficient immune responses to vaccines in most subjects pose a challenge. In this study, we tested the efficacy of a new cocaine vaccine (dAd5GNE) in antagonizing cocaine addiction-related behaviors in rats. This vaccine used a disrupted serotype 5 adenovirus (Ad) gene transfer vector coupled to a third-generation cocaine hapten, termed GNE (6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido-hexano...

  7. Co-expression of tumor antigen and interleukin-2 from an adenoviral vector augments the efficiency of therapeutic tumor vaccination

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech; Steffensen, Maria Abildgaard; Nørgaard Nielsen, Karen;

    2014-01-01

    approach where the target antigen fused to Ii is expressed from the adenoviral E1 region and IL-2 is expressed from the E3 region. Immunization of mice with this new vector construct resulted in an augmented primary effector CD8+ T-cell response. Furthermore, in a melanoma model we observed significantly...... prolonged tumor control in vaccinated wild type (WT) mice. The improved tumor control required antigen-specific cells, since no tumor control was observed, unless the melanoma cells expressed the vaccine targeted antigen. We also tested our new vaccine in immunodeficient (CD80/86 deficient) mice. Following...

  8. Biotechnology-based allergy diagnosis and vaccination.

    Science.gov (United States)

    Bhalla, Prem L; Singh, Mohan B

    2008-03-01

    The diagnosis and immunotherapy currently applied to allergic diseases involve the use of crude extracts of the allergen source without defining the allergy-eliciting molecule(s). Advances in recombinant DNA technology have made identification, cloning, expression and epitope mapping of clinically significant allergens possible. Recombinant allergens that retain the immunological features of natural allergens form the basis of accurate protein-chip-based methods for diagnosing allergic conditions. The ability to produce rationally designed hypoallergenic forms of allergens is leading to the development of novel and safe forms of allergy vaccines with improved efficacy. The initial clinical tests on recombinant-allergen-based vaccine preparations have provided positive results, and ongoing developments in areas such as alternative routes of vaccine delivery will enhance patient compliance.

  9. Automated production of plant-based vaccines and pharmaceuticals.

    Science.gov (United States)

    Wirz, Holger; Sauer-Budge, Alexis F; Briggs, John; Sharpe, Aaron; Shu, Sudong; Sharon, Andre

    2012-12-01

    A fully automated "factory" was developed that uses tobacco plants to produce large quantities of vaccines and other therapeutic biologics within weeks. This first-of-a-kind factory takes advantage of a plant viral vector technology to produce specific proteins within the leaves of rapidly growing plant biomass. The factory's custom-designed robotic machines plant seeds, nurture the growing plants, introduce a viral vector that directs the plant to produce a target protein, and harvest the biomass once the target protein has accumulated in the plants-all in compliance with Food and Drug Administration (FDA) guidelines (e.g., current Good Manufacturing Practices). The factory was designed to be time, cost, and space efficient. The plants are grown in custom multiplant trays. Robots ride up and down a track, servicing the plants and delivering the trays from the lighted, irrigated growth modules to each processing station as needed. Using preprogrammed robots and processing equipment eliminates the need for human contact, preventing potential contamination of the process and economizing the operation. To quickly produce large quantities of protein-based medicines, we transformed a laboratory-based biological process and scaled it into an industrial process. This enables quick, safe, and cost-effective vaccine production that would be required in case of a pandemic.

  10. Ad35 and ad26 vaccine vectors induce potent and cross-reactive antibody and T-cell responses to multiple filovirus species.

    Directory of Open Access Journals (Sweden)

    Roland Zahn

    Full Text Available Filoviruses cause sporadic but highly lethal outbreaks of hemorrhagic fever in Africa in the human population. Currently, no drug or vaccine is available for treatment or prevention. A previous study with a vaccine candidate based on the low seroprevalent adenoviruses 26 and 35 (Ad26 and Ad35 was shown to provide protection against homologous Ebola Zaire challenge in non human primates (NHP if applied in a prime-boost regimen. Here we have aimed to expand this principle to construct and evaluate Ad26 and Ad35 vectors for development of a vaccine to provide universal filovirus protection against all highly lethal strains that have caused major outbreaks in the past. We have therefore performed a phylogenetic analysis of filovirus glycoproteins to select the glycoproteins from two Ebola species (Ebola Zaire and Ebola Sudan/Gulu,, two Marburg strains (Marburg Angola and Marburg Ravn and added the more distant non-lethal Ebola Ivory Coast species for broadest coverage. Ad26 and Ad35 vectors expressing these five filovirus glycoproteins were evaluated to induce a potent cellular and humoral immune response in mice. All adenoviral vectors induced a humoral immune response after single vaccination in a dose dependent manner that was cross-reactive within the Ebola and Marburg lineages. In addition, both strain-specific as well as cross-reactive T cell responses could be detected. A heterologous Ad26-Ad35 prime-boost regime enhanced mainly the humoral and to a lower extend the cellular immune response against the transgene. Combination of the five selected filovirus glycoproteins in one multivalent vaccine potentially elicits protective immunity in man against all major filovirus strains that have caused lethal outbreaks in the last 20 years.

  11. DNA-Based Vaccine Guards Against Zika in Monkey Study

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_161106.html DNA-Based Vaccine Guards Against Zika in Monkey Study ... THURSDAY, Sept. 22, 2016 (HealthDay News) -- An experimental DNA-based vaccine protected monkeys from infection with the ...

  12. Vector Control Based on SVPWM for ACIM

    Directory of Open Access Journals (Sweden)

    Zhu Jun

    2013-05-01

    Full Text Available To solve the large torque ripple and current harmonics, low DC bus voltage problems, a new control strategy is proposed for AC induction motor by using space vector pulse width modulation, so that the static and dynamic performance are improved. The system simulation experiment mode was established based on SVPWM to verify the effectiveness of the system control mode. It is showed that it can reduce the current ripple and torque ripple, improve the utilization of DC bus voltage. It means that the control strategy based SVPWM can improve dynamic and static performance effectively for the ACIM servo system.

  13. Oral immunization of broiler chickens against necrotic enteritis with an attenuated Salmonella vaccine vector expressing Clostridium perfringens antigens.

    Science.gov (United States)

    Kulkarni, R R; Parreira, V R; Sharif, S; Prescott, J F

    2008-08-01

    Necrotic enteritis (NE) in broiler chickens is caused by Clostridium perfringens but currently no effective vaccine is available. Our previous study showed that certain C. perfringens secreted proteins when administered intramuscularly protected chickens against experimental infection. In the current study, genes encoding three C. perfringens proteins: fructose-biphosphate-aldolase (FBA), pyruvate:ferredoxin-oxidoreductase (PFOR) and hypothetical protein (HP), were cloned into an avirulent Salmonella enterica sv. typhimurium vaccine vector. Broiler chickens immunized orally with recombinant Salmonella expressing FBA or HP proteins were significantly protected against NE challenge. Immunized birds developed serum and mucosal antibodies to both clostridial and Salmonella antigens. This study showed the oral immunizing ability of two C. perfringens antigens against NE in broiler chickens through an attenuated Salmonella vaccine vector. PMID:18597901

  14. Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications

    Directory of Open Access Journals (Sweden)

    Minoru Kidokoro

    2014-10-01

    Full Text Available The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R from LC16m8 to derive LC16m8Δ. LC16m8∆ is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8∆ is >500-fold more effective than the non-replicating vaccinia virus (VV, Modified Vaccinia Ankara (MVA, at inducing murine immune responses against pathogenic VV. LC16m8∆, which expresses the SIV gag gene, also induced anti-Gag CD8+ T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs. Moreover, LC16m8∆ expressing HIV-1 Env in combination with a Sendai virus vector induced the production of anti-Env antibodies and CD8+ T-cells. Thus, the safety and efficacy of LC16m8∆ mean that it represents an outstanding platform for the development of human vaccine vectors.

  15. Robust Video Stabilization Based on Motion Vectors

    Institute of Scientific and Technical Information of China (English)

    宋利; 周源华; 周军

    2005-01-01

    This paper proposes a new robust video stabilization algorithm to remove unwanted vibrations in video sequences. A complete theoretical analysis is first established for video stabilization, providing a basis for new stabilization algorithm. Secondly, a new robust global motion estimation (GME) algorithm is proposed. Different from classic methods, the GME algorithm is based on spatlal-temporal filtered motion vectors computed by block-matching methods. In addition, effective schemes are employed in correction phase to prevent boundary artifacts and error accumulation. Experiments show that the proposed algorithm has satisfactory stabilization effects while maintaining good tradeoff between speed and precision.

  16. An influenza viral vector Brucella abortus vaccine induces good cross-protection against Brucella melitensis infection in pregnant heifers.

    Science.gov (United States)

    Tabynov, Kaissar; Ryskeldinova, Sholpan; Sansyzbay, Abylai

    2015-07-17

    Brucella melitensis can be transmitted and cause disease in cattle herds as a result of inadequate management of mixed livestock farms. Ideally, vaccines against Brucella abortus for cattle should also provide cross-protection against B. melitensis. Previously we created a novel influenza viral vector B. abortus (Flu-BA) vaccine expressing the Brucella ribosomal proteins L7/L12 or Omp16. This study demonstrated Flu-BA vaccine with adjuvant Montanide Gel01 provided 100% protection against abortion in vaccinated pregnant heifers and good cross-protection of the heifers and their calves or fetuses (90-100%) after challenge with B. melitensis 16M; the level of protection provided by Flu-BA was comparable to the commercial vaccine B. abortus S19. In terms of the index of infection and colonization of Brucella in tissues, both vaccines demonstrated significant (P=0.02 to P<0.0001) protection against B. melitensis 16M infection compared to the negative control group (PBS+Montanide Gel01). Thus, we conclude the Flu-BA vaccine provides cross-protection against B. melitensis infection in pregnant heifers. PMID:26093199

  17. A Prime-Boost Vaccination Strategy in Cattle to Prevent Foot-and-Mouth Disease Using a “Single-Cycle” Alphavirus Vector and Empty Capsid Particles

    Science.gov (United States)

    Gullberg, Maria; Lohse, Louise; Bøtner, Anette; McInerney, Gerald M.; Burman, Alison; Jackson, Terry; Polacek, Charlotta

    2016-01-01

    Foot-and-mouth disease (FMD) remains one of the most economically important infectious diseases of production animals globally. Vaccination can successfully control this disease, however, current vaccines are imperfect. They are made using chemically inactivated FMD virus (FMDV) that is produced in large-scale mammalian cell culture under high containment conditions. Here, we have expressed the FMDV capsid protein precursor (P1-2A) of strain O1 Manisa alone or with the FMDV 3C protease (3Cpro) using a “single cycle” packaged alphavirus self-replicating RNA based on Semliki Forest virus (SFV). When the FMDV P1-2A was expressed with 3Cpro then processing of the FMDV capsid precursor protein is observed within cells and the proteins assemble into empty capsid particles. The products interact with anti-FMDV antibodies in an ELISA and bind to the integrin αvβ6 (a cellular receptor for FMDV). In cattle vaccinated with these rSFV-FMDV vectors alone, anti-FMDV antibodies were elicited but the immune response was insufficient to give protection against FMDV challenge. However, the prior vaccination with these vectors resulted in a much stronger immune response against FMDV post-challenge and the viremia observed was decreased in level and duration. In subsequent experiments, cattle were sequentially vaccinated with a rSFV-FMDV followed by recombinant FMDV empty capsid particles, or vice versa, prior to challenge. Animals given a primary vaccination with the rSFV-FMDV vector and then boosted with FMDV empty capsids showed a strong anti-FMDV antibody response prior to challenge, they were protected against disease and no FMDV RNA was detected in their sera post-challenge. Initial inoculation with empty capsids followed by the rSFV-FMDV was much less effective at combating the FMDV challenge and a large post-challenge boost to the level of anti-FMDV antibodies was observed. This prime-boost system, using reagents that can be generated outside of high

  18. A Prime-Boost Vaccination Strategy in Cattle to Prevent Foot-and-Mouth Disease Using a "Single-Cycle" Alphavirus Vector and Empty Capsid Particles.

    Science.gov (United States)

    Gullberg, Maria; Lohse, Louise; Bøtner, Anette; McInerney, Gerald M; Burman, Alison; Jackson, Terry; Polacek, Charlotta; Belsham, Graham J

    2016-01-01

    Foot-and-mouth disease (FMD) remains one of the most economically important infectious diseases of production animals globally. Vaccination can successfully control this disease, however, current vaccines are imperfect. They are made using chemically inactivated FMD virus (FMDV) that is produced in large-scale mammalian cell culture under high containment conditions. Here, we have expressed the FMDV capsid protein precursor (P1-2A) of strain O1 Manisa alone or with the FMDV 3C protease (3Cpro) using a "single cycle" packaged alphavirus self-replicating RNA based on Semliki Forest virus (SFV). When the FMDV P1-2A was expressed with 3Cpro then processing of the FMDV capsid precursor protein is observed within cells and the proteins assemble into empty capsid particles. The products interact with anti-FMDV antibodies in an ELISA and bind to the integrin αvβ6 (a cellular receptor for FMDV). In cattle vaccinated with these rSFV-FMDV vectors alone, anti-FMDV antibodies were elicited but the immune response was insufficient to give protection against FMDV challenge. However, the prior vaccination with these vectors resulted in a much stronger immune response against FMDV post-challenge and the viremia observed was decreased in level and duration. In subsequent experiments, cattle were sequentially vaccinated with a rSFV-FMDV followed by recombinant FMDV empty capsid particles, or vice versa, prior to challenge. Animals given a primary vaccination with the rSFV-FMDV vector and then boosted with FMDV empty capsids showed a strong anti-FMDV antibody response prior to challenge, they were protected against disease and no FMDV RNA was detected in their sera post-challenge. Initial inoculation with empty capsids followed by the rSFV-FMDV was much less effective at combating the FMDV challenge and a large post-challenge boost to the level of anti-FMDV antibodies was observed. This prime-boost system, using reagents that can be generated outside of high-containment facilities

  19. DBSC-Based Grayscale Line Image Vectorization

    Institute of Scientific and Technical Information of China (English)

    Konstantin Melikhov; Feng Tian; Jie Qiu; Quan Chen; Hock Soon Seah

    2006-01-01

    Vector graphics plays an important role in computer animation and imaging technologies. However present techniques and tools cannot fully replace traditional pencil and paper. Additionally, vector representation of an image is not always available. There is not yet a good solution for vectorizing a picture drawn on a paper. This work attempts to solve the problem of vectorizing grayscale line drawings. The solution proposed uses Disk B-Spline curves to represent strokes of an image in vector form. The algorithm builds a vector representation from a grayscale raster image, which can be a scanned picture for instance. The proposed method uses a Gaussian sliding window to calculate skeleton and perceptive width of a stroke. As a result of vectorization, the given image is represented by a set of Disk B-Spline curves.

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

    Directory of Open Access Journals (Sweden)

    Samantha Sayers

    2012-01-01

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

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

    OpenAIRE

    Samantha Sayers; Guerlain Ulysse; Zuoshuang Xiang; Yongqun He

    2012-01-01

    Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bi...

  2. Protective Efficacy in Sheep of Adenovirus-Vectored Vaccines against Bluetongue Virus Is Associated with Specific T Cell Responses

    Science.gov (United States)

    Martín, Verónica; Pascual, Elena; Avia, Miguel; Peña, Lourdes; Valcárcel, Félix; Sevilla, Noemí

    2015-01-01

    Bluetongue virus (BTV) is an economically important Orbivirus of the Reoviridae family that causes a hemorrhagic disease in ruminants. Its control has been achieved by inactivated-vaccines that have proven to protect against homologous BTV challenge although unable to induce long-term immunity. Therefore, a more efficient control strategy needs to be developed. Recombinant adenovirus vectors are lead vaccine candidates for protection of several diseases, mainly because of their potency to induce potent T cell immunity. Here we report the induction of humoral and T-cell mediated responses able to protect animals against BTV challenge by recombinant replication-defective human adenovirus serotype 5 (Ad5) expressing either VP7, VP2 or NS3 BTV proteins. First we used the IFNAR(-/-) mouse model system to establish a proof of principle, and afterwards we assayed the protective efficacy in sheep, the natural host of BTV. Mice were completely protected against BTV challenge, developing humoral and BTV-specific CD8+- and CD4+-T cell responses by vaccination with the different rAd5. Sheep vaccinated with Ad5-BTV-VP2 and Ad5-BTV-VP7 or only with Ad5-BTV-VP7 and challenged with BTV showed mild disease symptoms and reduced viremia. This partial protection was achieved in the absence of neutralizing antibodies but strong BTV-specific CD8+ T cell responses in those sheep vaccinated with Ad5-BTV-VP7. These data indicate that rAd5 is a suitable vaccine vector to induce T cell immunity during BTV vaccination and provide new data regarding the relevance of T cell responses in protection during BTV infection. PMID:26619062

  3. A COMPREHENSIVE ANALYSIS OF SPACE VECTOR PWM TECHNIQUE BASED ON PLACEMENT OF ZERO-SPACE VECTOR

    Directory of Open Access Journals (Sweden)

    G.SAMBASIVA RAO,

    2011-04-01

    Full Text Available In this paper, the effect of placement of zero-space vector for the implementation of space vector based Pulse Width Modulation techniques for 3-phase Voltage Source Inverter is presented. Several pulse width modulation (PWM control strategies have been proposed for 3-phase voltage source inverter (VSI in the past. It is known that space vector modulation (SVM offers a degree of freedom in its implementation with regard to the placement of the zero-space vector. Apart from constructing a consistent theoretical framework, simulation results with conventional continuous SVM and various discontinuous SVM techniques are presented and all the cases are compared in this paper.

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

    Directory of Open Access Journals (Sweden)

    Thomas W Geisbert

    2008-11-01

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

  5. An Adenovirus-Vectored Nasal Vaccine Confers Rapid and Sustained Protection against Anthrax in a Single-Dose Regimen

    OpenAIRE

    Zhang, Jianfeng; Jex, Edward; Feng, Tsungwei; Sivko, Gloria S.; Baillie, Leslie W.; Goldman, Stanley; Van Kampen, Kent R; Tang, De-chu C.

    2013-01-01

    Bacillus anthracis is the causative agent of anthrax, and its spores have been developed into lethal bioweapons. To mitigate an onslaught from airborne anthrax spores that are maliciously disseminated, it is of paramount importance to develop a rapid-response anthrax vaccine that can be mass administered by nonmedical personnel during a crisis. We report here that intranasal instillation of a nonreplicating adenovirus vector encoding B. anthracis protective antigen could confer rapid and sust...

  6. Quality Control and Management of Preventive Vaccine Based on Live Virus Vectors%基于活病毒载体的预防用疫苗的质量控制及管理

    Institute of Scientific and Technical Information of China (English)

    周铁群

    2004-01-01

    笔者于2003年12月4日~5日,作为WHO)临时顾问赴瑞士日内瓦参加了WHO(IVR-Initiative for vaccine Research)召开的“采用活病毒载体的预防用疫苗的质量标准及管理的非正式磋商会议”。近年来,新一代的基于活病毒载体的疫苗的研发进展很快,有些已经完成临床Ⅰ-Ⅱ期,准备进入Ⅲ

  7. Stability of vaccinia-vectored recombinant oral rabies vaccine under field conditions: A 3-year study

    OpenAIRE

    Hermann, Joseph R.; Fry, Alethea M.; Siev, David; Slate, Dennis; Lewis, Charles; Gatewood, Donna M.

    2011-01-01

    Rabies is an incurable zoonotic disease caused by rabies virus, a member of the rhabdovirus family. It is transmitted through the bite of an infected animal. Control methods, including oral rabies vaccination (ORV) programs, have led to a reduction in the spread and prevalence of the disease in wildlife. This study evaluated the stability of RABORAL, a recombinant vaccinia virus vaccine that is used in oral rabies vaccination programs. The vaccine was studied in various field microenvironment...

  8. Differential CD4+ versus CD8+ T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates▿ †

    OpenAIRE

    Mooij, Petra; Balla-Jhagjhoorsingh, Sunita S.; Koopman, Gerrit; Beenhakker, Niels; van Haaften, Patricia; Baak, Ilona; Nieuwenhuis, Ivonne G.; Kondova, Ivanela; Wagner, Ralf; Wolf, Hans; Gómez, Carmen E.; José L Nájera; Jiménez, Victoria; Esteban, Mariano; Heeney, Jonathan L.

    2008-01-01

    Poxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in the gene expression of human dendritic cells infected with two leading poxvirus-based human immunodeficiency virus (HIV) vaccine candidates, New York vaccinia virus (NYVAC) and modified vaccinia virus Ankara (MVA). To understand how complex genomic changes in these two vaccine vectors translate into antigen-specific systemic immune response...

  9. Gene-based vaccines and immunotherapeutic strategies against neurodegenerative diseases: Potential utility and limitations.

    Science.gov (United States)

    Kudrna, Jeremy J; Ugen, Kenneth E

    2015-01-01

    There has been a recent expansion of vaccination and immunotherapeutic strategies from controlling infectious diseases to the targeting of non-infectious conditions including neurodegenerative disorders. In addition to conventional vaccine and immunotherapeutic modalities, gene-based methods that express antigens for presentation to the immune system by either live viral vectors or non-viral naked DNA plasmids have been developed and evaluated. This mini-review/commentary summarizes the advantages and disadvantages, as well as the research findings to date, of both of these gene-based vaccination approaches in terms of how they can be targeted against appropriate antigens within the Alzheimer and Parkinson disease pathogenesis processes as well as potentially against targets in other neurodegenerative diseases. Most recently, the novel utilization of these viral vector and naked DNA gene-based technologies includes the delivery of immunoglobulin genes from established biologically active monoclonal antibodies. This modified passive immunotherapeutic strategy has recently been applied to deliver passive antibody immunotherapy against the pathologically relevant amyloid β protein in Alzheimer disease. The advantages and disadvantages of this technological application of gene-based immune interventions, as well as research findings to date are also summarized. In sum, it is suggested that further evaluation of gene based vaccines and immunotherapies against neurodegenerative diseases are warranted to determine their potential clinical utility.

  10. Development of Mucosal Vaccines Based on Lactic Acid Bacteria

    Science.gov (United States)

    Bermúdez-Humarán, Luis G.; Innocentin, Silvia; Lefèvre, Francois; Chatel, Jean-Marc; Langella, Philippe

    Today, sufficient data are available to support the use of lactic acid bacteria (LAB), notably lactococci and lactobacilli, as delivery vehicles for the development of new mucosal vaccines. These non-pathogenic Gram-positive bacteria have been safely consumed by humans for centuries in fermented foods. They thus constitute an attractive alternative to the attenuated pathogens (most popular live vectors actually studied) which could recover their pathogenic potential and are thus not totally safe for use in humans. This chapter reviews the current research and advances in the use of LAB as live delivery vectors of proteins of interest for the development of new safe mucosal vaccines. The use of LAB as DNA vaccine vehicles to deliver DNA directly to antigen-presenting cells of the immune system is also discussed.

  11. Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants

    Directory of Open Access Journals (Sweden)

    Marie-Ève Lebel

    2015-08-01

    Full Text Available Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease.

  12. Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans.

    Science.gov (United States)

    Borggren, Marie; Nielsen, Jens; Bragstad, Karoline; Karlsson, Ingrid; Krog, Jesper S; Williams, James A; Fomsgaard, Anders

    2015-01-01

    The threat posed by the 2009 pandemic H1N1 virus emphasized the need for new influenza A virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. An effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages such as the induction of cellular and humoral immunity, inherent safety and rapid production time. We have previously developed a DNA vaccine encoding selected influenza proteins of pandemic origin and demonstrated broad protective immune responses in ferrets and pigs. In this study, we evaluated our DNA vaccine expressed by next-generation vectors. These new vectors can improve gene expression, but they are also efficiently produced on large scales and comply with regulatory guidelines by avoiding antibiotic resistance genes. In addition, a new needle-free delivery of the vaccine, convenient for mass vaccinations, was compared with intradermal needle injection followed by electroporation. We report that when our DNA vaccine is expressed by the new vectors and delivered to the skin with the needle-free device in the rabbit model, it can elicit an antibody response with the same titers as a conventional vector with intradermal electroporation. The needle-free delivery is already in use for traditional protein vaccines in pigs but should be considered as a practical alternative for the mass administration of broadly protective influenza DNA vaccines. PMID:25746201

  13. Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans

    DEFF Research Database (Denmark)

    Borggren, Marie; Nielsen, Jens; Bragstad, Karoline;

    2015-01-01

    , was compared with intradermal needle injection followed by electroporation. We report that when our DNA vaccine is expressed by the new vectors and delivered to the skin with the needle-free device in the rabbit model, it can elicit an antibody response with the same titers as a conventional vector...... with intradermal electroporation. The needle-free delivery is already in use for traditional protein vaccines in pigs but should be considered as a practical alternative for the mass administration of broadly protective influenza DNA vaccines....

  14. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  15. Recent progress in polymer-based gene delivery vectors

    Institute of Scientific and Technical Information of China (English)

    HUANG Shiwen; ZHUO Renxi

    2003-01-01

    The gene delivery system is one of the three components of a gene medicine, which is the bottle neck of current gene therapy. Nonviral vectors offer advantages over the viral system of safety, ease of manufacturing, etc. As important nonviral vectors, polymer gene delivery systems have gained increasing attention and have begun to show increasing promising. In this review, the fundamental and recent progress of polymer-based gene delivery vectors is reviewed.

  16. Bethe vectors in GL(3)-based quantum integrable models

    CERN Document Server

    Pakuliak, S; Slavnov, N A

    2015-01-01

    We consider a composite generalized quantum integrable model solvable by the nested algebraic Bethe ansatz. Using explicit formulas of the action of the monodromy matrix elements onto Bethe vectors in the GL(3)-based quantum integrable models we prove a formula for the Bethe vectors of composite model. We show that this representation is a particular case of general coproduct property of the weight functions (Bethe vectors) found in the theory of the deformed Knizhnik--Zamolodchokov equation.

  17. Support vector machines optimization based theory, algorithms, and extensions

    CERN Document Server

    Deng, Naiyang; Zhang, Chunhua

    2013-01-01

    Support Vector Machines: Optimization Based Theory, Algorithms, and Extensions presents an accessible treatment of the two main components of support vector machines (SVMs)-classification problems and regression problems. The book emphasizes the close connection between optimization theory and SVMs since optimization is one of the pillars on which SVMs are built.The authors share insight on many of their research achievements. They give a precise interpretation of statistical leaning theory for C-support vector classification. They also discuss regularized twi

  18. One-Dimensional Vector Based Pattern Matching

    Directory of Open Access Journals (Sweden)

    Y.M.Fouda

    2014-08-01

    Full Text Available Template matching is a basic method in image analysis to extract useful information from images. In this paper, we suggest a new method for pattern matching. Our method transform the template image from two dimensional image into one dimensional vector. Also all sub - windows (same size of template in the reference image will transform into one dimensional vectors. The three similarity measures SAD, SSD, and Euclidean are used to c ompute the likeness between template and all sub - windows in the reference image to find the best match. The experimental results show the superior performance of the proposed metho d over the conventional methods on various template of different sizes

  19. Efficacy of parainfluenza virus 5 (PIV5)-based tuberculosis vaccines in mice.

    Science.gov (United States)

    Chen, Zhenhai; Gupta, Tuhina; Xu, Pei; Phan, Shannon; Pickar, Adrian; Yau, Wilson; Karls, Russell K; Quinn, Frederick D; Sakamoto, Kaori; He, Biao

    2015-12-16

    Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an important human pathogen. Bacillus Calmette-Guérin (BCG), a live, attenuated variant of Mycobacterium bovis, is currently the only available TB vaccine despite its low efficacy against the infectious pulmonary form of the disease in adults. Thus, a more-effective TB vaccine is needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, has several characteristics that make it an attractive vaccine vector. It is safe, inexpensive to produce, and has been previously shown to be efficacious as the backbone of vaccines for influenza, rabies, and respiratory syncytial virus. In this work, recombinant PIV5 expressing M. tuberculosis antigens 85A (PIV5-85A) and 85B (PIV5-85B) have been generated and their immunogenicity and protective efficacy evaluated in a mouse aerosol infection model. In a long-term protection study, a single dose of PIV5-85A was found to be most effective in reducing M. tuberculosis colony forming units (CFU) in lungs when compared to unvaccinated, whereas the BCG vaccinated animals had similar numbers of CFUs to unvaccinated animals. BCG-prime followed by a PIV5-85A or PIV5-85B boost produced better outcomes highlighted by close to three-log units lower lung CFUs compared to PBS. The results indicate that PIV5-based M. tuberculosis vaccines are promising candidates for further development.

  20. Novel bivalent vectored vaccine for control of myxomatosis and rabbit haemorrhagic disease.

    Science.gov (United States)

    Spibey, N; McCabe, V J; Greenwood, N M; Jack, S C; Sutton, D; van der Waart, L

    2012-03-24

    A novel, recombinant myxoma virus-rabbit haemorrhagic disease virus (RHDV) vaccine has been developed for the prevention of myxomatosis and rabbit haemorrhagic disease (RHD). A number of laboratory studies are described illustrating the safety and efficacy of the vaccine following subcutaneous administration in laboratory rabbits from four weeks of age onwards. In these studies, both vaccinated and unvaccinated control rabbits were challenged using pathogenic strains of RHD and myxoma viruses, and 100 per cent of the vaccinated rabbits were protected against both myxomatosis and RHD. PMID:22266680

  1. Production of Rice Seed-Based Allergy Vaccines.

    Science.gov (United States)

    Takagi, Hidenori; Takaiwa, Fumio

    2016-01-01

    Recombinant hypoallergenic derivative is the next generation of tolerogen replacing the natural allergen extract to increase safety and efficacy. Japanese cedar pollinosis is the predominant seasonal allergy disease in Japan. A rice seed-based oral vaccine containing the recombinant hypoallergens derived from these allergens was developed. Efficacy of this rice-based allergy vaccine was evaluated by oral administration in animal models.

  2. Strategies to vaccinate against cancer of the cervix: feasibility of a school-based HPV vaccination program in Peru.

    Science.gov (United States)

    Penny, Mary; Bartolini, Rosario; Mosqueira, N Rocio; LaMontagne, D Scott; Mendoza, Maria Ana; Ramos, Irma; Winkler, Jennifer L; Villafana, Jose; Janmohamed, Amynah; Jumaan, Aisha O

    2011-07-12

    Operational research using a mixed method, cross-sectional, case-study approach assessed the feasibility and health system impact of large-scale implementation of human papillomavirus (HPV) vaccination into routine vaccine delivery by the Ministry of Health in Peru. The strategy was school-based vaccination of fifth grade girls in 527 primary schools in Piura region. Our evaluation showed that school-based HPV vaccination is feasible without major changes in existing health systems. This was reflected in the opinions of health personnel, the lack of impact on other vaccine coverage, and the high HPV vaccine coverage documented in routine records and by an independent community-based survey.

  3. Great Ellipse Route Planning Based on Space Vector

    Directory of Open Access Journals (Sweden)

    LIU Wenchao

    2015-07-01

    Full Text Available Aiming at the problem of navigation error caused by unified earth model in great circle route planning using sphere model and modern navigation equipment using ellipsoid mode, a method of great ellipse route planning based on space vector is studied. By using space vector algebra method, the vertex of great ellipse is solved directly, and description of great ellipse based on major-axis vector and minor-axis vector is presented. Then calculation formulas of great ellipse azimuth and distance are deduced using two basic vectors. Finally, algorithms of great ellipse route planning are studied, especially equal distance route planning algorithm based on Newton-Raphson(N-R method. Comparative examples show that the difference of route planning between great circle and great ellipse is significant, using algorithms of great ellipse route planning can eliminate the navigation error caused by the great circle route planning, and effectively improve the accuracy of navigation calculation.

  4. Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection

    Science.gov (United States)

    Marzi, Andrea; Murphy, Aisling A.; Feldmann, Friederike; Parkins, Christopher J.; Haddock, Elaine; Hanley, Patrick W.; Emery, Matthew J.; Engelmann, Flora; Messaoudi, Ilhem; Feldmann, Heinz; Jarvis, Michael A.

    2016-01-01

    Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity. PMID:26876974

  5. Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection.

    Science.gov (United States)

    Marzi, Andrea; Murphy, Aisling A; Feldmann, Friederike; Parkins, Christopher J; Haddock, Elaine; Hanley, Patrick W; Emery, Matthew J; Engelmann, Flora; Messaoudi, Ilhem; Feldmann, Heinz; Jarvis, Michael A

    2016-02-15

    Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity.

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

    Directory of Open Access Journals (Sweden)

    Yoshimi Tsuda

    2011-08-01

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

  7. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

    2011-02-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

  8. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

    2010-01-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

  9. Room Temperature Stabilization of Oral, Live Attenuated Salmonella enterica serovar Typhi-Vectored Vaccines

    Science.gov (United States)

    Ohtake, Satoshi; Martin, Russell; Saxena, Atul; Pham, Binh; Chiueh, Gary; Osorio, Manuel; Kopecko, Dennis; Xu, DeQi; Lechuga-Ballesteros, David; Truong-Le, Vu

    2011-01-01

    Foam drying, a modified freeze drying process, was utilized to produce a heat-stable, live attenuated Salmonella Typhi ‘Ty21a’ bacterial vaccine. Ty21a vaccine was formulated with pharmaceutically approved stabilizers, including sugars, plasticizers, amino acids, and proteins. Growth media and harvesting conditions of the bacteria were also studied to enhance resistance to desiccation stress encountered during processing as well as subsequent storage at elevated temperatures. The optimized Ty21a vaccine, formulated with trehalose, methionine, and gelatin, demonstrated stability for approximately 12 weeks at 37°C (i.e., time required for the vaccine to decrease in potency by 1log10 CFU) and no loss in titer at 4 and 25°C following storage for the same duration. Furthermore, the foam dried Ty21a elicited a similar immunogenic response in mice as well as protection in challenge studies compared to Vivotif™, the commercial Ty21a vaccine. The enhanced heat stability of the Ty21a oral vaccine, or Ty21a derivatives expressing foreign antigens (e.g. anthrax), could mitigate risks of vaccine potency loss during long term storage, shipping, delivery to geographical areas with warmer climates or during emergency distribution following a bioterrorist attack. Because the foam drying process is conducted using conventional freeze dryers and can be readily implemented at any freeze drying manufacturing facility, this technology appears ready and appropriate for large scale processing of foam dried vaccines. PMID:21300096

  10. Vaccine potential of recombinant antigens of Theileria annulata and Hyalomma anatolicum anatolicum against vector and parasite.

    Science.gov (United States)

    Jeyabal, L; Kumar, Binod; Ray, Debdatta; Azahahianambi, Palavesam; Ghosh, Srikanta

    2012-09-10

    In an attempt to develop vaccine against Hyalomma anatolicum anatolicum and Theileria annulata, three antigens were expressed in prokaryotic expression system and protective potentiality of the antigens was evaluated in cross bred calves. Two groups (grs. 1 and 4) of male cross-bred (Bos indicus × Bos taurus) calves were immunized with rHaa86, a Bm86 ortholog of H. a. anatolicum, while one group of calves (gr. 2) were immunized with cocktails of two antigens viz., surface antigens of T. annulata (rSPAG1, rTaSP). One group each was kept as negative controls (grs. 3 and 5). The animals of groups 1, 2 and 3 were challenged with T. annulata infected H. a. anatolicum adults while the animals of groups 1, 3, 4 and 5 were challenged with uninfected adult ticks. A significantly high (p<0.05) antibody responses to all the three antigens were detected in immunized calves, but the immune response was comparatively higher with rHaa86 followed by rTaSP and rSPAG1. Upon challenge with T. annulata infected ticks, animals of all groups showed symptoms of the disease but there was 50% survival of calves of group 1 while all non immunized control calves (group 3) and rSPAG1+rTaSP immunized calves died. The rHaa86 antigen was found efficacious to protect calves against more than 71.4-75.5% of the challenge infestation. The experiment has given a significant clue towards the development of rHaa86 based vaccine against both H. a. anatolicum and T. annulata. PMID:22546546

  11. DNA-based influenza vaccines as immunoprophylactic agents toward universality.

    Science.gov (United States)

    Zhang, Han; El Zowalaty, Mohamed E

    2016-01-01

    Influenza is an illness of global public health concern. Influenza viruses have been responsible for several pandemics affecting humans. Current influenza vaccines have proved satisfactory safety; however, they have limitations and do not provide protection against unexpected emerging influenza virus strains. Therefore, there is an urgent need for alternative approaches to conventional influenza vaccines. The development of universal influenza vaccines will help alleviate the severity of influenza pandemics. Influenza DNA vaccines have been the subject of many studies over the past decades due to their ability to induce broad-based protective immune responses in various animal models. The present review highlights the recent advances in influenza DNA vaccine research and its potential as an affordable universal influenza vaccine.

  12. A Fingerprint Minutiae Matching Method Based on Line Segment Vector

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Minutiae-based fingerprint matching is the most commonly used in an automatic fingerprint identification system. In this paper, we propose a minutia matching method based on line segment vector. This method uses all the detected minutiae (the ridge ending and the ridge bifurcation) in a fingerprint image to create a set of new vectors (line segment vector). Using these vectors, we can determine a truer reference point more efficiently. In addition, this new minutiae vector can also increase the accuracy of the minutiae matching. By experiment on the public domain collections of fingerprint images fvc2004 DB3 set A and DB4 set A, the result shows that our algorithm can obtain an improved verification performance.

  13. Development and applications of VSV vectors based on cell tropism

    Directory of Open Access Journals (Sweden)

    Hideki eTani

    2012-01-01

    Full Text Available Viral vectors have been available in various fields such as medical and biological research or gene therapy applications. Targeting vectors pseudotyped with distinct viral envelope proteins that influence cell tropism and transfection efficiency is a useful tool not only for examining entry mechanisms or cell tropisms but also for vaccine vector development. Vesicular stomatitis virus (VSV is an excellent candidate for development as a pseudotype vector. A recombinant VSV lacking its own envelope (G gene has been used to produce a pseudotype or recombinant VSV possessing the envelope proteins of heterologous viruses. These viruses possess a reporter gene instead of a VSV G gene in their genome, and therefore it is easy to evaluate their infectivity in the study of viral entry, including identification of viral receptors. Furthermore, advantage can be taken of a property of the pseudotype VSV, which is competence for single-round infection, in handling many different viruses that are either difficult to amplify in cultured cells or animals or that require specialized containment facilities. Here we describe procedures for producing pseudotype or recombinant VSVs and a few of the more prominent examples from among envelope viruses, such as hepatitis C virus, Japanese encephalitis virus, baculovirus, and hemorrhagic fever viruses.

  14. Image indexing based on vector quantization

    Science.gov (United States)

    Grana Romay, Manuel; Rebollo, Israel

    2000-10-01

    We propose the computation of the color palette of each image in isolation, using Vector Quantization methods. The image features are, then, the color palette and the histogram of the color quantization of the image with this color palette. We propose as a measure of similitude the weighted sum of the differences between the color palettes and the corresponding histograms. This approach allows the increase of the database without the recomputation of the image features and without substantial loss of discriminative power.

  15. Image Segmentation Based on Support Vector Machine

    Institute of Scientific and Technical Information of China (English)

    XU Hai-xiang; ZHU Guang-xi; TIAN Jin-wen; ZHANG Xiang; PENG Fu-yuan

    2005-01-01

    Image segmentation is a necessary step in image analysis. Support vector machine (SVM) approach is proposed to segment images and its segmentation performance is evaluated.Experimental results show that: the effects of kernel function and model parameters on the segmentation performance are significant; SVM approach is less sensitive to noise in image segmentation; The segmentation performance of SVM approach is better than that of back-propagation multi-layer perceptron (BP-MLP) approach and fuzzy c-means (FCM) approach.

  16. The successful induction of T-cell and antibody responses by a recombinant measles virus-vectored tetravalent dengue vaccine provides partial protection against dengue-2 infection.

    Science.gov (United States)

    Hu, Hui-Mei; Chen, Hsin-Wei; Hsiao, Yu-Ju; Wu, Szu-Hsien; Chung, Han-Hsuan; Hsieh, Chun-Hsiang; Chong, Pele; Leng, Chih-Hsiang; Pan, Chien-Hsiung

    2016-07-01

    Dengue has a major impact on global public health, and the use of dengue vaccine is very limited. In this study, we evaluated the immunogenicity and protective efficacy of a dengue vaccine made from a recombinant measles virus (MV) that expresses envelope protein domain III (ED3) of dengue-1 to 4. Following immunization with the MV-vectored dengue vaccine, mice developed specific interferon-gamma and antibody responses against dengue virus and MV. Neutralizing antibodies against MV and dengue viruses were also induced, and protective levels of FRNT50 ≥ 10 to 4 serotypes of dengue viruses were detected in the MV-vectored dengue vaccine-immunized mice. In addition, specific interferon-gamma and antibody responses to dengue viruses were still induced by the MV-vectored dengue vaccine in mice that were pre-infected with MV. This finding suggests that the pre-existing immunity to MV did not block the initiation of immune responses. By contrast, mice that were pre-infected with dengue-3 exhibited no effect in terms of their antibody responses to MV and dengue viruses, but a dominant dengue-3-specific T-cell response was observed. After injection with dengue-2, a detectable but significantly lower viremia and a higher titer of anti-dengue-2 neutralizing antibodies were observed in MV-vectored dengue vaccine-immunized mice versus the vector control, suggesting that an anamnestic antibody response that provided partial protection against dengue-2 was elicited. Our results with regard to T-cell responses and the effect of pre-immunity to MV or dengue viruses provide clues for the future applications of an MV-vectored dengue vaccine. PMID:26901482

  17. Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism.

    Directory of Open Access Journals (Sweden)

    Kenneth Plante

    2011-07-01

    Full Text Available Chikungunya virus (CHIKV is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. Therefore, vaccines remain the best strategy to prevent most vector-borne diseases. Ideally, vaccines for diseases of resource-limited countries should combine low cost and single dose efficacy, yet induce rapid and long-lived immunity with negligible risk of serious adverse reactions. To develop such a vaccine to protect against chikungunya fever, we employed a rational attenuation mechanism that also prevents the infection of mosquito vectors. The internal ribosome entry site (IRES from encephalomyocarditis virus replaced the subgenomic promoter in a cDNA CHIKV clone, thus altering the levels and host-specific mechanism of structural protein gene expression. Testing in both normal outbred and interferon response-defective mice indicated that the new vaccine candidate is highly attenuated, immunogenic and efficacious after a single dose. Furthermore, it is incapable of replicating in mosquito cells or infecting mosquitoes in vivo. This IRES-based attenuation platform technology may be useful for the predictable attenuation of any alphavirus.

  18. LandSat-Based Land Use-Land Cover (Vector)

    Data.gov (United States)

    Minnesota Department of Natural Resources — Vector-based land cover data set derived from classified 30 meter resolution Thematic Mapper satellite imagery. Classification is divided into 16 classes with...

  19. M2e-Based Universal Influenza A Vaccines

    Directory of Open Access Journals (Sweden)

    Lei Deng

    2015-02-01

    Full Text Available The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.

  20. Vaccination to conserved influenza antigens in mice using a novel Simian adenovirus vector, PanAd3, derived from the bonobo Pan paniscus.

    Directory of Open Access Journals (Sweden)

    Alessandra Vitelli

    Full Text Available Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP and matrix 1 (M1. We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines.

  1. Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza.

    Science.gov (United States)

    Rosas, Cristina; Van de Walle, Gerlinde R; Metzger, Stephan M; Hoelzer, Karin; Dubovi, Edward J; Kim, Sung G; Parrish, Colin R; Osterrieder, Nikolaus

    2008-05-01

    In 2004, canine influenza virus (CIV) was identified as a respiratory pathogen of dogs for the first time and found to be closely related to H3N8 equine influenza virus (EIV). We generated a recombinant vectored vaccine that expresses H3 of a recent isolate of EIV using equine herpesvirus type 1 (EHV-1) as the delivery vehicle. This EHV-1 vectored vaccine exhibited robust and stable EIV H3 expression and induced a strong influenza virus-specific response in both mice and dogs upon intranasal or subcutaneous administration. Furthermore, upon challenge with the recent CIV isolate A/canine/PA/10915-07, protection of vaccinated dogs could be demonstrated by a significant reduction in clinical sings, and, more importantly, by a significant reduction in virus shedding. We concluded that the EHV-1/H3 recombinant vector can be a valuable alternative for protection of dogs against clinical disease induced by CIV and can significantly reduce virus spread.

  2. Infection of Nonhost Species Dendritic Cells In Vitro with an Attenuated Myxoma Virus Induces Gene Expression That Predicts Its Efficacy as a Vaccine Vector ▿ †

    OpenAIRE

    TOP, S.; E. Foulon; Pignolet, B.; Deplanche, M; Caubet, C.; Tasca, C; Bertagnoli, S; Meyer, G.; Foucras, G.

    2011-01-01

    Recombinant myxoma virus (MYXV) can be produced without a loss of infectivity, and its highly specific host range makes it an ideal vaccine vector candidate, although careful examination of its interaction with the immune system is necessary. Similar to rabbit bone marrow-derived dendritic cells (BM-DCs), ovine dendritic cells can be infected by SG33, a MYXV vaccine strain, and support recombinant antigen expression. The frequency of infected cells in the nonhost was lower and the virus cycle...

  3. A novel replication-competent vaccinia vector MVTT is superior to MVA for inducing high levels of neutralizing antibody via mucosal vaccination

    OpenAIRE

    Xiaoxing Huang; Bin Lu; Wenbo Yu; Qing Fang; Li Liu; Ke Zhuang; Tingting Shen; Haibo Wang; Po Tian; Linqi Zhang; Zhiwei Chen

    2009-01-01

    Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallp...

  4. Combining Viral Vectored and Protein-in-adjuvant Vaccines Against the Blood-stage Malaria Antigen AMA1: Report on a Phase 1a Clinical Trial

    OpenAIRE

    Susanne H. Hodgson; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Thomas W Rampling; Biswas, Sumi; Ian D Poulton; Miura, Kazutoyo; Douglas, Alexander D.; Alanine, Daniel GW; Illingworth, Joseph J.; de Cassan, Simone C.; ZHU, DAMING; Nicosia, Alfredo; Long, Carole A.

    2014-01-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines—chimpanzee adenovir...

  5. Protective immunization of horses with a recombinant canarypox virus vectored vaccine co-expressing genes encoding the outer capsid proteins of African horse sickness virus.

    Science.gov (United States)

    Guthrie, Alan J; Quan, Melvyn; Lourens, Carina W; Audonnet, Jean-Christophe; Minke, Jules M; Yao, Jiansheng; He, Ling; Nordgren, Robert; Gardner, Ian A; Maclachlan, N James

    2009-07-16

    We describe the development and preliminary characterization of a recombinant canarypox virus vectored (ALVAC) vaccine for protective immunization of equids against African horse sickness virus (AHSV) infection. Horses (n=8) immunized with either of two concentrations of recombinant canarypox virus vector (ALVAC-AHSV) co-expressing synthetic genes encoding the outer capsid proteins (VP2 and VP5) of AHSV serotype 4 (AHSV-4) developed variable titres (horse immunized with a commercial recombinant canarypox virus vectored vaccine expressing the haemagglutinin genes of two equine influenza H3N8 viruses was seronegative to AHSV and following infection with virulent AHSV-4 developed pyrexia, thrombocytopenia and marked oedema of the supraorbital fossae typical of the "dikkop" or cardiac form of African horse sickness. AHSV was detected by virus isolation and quantitative reverse transcriptase polymerase chain reaction in the blood of the control horse from 8 days onwards after challenge infection whereas AHSV was not detected at any time in the blood of the ALVAC-AHSV vaccinated horses. The control horse seroconverted to AHSV by 2 weeks after challenge infection as determined by both virus neutralization and ELISA assays, whereas six of eight of the ALVAC-AHSV vaccinated horses did not seroconvert by either assay following challenge infection with virulent AHSV-4. These data confirm that the ALVAC-AHSV vaccine will be useful for the protective immunization of equids against African horse sickness, and avoids many of the problems inherent to live-attenuated AHSV vaccines.

  6. Fuzzy rule-based support vector regression system

    Institute of Scientific and Technical Information of China (English)

    Ling WANG; Zhichun MU; Hui GUO

    2005-01-01

    In this paper,we design a fuzzy rule-based support vector regression system.The proposed system utilizes the advantages of fuzzy model and support vector regression to extract support vectors to generate fuzzy if-then rules from the training data set.Based on the first-order linear Tagaki-Sugeno (TS) model,the structure of rules is identified by the support vector regression and then the consequent parameters of rules are tuned by the global least squares method.Our model is applied to the real world regression task.The simulation results gives promising performances in terms of a set of fuzzy rules,which can be easily interpreted by humans.

  7. Prospects of HA-Based Universal Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Anwar M. Hashem

    2015-01-01

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

  8. RNA-Based Vaccines in Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Megan A. McNamara

    2015-01-01

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

  9. RNA-Based Vaccines in Cancer Immunotherapy.

    Science.gov (United States)

    McNamara, Megan A; Nair, Smita K; Holl, Eda K

    2015-01-01

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

  10. A novel method for synthetic vaccine construction based on protein assembly

    OpenAIRE

    Zhida Liu; Hang Zhou; Wenjun Wang; Wenjie Tan; Yang-Xin Fu; Mingzhao Zhu

    2014-01-01

    In the history of vaccine development, the synthetic vaccine is a milestone that is in stark contrast with traditional vaccines based on live-attenuated or inactivated microorganisms. Synthetic vaccines not only are safer than attenuated or inactivated microorganisms but also provide the opportunity for vaccine design for specific purposes. The first generation of synthetic vaccines has been largely based on DNA recombination technology and genetic manipulation. This de novo generation is occ...

  11. Cellular Changes Induced by Adenovirus Vaccine Vectors Expressing Foot-and-Mouth Disease Virus Structural and Nonstructural Proteins

    Science.gov (United States)

    Foot-and-mouth disease virus (FMDV) is the most contagious pathogen of cloven-hoofed animals including swine and bovines. The emergency control of outbreaks is dependent on rapid protection and prevention of virus spread. Adenovirus-based FMD subunit vaccines containing the coding region of viral ca...

  12. A novel replication-competent vaccinia vector MVTT is superior to MVA for inducing high levels of neutralizing antibody via mucosal vaccination.

    Science.gov (United States)

    Huang, Xiaoxing; Lu, Bin; Yu, Wenbo; Fang, Qing; Liu, Li; Zhuang, Ke; Shen, Tingting; Wang, Haibo; Tian, Po; Zhang, Linqi; Chen, Zhiwei

    2009-01-01

    Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels ( approximately 2-3-fold) of anti- SARS-CoV neutralizing antibodies (Nabs) than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (approximately 10-fold) higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.

  13. A novel replication-competent vaccinia vector MVTT is superior to MVA for inducing high levels of neutralizing antibody via mucosal vaccination.

    Directory of Open Access Journals (Sweden)

    Xiaoxing Huang

    Full Text Available Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA and a novel replication-competent modified vaccinia Tian Tan (MVTT for inducing neutralizing antibodies (Nabs via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels ( approximately 2-3-fold of anti- SARS-CoV neutralizing antibodies (Nabs than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (approximately 10-fold higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.

  14. Adenovirus serotype 5 vectored foot-and-mouth disease subunit vaccines: the first decade

    Science.gov (United States)

    Here we present the results of the first decade of development of a replication-defective human adenovirus (Ad5) containing the capsid and 3C protease coding regions of foot-and-mouth disease virus (FMDV) as a vaccine candidate. In proof-of concept studies we demonstrated that a single inoculation w...

  15. Carbohydrate-Based Ice Recrystallization Inhibitors Increase Infectivity and Thermostability of Viral Vectors

    Science.gov (United States)

    Ghobadloo, Shahrokh M.; Balcerzak, Anna K.; Gargaun, Ana; Muharemagic, Darija; Mironov, Gleb G.; Capicciotti, Chantelle J.; Briard, Jennie G.; Ben, Robert N.; Berezovski, Maxim V.

    2014-07-01

    The inability of vaccines to retain sufficient thermostability has been an obstacle to global vaccination programs. To address this major limitation, we utilized carbohydrate-based ice recrystallization inhibitors (IRIs) to eliminate the cold chain and stabilize the potency of Vaccinia virus (VV), Vesicular Stomatitis virus (VSV) and Herpes virus-1 (HSV-1). The impact of these IRIs was tested on the potency of the viral vectors using a plaque forming unit assay following room temperature storage, cryopreservation with successive freeze-thaw cycles and lyophilization. Viral potency after storage with all three conditions demonstrated that N-octyl-gluconamide (NOGlc) recovered the infectivity of shelf stored VV, 5.6 Log10 PFU mL-1 during 40 days, and HSV-1, 2.7 Log10 PFU mL-1 during 9 days. Carbon-linked antifreeze glycoprotein analogue ornithine-glycine-glycine-galactose (OGG-Gal) increases the recovery of VV and VSV more than 1 Log10 PFU mL-1 after 10 freeze-thaw cycles. In VSV, cryostorage with OGG-Gal maintains high infectivity and reduces temperature-induced aggregation of viral particles by 2 times that of the control. In total, OGG-Gal and NOGlc preserve virus potency during cryostorage. Remarkably, NOGlc has potential to eliminate the cold chain and permit room temperature storage of viral vectors.

  16. Carbohydrate-based ice recrystallization inhibitors increase infectivity and thermostability of viral vectors.

    Science.gov (United States)

    Ghobadloo, Shahrokh M; Balcerzak, Anna K; Gargaun, Ana; Muharemagic, Darija; Mironov, Gleb G; Capicciotti, Chantelle J; Briard, Jennie G; Ben, Robert N; Berezovski, Maxim V

    2014-01-01

    The inability of vaccines to retain sufficient thermostability has been an obstacle to global vaccination programs. To address this major limitation, we utilized carbohydrate-based ice recrystallization inhibitors (IRIs) to eliminate the cold chain and stabilize the potency of Vaccinia virus (VV), Vesicular Stomatitis virus (VSV) and Herpes virus-1 (HSV-1). The impact of these IRIs was tested on the potency of the viral vectors using a plaque forming unit assay following room temperature storage, cryopreservation with successive freeze-thaw cycles and lyophilization. Viral potency after storage with all three conditions demonstrated that N-octyl-gluconamide (NOGlc) recovered the infectivity of shelf stored VV, 5.6 Log₁₀ PFU mL(-1) during 40 days, and HSV-1, 2.7 Log₁₀ PFU mL(-1) during 9 days. Carbon-linked antifreeze glycoprotein analogue ornithine-glycine-glycine-galactose (OGG-Gal) increases the recovery of VV and VSV more than 1 Log₁₀ PFU mL(-1) after 10 freeze-thaw cycles. In VSV, cryostorage with OGG-Gal maintains high infectivity and reduces temperature-induced aggregation of viral particles by 2 times that of the control. In total, OGG-Gal and NOGlc preserve virus potency during cryostorage. Remarkably, NOGlc has potential to eliminate the cold chain and permit room temperature storage of viral vectors.

  17. Risk based surveillance for vector borne diseases

    DEFF Research Database (Denmark)

    Bødker, Rene

    in Northern Europe. This model approach may be used as a basis for risk based surveillance. In risk based surveillance limited resources for surveillance are targeted at geographical areas most at risk and only when the risk is high. This makes risk based surveillance a cost effective alternative...... to the present surveillance strategies based on random samples. We still don’t understand the mechanisms underlying the recent outbreaks of bluetongue, Schmallenberg, Usutu virus, tick borne encephalitis or dirofilarial worms in the Baltic See Region. It is therefore not possible to use mathematical models...... sample to a diagnostic laboratory. Risk based surveillance models may reduce this delay. An important feature of risk based surveillance models is their ability to continuously communicate the level of risk to veterinarians and hence increase awareness when risk is high. This is essential for submission...

  18. The integration profile of EIAV-based vectors.

    Science.gov (United States)

    Hacker, Caroline V; Vink, Conrad A; Wardell, Theresa W; Lee, Sheena; Treasure, Peter; Kingsman, Susan M; Mitrophanous, Kyriacos A; Miskin, James E

    2006-10-01

    Lentiviral vectors based on equine infectious anemia virus (EIAV) stably integrate into dividing and nondividing cells such as neurons, conferring long-term expression of their transgene. The integration profile of an EIAV vector was analyzed in dividing HEK293T cells, alongside an HIV-1 vector as a control, and compared to a random dataset generated in silico. A multivariate regression model was generated and the influence of the following parameters on integration site selection determined: (a) within/not within a gene, (b) GC content within 20 kb, (c) within 10 kb of a CpG island, (d) gene density within a 2-Mb window, and (e) chromosome number. The majority of the EIAV integration sites (68%; n = 458) and HIV-1 integration sites (72%; n = 162) were within a gene, and both vectors favored AT-rich regions. Sites within genes were examined using a second model to determine the influence of the gene-specific parameters, gene region, and transcriptional activity. Both EIAV and HIV-1 vectors preferentially integrated within active genes. Unlike the gammaretrovirus MLV, EIAV and HIV-1 vectors do not integrate preferentially into the promoter region or the 5' end of the transcription unit. PMID:16950499

  19. Support Vector Machine-Based Nonlinear System Modeling and Control

    Institute of Scientific and Technical Information of China (English)

    张浩然; 韩正之; 冯瑞; 于志强

    2003-01-01

    This paper provides an introduction to a support vector machine, a new kernel-based technique introduced in statistical learning theory and structural risk minimization, then presents a modeling-control framework based on SVM.At last a numerical experiment is taken to demonstrate the proposed approach's correctness and effectiveness.

  20. Have we found an optimal insertion site in a Newcastle disease virus vector to express a foreign gene for vaccine and gene therapy purposes?

    Science.gov (United States)

    Using reverse genetics technology, many strains of Newcastle disease virus (NDV) have been developed as vectors to express foreign genes for vaccine and gene therapy purposes. The foreign gene is usually inserted into a non-coding region of the NDV genome as an independent transcription unit. Eval...

  1. Oral immunization of mice against Clostridium perfringens epsilon toxin with a Lactobacillus casei vector vaccine expressing epsilon toxoid.

    Science.gov (United States)

    Alimolaei, Mojtaba; Golchin, Mehdi; Daneshvar, Hamid

    2016-06-01

    Clostridium perfringens type D infects ruminants and causes the enterotoxemia disease by ε-toxin. A mutated ε-toxin gene lacking toxicity was designed, synthesized, and cloned into the pT1NX vector and electroporated into Lactobacillus casei competent cells to yield LC-pT1NX-ε recombinant strain. BALB/c mice, immunized orally with this strain, highly induced mucosal, humoral, and cell-mediated immune responses and developed a protection against 200 MLD/ml of the activated ε-toxin. This study showed that the LC-pT1NX-ε could be a promising vaccine candidate against the enterotoxemia disease. PMID:27012151

  2. Quality of the transgene-specific CD8+ T cell response induced by adenoviral vector immunization is critically influenced by virus dose and route of vaccination

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Ørskov, Cathrine; Thomsen, Allan Randrup;

    2010-01-01

    Adenoviral vectors have been widely used for experimental gene therapy and vaccination, yet there is a surprising lack of knowledge connecting the route and dose of adenovirus administration to the induced transgene-specific immune response. We have recently demonstrated polyfunctional CD8(+) T c...... effector functions, accumulated in the spleen. These findings indicate that the localization of the adenoviral inoculum and not the total Ag load determines the quality of the CD8(+) T cell response induced with adenoviral vaccines.......Adenoviral vectors have been widely used for experimental gene therapy and vaccination, yet there is a surprising lack of knowledge connecting the route and dose of adenovirus administration to the induced transgene-specific immune response. We have recently demonstrated polyfunctional CD8(+) T...

  3. A candidate therapeutic vaccine against hepatitis C virus infection: Use of a recombinant alphavirus vector

    OpenAIRE

    Ip, Peng

    2014-01-01

    Peng Peng Ip beschrijft in dit proefschrift haar onderzoek naar de ontwikkeling van een immuuntherapie gericht tegen hepatitis C virus infecties. Wereldwijd zijn ongeveer 150 miljoen mensen chronisch besmet met hepatitis C virus (HCV) en jaarlijks sterven 350.000 mensen aan een HCV-gerelateerde leverziekte zoals cirrose of leverkanker. In Nederland zijn ongeveer 60.000 mensen besmet met HCV, vaak nog zonder het te weten. Het doel van het promotie onderzoek was om een vaccin tegen HCV infectie...

  4. Lactobacillus plantarum vaccine vector expressing hemagglutinin provides protection against H9N2 challenge infection.

    Science.gov (United States)

    Shi, Shao-Hua; Yang, Wen-Tao; Yang, Gui-Lian; Zhang, Xu-Ke; Liu, Yu-Ying; Zhang, Li-Jiao; Ye, Li-Ping; Hu, Jing-Tao; Xing, Xin; Qi, Chong; Li, Yu; Wang, Chun-Feng

    2016-01-01

    Hemagglutinin (HA) has been demonstrated as an effective candidate vaccine antigen against AIVs. Dendritic cell-targeting peptide (DCpep) can enhance the robustness of immune responses. The purpose of this study was to evaluate whether DCpep could enhance the immune response against H9N2 AIV when utilizing Lactobacillus plantarum NC8 (NC8) to present HA-DCpep in mouse and chicken models. To accomplish this, a mucosal vaccine of a recombinant NC8 strain expressing HA and DCpep that was constructed in a previous study was employed. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. These results revealed that recombinant L. plantarum NC8-pSIP409-HA-DCpep is an effective vaccine candidate against H9N2 AIVs.

  5. Lactic acid bacteria--20 years exploring their potential as live vectors for mucosal vaccination.

    Science.gov (United States)

    Wyszyńska, Agnieszka; Kobierecka, Patrycja; Bardowski, Jacek; Jagusztyn-Krynicka, Elżbieta Katarzyna

    2015-04-01

    Lactic acid bacteria (LAB) are a diverse group of Gram-positive, nonsporulating, low G + C content bacteria. Many of them have been given generally regarded as safe status. Over the past two decades, intensive genetic and molecular research carried out on LAB, mainly Lactococcus lactis and some species of the Lactobacillus genus, has revealed new, potential biomedical LAB applications, including the use of LAB as adjuvants, immunostimulators, or therapeutic drug delivery systems, or as factories to produce therapeutic molecules. LAB enable immunization via the mucosal route, which increases effectiveness against pathogens that use the mucosa as the major route of entry into the human body. In this review, we concentrate on the encouraging application of Lactococcus and Lactobacillus genera for the development of live mucosal vaccines. First, we present the progress that has recently been made in the field of developing tools for LAB genetic manipulations, which has resulted in the successful expression of many bacterial, parasitic, and viral antigens in LAB strains. Next, we discuss the factors influencing the efficacy of the constructed vaccine prototypes that have been tested in various animal models. Apart from the research focused on an application of live LABs as carriers of foreign antigens, a lot of work has been recently done on the potential usage of nonliving, nonrecombinant L. lactis designated as Gram-positive enhancer matrix (GEM), as a delivery system for mucosal vaccination. The advantages and disadvantages of both strategies are also presented. PMID:25750046

  6. Adenovirus-based vaccine against Listeria monocytogenes

    DEFF Research Database (Denmark)

    Jensen, Søren; Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech;

    2013-01-01

    The use of replication-deficient adenoviruses as vehicles for transfer of foreign genes offers many advantages in a vaccine setting, eliciting strong cellular immune responses involving both CD8(+) and CD4(+) T cells. Further improving the immunogenicity, tethering of the inserted target Ag to MHC...

  7. Enhancing DNA vaccine potency against hantavirus by co-administration of interleukin-12 expression vector as a genetic adjuvant

    Institute of Scientific and Technical Information of China (English)

    ZHENG Lan-yan; MOU Ling; LIN Song; LU Run-ming; LUO En-jie

    2005-01-01

    Background The heavy incidence and mortality of hemorrhagic fever with renal syndrome, as well as no specific drugs in curing the disease,clearly indicate the need for development of the more effective hantavirus vaccine. Refining the DNA vaccination strategy to elicit more clinically efficacious immune responses is now under intensive investigation. In the present study, we examined the effects of using an interleukin-12 expression plasmid as a genetic adjuvant to enhance the immune responses induced by a DNA vaccine based on the S gene encoding nucleocapsid protein against hantavirus. Methods BALB/c mice were immunized three times by intramuscular inoculations of DNA vaccine encoding of hantanvirus nucleocapsid protein alone or in combination with a plasmid expressing murine interleukin-12 (pcIL-12). Booster immunizations were employed 2 times at 2-week interval. To evaluate the humoral and cellular immune responses, antigen-specific lymphocyte proliferation and antibody production were assayed by MTT method and ELISA respectively. The level of interleukin-4 and interferon-γ in the splenic lymphocytic cultured supernatant were detected with ELISA kit at day 5, 10, 17, 35 and 42 after primary immunization.Conclusion Humoral and cytokine responses elicited by pcDNA3.1+S inoculation can be modulated by co-inoculation with pcIL-12 and efficiently induced Th1-dominant immune responses.

  8. HCV prototype vaccine based on hepatitis B core virus-like particles

    OpenAIRE

    Marija Mihailova

    2008-01-01

    HCV prototype vaccine based on hepatitis B core virus-like particles Abstract In the current study the C-terminally truncated HBc expression vectors were used for exposure of different hepatitis C virus (HCV) protein (core, E2, and NS3) fragments. All created chimeric constructs directed high level of recombinant protein synthesis in E.coli. However, not all chimeric proteins were able to self-assemble into virus-like particles (VLPs). HBcCterm/HVR1tetramer VLPs turned ou...

  9. Construction and Immunogenicity Testing of Whole Recombinant Yeast-Based T-Cell Vaccines.

    Science.gov (United States)

    King, Thomas H; Guo, Zhimin; Hermreck, Melanie; Bellgrau, Donald; Rodell, Timothy C

    2016-01-01

    GlobeImmune's Tarmogen(®) immunotherapy platform utilizes recombinant Saccharomyces cerevisiae yeast as a vaccine vector to deliver heterologous antigens for activation of disease-specific, targeted cellular immunity. The vaccines elicit immune-mediated killing of target cells expressing viral and cancer antigens in vivo via a CD8(+) CTL-mediated mechanism. Tarmogens are not neutralized by host immune responses and can be administered repeatedly to boost antigen-specific immunity. Production of the vaccines yields stable off-the-shelf products that avoid the need for patient-specific manufacturing found with other immunotherapeutic approaches. Tarmogens for the treatment of chronic hepatitis B and C and various cancers were well tolerated and immunogenic in phase 1 and 2 clinical trials encompassing >600 subjects. The platform is being widely utilized in basic vaccine research and the most rapid path to success in these endeavors follows from optimal immunoassay selection and execution. This chapter provides detailed methods for the construction and preclinical immunogenicity testing of yeast-based immunotherapeutic products to support the rapid and efficient use of this versatile technology. PMID:27076321

  10. Development of CpG ODN Based Vaccine Adjuvant Formulations.

    Science.gov (United States)

    Gursel, Mayda; Gursel, Ihsan

    2016-01-01

    Development of effective vaccine mediated immune responses relies on the use of vaccine adjuvants capable of enhancing and directing the adaptive immune response to the antigen. When used as vaccine adjuvants, type I interferon inducing agents can elicit potent effector/memory T cell responses and humoral immunity. Distinct sequences of single stranded synthetic oligodeoxynucleotides containing unmethylated cytosine-phosphate-guanine oligodeoxynucleotide motifs (CpG ODN) can generate type I interferon production via a TLR9-MyD88-IRF7-mediated signaling pathway. Here, we describe two different methods of preparing CpG ODN-based vaccine adjuvant formulations that can induce a robust IFNα response from human peripheral blood mononuclear cells. PMID:27076306

  11. 甲病毒载体的研究进展%Review on Alphavirus-based Vectors

    Institute of Scientific and Technical Information of China (English)

    龚文芝; 刘灿; 张东东; 宁宜宝

    2015-01-01

    Alphaviruses belong to the family of Togaviridae, which are encapsulated by a capsid protein and possess single strand plus RNA. In recent years, the domestic and foreign research on alphavirus-based vectors is active and the alphavirus-based vectors have been used for vaccine research, gene therapy and molecular biology research. Based on the structural principle, the alphavirus vectors are classified into three main types:replication-competent vector, replication-deficient vectors and DNA-layered vector. In this review, the transformation, characteristics and application of three different alphavirus-based vectors are discussed in order to provide references for the development of safer, more effective alphavirus-based vectors.%甲病毒属于披膜病毒科,是一类有包膜的单股正链RNA病毒。近些年来,国内外有关甲病毒载体的研究非常活跃,其已被用于疫苗研究、基因治疗以及分子生物学等研究领域。基于甲病毒载体的构造原理,将其分为三类,分别为复制完全型载体、复制缺陷型载体和DNA/RNA载体。就这三类载体的改造过程进行了探讨,并对这三类载体的特点及其应用研究进展等方面进行了阐述,以期为开发出更安全、更有效的甲病毒载体提供参考。

  12. 禽流感基因重组活载体疫苗和表位疫苗的研究进展%Research advance in the development of avian influenza recombinant live vector vaccines and epitope vaccines

    Institute of Scientific and Technical Information of China (English)

    张文慧; 钱爱东

    2011-01-01

    In order to understand the status of new avian influenza virus(AIV) vaccines,the research advances in recombinant live vector vaccines and epitope vaccines against avian influenza were discussed on the aspects of carrier selection and candidate genes,as well as the prospect of these two kinds of vaccines to provide references for their future research.%为了解禽流感新型疫苗的研究现状,从载体选择和候选基因等方面论述了基因重组活载体疫苗和表位疫苗的研究进展,并对这两种疫苗的发展前景进行了展望,以期为禽流感新型疫苗的研究提供参考。

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

    Directory of Open Access Journals (Sweden)

    Zhiwen Yu

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

  14. Dynamic Vector Space Secret Sharing Based on Certificates

    Institute of Scientific and Technical Information of China (English)

    XU Chunxiang; LI Jiajia; LIU Dongsu

    2006-01-01

    A vector space secret sharing scheme based on certificates is proposed in this paper. The difficulties of solving discrete logarithm assure confidential information's security, and the use of each participant's certificate makes the dealer have no need to transfer secret information to the participants. The proposed scheme is dynamic. It can effectively check cheaters and does not have secure channel requirements.

  15. Graph- versus Vector-Based Analysis of a Consensus Protocol

    NARCIS (Netherlands)

    Delzanno, Giorgio; Rensink, Arend; Traverso, Riccardo; Bošnački, Dragan; Edelkamp, Stefan; Lluch Lafuente, Alberto; Wijs, Anton

    2014-01-01

    The Paxos distributed consensus algorithm is a challenging case-study for standard, vector-based model checking techniques. Due to asynchronous communication, exhaustive analysis may generate very large state spaces already for small model instances. In this paper, we show the advantages of graph tr

  16. Prediction of Banking Systemic Risk Based on Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Shouwei Li

    2013-01-01

    Full Text Available Banking systemic risk is a complex nonlinear phenomenon and has shed light on the importance of safeguarding financial stability by recent financial crisis. According to the complex nonlinear characteristics of banking systemic risk, in this paper we apply support vector machine (SVM to the prediction of banking systemic risk in an attempt to suggest a new model with better explanatory power and stability. We conduct a case study of an SVM-based prediction model for Chinese banking systemic risk and find the experiment results showing that support vector machine is an efficient method in such case.

  17. Estimation of sand liquefaction based on support vector machines

    Institute of Scientific and Technical Information of China (English)

    苏永华; 马宁; 胡检; 杨小礼

    2008-01-01

    The origin and influence factors of sand liquefaction were analyzed, and the relation between liquefaction and its influence factors was founded. A model based on support vector machines (SVM) was established whose input parameters were selected as following influence factors of sand liquefaction: magnitude (M), the value of SPT, effective pressure of superstratum, the content of clay and the average of grain diameter. Sand was divided into two classes: liquefaction and non-liquefaction, and the class label was treated as output parameter of the model. Then the model was used to estimate sand samples, 20 support vectors and 17 borderline support vectors were gotten, then the parameters were optimized, 14 support vectors and 6 borderline support vectors were gotten, and the prediction precision reaches 100%. In order to verify the generalization of the SVM method, two other practical samples’ data from two cities, Tangshan of Hebei province and Sanshui of Guangdong province, were dealt with by another more intricate model for polytomies, which also considered some influence factors of sand liquefaction as the input parameters and divided sand into four liquefaction grades: serious liquefaction, medium liquefaction, slight liquefaction and non-liquefaction as the output parameters. The simulation results show that the latter model has a very high precision, and using SVM model to estimate sand liquefaction is completely feasible.

  18. Vaccines based on structure-based design provide protection against infectious diseases.

    Science.gov (United States)

    Thomas, Sunil; Luxon, Bruce A

    2013-11-01

    Vaccines elicit immune responses, provide protection against microorganisms and are considered as one of the most successful medical interventions against infectious diseases. Vaccines can be produced using attenuated virus or bacteria, recombinant proteins, bacterial polysaccharides, carbohydrates or plasmid DNA. Conventional vaccines rely on the induction of immune responses against antigenic proteins to be effective. The genetic diversity of microorganisms, coupled with the high degree of sequence variability in antigenic proteins, presents a challenge to developing broadly effective conventional vaccines. The observation that whole protein antigens are not necessarily essential for inducing immunity has led to the emergence of a new branch of vaccine design termed 'structural vaccinology'. Structure-based vaccines are designed on the rationale that protective epitopes should be sufficient to induce immune responses and provide protection against pathogens. Recent studies demonstrated that designing structure-based vaccine candidates with multiple epitopes induce a higher immune response. As yet there are no commercial vaccines available based on structure-based design and most of the structure-based vaccine candidates are in the preclinical stages of development. This review focuses on recent advances in structure-based vaccine candidates and their application in providing protection against infectious diseases.

  19. Efficient Vector-Based Forwarding for Underwater Sensor Networks

    Directory of Open Access Journals (Sweden)

    Peng Xie

    2010-01-01

    Full Text Available Underwater Sensor Networks (UWSNs are significantly different from terrestrial sensor networks in the following aspects: low bandwidth, high latency, node mobility, high error probability, and 3-dimensional space. These new features bring many challenges to the network protocol design of UWSNs. In this paper, we tackle one fundamental problem in UWSNs: robust, scalable, and energy efficient routing. We propose vector-based forwarding (VBF, a geographic routing protocol. In VBF, the forwarding path is guided by a vector from the source to the target, no state information is required on the sensor nodes, and only a small fraction of the nodes is involved in routing. To improve the robustness, packets are forwarded in redundant and interleaved paths. Further, a localized and distributed self-adaptation algorithm allows the nodes to reduce energy consumption by discarding redundant packets. VBF performs well in dense networks. For sparse networks, we propose a hop-by-hop vector-based forwarding (HH-VBF protocol, which adapts the vector-based approach at every hop. We evaluate the performance of VBF and HH-VBF through extensive simulations. The simulation results show that VBF achieves high packet delivery ratio and energy efficiency in dense networks and HH-VBF has high packet delivery ratio even in sparse networks.

  20. Dendritic Cell-Based Vaccine Against Fungal Infection.

    Science.gov (United States)

    Ueno, Keigo; Urai, Makoto; Ohkouchi, Kayo; Miyazaki, Yoshitsugu; Kinjo, Yuki

    2016-01-01

    Several pathogenic fungi, including Cryptococcus gattii, Histoplasma capsulatum, Coccidioides immitis, and Penicillium marneffei, cause serious infectious diseases in immunocompetent humans. However, currently, prophylactic and therapeutic vaccines are not clinically used. In particular, C. gattii is an emerging pathogen and thus far protective immunity against this pathogen has not been well characterized. Experimental vaccines such as component and attenuated live vaccines have been used as tools to study protective immunity against fungal infection. Recently, we developed a dendritic cell (DC)-based vaccine to study protective immunity against pulmonary infection by highly virulent C. gattii strain R265 that was clinically isolated from bronchial washings of infected patients during the Vancouver Island outbreak. In this approach, bone marrow-derived DCs (BMDCs) are pulsed with heat-killed C. gattii and then transferred into mice prior to intratracheal infection. This DC vaccine significantly increases interleukin 17A (IL-17A)-, interferon gamma (IFN-γ)-, and tumor necrosis factor alpha (TNF-α)-producing T cells in the lungs and spleen and ameliorates the pathology, fungal burden, and mortality following C. gattii infection. This approach may result in the development of a new means of controlling lethal fungal infections. In this chapter, we describe the procedures of DC vaccine preparation and murine pulmonary infection model for analysis of immune response against C. gattii.

  1. Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus.

    OpenAIRE

    Lubeck, M D; Davis, A R; Chengalvala, M; Natuk, R J; Morin, J E; Molnar-Kimber, K; Mason, B. B.; Bhat, B M; Mizutani, S; Hung, P P

    1989-01-01

    As a major cause of acute and chronic liver disease as well as hepatocellular carcinoma, hepatitis B virus (HBV) continues to pose significant health problems world-wide. Recombinant hepatitis B vaccines based on adenovirus vectors have been developed to address global needs for effective control of hepatitis B infection. Although considerable progress has been made in the construction of recombinant adenoviruses that express large amounts of HBV gene products, preclinical immunogenicity and ...

  2. Digital video steganalysis using motion vector recovery-based features.

    Science.gov (United States)

    Deng, Yu; Wu, Yunjie; Zhou, Linna

    2012-07-10

    As a novel digital video steganography, the motion vector (MV)-based steganographic algorithm leverages the MVs as the information carriers to hide the secret messages. The existing steganalyzers based on the statistical characteristics of the spatial/frequency coefficients of the video frames cannot attack the MV-based steganography. In order to detect the presence of information hidden in the MVs of video streams, we design a novel MV recovery algorithm and propose the calibration distance histogram-based statistical features for steganalysis. The support vector machine (SVM) is trained with the proposed features and used as the steganalyzer. Experimental results demonstrate that the proposed steganalyzer can effectively detect the presence of hidden messages and outperform others by the significant improvements in detection accuracy even with low embedding rates.

  3. Plant based oral vaccines for human and animal pathogens – a new era of prophylaxis: current and future perspectives

    Directory of Open Access Journals (Sweden)

    Kuldeep Dhama

    Full Text Available Vaccination remains a high priority for animal disease prevention and control especially on account of rising antimicrobial resistant strains of pathogens and frightening increase in new emerging and reemerging pathogens. Traditional vaccines have limitation like residual virulence, need of extensive safety precautions, production difficulty and huge initial investments. Additionally, they are inefficient in producing a protective response at mucosal surfaces such as of lungs and intestinal tract, the actual sites where disease agents enter the body. Recent advances in plant molecular farming has resulted in genetic manipulations in plants to make them bioreactors for production of various recombinant proteins, by using infectious vectors or stable transgenic systems, which formulate the edible/oral vaccines. Such plant-based oral/edible vaccines have several advantages like they are functionally similar to conventional vaccines, demonstrate extended storage period in food grains, are heat-stable and does not require cold storage, eliminate need for expensive purification steps, are free from contaminating pathogens, can be produced in large scale in a time bound fashion and their delivery is easier with practical feasibility for large masses application. Additionally, these are also ideal for vaccination of animals and birds living in the wild areas thereby preventing many zoonoses. However, at this moment there are many practical challenges like degradation of vaccine antigen by enzymes of upper digestive tract, dosage regime, oral tolerance and the issues concerned to the use of genetically modified plant. In the near future the biomedical applications of these vaccines could become a common alternative to conventional vaccines, for which there is a great need to strengthen research and development activities in this promising area for protecting health of animals as well as of humans.

  4. Establishment of human sperm-specific voltage-dependent anion channel 3 recombinant vector for the production of a male contraceptive vaccine

    Directory of Open Access Journals (Sweden)

    Asmarinah Asmarinah

    2012-05-01

    Full Text Available Background: The aim of this study was to construct a recombinant vector of human sperm specific VDAC3 gene for production of VDAC3 antibody, which is potential as male contraception vaccine.Methods: Target fragment sequence of VDAC3 gene was obtained through amplification of human sperm VDAC3 cDNA with primers covering exon 5 to exon 8. Its PCR product in size of 435 bp was cloned to the pET101/D-TOPO expression vector (5753 bp. E. coli bacteria were transformed with this vector. Cloning of VDAC3 fragment gene to the vector was confirmed by the using of XbaI restriction enzyme and PCR colony method with primers covering exons 5-8 of the human VDAC3 gene.Results: Alignment analysis of amplified fragment covering exon 5 to exon 8 of VDAC3 gene showed 94% homology to human VDAC3 gene from databank. After cloning to the expression vector and transformation to E. coli competent cells, twelve colonies could grow in culture media. Gel electrophoresis of sliced VDAC3 recombinant vector showed a single band in the size of 6181 bp in 8 colonies. After application of PCR colony and amplicon sequencing, the result showed a single band in the size of 435 bp and fragment sequence with 94% identity to human VDAC3 gene.Conclusion: The construction of human sperm specific VDAC3 gene recombinant vector was established in this study. In the future, this recombinant vector will be used to produce VDAC3 antibody for the development of a male contraception vaccine. (Med J Indones. 2012;21:61-5Keywords: Contraception, recombinant vector, sperm, VDAC3

  5. Versatile Supramolecular Gene Vector Based on Host-Guest Interaction.

    Science.gov (United States)

    Liu, Jia; Hennink, Wim E; van Steenbergen, Mies J; Zhuo, Renxi; Jiang, Xulin

    2016-04-20

    It is a great challenge to arrange multiple functional components into one gene vector system to overcome the extra- and intracellular obstacles for gene therapy. In this study, we developed a supramolecular approach for constructing a versatile gene delivery system composed of adamantyl-terminated functional polymers and a β-cyclodextrin based polymer. Adamantyl-functionalized low molecular weight PEIs (PEI-Ad) and PEG (Ad-PEG) as well as poly(β-cyclodextrin) (PCD) were synthesized by one-step chemical reactions. The supramolecular inclusion complex formed from PCD to assemble LMW PEI-Ad4 via host-guest interactions can condense plasmid DNA to form nanopolyplexes by electrostatic interactions. The supramolecular polyplexes can be further PEGylated with Ad-PEG to form inclusion complexes, which showed increased salt and serum stability. In vitro experiments revealed that these supramolecular assembly polyplexes had good cytocompatibility and showed high transfection activity close to that of the commercial ExGen 500 at high dose of DNA. Also, the supramolecular vector system exhibited about 60% silencing efficiency as a siRNA vector. Thus, a versatile effective supramolecular gene vector based on host-guest complexes was fabricated with good cytocompatbility and transfection activity. PMID:27019340

  6. Expression of chicken parvovirus VP2 in chicken embryo fibroblasts requires codon optimization for production of naked DNA and vectored meleagrid herpesvirus type 1 vaccines.

    Science.gov (United States)

    Spatz, Stephen J; Volkening, Jeremy D; Mullis, Robert; Li, Fenglan; Mercado, John; Zsak, Laszlo

    2013-10-01

    Meleagrid herpesvirus type 1 (MeHV-1) is an ideal vector for the expression of antigens from pathogenic avian organisms in order to generate vaccines. Chicken parvovirus (ChPV) is a widespread infectious virus that causes serious disease in chickens. It is one of the etiological agents largely suspected in causing Runting Stunting Syndrome (RSS) in chickens. Initial attempts to express the wild-type gene encoding the capsid protein VP2 of ChPV by insertion into the thymidine kinase gene of MeHV-1 were unsuccessful. However, transient expression of a codon-optimized synthetic VP2 gene cloned into the bicistronic vector pIRES2-Ds-Red2, could be demonstrated by immunocytochemical staining of transfected chicken embryo fibroblasts (CEFs). Red fluorescence could also be detected in these transfected cells since the red fluorescent protein gene is downstream from the internal ribosome entry site (IRES). Strikingly, fluorescence could not be demonstrated in cells transiently transfected with the bicistronic vector containing the wild-type or non-codon-optimized VP2 gene. Immunocytochemical staining of these cells also failed to demonstrate expression of wild-type VP2, indicating that the lack of expression was at the RNA level and the VP2 protein was not toxic to CEFs. Chickens vaccinated with a DNA vaccine consisting of the bicistronic vector containing the codon-optimized VP2 elicited a humoral immune response as measured by a VP2-specific ELISA. This VP2 codon-optimized bicistronic cassette was rescued into the MeHV-1 genome generating a vectored vaccine against ChPV disease.

  7. Convex Decomposition Based Cluster Labeling Method for Support Vector Clustering

    Institute of Scientific and Technical Information of China (English)

    Yuan Ping; Ying-Jie Tian; Ya-Jian Zhou; Yi-Xian Yang

    2012-01-01

    Support vector clustering (SVC) is an important boundary-based clustering algorithm in multiple applications for its capability of handling arbitrary cluster shapes. However,SVC's popularity is degraded by its highly intensive time complexity and poor label performance.To overcome such problems,we present a novel efficient and robust convex decomposition based cluster labeling (CDCL) method based on the topological property of dataset.The CDCL decomposes the implicit cluster into convex hulls and each one is comprised by a subset of support vectors (SVs).According to a robust algorithm applied in the nearest neighboring convex hulls,the adjacency matrix of convex hulls is built up for finding the connected components; and the remaining data points would be assigned the label of the nearest convex hull appropriately.The approach's validation is guaranteed by geometric proofs.Time complexity analysis and comparative experiments suggest that CDCL improves both the efficiency and clustering quality significantly.

  8. Replication-Competent Foamy Virus Vaccine Vectors as Novel Epitope Scaffolds for Immunotherapy.

    Directory of Open Access Journals (Sweden)

    Janet Lei

    Full Text Available The use of whole viruses as antigen scaffolds is a recent development in vaccination that improves immunogenicity without the need for additional adjuvants. Previous studies highlighted the potential of foamy viruses (FVs in prophylactic vaccination and gene therapy. Replication-competent FVs can trigger immune signaling and integrate into the host genome, resulting in persistent antigen expression and a robust immune response. Here, we explored feline foamy virus (FFV proteins as scaffolds for therapeutic B and T cell epitope delivery in vitro. Infection- and cancer-related B and T cell epitopes were grafted into FFV Gag, Env, or Bet by residue replacement, either at sites of high local sequence homology between the epitope and the host protein or in regions known to tolerate sequence alterations. Modified proviruses were evaluated in vitro for protein steady state levels, particle release, and virus titer in permissive cells. Modification of Gag and Env was mostly detrimental to their function. As anticipated, modification of Bet had no impact on virion release and affected virus titers of only some recombinants. Further evaluation of Bet as an epitope carrier was performed using T cell epitopes from the model antigen chicken ovalbumin (OVA, human tyrosinase-related protein 2 (TRP-2, and oncoprotein E7 of human papillomavirus type 16 (HPV16E7. Transfection of murine cells with constructs encoding Bet-epitope chimeric proteins led to efficient MHC-I-restricted epitope presentation as confirmed by interferon-gamma enzyme-linked immunospot assays using epitope-specific cytotoxic T lymphocyte (CTL lines. FFV infection-mediated transduction of cells with epitope-carrying Bet also induced T-cell responses, albeit with reduced efficacy, in a process independent from the presence of free peptides. We show that primate FV Bet is also a promising T cell epitope carrier for clinical translation. The data demonstrate the utility of replication

  9. Progress and prospects for L2-based human papillomavirus vaccines.

    Science.gov (United States)

    Jiang, Rosie T; Schellenbacher, Christina; Chackerian, Bryce; Roden, Richard B S

    2016-07-01

    Human papillomavirus (HPV) is a worldwide public health problem, particularly in resource-limited countries. Fifteen high-risk genital HPV types are sexually transmitted and cause 5% of all cancers worldwide, primarily cervical, anogenital and oropharyngeal carcinomas. Skin HPV types are generally associated with benign disease, but a subset is linked to non-melanoma skin cancer. Licensed HPV vaccines based on virus-like particles (VLPs) derived from L1 major capsid antigen of key high risk HPVs are effective at preventing these infections but do not cover cutaneous types and are not therapeutic. Vaccines targeting L2 minor capsid antigen, some using capsid display, adjuvant and fusions with early HPV antigens or Toll-like receptor agonists, are in development to fill these gaps. Progress and challenges with L2-based vaccines are summarized. PMID:26901354

  10. Oral vaccination with a recombinant Salmonella vaccine vector provokes systemic HIV-1 subtype C Gag-specific CD4+ Th1 and Th2 cell immune responses in mice

    Directory of Open Access Journals (Sweden)

    Williamson Anna-Lise

    2009-06-01

    Full Text Available Abstract Background Recombinant Salmonella vaccine vectors may potentially be used to induce specific CD4+ T cell responses against foreign viral antigens. Such immune responses are required features of vaccines against pathogens such as human immunodeficiency virus type 1 (HIV-1. The aim of this study was to investigate the induction of systemic HIV-1-specific CD4+ T helper (Th responses in mice after oral immunization with a live attenuated Salmonella vaccine vector that expressed HIV-1 subtype C Gag. Groups of BALB/c mice were vaccinated orally three times (4 weeks apart with this recombinant Salmonella. At sacrifice, 28 days after the last immunization, systemic CD4+ Th1 and Th2 cytokine responses were evaluated by enzyme-linked immunospot assay and cytometric bead array. HIV-1 Gag-specific IgG1 and IgG2a humoral responses in the serum were determined by enzyme-linked immunosorbent assay. Results Mice vaccinated with the recombinant Salmonella elicited both HIV-1-specific Th1 (interferon-gamma (IFN-γ and tumour necrosis factor-alpha (TNF-α and Th2 (interleukin-4 (IL-4 and interleukin-5 (IL-5 cytokine responses. The vaccine induced 70 (IFN-γ spot-forming units (SFUs/10e6 splenocytes and 238 IL-4 SFUs/10e6 splenocytes. Splenocytes from vaccinated mice also produced high levels of Th1 and Th2 cytokines upon stimulation with a Gag CD4 peptide. The levels of IFN-γ, TNF-α, IL-4 and IL-5 were 7.5-, 29.1-, 26.2- and 89.3-fold above the background, respectively. Both HIV-1 Gag-specific IgG1 and IgG2a antibodies were detected in the sera of vaccinated mice. Conclusion The study highlights the potential of orally-delivered attenuated Salmonella as mucosal vaccine vectors for HIV-1 Subtype C Gag to induce Gag-specific CD4+ Th1 and Th2 cellular immune responses and antibodies which may be important characteristics required for protection against HIV-1 infection.

  11. Novel synthetic (poly)glycerolphosphate-based antistaphylococcal conjugate vaccine.

    Science.gov (United States)

    Chen, Quanyi; Dintaman, Jay; Lees, Andrew; Sen, Goutam; Schwartz, David; Shirtliff, Mark E; Park, Saeyoung; Lee, Jean C; Mond, James J; Snapper, Clifford M

    2013-07-01

    Staphylococcal infections are a major source of global morbidity and mortality. Currently there exists no antistaphylococcal vaccine in clinical use. Previous animal studies suggested a possible role for purified lipoteichoic acid as a vaccine target for eliciting protective IgG to several Gram-positive pathogens. Since the highly conserved (poly)glycerolphosphate backbone of lipoteichoic acid is a major antigenic target of the humoral immune system during staphylococcal infections, we developed a synthetic method for producing glycerol phosphoramidites to create a covalent 10-mer of (poly)glycerolphosphate for potential use in a conjugate vaccine. We initially demonstrated that intact Staphylococcus aureus elicits murine CD4(+) T cell-dependent (poly)glycerolphosphate-specific IgM and IgG responses in vivo. Naive mice immunized with a covalent conjugate of (poly)glycerolphosphate and tetanus toxoid in alum plus CpG-oligodeoxynucleotides produced high secondary titers of serum (poly)glycerolphosphate-specific IgG. Sera from immunized mice enhanced opsonophagocytic killing of live Staphylococcus aureus in vitro. Mice actively immunized with the (poly)glycerolphosphate conjugate vaccine showed rapid clearance of staphylococcal bacteremia in vivo relative to mice similarly immunized with an irrelevant conjugate vaccine. In contrast to purified, natural lipoteichoic acid, the (poly)glycerolphosphate conjugate vaccine itself exhibited no detectable inflammatory activity. These data suggest that a synthetic (poly)glycerolphosphate-based conjugate vaccine will contribute to active protection against extracellular Gram-positive pathogens expressing this highly conserved backbone structure in their membrane-associated lipoteichoic acid. PMID:23649092

  12. Support vector machine-based multi-model predictive control

    Institute of Scientific and Technical Information of China (English)

    Zhejing BA; Youxian SUN

    2008-01-01

    In this paper,a support vector machine-based multi-model predictive control is proposed,in which SVM classification combines well with SVM regression.At first,each working environment is modeled by SVM regression and the support vector machine network-based model predictive control(SVMN-MPC)algorithm corresponding to each environment is developed,and then a multi-class SVM model is established to recognize multiple operating conditions.As for control,the current environment is identified by the multi-class SVM model and then the corresponding SVMN.MPCcontroller is activated at each sampling instant.The proposed modeling,switching and controller design is demonstrated in simulation results.

  13. Biosensor method and system based on feature vector extraction

    Science.gov (United States)

    Greenbaum, Elias; Rodriguez, Jr., Miguel; Qi, Hairong; Wang, Xiaoling

    2012-04-17

    A method of biosensor-based detection of toxins comprises the steps of providing at least one time-dependent control signal generated by a biosensor in a gas or liquid medium, and obtaining a time-dependent biosensor signal from the biosensor in the gas or liquid medium to be monitored or analyzed for the presence of one or more toxins selected from chemical, biological or radiological agents. The time-dependent biosensor signal is processed to obtain a plurality of feature vectors using at least one of amplitude statistics and a time-frequency analysis. At least one parameter relating to toxicity of the gas or liquid medium is then determined from the feature vectors based on reference to the control signal.

  14. Study on Support Vector Machine Based on 1-Norm

    Institute of Scientific and Technical Information of China (English)

    PAN Mei-qin; HE Guo-ping; HAN Cong-ying; XUE Xin; SHI You-qun

    2006-01-01

    The model of optimization problem for Support Vector Machine(SVM) is provided, which based on the definitions of the dual norm and the distance between a point and its projection onto a given plane. The model of improved Support Vector Machine based on 1-norm (1 - SVM) is provided from the optimization problem, yet it is a discrete programming. With the smoothing technique and optimality knowledge, the discrete programming is changed into a continuous programming. Experimental results show that the algorithm is easy to implement and this method can select and suppress the problem features more efficiently.Illustrative examples show that the 1 - SVM deal with the linear or nonlinear classification well.

  15. Endpoint Prediction of EAF Based on Multiple Support Vector Machines

    Institute of Scientific and Technical Information of China (English)

    YUAN Ping; MAO Zhi-zhong; WANG Fu-li

    2007-01-01

    The endpoint parameters are very important to the process of EAF steel-making, but their on-line measurement is difficult. The soft sensor technology is widely used for the prediction of endpoint parameters. Based on the analysis of the smelting process of EAF and the advantages of support vector machines, a soft sensor model for predicting the endpoint parameters was built using multiple support vector machines (MSVM). In this model, the input space was divided by subtractive clustering and a sub-model based on LS-SVM was built in each sub-space. To decrease the correlation among the sub-models and to improve the accuracy and robustness of the model, the sub-models were combined by Principal Components Regression. The accuracy of the soft sensor model is perfectly improved. The simulation result demonstrates the practicability and efficiency of the MSVM model for the endpoint prediction of EAF.

  16. Virus-like particle-based human vaccines: quality assessment based on structural and functional properties.

    Science.gov (United States)

    Zhao, Qinjian; Li, Shaowei; Yu, Hai; Xia, Ningshao; Modis, Yorgo

    2013-11-01

    Human vaccines against three viruses use recombinant virus-like particles (VLPs) as the antigen: hepatitis B virus, human papillomavirus, and hepatitis E virus. VLPs are excellent prophylactic vaccine antigens because they are self-assembling bionanoparticles (20 to 60 nm in diameter) that expose multiple epitopes on their surface and faithfully mimic the native virions. Here we summarize the long journey of these vaccines from bench to patients. The physical properties and structural features of each recombinant VLP vaccine are described. With the recent licensure of Hecolin against hepatitis E virus adding a third disease indication to prophylactic VLP-based vaccines, we review how the crucial quality attributes of VLP-based human vaccines against all three disease indications were assessed, controlled, and improved during bioprocessing through an array of structural and functional analyses.

  17. Available Bandwidth Estimation Strategy Based on the Network Allocation Vector

    OpenAIRE

    Hongtao Liu; Lianglun Cheng

    2012-01-01

    Available bandwidth is of great importance to network Quality of Service assurance, network load balancing, streaming media rate control, routing, and congestion control, etc.. In this paper, the available bandwidth estimation strategy based on the Network Allocation Vector for Wireless Sensor Networks is proposed. According to the size of the average contention window, network nodes predict the probability of collision in process of frame transmission, and then estimate the number of retrans...

  18. Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax.

    Science.gov (United States)

    Blagborough, A M; Musiychuk, K; Bi, H; Jones, R M; Chichester, J A; Streatfield, S; Sala, K A; Zakutansky, S E; Upton, L M; Sinden, R E; Brian, I; Biswas, S; Sattabonkot, J; Yusibov, V

    2016-06-14

    Malaria transmission blocking (TB) vaccines (TBVs) directed against proteins expressed on the sexual stages of Plasmodium parasites are a potentially effective means to reduce transmission. Antibodies induced by TBVs block parasite development in the mosquito, and thus inhibit transmission to further human hosts. The ookinete surface protein P25 is a primary target for TBV development. Recently, transient expression in plants using hybrid viral vectors has demonstrated potential as a strategy for cost-effective and scalable production of recombinant vaccines. Using a plant virus-based expression system, we produced recombinant P25 protein of Plasmodium vivax (Pvs25) in Nicotiana benthamiana fused to a modified lichenase carrier protein. This candidate vaccine, Pvs25-FhCMB, was purified, characterized and evaluated for immunogenicity and efficacy using multiple adjuvants in a transgenic rodent model. An in vivo TB effect of up to a 65% reduction in intensity and 54% reduction in prevalence was observed using Abisco-100 adjuvant. The ability of this immunogen to induce a TB response was additionally combined with heterologous prime-boost vaccination with viral vectors expressing Pvs25. Significant blockade was observed when combining both platforms, achieving a 74% and 68% reduction in intensity and prevalence, respectively. This observation was confirmed by direct membrane feeding on field P. vivax samples, resulting in reductions in intensity/prevalence of 85.3% and 25.5%. These data demonstrate the potential of this vaccine candidate and support the feasibility of expressing Plasmodium antigens in a plant-based system for the production of TBVs, while demonstrating the potential advantages of combining multiple vaccine delivery systems to maximize efficacy. PMID:27177945

  19. Host defense mechanism-based rational design of live vaccine.

    Directory of Open Access Journals (Sweden)

    Yo Han Jang

    Full Text Available Live attenuated vaccine (LAV, mimicking natural infection, provides an excellent protection against microbial infection. The development of LAV, however, still remains highly empirical and the rational design of clinically useful LAV is scarcely available. Apoptosis and caspase activation are general host antiviral responses in virus-infected cells. Utilizing these tightly regulated host defense mechanisms, we present a novel apoptosis-triggered attenuation of viral virulence as a rational design of live attenuated vaccine with desired levels of safety, efficacy, and productivity. Mutant influenza viruses carrying caspase recognition motifs in viral NP and the interferon-antagonist NS1 proteins were highly attenuated both in vitro and in vivo by caspase-mediated cleavage of those proteins in infected cells. Both viral replication and interferon-resistance were substantially reduced, resulting in a marked attenuation of virulence of the virus. Despite pronounced attenuation, the viruses demonstrated high growth phenotype in embryonated eggs at lower temperature, ensuring its productivity. A single dose vaccination with the mutant virus elicited high levels of systemic and mucosal antibody responses and provided complete protection against both homologous and heterologous lethal challenges in mouse model. While providing a practical means to generate seasonal or pandemic influenza live vaccines, the sensitization of viral proteins to pathogen-triggered apoptotic signals presents a potentially universal, mechanism-based rational design of live vaccines against many viral infections.

  20. Host defense mechanism-based rational design of live vaccine.

    Science.gov (United States)

    Jang, Yo Han; Byun, Young Ho; Lee, Kwang-Hee; Park, Eun-Sook; Lee, Yun Ha; Lee, Yoon-Jae; Lee, Jinhee; Kim, Kyun-Hwan; Seong, Baik Lin

    2013-01-01

    Live attenuated vaccine (LAV), mimicking natural infection, provides an excellent protection against microbial infection. The development of LAV, however, still remains highly empirical and the rational design of clinically useful LAV is scarcely available. Apoptosis and caspase activation are general host antiviral responses in virus-infected cells. Utilizing these tightly regulated host defense mechanisms, we present a novel apoptosis-triggered attenuation of viral virulence as a rational design of live attenuated vaccine with desired levels of safety, efficacy, and productivity. Mutant influenza viruses carrying caspase recognition motifs in viral NP and the interferon-antagonist NS1 proteins were highly attenuated both in vitro and in vivo by caspase-mediated cleavage of those proteins in infected cells. Both viral replication and interferon-resistance were substantially reduced, resulting in a marked attenuation of virulence of the virus. Despite pronounced attenuation, the viruses demonstrated high growth phenotype in embryonated eggs at lower temperature, ensuring its productivity. A single dose vaccination with the mutant virus elicited high levels of systemic and mucosal antibody responses and provided complete protection against both homologous and heterologous lethal challenges in mouse model. While providing a practical means to generate seasonal or pandemic influenza live vaccines, the sensitization of viral proteins to pathogen-triggered apoptotic signals presents a potentially universal, mechanism-based rational design of live vaccines against many viral infections.

  1. Cationic Lipid-Formulated DNA Vaccine against Hepatitis B Virus : Immunogenicity of MIDGE-Th1 Vectors Encoding Small and Large Surface Antigen in Comparison to a Licensed Protein Vaccine

    NARCIS (Netherlands)

    Endmann, Anne; Klunder, Katharina; Kapp, Kerstin; Riede, Oliver; Oswald, Detlef; Talman, Eduard G.; Schroff, Matthias; Kleuss, Christiane; Ruiters, Marcel H. J.; Juhls, Christiane

    2014-01-01

    Currently marketed vaccines against hepatitis B virus (HBV) based on the small (S) hepatitis B surface antigen (HBsAg) fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible

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

    Science.gov (United States)

    Oyarzún, Patricio; Kobe, Bostjan

    2016-03-01

    Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process. PMID:26430814

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

    Science.gov (United States)

    Oyarzún, Patricio; Kobe, Bostjan

    2016-03-01

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

  4. Virus-based nanoparticles as platform technologies for modern vaccines.

    Science.gov (United States)

    Lee, Karin L; Twyman, Richard M; Fiering, Steven; Steinmetz, Nicole F

    2016-07-01

    Nanoscale engineering is revolutionizing the development of vaccines and immunotherapies. Viruses have played a key role in this field because they can function as prefabricated nanoscaffolds with unique properties that are easy to modify. Viruses are immunogenic via multiple pathways, and antigens displayed naturally or by engineering on the surface can be used to create vaccines against the cognate virus, other pathogens, specific molecules or cellular targets such as tumors. This review focuses on the development of virus-based nanoparticle systems as vaccines indicated for the prevention or treatment of infectious diseases, chronic diseases, cancer, and addiction. WIREs Nanomed Nanobiotechnol 2016, 8:554-578. doi: 10.1002/wnan.1383 For further resources related to this article, please visit the WIREs website. PMID:26782096

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

    Science.gov (United States)

    Dimitrov, Dobromir; Kublin, James G; Ramsey, Scott; Corey, Lawrence

    2015-12-01

    As HIV-1 envelope immune responses are critical to vaccine related protection, most candidate HIV vaccines entering efficacy trials are based upon a clade specific design. This need for clade specific vaccine prototypes markedly reduces the implementation of potentially effective HIV vaccines. We utilized a mathematical model to determine the effectiveness of immediate roll-out of a non-clade matched vaccine with reduced efficacy compared to constructing clade specific vaccines, which would take considerable time to manufacture and test in safety and efficacy trials. We simulated the HIV epidemic in San Francisco (SF) and South Africa (SA) and projected effectiveness of three vaccination strategies: i) immediate intervention with a 20-40% vaccine efficacy (VE) non-matched vaccine, ii) delayed intervention by developing a 50% VE clade-specific vaccine, and iii) immediate intervention with a non-matched vaccine replaced by a clade-specific vaccine when developed. Immediate vaccination with a non-clade matched vaccine, even with reduced efficacy, would prevent thousands of new infections in SF and millions in SA over 30 years. Vaccination with 50% VE delayed for five years needs six and 12 years in SA to break-even with immediate 20 and 30% VE vaccination, respectively, while not able to surpass the impact of immediate 40% VE vaccination over 30 years. Replacing a 30% VE with a 50% VE vaccine after 5 years reduces the HIV acquisition by 5% compared to delayed vaccination. The immediate use of an HIV vaccine with reduced VE in high risk communities appears desirable over a short time line but higher VE should be the pursued to achieve strong long-term impact. Our analysis illustrates the importance of developing surrogate markers (correlates of protection) to allow bridging types of immunogenicity studies to support more rapid assessment of clade specific vaccines. PMID:26844286

  6. A new generation of pPRIG-based retroviral vectors

    Directory of Open Access Journals (Sweden)

    Boulukos Kim E

    2007-11-01

    Full Text Available Abstract Background Retroviral vectors are valuable tools for gene transfer. Particularly convenient are IRES-containing retroviral vectors expressing both the protein of interest and a marker protein from a single bicistronic mRNA. This coupled expression increases the relevance of tracking and/or selection of transduced cells based on the detection of a marker protein. pAP2 is a retroviral vector containing eGFP downstream of a modified IRES element of EMCV origin, and a CMV enhancer-promoter instead of the U3 region of the 5'LTR, which increases its efficiency in transient transfection. However, pAP2 contains a limited multicloning site (MCS and shows weak eGFP expression, which previously led us to engineer an improved version, termed pPRIG, harboring: i the wild-type ECMV IRES sequence, thereby restoring its full activity; ii an optimized MCS flanked by T7 and SP6 sequences; and iii a HA tag encoding sequence 5' of the MCS (pPRIG HAa/b/c. Results The convenience of pPRIG makes it a good basic vector to generate additional derivatives for an extended range of use. Here we present several novel pPRIG-based vectors (collectively referred to as PRIGs in which : i the HA tag sequence was inserted in the three reading frames 3' of the MCS (3'HA PRIGs; ii a functional domain (ER, VP16 or KRAB was inserted either 5' or 3' of the MCS (« modular » PRIGs; iii eGFP was replaced by either eCFP, eYFP, mCherry or puro-R (« single color/resistance » PRIGs; and iv mCherry, eYFP or eGFP was inserted 5' of the MCS of the IRES-eGFP, IRES-eCFP or IRES-Puro-R containing PRIGs, respectively (« dual color/selection » PRIGs. Additionally, some of these PRIGs were also constructed in a pMigR MSCV background which has been widely used in pluripotent cells. Conclusion These novel vectors allow for straightforward detection of any expressed protein (3'HA PRIGs, for functional studies of chimeric proteins (« modular » PRIGs, for multiple transductions and

  7. Development of an APC-targeted multivalent E2-based vaccine against Bovine Viral Diarrhea Virus types 1 and 2.

    Science.gov (United States)

    Pecora, A; Malacari, D A; Perez Aguirreburualde, M S; Bellido, D; Nuñez, M C; Dus Santos, M J; Escribano, J M; Wigdorovitz, A

    2015-09-22

    The aim of this study was to develop and test a multivalent subunit vaccine against Bovine Viral Diarrhea Virus (BVDV) based on the E2 virus glycoprotein belonging to genotypes 1a, 1b and 2a, immunopotentiated by targeting these antigens to antigen-presenting cells. The E2 antigens were expressed in insect cells by a baculovirus vector as fusion proteins with a single chain antibody, named APCH I, which recognizes the β-chain of the MHC Class II antigen. The three chimeric proteins were evaluated for their immunogenicity in a guinea pig model as well as in colostrum-deprived calves. Once the immune response in experimentally vaccinated calves was evaluated, immunized animals were challenged with type 1b or type 2b BVDV in order to study the protection conferred by the experimental vaccine. The recombinant APCH I-tE21a-1b-2a vaccine was immunogenic both in guinea pigs and calves, inducing neutralizing antibodies. After BVDV type 1b and type 2 challenge of vaccinated calves in a proof of concept, the type 1b virus could not be isolated in any animal; meanwhile it was detected in all challenged non-vaccinated control animals. However, the type 2 BVDV was isolated to a lesser extent compared to unvaccinated animals challenged with type 2 BVDV. Clinical signs associated to BVDV, hyperthermia and leukopenia were reduced with respect to controls in all vaccinated calves. Given these results, this multivalent vaccine holds promise for a safe and effective tool to control BVDV in herds. PMID:26279338

  8. Infection of Nonhost Species Dendritic Cells In Vitro with an Attenuated Myxoma Virus Induces Gene Expression That Predicts Its Efficacy as a Vaccine Vector ▿ †

    Science.gov (United States)

    Top, S.; Foulon, E.; Pignolet, B.; Deplanche, M.; Caubet, C.; Tasca, C.; Bertagnoli, S.; Meyer, G.; Foucras, G.

    2011-01-01

    Recombinant myxoma virus (MYXV) can be produced without a loss of infectivity, and its highly specific host range makes it an ideal vaccine vector candidate, although careful examination of its interaction with the immune system is necessary. Similar to rabbit bone marrow-derived dendritic cells (BM-DCs), ovine dendritic cells can be infected by SG33, a MYXV vaccine strain, and support recombinant antigen expression. The frequency of infected cells in the nonhost was lower and the virus cycle was abortive in these cell types. Among BM-DC subpopulations, Langerhans cell-like DCs were preferentially infected at low multiplicities of infection. Interestingly, ovine BM-DCs remained susceptible to MYXV after maturation, although apoptosis occurred shortly after infection as a function of the virus titer. When gene expression was assessed in infected BM-DC cultures, type I interferon (IFN)-related and inflammatory genes were strongly upregulated. DC gene expression profiles were compared with the profiles produced by other poxviruses in interaction with DCs, but very few commonalities were found, although genes that were previously shown to predict vaccine efficacy were present. Collectively, these data support the idea that MYXV permits efficient priming of adaptive immune responses and should be considered a promising vaccine vector along with other poxviruses. PMID:21835800

  9. Novel DNA vaccine based on hepatitis B virus core gene induces specific immune responses in Balb/c mice

    Institute of Scientific and Technical Information of China (English)

    Yi-Ping Xing; Zu-Hu Huang; Shi-Xia Wang; Jie Cai; Jun Li; Te-Hui W Chou; Shan Lu

    2005-01-01

    AIM: To investigate the immunogenicity of a novel DNA vaccine,pSW3891/HBc, based on HBV core gene in Balb/c mice.METHODS: A novel DNA vaccine, pSW3891/HBc, encoding HBV core gene was constructed using a vector plasmid pSW3891. Balb/c mice were immunized with either pSW3891/HBc or empty vector DNA via gene gun. IgG anti-HBc responses in mouse sera were demonstrated by ELISA. Specific cytotoxicity of cytotoxic T lymphocytes (CTLs) of mice was quantitatively measured by lactate dehydrogenase release assay.RESULTS: HBcAg was expressed effectively in 293T cell line transiently transfected with pSW3891/HBc. Strong IgG anti-HBc responses were elicited in mice immunized with pSW3891/HBc. The end-point titers of anti-HBc reached the highest 1:97 200, 4 wk after the third immunization. The specific CTL killing with the highest specific lysis reached 73.25% at effector:target ratio of 20:1 in mice that received pSW3891/HBc DNA vaccine.CONCLUSION: pSW3891/HBc vaccination elicits specific anti-HBc response and induces HBc-specific CTL response in immunized Balb/c mice.

  10. Efficient Satellite Scheduling Based on Improved Vector Evaluated Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Tengyue Mao

    2012-03-01

    Full Text Available Satellite scheduling is a typical multi-peak, many-valley, nonlinear multi-objective optimization problem. How to effectively implement the satellite scheduling is a crucial research in space areas.This paper mainly discusses the performance of VEGA (Vector Evaluated Genetic Algorithm based on the study of basic principles of VEGA algorithm, algorithm realization and test function, and then improves VEGA algorithm through introducing vector coding, new crossover and mutation operators, new methods to assign fitness and hold good individuals. As a result, the diversity and convergence of improved VEGA algorithm of improved VEGA algorithm have been significantly enhanced and will be applied to Earth-Mars orbit optimization. At the same time, this paper analyzes the results of the improved VEGA, whose results of performance analysis and evaluation show that although VEGA has a profound impact upon multi-objective evolutionary research,  multi-objective evolutionary algorithm on the basis of Pareto seems to be a more effective method to get the non-dominated solutions from the perspective of diversity and convergence of experimental result. Finally, based on Visual C + + integrated development environment, we have implemented improved vector evaluation algorithm in the satellite scheduling.

  11. Available Bandwidth Estimation Strategy Based on the Network Allocation Vector

    Directory of Open Access Journals (Sweden)

    Hongtao Liu

    2012-12-01

    Full Text Available Available bandwidth is of great importance to network Quality of Service assurance, network load balancing, streaming media rate control, routing, and congestion control, etc.. In this paper, the available bandwidth estimation strategy based on the Network Allocation Vector for Wireless Sensor Networks is proposed. According to the size of the average contention window, network nodes predict the probability of collision in process of frame transmission, and then estimate the number of retransmission. Through the collection of Hello packets periodically sent by neighbors, nodes obtain their Network Allocation Vector, and then estimate the available bandwidth. The simulation results show that the strategy is simple and effective, can accurately estimate the collision of data frames as well as the available bandwidth of Wireless Sensor Networks.

  12. Riesz multiwavelet bases generated by vector refinement equation

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In this paper, we investigate compactly supported Riesz multiwavelet sequences and Riesz multiwavelet bases for L2(Rs). Suppose ψ = (ψ1, . . . , ψr)T and ψ = ( ψ1, . . . , ψr)T are two compactly supported vectors of functions in the Sobolev space (Hμ(Rs))r for some μ > 0. We provide a characterization for the sequences {ψjk : = 1, . . . , r, j ∈ Z, k ∈ Zs} and {ψ jk : = 1, . . . , r, j ∈ Z, k ∈ Zs} to form two Riesz sequences for L2(Rs), where ψjk = mj/2ψ (M j ·k) and ψjk = mj/2 ψ (M j ·k), M is an s × s integer matrix such that limn→∞ Mn = 0 and m = |detM|. Furthermore, let = (1, . . . , r)T and = ( 1, . . . , r)T be a pair of compactly supported biorthogonal refinable vectors of functions associated with the refinement masks a, a and M, where a and a are finitely supported sequences of r × r matrices. We obtain a general principle for characterizing vectors of functions ψν = (ψν1, . . . , ψνr)T and ψν = ( ψν1, . . . , ψ?νr)T , ν = 1, . . . , m 1 such that two sequences {ψjνk : ν = 1, . . . , m 1, = 1, . . . , r, j ∈ Z, k ∈ Zs} and {ψ jνk : ν = 1, . . . , m 1, = 1, . . . , r, j ∈ Z, k ∈ Zs} form two Riesz multiwavelet bases for L2(Rs). The bracket product [f, g] of two vectors of functions f, g in (L2(Rs))r is an indispensable tool for our characterization.

  13. Recent innovations in mRNA vaccines.

    Science.gov (United States)

    Ulmer, Jeffrey B; Geall, Andrew J

    2016-08-01

    Nucleic acid-based vaccines are being developed as a means to combine the positive attributes of both live-attenuated and subunit vaccines. Viral vectors and plasmid DNA vaccines have been extensively evaluated in human clinical trials and have been shown to be safe and immunogenic, although none have yet been licensed for human use. Recently, mRNA based vaccines have emerged as an alternative approach. They promise the flexibility of plasmid DNA vaccines, without the need for electroporation, but with enhanced immunogenicity and safety. In addition, they avoid the limitations of anti-vector immunity seen with viral vectors, and can be dosed repeatedly. This review highlights the key papers published over the past few years and summarizes prospects for the near future.

  14. Seed-based oral vaccines as allergen-specific immunotherapies.

    Science.gov (United States)

    Takaiwa, Fumio

    2011-03-01

    Plant-based vaccines have advantages over conventional vaccines in terms of scalability, lack of requirement for cold chain logistics, stability, safety, cost-effectiveness and needle-free administration. In particular, when antigen is expressed in seeds, high production is possible and immunogenicity is not lost even if stocked at ambient temperature for several years. Induction of immune tolerance (desensitization) to allergen is a principle strategy for controlling allergic diseases, and is generally carried out by subcutaneous injection. Seed-based oral administration offers a straightforward and inexpensive alternative approach to deliver vaccines effectively to the GALT without loss of activity. Consumption of transgenic seeds containing modified hypo-allergenic tolerogen or T-cell epitope peptides derived from allergens has no or very few severe side effects and can induce immune tolerance leading to reduction of allergen-specific IgE production, T-cell proliferation and release of histamine. Suppression of allergen-specific clinical symptoms results. Thus, seed-based allergy vaccines offer an innovative and convenient allergen-specific immunotherapeutic approach as an alternative to conventional allergen-specific immunotherapy.

  15. Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Zhou Xing

    Full Text Available BACKGROUND: Recombinant adenovirus-vectored (Ad tuberculosis (TB vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. METHODS AND FINDINGS: Specific pathogen-free guinea pigs were immunized with BCG, AdAg85A intranasally (i.n, AdAg85A intramuscularly (i.m, BCG boosted with AdAg85A i.n, BCG boosted with AdAg85A i.m, or treated only with saline. The animals were then infected by a low-dose aerosol of M. tuberculosis (M.tb. At the specified times, the animals were sacrificed and the levels of infection in the lung and spleen were assessed. In separate studies, the long-term disease outcome of infected animals was monitored until the termination of this study. Immunization with Ad vaccine alone had minimal beneficial effects. Immunization with BCG alone and BCG prime-Ad vaccine boost regimens significantly reduced the level of M.tb infection in the tissues to a similar extent. However, while BCG alone prolonged the survival of infected guinea pigs, the majority of BCG-immunized animals succumbed by 53 weeks post-M.tb challenge. In contrast, intranasal or intramuscular Ad vaccine boosting of BCG-primed animals markedly improved the survival rate with 60% of BCG/Ad i.n- and 40% of BCG/Ad i.m-immunized guinea pigs still surviving by 74 weeks post-aerosol challenge. CONCLUSIONS: Boosting, particularly via the intranasal mucosal route, with AdAg85A vaccine is able to significantly enhance the long-term survival of BCG-primed guinea pigs following pulmonary M.tb challenge. Our results thus support further evaluation of this viral-vectored TB vaccine in clinical trials.

  16. Highest Vaccine Uptake after School-Based Delivery - A County-Level Evaluation of the Implementation Strategies for HPV Catch-Up Vaccination in Sweden

    OpenAIRE

    Rehn, Moa; Uhnoo, Ingrid; Kuhlmann-Berenzon, Sharon; Wallensten, Anders; Sparen, Par; Netterlid, Eva

    2016-01-01

    Background The Swedish school-based vaccination programme offers HPV vaccine to girls born >= 1999 in 5-6th grade. In 2012, all counties introduced free-of-charge catch-up vaccination campaigns targeting girls born 1993-1998. Varying vaccine uptake in the catch-up group by December 2012 suggested that some implementation strategies were more successful than others. In order to inform future vaccination campaigns, we assessed the impact of different implementation strategies on the county-l...

  17. Support vector based battery state of charge estimator

    Science.gov (United States)

    Hansen, Terry; Wang, Chia-Jiu

    This paper investigates the use of a support vector machine (SVM) to estimate the state-of-charge (SOC) of a large-scale lithium-ion-polymer (LiP) battery pack. The SOC of a battery cannot be measured directly and must be estimated from measurable battery parameters such as current and voltage. The coulomb counting SOC estimator has been used in many applications but it has many drawbacks [S. Piller, M. Perrin, Methods for state-of-charge determination and their application, J. Power Sources 96 (2001) 113-120]. The proposed SVM based solution not only removes the drawbacks of the coulomb counting SOC estimator but also produces accurate SOC estimates, using industry standard US06 [V.H. Johnson, A.A. Pesaran, T. Sack, Temperature-dependent battery models for high-power lithium-ion batteries, in: Presented at the 17th Annual Electric Vehicle Symposium Montreal, Canada, October 15-18, 2000. The paper is downloadable at website http://www.nrel.gov/docs/fy01osti/28716.pdf] aggressive driving cycle test procedures. The proposed SOC estimator extracts support vectors from a battery operation history then uses only these support vectors to estimate SOC, resulting in minimal computation load and suitable for real-time embedded system applications.

  18. Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection.

    Science.gov (United States)

    Swadling, Leo; Halliday, John; Kelly, Christabel; Brown, Anthony; Capone, Stefania; Ansari, M Azim; Bonsall, David; Richardson, Rachel; Hartnell, Felicity; Collier, Jane; Ammendola, Virginia; Del Sorbo, Mariarosaria; Von Delft, Annette; Traboni, Cinzia; Hill, Adrian V S; Colloca, Stefano; Nicosia, Alfredo; Cortese, Riccardo; Klenerman, Paul; Folgori, Antonella; Barnes, Eleanor

    2016-01-01

    An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA), encoding the non-structural proteins of HCV (NSmut), used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine regimen in HCV infected patients (including patients with a low viral load suppressed with interferon/ribavirin therapy), determine T-cell cross-reactivity to endogenous virus, and compare immunogenicity with that observed previously in both healthy volunteers and in HCV infected patients vaccinated with the heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3-NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses were detected in 8/12 patients; however, CD4+ T-cell responses were rarely detected, and the overall magnitude of HCV-specific T-cell responses was markedly reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific cells had a distinct partially-functional phenotype (lower expression of activation markers, granzyme B, and TNFα production, weaker in vitro proliferation, and higher Tim3 expression, with comparable Tbet and Eomes expression) compared to healthy volunteers. Robust anti-vector T-cells and antibodies were induced, showing that there is no global defect in immunity. The level of viremia at the time of vaccination did not correlate with the magnitude of the vaccine-induced T-cell response. Full-length, next-generation sequencing of the circulating virus demonstrated that T-cells were

  19. Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection

    Directory of Open Access Journals (Sweden)

    Leo Swadling

    2016-08-01

    Full Text Available An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV infection, as an adjunct to newly developed directly-acting antivirals (DAA, or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3 vector and a modified vaccinia Ankara (MVA, encoding the non-structural proteins of HCV (NSmut, used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine regimen in HCV infected patients (including patients with a low viral load suppressed with interferon/ribavirin therapy, determine T-cell cross-reactivity to endogenous virus, and compare immunogenicity with that observed previously in both healthy volunteers and in HCV infected patients vaccinated with the heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3-NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses were detected in 8/12 patients; however, CD4+ T-cell responses were rarely detected, and the overall magnitude of HCV-specific T-cell responses was markedly reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific cells had a distinct partially-functional phenotype (lower expression of activation markers, granzyme B, and TNFα production, weaker in vitro proliferation, and higher Tim3 expression, with comparable Tbet and Eomes expression compared to healthy volunteers. Robust anti-vector T-cells and antibodies were induced, showing that there is no global defect in immunity. The level of viremia at the time of vaccination did not correlate with the magnitude of the vaccine-induced T-cell response. Full-length, next-generation sequencing of the circulating virus demonstrated that T

  20. Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection

    Science.gov (United States)

    Swadling, Leo; Halliday, John; Kelly, Christabel; Brown, Anthony; Capone, Stefania; Ansari, M. Azim; Bonsall, David; Richardson, Rachel; Hartnell, Felicity; Collier, Jane; Ammendola, Virginia; Del Sorbo, Mariarosaria; Von Delft, Annette; Traboni, Cinzia; Hill, Adrian V. S.; Colloca, Stefano; Nicosia, Alfredo; Cortese, Riccardo; Klenerman, Paul; Folgori, Antonella; Barnes, Eleanor

    2016-01-01

    An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA), encoding the non-structural proteins of HCV (NSmut), used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine regimen in HCV infected patients (including patients with a low viral load suppressed with interferon/ribavirin therapy), determine T-cell cross-reactivity to endogenous virus, and compare immunogenicity with that observed previously in both healthy volunteers and in HCV infected patients vaccinated with the heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3-NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses were detected in 8/12 patients; however, CD4+ T-cell responses were rarely detected, and the overall magnitude of HCV-specific T-cell responses was markedly reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific cells had a distinct partially-functional phenotype (lower expression of activation markers, granzyme B, and TNFα production, weaker in vitro proliferation, and higher Tim3 expression, with comparable Tbet and Eomes expression) compared to healthy volunteers. Robust anti-vector T-cells and antibodies were induced, showing that there is no global defect in immunity. The level of viremia at the time of vaccination did not correlate with the magnitude of the vaccine-induced T-cell response. Full-length, next-generation sequencing of the circulating virus demonstrated that T-cells were

  1. BoHV-4-Based Vector Single Heterologous Antigen Delivery Protects STAT1(-/- Mice from Monkeypoxvirus Lethal Challenge.

    Directory of Open Access Journals (Sweden)

    Valentina Franceschi

    2015-06-01

    Full Text Available Monkeypox virus (MPXV is the etiological agent of human (MPX. It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic in West Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV, and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980, meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies against MPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4 vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD106ΔTK, BoHV-4-A-EF1α-M1RgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weight-loss or obvious adverse events following intraperitoneal administration. Further, BoHV-4-A-EF1α-M1RgD106ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK, was shown to be able to protect, 100% alone and 80% in combination, STAT1(-/- mice

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

    DEFF Research Database (Denmark)

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

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

  3. Interframe hierarchical vector quantization using hashing-based reorganized codebook

    Science.gov (United States)

    Choo, Chang Y.; Cheng, Che H.; Nasrabadi, Nasser M.

    1995-12-01

    Real-time multimedia communication over PSTN (Public Switched Telephone Network) or wireless channel requires video signals to be encoded at the bit rate well below 64 kbits/second. Most of the current works on such very low bit rate video coding are based on H.261 or H.263 scheme. The H.263 encoding scheme, for example, consists mainly of motion estimation and compensation, discrete cosine transform, and run and variable/fixed length coding. Vector quantization (VQ) is an efficient and alternative scheme for coding at very low bit rate. One such VQ code applied to video coding is interframe hierarchical vector quantization (IHVQ). One problem of IHVQ, and VQ in general, is the computational complexity due to codebook search. A number of techniques have been proposed to reduce the search time which include tree-structured VQ, finite-state VQ, cache VQ, and hashing based codebook reorganization. In this paper, we present an IHVQ code with a hashing based scheme to reorganize the codebook so that codebook search time, and thus encoding time, can be significantly reduced. We applied the algorithm to the same test environment as in H.263 and evaluated coding performance. It turned out that the performance of the proposed scheme is significantly better than that of IHVQ without hashed codebook. Also, the performance of the proposed scheme was comparable to and often better than that of the H.263, due mainly to hashing based reorganized codebook.

  4. 2D Vector Field Simplification Based on Robustness

    KAUST Repository

    Skraba, Primoz

    2014-03-01

    Vector field simplification aims to reduce the complexity of the flow by removing features in order of their relevance and importance, to reveal prominent behavior and obtain a compact representation for interpretation. Most existing simplification techniques based on the topological skeleton successively remove pairs of critical points connected by separatrices, using distance or area-based relevance measures. These methods rely on the stable extraction of the topological skeleton, which can be difficult due to instability in numerical integration, especially when processing highly rotational flows. These geometric metrics do not consider the flow magnitude, an important physical property of the flow. In this paper, we propose a novel simplification scheme derived from the recently introduced topological notion of robustness, which provides a complementary view on flow structure compared to the traditional topological-skeleton-based approaches. Robustness enables the pruning of sets of critical points according to a quantitative measure of their stability, that is, the minimum amount of vector field perturbation required to remove them. This leads to a hierarchical simplification scheme that encodes flow magnitude in its perturbation metric. Our novel simplification algorithm is based on degree theory, has fewer boundary restrictions, and so can handle more general cases. Finally, we provide an implementation under the piecewise-linear setting and apply it to both synthetic and real-world datasets. © 2014 IEEE.

  5. Analysis of Antibody Responses to Protective Antigen-Based Anthrax Vaccines through Use of Competitive Assays▿

    OpenAIRE

    Rebecca A Brady; Verma, Anita; Meade, Bruce D.; Burns, Drusilla L.

    2010-01-01

    The licensed anthrax vaccine and many of the new anthrax vaccines being developed are based on protective antigen (PA), a nontoxic component of anthrax toxin. For this reason, an understanding of the immune response to PA vaccination is important. In this study, we examined the antibody response elicited by PA-based vaccines and identified the domains of PA that contribute to that response in humans as well as nonhuman primates (NHPs) and rabbits, animal species that will be used to generate ...

  6. Role of regulatory T-cells in immunization strategies involving a recombinant alphavirus vector system

    NARCIS (Netherlands)

    Walczak, Mateusz; Regts, Joke; van Oosterhout, Antoon J. M.; Boon, Louis; Wilschut, Jan; Nijman, Hans W.; Daemen, Toos

    2011-01-01

    Background: Regulatory T-cells (Treg) hamper immune responses elicited by cancer vaccines. Therefore, depletion of Treg is being used to improve the outcome of vaccinations. Methods: We studied whether an alphavirus vector-based immunotherapeutic vaccine changes the number and/or activity of Treg an

  7. Slope Deformation Prediction Based on Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Lei JIA

    2013-07-01

    Full Text Available This paper principally studies the prediction of slope deformation based on Support Vector Machine (SVM. In the prediction process,explore how to reconstruct the phase space. The geological body’s displacement data obtained from chaotic time series are used as SVM’s training samples. Slope displacement caused by multivariable coupling is predicted by means of single variable. Results show that this model is of high fitting accuracy and generalization, and provides reference for deformation prediction in slope engineering.

  8. Support vector classification algorithm based on variable parameter linear programming

    Institute of Scientific and Technical Information of China (English)

    Xiao Jianhua; Lin Jian

    2007-01-01

    To solve the problems of SVM in dealing with large sample size and asymmetric distributed samples, a support vector classification algorithm based on variable parameter linear programming is proposed.In the proposed algorithm, linear programming is employed to solve the optimization problem of classification to decrease the computation time and to reduce its complexity when compared with the original model.The adjusted punishment parameter greatly reduced the classification error resulting from asymmetric distributed samples and the detailed procedure of the proposed algorithm is given.An experiment is conducted to verify whether the proposed algorithm is suitable for asymmetric distributed samples.

  9. Debris Flow Hazard Assessment Based on Support Vector Machine

    Institute of Scientific and Technical Information of China (English)

    YUAN Lifeng; ZHANG Youshui

    2006-01-01

    Seven factors, including the maximum volume of once flow , occurrence frequency of debris flow , watershed area , main channel length , watershed relative height difference , valley incision density and the length ratio of sediment supplement are chosen as evaluation factors of debris flow hazard degree. Using support vector machine (SVM) theory, we selected 259 basic data of 37 debris flow channels in Yunnan Province as learning samples in this study. We create a debris flow hazard assessment model based on SVM. The model was validated though instance applications and showed encouraging results.

  10. In vivo image analysis of BoHV-4-based vector in mice.

    Directory of Open Access Journals (Sweden)

    Valentina Franceschi

    Full Text Available Due to its biological characteristics bovine herpesvirus 4 (BoHV-4 has been considered as an appropriate gene delivery vector. Its genomic clone, modified as a bacterial artificial chromosome (BAC, is better genetically manipulable and can be used as an efficient gene delivery and vaccine vector. Although a large amount of data have been accumulated in vitro on this specific aspect, the same cannot be asserted for the in vivo condition. Therefore, here we investigated the fate of a recombinant BoHV-4 strain expressing luciferase (BoHV-4-A-CMVlucΔTK after intraperitoneal or intravenous inoculation in mice, by generating a novel recombinant BoHV-4 expressing luciferase (BoHV-4-A-CMVlucΔTK and by following the virus replication through in vivo imaging analysis. BoHV-4-A-CMVlucΔTK was first characterized in vitro where it was shown, on one hand that its replication properties are identical to those of the parental virus, and on the other that the transduced/infected cells strongly express luciferase. When BoHV-4-A-CMVlucΔTK was inoculated in mice, either intraperitoneally or intravenously, BoHV-4-A-CMVlucΔTK infection/transduction was exclusively localized to the liver, as detected by in vivo image analysis, and in particular almost exclusively in the hepatocytes, as determined by immuno-histochemistry. These data, that add a new insight on the biology of BoHV-4 in vivo, provide the first indication for the potential use of a BoHV-4-based vector in gene-transfer in the liver.

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

    International Nuclear Information System (INIS)

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

  12. Ship detection in Polarimetric SAR based on Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Xuwu Su

    2012-08-01

    Full Text Available A Support Vector Machine (SVM based method for ship detection in Polarimetric SAR (POLSAR is proposed in this study. Because of similarities of ship and man-made structures on land in scattering mechanisms, land and sea are first segmented by SVM according to polarimetric features and texture features; The SVM-based Recursive Feature Elimination (RFE-SVM approach is adopted to improve the performance of the segmentation algorithm. Then ship targets are extracted from sea by SVM classifier; Threshold-based rules and SVM-based rules are established for discriminating ship from non-ship target at last. The experiments are carried out on POLSAR data from Radarsat-2. For the available SAR images, the average accuracy of ship detection is over 95%.

  13. Terminal Design in Vector Network based on Windows Platform

    Directory of Open Access Journals (Sweden)

    Aqun Zhao

    2013-03-01

    Full Text Available The research work of this study focuses on the design and implementation technology of terminal in Vector Network (VN based indows platform. The VN is a kind of new communication network with vector address as the switching adon Wdress. The premise of successful deployment of VN is its integration with the current IP networks, so it is necessary to study the implementation technology of VN terminal on the base of IP terminal. Firstly, a kind of software implementation method of VN terminal and a kind of integration method of VN and IP networks named “IP over VN” were proposed in this study. Secondly, the VN driver module was designed and implemented based on the NDIS driver interface and the key technique in the implementation was summarized. Finally, the experiment network was built to test the functions of VN terminal. The test results validated the rationality of the design and implementation scheme of VN terminal. The work of this study establishes the foundation for the deployment of VN and provides an example to the development of similar systems.

  14. Development of prophylactic recombinant HPV58-attenuated Shigeila live vector vaccine and evaluation of its protective efficacy and immunogenicity in the guinea pig keratoconjunctivitis model

    Institute of Scientific and Technical Information of China (English)

    Wensheng Li; Hongli Liu; Xiaofeng Yang; Jin Zheng; Yili Wang; Lusheng Si

    2009-01-01

    To develop a prophylactic recombinant HPV58L1-attenuated Shigella live vector vaccine and evaluate its protective efficacy and immunogenicity in the guinea pig keratoconjunctivitis model, the HPV58L1 gene was cloned into vector pUCmt, and then subcloned into the suicide vector pCVD442. The recombinant plasmid pCVD442-HPV58L1 was introduced into attenuated Shigella (sf301:△virG) with the helper plasmid PRK2013 by filter mating. The positive colonies were harvested and confirmed by polymerase chain reaction. The expression of the HPV58L1 protein with a molecu-lar weight of 60 kDa was confirmed by western blot. The ability of the interested protein to self-assemble into virus-like particles was identified by transmission electron microscope, and murine erythrocyte hemagglu-tination assay. The guinea pig keratoconjunctivitis model was used to evaluate the protective efficacy and immunogenicity of the vaccine. Animal experiments showed that there was no keratoconjunctivitis occurred in the immunized group (HPV58-attenuated Shigella), and the serum levels of anti-HPV58L1-IgG and -IgA were obviously increased (P0.05). Enzyme-linked immunosorbent spot assay showed that HPV58L1-specific IgA-antibody-secreting cells (ASC) and IgG-ASC of spleen and lymph nodes were also obviously increased (P<0.01). In this study, a recombi-nant HPV58L1-attenuated Shigella live vector vaccine was successfully constructed, and it could induce strong humoral immune responses in the immunized animals, and induce protective antibody production.

  15. Virtual-vector-based space vector pulse width modulation of the DC-AC multilevel-clamped multilevel converter (MLC2)

    DEFF Research Database (Denmark)

    Rodriguez, Pedro; Busquets-Monge, Sergio; Blaabjerg, Frede;

    2011-01-01

    This work presents the development of the space vector pulse width modulation (SVPWM) of a new multi-level converter topology. First, the proposed converter and its natural space vector diagram are presented. Secondly, a modified space vector diagram based on the virtual-vectors technique is shown....... Simulation results by using a space vector approach are presented. Special emphasis is given on the total harmonic distortion (THD) by making a comparison with those of the classical NPC topologies....

  16. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

    Science.gov (United States)

    Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

    2015-01-01

    Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

  17. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

    Directory of Open Access Journals (Sweden)

    Xiao-Xin Wu

    2015-11-01

    Full Text Available Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD in humans and non-human primates (NHPs. Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs, vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirus∆VP30, recombinant cytomegalovirus (CMV-based vaccines, recombinant rabies virus (RABV-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

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

    Science.gov (United States)

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

    2013-08-20

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

  19. Threat Assessment of Targets Based on Support Vector Machine

    Institute of Scientific and Technical Information of China (English)

    CAI Huai-ping; LIU Jing-xu; CHEN Ying-wu

    2006-01-01

    In the context of cooperative engagement of armored vehicles, the threat factors of offensive targets are analyzed, and a threat assessment (TA) model is built based on a support v.ector machine (SVM) method. The SVM-based model has some advantages over the traditional method-based models: the complex factors of threat are considered in the cooperative engagement; the shortcomings of neural networks, such as local minimum and "over fitting", are overcome to improve the generalization ability; its operation speed is high and meets the needs of real time C2 of cooperative engagement; the assessment results could be more reasonable because of its self-learning capability. The analysis and simulation indicate that the SVM method is an effective method to resolve the TA problems.

  20. Innovation, Vector of the Knowledge-based Society

    Directory of Open Access Journals (Sweden)

    Vladimir-Codrin Ionescu

    2013-12-01

    Full Text Available The innovative potential of a nation is determined by its members’ creative capacity, as well as by the design and implementation of strategies and policies that are meant to support the devise, experimentation and application of new ideas, respectively the transformation thereof both into tangible goods (products and services and intangible ones (knowledge. The present paper approaches innovation as a vector of the new knowledge-based society, which consists of the main actions undertaken by the EU within the context of the “European Year of Creativity and Innovation”, as well as of the actions promoted through the Initiative known as “A Union of Innovation”, comprised by the Europe Strategy 2020. The final part of the paper illustrates the essential role of universities in developing knowledge-based and innovation-based society.

  1. INNOVATION, VECTOR OF THE KNOWLEDGE-BASED SOCIETY

    Directory of Open Access Journals (Sweden)

    VLADIMIR-CODRIN IONESCU

    2013-05-01

    Full Text Available The innovative potential of a nation is determined by its members’ creative capacity, as well as by the design and implementation of strategies and policies that are meant to support the devise, experimentation and application of new ideas, respectively the transformation thereof both into tangible goods (products and services and intangible ones (knowledge. The present paper approaches innovation as a vector of the new knowledge-based society, which consists of the main actions undertaken by the EU within the context of the “European Year of Creativity and Innovation”, as well as of the actions promoted through the Initiative known as “A Union of Innovation”, comprised by the Europe Strategy 2020. The final part of the paper illustrates the essential role of universities in developing knowledge-based and innovation-based society.

  2. Attenuated Salmonella choleraesuis as DNA vaccine vector%DNA疫苗的运送载体——减毒霍乱沙门氏菌

    Institute of Scientific and Technical Information of China (English)

    惠锋明; 茆达干; 蒋进

    2011-01-01

    Salmonella choleraesuis is one of the pathogens that can be transmitted between human and animals. Its genetic background is clear. As a DNA vaccine vector, it has been widely used to express various antigens and certain results have been achieved. This review gives a brief introduction of attenuated Salmonella choleraesuis as DNA vaccine vector, including the invasion way, the mechanism for processing genetic vaccine and inducing immune responses, the advantages and limitations.%霍乱沙门氏菌是人兽共患病原菌,遗传背景清楚,利用它作为载体表达外源抗原基因已得到较广泛的研究并取得了一定的效果.本文从沙门氏菌的侵入途径、减毒重组菌对基因疫苗的呈递及诱发免疫应答的机制、作为载体的优势以及免疫存在的问题等方面就减毒霍乱沙门氏菌作为运送DNA疫苗的载体作简要概述.

  3. Genetic manipulation of endosymbionts to control vector and vector borne diseases

    Directory of Open Access Journals (Sweden)

    Jay Prakash Gupta

    Full Text Available Vector borne diseases (VBD are on the rise because of failure of the existing methods of control of vector and vector borne diseases and the climate change. A steep rise of VBDs are due to several factors like selection of insecticide resistant vector population, drug resistant parasite population and lack of effective vaccines against the VBDs. Environmental pollution, public health hazard and insecticide resistant vector population indicate that the insecticides are no longer a sustainable control method of vector and vector-borne diseases. Amongst the various alternative control strategies, symbiont based approach utilizing endosymbionts of arthropod vectors could be explored to control the vector and vector borne diseases. The endosymbiont population of arthropod vectors could be exploited in different ways viz., as a chemotherapeutic target, vaccine target for the control of vectors. Expression of molecules with antiparasitic activity by genetically transformed symbiotic bacteria of disease-transmitting arthropods may serve as a powerful approach to control certain arthropod-borne diseases. Genetic transformation of symbiotic bacteria of the arthropod vector to alter the vector’s ability to transmit pathogen is an alternative means of blocking the transmission of VBDs. In Indian scenario, where dengue, chikungunya, malaria and filariosis are prevalent, paratransgenic based approach can be used effectively. [Vet World 2012; 5(9.000: 571-576

  4. Two initial vaccinations with the Bm86-based Gavacplus vaccine against Rhipicephalus (Boophilus) microplus induce similar reproductive suppression to three initial vaccinations under production conditions

    OpenAIRE

    Fernández Erlinda; Suárez Marisela; Lleonart Ricardo; Méndez Luis; Rodríguez Elsa; Machado Héctor; Joglar Marisdania; Alfonso Aymé; Valdés Mario; Pérez Danny; Sánchez Dunia; Montero Carlos; Vargas Milagros; Estrada Mario P; Rodríguez-Mallón Alina

    2010-01-01

    Abstract Background The cattle tick, Rhipicephalus (Boophilus) microplus, affects livestock production in many regions of the world. Up to now, the widespread use of chemical acaricides has led to the selection of acaricide-resistant ticks and to environmental contamination. Gavacplus is a subunit vaccine based on the recombinant Bm86 tick antigen expressed in yeast, capable to control infestations of R. microplus under controlled and production conditions. The vaccine constitutes the core el...

  5. A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults.

    Directory of Open Access Journals (Sweden)

    Michael C Keefer

    Full Text Available BACKGROUND: We conducted a phase I, randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of escalating doses of two recombinant replication defective adenovirus serotype 35 (Ad35 vectors containing gag, reverse transcriptase, integrase and nef (Ad35-GRIN and env (Ad35-ENV, both derived from HIV-1 subtype A isolates. The trial enrolled 56 healthy HIV-uninfected adults. METHODS: Ad35-GRIN/ENV (Ad35-GRIN and Ad35-ENV mixed in the same vial in equal proportions or Ad35-GRIN was administered intramuscularly at 0 and 6 months. Participants were randomized to receive either vaccine or placebo (10/4 per group, respectively within one of four dosage groups: Ad35-GRIN/ENV 2×10(9 (A, 2×10(10 (B, 2×10(11 (C, or Ad35-GRIN 1×10(10 (D viral particles. RESULTS: No vaccine-related serious adverse event was reported. Reactogenicity events reported were dose-dependent, mostly mild or moderate, some severe in Group C volunteers, all transient and resolving spontaneously. IFN-γ ELISPOT responses to any vaccine antigen were detected in 50, 56, 70 and 90% after the first vaccination, and in 75, 100, 88 and 86% of Groups A-D vaccine recipients after the second vaccination, respectively. The median spot forming cells (SFC per 10(6 PBMC to any antigen was 78-139 across Groups A-C and 158-174 in Group D, after each of the vaccinations with a maximum of 2991 SFC. Four to five HIV proteins were commonly recognized across all the groups and over multiple timepoints. CD4+ and CD8+ T-cell responses were polyfunctional. Env antibodies were detected in all Group A-C vaccinees and Gag antibodies in most vaccinees after the second immunization. Ad35 neutralizing titers remained low after the second vaccination. CONCLUSION/SIGNIFICANCE: Ad35-GRIN/ENV reactogenicity was dose-related. HIV-specific cellular and humoral responses were seen in the majority of volunteers immunized with Ad35-GRIN/ENV or Ad35-GRIN and increased after the second

  6. The yellow fever 17D vaccine virus as a vector for the expression of foreign proteins: development of new live flavivirus vaccines

    Directory of Open Access Journals (Sweden)

    Myrna C Bonaldo

    2000-01-01

    Full Text Available The Flaviviridae is a family of about 70 mostly arthropod-borne viruses many of which are major public health problems with members being present in most continents. Among the most important are yellow fever (YF, dengue with its four serotypes and Japanese encephalitis virus. A live attenuated virus is used as a cost effective, safe and efficacious vaccine against YF but no other live flavivirus vaccines have been licensed. The rise of recombinant DNA technology and its application to study flavivirus genome structure and expression has opened new possibilities for flavivirus vaccine development. One new approach is the use of cDNAs encopassing the whole viral genome to generate infectious RNA after in vitro transcription. This methodology allows the genetic mapping of specific viral functions and the design of viral mutants with considerable potential as new live attenuated viruses. The use of infectious cDNA as a carrier for heterologous antigens is gaining importance as chimeric viruses are shown to be viable, immunogenic and less virulent as compared to the parental viruses. The use of DNA to overcome mutation rates intrinsic of RNA virus populations in conjunction with vaccine production in cell culture should improve the reliability and lower the cost for production of live attenuated vaccines. The YF virus despite a long period ignored by researchers probably due to the effectiveness of the vaccine has made a come back, both in nature as human populations grow and reach endemic areas as well as in the laboratory being a suitable model to understand the biology of flaviviruses in general and providing new alternatives for vaccine development through the use of the 17D vaccine strain.

  7. 携带人卵泡刺激素受体的慢病毒载体疫苗的构建及其免疫效应检测%Development of a Lentivirus Vector-based Vaccine Carrying Follicle-stimulating Hormone Receptor and Assay of Its Immunological Effect

    Institute of Scientific and Technical Information of China (English)

    马晓玲; 刘红春; 李江伟

    2016-01-01

    制备携带卵泡刺激素受体的慢病毒载体疫苗,并研究其对小鼠的免疫效应。将卵泡刺激素受体胞外区(fshr366)基因克隆到慢病毒载体上,采用脂质体转染法将重组质粒转染至293T细胞中,包装并产生含有目的基因的病毒颗粒;分别利用RT-PCR和Western blot检测感染病毒颗粒的293T细胞中fshr366在mRNA水平及蛋白水平的表达情况;用携带fshr366的病毒颗粒单次腹腔免疫BALB/c小鼠,分别在免疫0、14、21和28 d对小鼠眼眶采血,ELISA法检测免疫小鼠血清的特异性并测定抗体滴度。酶切和测序结果表明fshr366基因片段成功构建到慢病毒载体上。将包装产生的携带fshr366的慢病毒颗粒感染293T细胞后, RT-PCR和Western blot检测结果表明细胞在转录水平和蛋白水平均表达fshr基因。ELISA结果显示携带fshr366的慢病毒颗粒单次腹腔免疫小鼠后,免疫14 d就激起了机体的体液免疫反应,抗体滴度达到1∶1600。成功制备了携带卵泡刺激素受体的慢病毒载体疫苗,其可以在小鼠体内激发FSHR抗原特异的早期持续性免疫反应。%This work aims to prepare lentivirus vaccine with a follicle-stimulating hormone receptor(FSHR)and investigate the immunological effect of it on mice. The gene(fshr366)of extracellular region of FSHR was cloned into lentivirus vector. The recombinant plasmids were transfected into the 239T cells by the method of lipidosome transfection,and the virus particles(Lenti-FSHR366)with target gene were produced after encapsulation. The expressions offshr366mRNA and FSHR366 protein in 293T cells infected by Lenti-FSHR366 were detected by RT-PCR and Western blot. For evaluating the immunological effects,BALB/c mice were intraperitoneally inoculated with single immunization offshr366-carring virus,collecting the blood samples from the orbits of mice at day 0,14,21 and 28 after immunization,then ELISA method was used to detect

  8. Support vector classifier based on principal component analysis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Support vector classifier (SVC) has the superior advantages for small sample learning problems with high dimensions,with especially better generalization ability.However there is some redundancy among the high dimensions of the original samples and the main features of the samples may be picked up first to improve the performance of SVC.A principal component analysis (PCA) is employed to reduce the feature dimensions of the original samples and the pre-selected main features efficiently,and an SVC is constructed in the selected feature space to improve the learning speed and identification rate of SVC.Furthermore,a heuristic genetic algorithm-based automatic model selection is proposed to determine the hyperparameters of SVC to evaluate the performance of the learning machines.Experiments performed on the Heart and Adult benchmark data sets demonstrate that the proposed PCA-based SVC not only reduces the test time drastically,but also improves the identify rates effectively.

  9. Typhoid vaccine introduction: An evidence-based pilot implementation project in Nepal and Pakistan.

    Science.gov (United States)

    Khan, M Imran; Pach, Alfred; Khan, Ghulam Mustafa; Bajracharya, Deepak; Sahastrabuddhe, Sushant; Bhutta, Waqaas; Tahir, Rehman; Soofi, Sajid; Thapa, Chandra B; Joshi, Nilesh; Puri, Mahesh K; Shrestha, Parisha; Upreti, Shyam Raj; Clemens, John D; Bhutta, Zulfiqar; Ochiai, R Leon

    2015-06-19

    The World Health Organization (WHO) in 2008 recommended the use of currently licensed typhoid vaccines using a high risk or targeted approach. The epidemiology of disease and the vaccine characteristics make school-based vaccination most feasible in reducing typhoid disease burden in many settings. To assess feasibility of school-based typhoid vaccination, two districts in Kathmandu, Nepal and two towns in Karachi, Pakistan were selected for pilot program. Vaccination campaigns were conducted through the departments of health and in partnerships with not-for-profit organizations. In total 257,015 doses of Vi polysaccharide vaccine were given to students in grades 1-10 of participating schools. The vaccination coverage ranged from 39 percent (38,389/99,503) in Gulshan town in Karachi, to 81 percent (62,615/77,341) in Bhaktapur in Kathmandu valley. No serious adverse event was reported post vaccination. The coverage increased for vaccination of the second district in Pakistan as well as in Nepal. There was an initial concern of vaccine safety. However, as the campaign progressed, parents were more comfortable with vaccinating their children in schools. Supported and conducted by departments of health in Pakistan and Nepal, a school-based typhoid vaccination was found to be safe and feasible.

  10. The use of chromosome-based vectors for animal transgenesis.

    Science.gov (United States)

    Kuroiwa, Y; Yoshida, H; Ohshima, T; Shinohara, T; Ohguma, A; Kazuki, Y; Oshimura, M; Ishida, I; Tomizuka, K

    2002-06-01

    This article summarizes our efforts to use chromosome-based vectors for animal transgenesis, which may have a benefit for overcoming the size constraints of cloned transgenes in conventional techniques. Since the initial trial for introducing naturally occurring human chromosome fragments (hCFs) with large and complex immunogulobulin (Ig) loci into mice we have obtained several lines of trans-chromosomic (Tc) mice with transmittable hCFs. As expected the normal tissue-specific expression of introduced human genes was reproduced in them by inclusion of essential remote regulatory elements. Recent development of 'chromosome cloning' technique that enable construction of human artificial chromosomes (HACs) containing a defined chromosomal region should prevent the introduction of additional genes other than genes of interest and thus enhance the utility of chromosome vector system. Using this technique a panel of HACs harboring inserts ranging in size from 1.5 to 10 Mb from three human chromosomes (hChr2, 7, 22) has been constructed. Tc animals containing the HACs may be valuable not only as a powerful tool for functional genomics but also as an in vivo model to study therapeutic gene delivery by HACs.

  11. Normal Vector Based Subdivision Scheme to Generate Fractal Curves

    Directory of Open Access Journals (Sweden)

    Yi Li

    2013-08-01

    Full Text Available In this paper, we firstly devise a new and general p-ary subdivision scheme based on normal vectors with multi-parameters to generate fractals. Rich and colorful fractals including some known fractals and a lot of unknown ones can be generated directly and conveniently by using it uniformly. The method is easy to use and effective in generating fractals since the values of the parameters and the directions of normal vectors can be designed freely to control the shape of generated fractals. Secondly, we illustrate the technique with some design results of fractal generation and the corresponding fractal examples from the point of view of visualization, including the classical Lévy curves, Dragon curves, Sierpiński gasket, Koch curve, Koch-type curves and other fractals. Finally, some fractal properties of the limit of the presented subdivision scheme, including existence, self-similarity, non-rectifiability, and continuity but nowhere differentiability are described from the point of view of theoretical analysis.

  12. Facial biometrics based on 2D vector geometry

    Science.gov (United States)

    Malek, Obaidul; Venetsanopoulos, Anastasios; Androutsos, Dimitrios

    2014-05-01

    The main challenge of facial biometrics is its robustness and ability to adapt to changes in position orientation, facial expression, and illumination effects. This research addresses the predominant deficiencies in this regard and systematically investigates a facial authentication system in the Euclidean domain. In the proposed method, Euclidean geometry in 2D vector space is being constructed for features extraction and the authentication method. In particular, each assigned point of the candidates' biometric features is considered to be a 2D geometrical coordinate in the Euclidean vector space. Algebraic shapes of the extracted candidate features are also computed and compared. The proposed authentication method is being tested on images from the public "Put Face Database". The performance of the proposed method is evaluated based on Correct Recognition (CRR), False Acceptance (FAR), and False Rejection (FRR) rates. The theoretical foundation of the proposed method along with the experimental results are also presented in this paper. The experimental results demonstrate the effectiveness of the proposed method.

  13. Parallel Kalman filter track fit based on vector classes

    International Nuclear Information System (INIS)

    Modern high energy physics experiments have to process terabytes of input data produced in particle collisions. The core of the data reconstruction in high energy physics is the Kalman filter. Therefore, developing the fast Kalman filter algorithm, which uses maximum available power of modern processors, is important, in particular for initial selection of events interesting for the new physics. One of processors features, which can speed up the algorithm, is a SIMD instruction set, which allows to pack several data items in one register and operate on all of them in one go, thus achieving more operations per clock cycle. Therefore a flexible and useful interface, which uses the SIMD instruction set on different CPU and GPU processors architectures, has been realized as a vector classes library. The Kalman filter based track fitting algorithm has been implemented with use of the vector classes. Fitting quality tests show good results with the residuals equal to 49 μm and 44 μm for x and y track parameters and relative momentum resolution of 0.7%. The fitting time of 0.053 μs per track has been achieved on Intel Xeon X5550 with 8 cores at 2.6 GHz by using in addition Intel Threading Building Blocks.

  14. Robust Source Localization in Shallow Water Based on Vector Optimization

    Institute of Scientific and Technical Information of China (English)

    SONG Hai-yan; SHI Jie; LIU Bo-sheng

    2013-01-01

    Owing to the multipath effect,the source localization in shallow water has been an area of active interest.However,most methods for source localization in shallow water are sensitive to the assumed model of the underwater environment and have poor robustness against the underwater channel uncertainty,which limit their further application in practical engineering.In this paper,a new method of source localization in shallow water,based on vector optimization concept,is described,which is highly robust against environmental factors affecting the localization,such as the channel depth,the bottom reflection coefficients,and so on.Through constructing the uncertainty set of the source vector errors and extracting the multi-path sound rays from the sea surface and bottom,the proposed method can accurately localize one or more sources in shallow water dominated by multipath propagation.It turns out that the natural formulation of our approach involves minimization of two quadratic functions subject to infinitely many nonconvex quadratic constraints.It shows that this problem (originally intractable) can be reformulated in a convex form as the so-called second-order cone program (SOCP) and solved efficiently by using the well-established interior point method,such as the software tool,SeDuMi.Computer simulations show better performance of the proposed method as compared with existing algorithms and establish a theoretical foundation for the practical engineering application.

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

    Directory of Open Access Journals (Sweden)

    Joseph W Golden

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

  16. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

    OpenAIRE

    Jiang, Xiaohong; Dalebout, Tim J.; Peter J Bredenbeek; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

    2010-01-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison...

  17. BEHAVIOR BASED CREDIT CARD FRAUD DETECTION USING SUPPORT VECTOR MACHINES

    Directory of Open Access Journals (Sweden)

    V. Dheepa

    2012-07-01

    Full Text Available Along with the great increase of internet and e-commerce, the use of credit card is an unavoidable one. Due to the increase of credit card usage, the frauds associated with this have also increased. There are a lot of approaches used to detect the frauds. In this paper, behavior based classification approach using Support Vector Machines are employed and efficient feature extraction method also adopted. If any discrepancies occur in the behaviors transaction pattern then it is predicted as suspicious and taken for further consideration to find the frauds. Generally credit card fraud detection problem suffers from a large amount of data, which is rectified by the proposed method. Achieving finest accuracy, high fraud catching rate and low false alarms are the main tasks of this approach.

  18. SENSITIVITY ANALYSIS FOR ROLLING PROCESS BASED ON SUPPORT VECTOR MACHINE

    Institute of Scientific and Technical Information of China (English)

    Huang Yanwei; Wu Tihua; Zhao Jingyi; Wang Yiqun

    2005-01-01

    A method for the calculation of the sensitivity factors of the rolling process has been obtained by differentiating the roll force model based on support vector machine. It can eliminate the algebraic loop of the analytical model of the rolling process. The simulations in the first stand of five stand cold tandem rolling mill indicate that the calculation for sensitivities by this proposed method can obtain a good accuracy, and an appropriate adjustment on the control variables determined directly by the sensitivity has an excellent compensation accuracy. Moreover, the roll gap has larger effect on the exit thickness than both front tension and back tension, and it is more efficient to select the roll gap as the controlvariable of the thickness control system in the first stand.

  19. Temperature prediction control based on least squares support vector machines

    Institute of Scientific and Technical Information of China (English)

    Bin LIU; Hongye SU; Weihua HUANG; Jian CHU

    2004-01-01

    A prediction control algorithm is presented based on least squares support vector machines (LS-SVM) model for a class of complex systems with strong nonlinearity.The nonlinear off-line model of the controlled plant is built by LS-SVM with radial basis function (RBF) kernel.In the process of system running,the off-line model is linearized at each sampling instant,and the generalized prediction control (GPC) algorithm is employed to implement the prediction control for the controlled plant.The obtained algorithm is applied to a boiler temperature control system with complicated nonlinearity and large time delay.The results of the experiment verify the effectiveness and merit of the algorithm.

  20. TYRE DYNAMICS MODELLING OF VEHICLE BASED ON SUPPORT VECTOR MACHINES

    Institute of Scientific and Technical Information of China (English)

    ZHENG Shuibo; TANG Houjun; HAN Zhengzhi; ZHANG Yong

    2006-01-01

    Various methods of tyre modelling are implemented from pure theoretical to empirical or semi-empirical models based on experimental results. A new way of representing tyre data obtained from measurements is presented via support vector machines (SVMs). The feasibility of applying SVMs to steady-state tyre modelling is investigated by comparison with three-layer backpropagation(BP) neural network at pure slip and combined slip. The results indicate SVMs outperform the BP neural network in modelling the tyre characteristics with better generalization performance. The SVMs-tyre is implemented in 8-DOF vehicle model for vehicle dynamics simulation by means of the PAC 2002 Magic Formula as reference. The SVMs-tyre can be a competitive and accurate method to model a tyre for vehicle dynamics simulation.

  1. Three—Dimensional Vector Field Visualization Based on Tensor Decomposition

    Institute of Scientific and Technical Information of China (English)

    梁训东; 李斌; 等

    1996-01-01

    This paper presents a visualization method called the deformed cube for visualizing 3D velocity vector field.Based on the decomposition of the tensor which describes the changes of the velocity,it provides a technique for visualizing local flow.A deformed cube,a cube transformed by a tensor in a local coordinate frame,shows the local stretch,shear and rigid body rotation of the local flow corresponding to the decomposed component of the tensor.Users can interactively view the local deformation or any component of the changes.The animation of the deformed cube moving along a streamline achieves a more global impression of the flow field.This method is intended as a complement to global visualization methods.

  2. 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. PMID:27154390

  3. High stability vector-based direct power control for DFIG-based wind turbine

    DEFF Research Database (Denmark)

    Zhu, Rongwu; Chen, Zhe; Wu, Xiaojie

    2015-01-01

    This paper proposes an improved vector-based direct power control (DPC) strategy for the doubly-fed induction generator (DFIG)-based wind energy conversion system. Based on the small signal model, the proposed DPC improves the stability of the DFIG, and avoids the DFIG operating in the marginal...

  4. A Versatile System for USER Cloning-Based Assembly of Expression Vectors for Mammalian Cell Engineering

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Kildegaard, Helene Faustrup; Petersen, Maja Borup Kjær;

    2014-01-01

    A new versatile mammalian vector system for protein production, cell biology analyses, and cell factory engineering was developed. The vector system applies the ligation-free uracil-excision based technique – USER cloning – to rapidly construct mammalian expression vectors of multiple DNA fragments...... efficiency above 90%. The functionality of basic vectors for FAST assembly was tested and validated by transient expression of fluorescent model proteins in CHO, U-2-OS and HEK293 cell lines. In this test, we included many of the most common vector elements for heterologous gene expression in mammalian cells...... and with maximum flexibility, both for choice of vector backbone and cargo. The vector system includes a set of basic vectors and a toolbox containing a multitude of DNA building blocks including promoters, terminators, selectable marker- and reporter genes, and sequences encoding an internal ribosome entry site...

  5. Toolbox for Non-Intrusive Structural and Functional Analysis of Recombinant VLP Based Vaccines: A Case Study with Hepatitis B Vaccine

    OpenAIRE

    Mulder, Anke M.; Bridget Carragher; Victoria Towne; Yuan Meng; Yang Wang; Lance Dieter; Potter, Clinton S.; Washabaugh, Michael W.; Sitrin, Robert D; Qinjian Zhao

    2012-01-01

    BACKGROUND: Fundamental to vaccine development, manufacturing consistency, and product stability is an understanding of the vaccine structure-activity relationship. With the virus-like particle (VLP) approach for recombinant vaccines gaining popularity, there is growing demand for tools that define their key characteristics. We assessed a suite of non-intrusive VLP epitope structure and function characterization tools by application to the Hepatitis B surface antigen (rHBsAg) VLP-based vaccin...

  6. Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection.

    Science.gov (United States)

    Lauretti, Flavio; Chattopadhyay, Anasuya; de Oliveira França, Rafael Freitas; Castro-Jorge, Luiza; Rose, John; Fonseca, Benedito A L da

    2016-09-01

    Dengue is the most important arbovirus disease throughout the world and it is responsible for more than 500,000 dengue hemorrhagic cases and 22,000 deaths every year. One vaccine was recently licensed for human use in Brazil, Mexico and Philippines and although at least seven candidates have been in clinical trials the results of the most developed CYD vaccine have demonstrated immunization problems, such as uneven protection and interference between serotypes. We constructed a vaccine candidate based on vesicular stomatitis virus (VSV) expression of pre-membrane (prM) and envelope (E) proteins of dengue-2 virus (DENV-2) and tested it in mice to evaluate immunogenicity and protection against DENV-2 infection. VSV has been successfully used as vaccine vectors for several viruses to induce strong humoral and cellular immune responses. The VSV-DENV-2 recombinant was constructed by inserting the DENV-2 structural proteins into a VSV plasmid DNA for recombinant VSV-DENV-2 recovery. Infectious recombinant VSV viruses were plaque purified and prM and E expression were confirmed by immunofluorescence and radiolabeling of proteins of infected cells. Forty Balb/C mice were inoculated through subcutaneous (s.c.) route with VSV-DENV-2 vaccine in a two doses schedule 15 d apart and 29 d after first inoculation, sera were collected and the mice were challenged with 50 lethal doses (LD50) of a neurovirulent DENV-2. The VSV-DENV-2 induced anti-DENV-2 antibodies and protected animals in the challenge experiment comparable to DENV-2 immunization control group. We conclude that VSV is a promising platform to test as a DENV vaccine and perhaps against others Flaviviridae.

  7. GA SPEED AND DQ CURRNETS CONTROL OF PMSM WITH VECTOR CONTROL BASED SPACE VECTOR MODULATION USING MATLAB/SIMULINK

    Directory of Open Access Journals (Sweden)

    A. El Janati El Idrissi

    2011-08-01

    Full Text Available In recent years, permanent magnet synchronous motors (PMSM have gained variety industrial applications, because of simple structures, high efficiency and ease of maintenance. But these motors have a nonlinear mathematical model. To resolve this problem several studies have suggested the application of soft-computing technique. This paper presents vector control of PMSM fed by space vector modulation inverter using genetic algorithm (GA controllers to improve speed, currents and the electric torque by significantly reducing their ripples, which offer an extra advantage of this study. The proposed method effectiveness has been verified by computer simulations using Matlab/Simulink®. These results are compared with the ones obtained with a vector control using PI controllers for speed and current [1] and the second obtained with adaptive controller based speed estimation technique [2].

  8. Influenza Vaccination Coverage Rate for Medical Staff: Influence of Hospital-Based Vaccination Campaign.

    Science.gov (United States)

    Zielonka, T M; Szymańczak, M; Jakubiak, J; Nitsch-Osuch, A; Życińska, K

    2016-01-01

    Despite intensive recommendations, influenza vaccination rate in medical staff in Poland ranges from about 20 % in physicians to 10 % in nurses. The objective of this work was to assess the influence of hospital influenza vaccination campaign directed toward health care workers, combined with dispensing free of charge vaccine, on vaccination rate. The campaign was conducted by the Hospital Infection Control Team of the Czerniakowski Hospital in Warsaw, Poland, separately for physicians, nurses, and physiotherapists. Overall, 37 % of medical staff were vaccinated, including 55 % of physicians and 21 % of nurses. Concerning physicians, the greatest vaccination rate was in the orthopedic (80 %) and ophthalmology units (73 %), whereas the lowest rate was in the intensive care (22 %) and neurology units (20 %). Concerning nurses, the greatest vaccination rate was in those working in the outpatient (40 %) and emergency units (29 %), whereas the lowest rate was in the ophthalmology (6 %) and surgery units (11 %). We conclude that the professional knowledge campaign combined with the incentive of free of charge vaccine substantially raises the vaccination rate among medical staff.

  9. DBCSVM: Density Based Clustering Using Support VectorMachines

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Rai

    2012-07-01

    Full Text Available Data categorization is challenging job in a current scenario. The growth rate of a multimedia data are increase day to day in an internet technology. For the better retrieval and efficient searching of a data, a process required for grouping the data. However, data mining can find out helpful implicit information in large databases. To detect the implicit useful information from large databases various data mining techniques are use. Data clustering is an important data mining technique for grouping data sets into different clusters and each cluster having same properties of data. In this paper we have taken image data sets and firstly applying the density based clustering to grouped the images, density based clustering grouped the images according to the nearest feature sets but not grouped outliers, then we used an important super hyperplane classifier support vector machine (SVM which classify the all outlier left from density based clustering. This method improves the efficiency of image grouping and gives better results.

  10. Support Vector Machine Ensemble Based on Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    LI Ye; YIN Ru-po; CAI Yun-ze; XU Xiao-ming

    2006-01-01

    Support vector machines (SVMs) have been introduced as effective methods for solving classification problems.However, due to some limitations in practical applications,their generalization performance is sometimes far from the expected level. Therefore, it is meaningful to study SVM ensemble learning. In this paper, a novel genetic algorithm based ensemble learning method, namely Direct Genetic Ensemble (DGE), is proposed. DGE adopts the predictive accuracy of ensemble as the fitness function and searches a good ensemble from the ensemble space. In essence, DGE is also a selective ensemble learning method because the base classifiers of the ensemble are selected according to the solution of genetic algorithm. In comparison with other ensemble learning methods, DGE works on a higher level and is more direct. Different strategies of constructing diverse base classifiers can be utilized in DGE.Experimental results show that SVM ensembles constructed by DGE can achieve better performance than single SVMs,bagged and boosted SVM ensembles. In addition, some valuable conclusions are obtained.

  11. Dengue vaccine: an update on recombinant subunit strategies.

    Science.gov (United States)

    Martin, J; Hermida, L

    2016-03-01

    Dengue is an increasing public health problem worldwide, with the four serotypes of the virus infecting over 390 million people annually. There is no specific treatment or antiviral drug for dengue, and prevention is largely limited to controlling the mosquito vectors or disrupting the human-vector contact. Despite the considerable progress made in recent years, an effective vaccine against the virus is not yet available. The development of a dengue vaccine has been hampered by many unique challenges, including the need to ensure the absence of vaccine-induced enhanced severity of disease. Recombinant protein subunit vaccines offer a safer alternative to other vaccine approaches. Several subunit vaccine candidates are presently under development, based on different structural and non-structural proteins of the virus. Novel adjuvants or immunopotentiating strategies are also being tested to improve their immunogenicity. This review summarizes the current status and development trends of subunit dengue vaccines. PMID:26982462

  12. Dengue vaccine: an update on recombinant subunit strategies.

    Science.gov (United States)

    Martin, J; Hermida, L

    2016-03-01

    Dengue is an increasing public health problem worldwide, with the four serotypes of the virus infecting over 390 million people annually. There is no specific treatment or antiviral drug for dengue, and prevention is largely limited to controlling the mosquito vectors or disrupting the human-vector contact. Despite the considerable progress made in recent years, an effective vaccine against the virus is not yet available. The development of a dengue vaccine has been hampered by many unique challenges, including the need to ensure the absence of vaccine-induced enhanced severity of disease. Recombinant protein subunit vaccines offer a safer alternative to other vaccine approaches. Several subunit vaccine candidates are presently under development, based on different structural and non-structural proteins of the virus. Novel adjuvants or immunopotentiating strategies are also being tested to improve their immunogenicity. This review summarizes the current status and development trends of subunit dengue vaccines.

  13. Magnetic vector sensors based on the Hall effect

    Science.gov (United States)

    Roumenin, Ch. S.

    Integrated two- and three-dimensional vector versions of the parallel-field Hall microsensor proposed by Roumenin (1987) are presented. The characteristics of Roumenin's microsensor, which is activated by the external magnetic field parallel to the IC plane, are reviewed. The configurations of the magnetic two- and three-dimensional vector microsensors are illustrated and the operation of the microsensors is discussed.

  14. Hexavalent IPV-based combination vaccines for public-sector markets of low-resource countries.

    Science.gov (United States)

    Mahmood, Kutub; Pelkowski, Sonia; Atherly, Deborah; Sitrin, Robert D; Donnelly, John J

    2013-09-01

    In anticipation of the successful eradication of wild polio virus, alternative vaccination strategies for public-sector markets of low-resource countries are extremely important, but are still under development. Following polio eradication, inactivated polio vaccine (IPV) would be the only polio vaccine available, and would be needed for early childhood immunization for several years, as maintenance of herd immunity will be important for sustaining polio eradication. Low-cost combination vaccines containing IPV could provide reliable and continuous immunization in the post-polio eradication period. Combination vaccines can potentially simplify complex pediatric routine immunization schedules, improve compliance, and reduce costs. Hexavalent vaccines containing Diphtheria (D), Tetanus (T), whole cell pertussis (wP), Hepatitis B (HBV), Haemophilus b (Hib) and the three IPV serotype antigens have been considered as the ultimate combination vaccine for routine immunization. This product review evaluates potential hexavalent vaccine candidates by composition, probable time to market, expected cost of goods, presentation, and technical feasibility and offers suggestions for development of low-cost hexavalent combination vaccines. Because there are significant technical challenges facing wP-based hexavalent vaccine development, this review also discusses other alternative approaches to hexavalent that could also ensure a timely and reliable supply of low-cost IPV based combination vaccines. PMID:23787559

  15. Poly(I:C/alum mixed adjuvant priming enhances HBV subunit vaccine-induced immunity in mice when combined with recombinant adenoviral-based HBV vaccine boosting.

    Directory of Open Access Journals (Sweden)

    Xia Chuai

    Full Text Available BACKGROUND: Virus-specific cellular immune responses play a critical role in virus clearance during acute or chronic HBV infection. Currently, the commercially available HBV vaccine is combined with alum adjuvant, which stimulates mainly Th2 immune responses. Therefore, development of new therapeutic HBV vaccine adjuvants and immune strategies that also promote Th1 and CTL responses is urgently needed. METHODOLOGY/PRINCIPAL FINDINGS: To improve the immunity induced by the novel HBSS1 HBV vaccine, we evaluated the ability of adjuvants, including alum, CpG and polyriboinosinic polyribocytidylic acid [poly(I:C], to enhance the response when boosted with the recombinant adenoviral vector vaccine rAdSS1. The immune responses to different adjuvant combinations were assessed in C57BL/6 mice by enzyme-linked immunosorbent assay (ELISA, ELISpot and cytokine release assays. Among the combinations tested, a HBV protein particle vaccine with CpG/alum and poly(I:C/alum priming combinations accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody titres with a Th1 bias. After boosting with recombinant adenoviral vector vaccine rAdSS1, both groups produced a strong multi-antigen (S and PreS1-specific cellular immune response. HBSS1 immunisation with poly(I:C/alum priming also generated high-level CD4(+ and CD8(+ T cell responses in terms of Th1 cytokines (IFN-γ and IL-2. CONCLUSIONS: The protein-vaccine HBSS1 with mixed poly(I:C/alum adjuvant priming, followed by a rAdSS1 vaccine boost, maximises specific antibody and Th1-biased cellular immune responses. This regime might prove useful in the development of HBV therapeutic vaccines. Furthermore, this promising strategy might be applied to vaccines against other persistent infections, such as human immunodeficiency virus and tuberculosis.

  16. Hybrid Support Vector Machines-Based Multi-fault Classification

    Institute of Scientific and Technical Information of China (English)

    GAO Guo-hua; ZHANG Yong-zhong; ZHU Yu; DUAN Guang-huang

    2007-01-01

    Support Vector Machines (SVM) is a new general machine-learning tool based on structural risk minimization principle. This characteristic is very signific ant for the fault diagnostics when the number of fault samples is limited. Considering that SVM theory is originally designed for a two-class classification, a hybrid SVM scheme is proposed for multi-fault classification of rotating machinery in our paper. Two SVM strategies, 1-v-1 (one versus one) and 1-v-r (one versus rest), are respectively adopted at different classification levels. At the parallel classification level, using 1-v-1 strategy, the fault features extracted by various signal analysis methods are transferred into the multiple parallel SVM and the local classification results are obtained. At the serial classification level, these local results values are fused by one serial SVM based on 1-v-r strategy. The hybrid SVM scheme introduced in our paper not only generalizes the performance of signal binary SVMs but improves the precision and reliability of the fault classification results. The actually testing results show the availability suitability of this new method.

  17. A vectored equine herpesvirus type 1 (EHV-1) vaccine elicits protective immune responses against EHV-1 and H3N8 equine influenza virus.

    Science.gov (United States)

    Van de Walle, Gerlinde R; May, Maeva A; Peters, Sarah T; Metzger, Stephan M; Rosas, Cristina T; Osterrieder, Nikolaus

    2010-01-22

    Vaccination is commonly used to control equine respiratory pathogens such as equine herpesvirus type 1 (EHV-1) and equine influenza virus (EIV). Here, we describe the generation and characterization of a recombinant EHV-1 modified live virus vaccine (MLV) based on a recent abortogenic EHV-1 strain, NY03. The immunogenicity and efficacy of the MLV was tested in horses in an EHV-1 vaccination/challenge experiment using the highly virulent neurovirulent EHV-1 strain OH03. Induction of a robust EHV-1-specific immune response was observed. Upon challenge infection, vaccinated horses were partially protected against disease as demonstrated by a significant reduction in clinical signs, nasal shedding and viremia levels. In addition, the NY03-based MLV was used to express the EIV H3 protein and immunogenicity was tested in horses. Expression of H3 was readily detected in NY03-H3-infected cells in vitro. Vaccination of horses resulted in the induction of a robust serological immune responses against two recent but genetically distinct EIV representatives, VA05 and NY-99, which were above the threshold predicted to be protective against development of clinical disease.

  18. Progress in Chimeric Vector and Chimeric Gene Based Cardiovascular Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    HU Chun-Song; YOON Young-sup; ISNER Jeffrey M.; LOSORDO Douglas W.

    2003-01-01

    Gene therapy for cardiovascular diseases has developed from preliminary animal experiments to clinical trials. However, vectors and target genes used currently in gene therapy are mainly focused on viral, nonviral vector and single target gene or monogene. Each vector system has a series of advantages and limitations. Chimeric vectors which combine the advantages of viral and nonviral vector,chimeric target genes which combine two or more target genes and novel gene delivery modes are being developed. In this article, we summarized the progress in chimeric vectors and chimeric genes based cardiovascular gene therapy, which including proliferative or occlusive vascular diseases such as atheroslerosis and restenosis, hypertonic vascular disease such as hypertension and cardiac diseases such as myocardium ischemia, dilated cardiomyopathy and heart failure, even heart transplantation. The development of chimeric vector, chimeric gene and their cardiovascular gene therapy is promising.

  19. Generating Fuzzy Rule-based Systems from Examples Based on Robust Support Vector Machine

    Institute of Scientific and Technical Information of China (English)

    JIA Jiong; ZHANG Hao-ran

    2006-01-01

    This paper firstly proposes a new support vector machine regression (SVR) with a robust loss function, and designs a gradient based algorithm for implementation of the SVR,then uses the SVR to extract fuzzy rules and designs fuzzy rule-based system. Simulations show that fuzzy rule-based system technique based on robust SVR achieves superior performance to the conventional fuzzy inference method, the proposed method provides satisfactory performance with excellent approximation and generalization property than the existing algorithm.

  20. A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is highly immunogenic and protects mice in active and passive immunizations.

    Directory of Open Access Journals (Sweden)

    Annett Hessel

    Full Text Available BACKGROUND: The development of novel influenza vaccines inducing a broad immune response is an important objective. The aim of this study was to evaluate live vaccines which induce both strong humoral and cell-mediated immune responses against the novel human pandemic H1N1 influenza virus, and to show protection in a lethal animal challenge model. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, the hemagglutinin (HA and neuraminidase (NA genes of the influenza A/California/07/2009 (H1N1 strain (CA/07 were inserted into the replication-deficient modified vaccinia Ankara (MVA virus--a safe poxviral live vector--resulting in MVA-H1-Ca and MVA-N1-Ca vectors. These live vaccines, together with an inactivated whole virus vaccine, were assessed in a lung infection model using immune competent Balb/c mice, and in a lethal challenge model using severe combined immunodeficient (SCID mice after passive serum transfer from immunized mice. Balb/c mice vaccinated with the MVA-H1-Ca virus or the inactivated vaccine were fully protected from lung infection after challenge with the influenza H1N1 wild-type strain, while the neuraminidase virus MVA-N1-Ca induced only partial protection. The live vaccines were already protective after a single dose and induced substantial amounts of neutralizing antibodies and of interferon-gamma-secreting (IFN-gamma CD4- and CD8 T-cells in lungs and spleens. In the lungs, a rapid increase of HA-specific CD4- and CD8 T cells was observed in vaccinated mice shortly after challenge with influenza swine flu virus, which probably contributes to the strong inhibition of pulmonary viral replication observed. In addition, passive transfer of antisera raised in MVA-H1-Ca vaccinated immune-competent mice protected SCID mice from lethal challenge with the CA/07 wild-type virus. CONCLUSIONS/SIGNIFICANCE: The non-replicating MVA-based H1N1 live vaccines induce a broad protective immune response and are promising vaccine candidates for

  1. A Wavelet Kernel-Based Primal Twin Support Vector Machine for Economic Development Prediction

    Directory of Open Access Journals (Sweden)

    Fang Su

    2013-01-01

    Full Text Available Economic development forecasting allows planners to choose the right strategies for the future. This study is to propose economic development prediction method based on the wavelet kernel-based primal twin support vector machine algorithm. As gross domestic product (GDP is an important indicator to measure economic development, economic development prediction means GDP prediction in this study. The wavelet kernel-based primal twin support vector machine algorithm can solve two smaller sized quadratic programming problems instead of solving a large one as in the traditional support vector machine algorithm. Economic development data of Anhui province from 1992 to 2009 are used to study the prediction performance of the wavelet kernel-based primal twin support vector machine algorithm. The comparison of mean error of economic development prediction between wavelet kernel-based primal twin support vector machine and traditional support vector machine models trained by the training samples with the 3–5 dimensional input vectors, respectively, is given in this paper. The testing results show that the economic development prediction accuracy of the wavelet kernel-based primal twin support vector machine model is better than that of traditional support vector machine.

  2. Evaluation of a Salmonella vectored vaccine expressing Mycobacterium avium subsp. paratuberculosis antigens against challenge in a goat model.

    Directory of Open Access Journals (Sweden)

    Syed M Faisal

    Full Text Available Johnes disease (JD, caused by Mycobacterium avium subsp paratuberculosis (MAP, occurs worldwide as chronic granulomatous enteritis of domestic and wild ruminants. To develop a cost effective vaccine, in a previous study we constructed an attenuated Salmonella strain that expressed a fusion product made up of partial fragments of MAP antigens (Ag85A, Ag85B and SOD that imparted protection against challenge in a mouse model. In the current study we evaluated the differential immune response and protective efficacy of the Sal-Ag vaccine against challenge in a goat model as compared to the live attenuated vaccine MAP316F. PBMCs from goats vaccinated with Sal-Ag and challenged with MAP generated significantly lower levels of IFN-γ, following in vitro stimulation with either Antigen-mix or PPD jhonin, than PBMC from MAP316F vaccinated animals. Flow cytometric analysis showed the increase in IFN-γ correlated with a significantly higher level of proliferation of CD4, CD8 and γδT cells and an increased expression of CD25 and CD45R0 in MAP316F vaccinated animals as compared to control animals. Evaluation of a range of cytokines involved in Th1, Th2, Treg, and Th17 immune responses by quantitative PCR showed low levels of expression of Th1 (IFN-γ, IL-2, IL-12 and proinflammatory cytokines (IL-6, IL-8, IL-18, TNF-α in the Sal-Ag immunized group. Significant levels of Th2 and anti-inflammatory cytokines transcripts (IL-4, IL-10, IL-13, TGF-β were expressed but their level was low and with a pattern similar to the control group. Over all, Sal-Ag vaccine imparted partial protection that limited colonization in tissues of some animals upon challenge with wild type MAP but not to the level achieved with MAP316F. In conclusion, the data indicates that Sal-Ag vaccine induced only a low level of protective immunity that failed to limit the colonization of MAP in infected animals. Hence the Sal-Ag vaccine needs further refinement to increase its efficacy.

  3. Need for a safe vaccine against respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Joo-Young Kim

    2012-09-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of severe respiratory tract illnesses in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for HRSV. Following failure of the initial trial of formalin-inactivated virus particle vaccine, continuous efforts have been made for the development of safe and efficacious vaccines against HRSV. However, several obstacles persist that delay the development of HRSV vaccine, such as the immature immune system of newborn infants and the possible Th2-biased immune responses leading to subsequent vaccine-enhanced diseases. Many HRSV vaccine strategies are currently being developed and evaluated, including live-attenuated viruses, subunit-based, and vector-based candidates. In this review, the current HRSV vaccines are overviewed and the safety issues regarding asthma and vaccine-induced pathology are discussed.

  4. Priori Information Based Support Vector Regression and Its Applications

    Directory of Open Access Journals (Sweden)

    Litao Ma

    2015-01-01

    Full Text Available In order to extract the priori information (PI provided by real monitored values of peak particle velocity (PPV and increase the prediction accuracy of PPV, PI based support vector regression (SVR is established. Firstly, to extract the PI provided by monitored data from the aspect of mathematics, the probability density of PPV is estimated with ε-SVR. Secondly, in order to make full use of the PI about fluctuation of PPV between the maximal value and the minimal value in a certain period of time, probability density estimated with ε-SVR is incorporated into training data, and then the dimensionality of training data is increased. Thirdly, using the training data with a higher dimension, a method of predicting PPV called PI-ε-SVR is proposed. Finally, with the collected values of PPV induced by underwater blasting at Dajin Island in Taishan nuclear power station in China, contrastive experiments are made to show the effectiveness of the proposed method.

  5. Epitope-based recombinant diagnostic antigen to distinguish natural infection from vaccination with hepatitis A virus vaccines.

    Science.gov (United States)

    Su, Qiudong; Guo, Minzhuo; Jia, Zhiyuan; Qiu, Feng; Lu, Xuexin; Gao, Yan; Meng, Qingling; Tian, Ruiguang; Bi, Shengli; Yi, Yao

    2016-07-01

    Hepatitis A virus (HAV) infection can stimulate the production of antibodies to structural and non-structural proteins of the virus. However, vaccination with an inactivated or attenuated HAV vaccine produces antibodies mainly against structural proteins, whereas no or very limited antibodies are produced against the non-structural proteins. Current diagnostic assays to determine exposure to HAV, such as the Abbott HAV AB test, detect antibodies only to the structural proteins and so are not able to distinguish a natural infection from vaccination with an inactivated or attenuated virus. Here, we constructed a recombinant tandem multi-epitope diagnostic antigen (designated 'H1') based on the immune-dominant epitopes of the non-structural proteins of HAV to distinguish the two situations. H1 protein expressed in Escherichia coli and purified by affinity and anion exchange chromatography was applied in a double-antigen sandwich ELISA for the detection of anti-non-structural HAV proteins, which was confirmed to distinguish a natural infection from vaccination with an inactivated or attenuated HAV vaccine. PMID:26994964

  6. Explaining Support Vector Machines: A Color Based Nomogram

    Science.gov (United States)

    Van Belle, Vanya; Van Calster, Ben; Van Huffel, Sabine; Suykens, Johan A. K.; Lisboa, Paulo

    2016-01-01

    Problem setting Support vector machines (SVMs) are very popular tools for classification, regression and other problems. Due to the large choice of kernels they can be applied with, a large variety of data can be analysed using these tools. Machine learning thanks its popularity to the good performance of the resulting models. However, interpreting the models is far from obvious, especially when non-linear kernels are used. Hence, the methods are used as black boxes. As a consequence, the use of SVMs is less supported in areas where interpretability is important and where people are held responsible for the decisions made by models. Objective In this work, we investigate whether SVMs using linear, polynomial and RBF kernels can be explained such that interpretations for model-based decisions can be provided. We further indicate when SVMs can be explained and in which situations interpretation of SVMs is (hitherto) not possible. Here, explainability is defined as the ability to produce the final decision based on a sum of contributions which depend on one single or at most two input variables. Results Our experiments on simulated and real-life data show that explainability of an SVM depends on the chosen parameter values (degree of polynomial kernel, width of RBF kernel and regularization constant). When several combinations of parameter values yield the same cross-validation performance, combinations with a lower polynomial degree or a larger kernel width have a higher chance of being explainable. Conclusions This work summarizes SVM classifiers obtained with linear, polynomial and RBF kernels in a single plot. Linear and polynomial kernels up to the second degree are represented exactly. For other kernels an indication of the reliability of the approximation is presented. The complete methodology is available as an R package and two apps and a movie are provided to illustrate the possibilities offered by the method. PMID:27723811

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

    International Nuclear Information System (INIS)

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

  8. Using a geographical-information-system-based decision support to enhance malaria vector control in zambia.

    Science.gov (United States)

    Chanda, Emmanuel; Mukonka, Victor Munyongwe; Mthembu, David; Kamuliwo, Mulakwa; Coetzer, Sarel; Shinondo, Cecilia Jill

    2012-01-01

    Geographic information systems (GISs) with emerging technologies are being harnessed for studying spatial patterns in vector-borne diseases to reduce transmission. To implement effective vector control, increased knowledge on interactions of epidemiological and entomological malaria transmission determinants in the assessment of impact of interventions is critical. This requires availability of relevant spatial and attribute data to support malaria surveillance, monitoring, and evaluation. Monitoring the impact of vector control through a GIS-based decision support (DSS) has revealed spatial relative change in prevalence of infection and vector susceptibility to insecticides and has enabled measurement of spatial heterogeneity of trend or impact. The revealed trends and interrelationships have allowed the identification of areas with reduced parasitaemia and increased insecticide resistance thus demonstrating the impact of resistance on vector control. The GIS-based DSS provides opportunity for rational policy formulation and cost-effective utilization of limited resources for enhanced malaria vector control.

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

    Science.gov (United States)

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

    2015-01-01

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

  10. Efficacy of a Vaccine Based on Protective Antigen and Killed Spores against Experimental Inhalational Anthrax▿ ‡

    OpenAIRE

    Gauthier, Yves P.; Tournier, Jean-Nicolas; Paucod, Jean-Charles; Corre, Jean-Philippe; Mock, Michèle; Goossens, Pierre L.; Vidal, Dominique R.

    2008-01-01

    Protective antigen (PA)-based anthrax vaccines acting on toxins are less effective than live attenuated vaccines, suggesting that additional antigens may contribute to protective immunity. Several reports indicate that capsule or spore-associated antigens may enhance the protection afforded by PA. Addition of formaldehyde-inactivated spores (FIS) to PA (PA-FIS) elicits total protection against cutaneous anthrax. Nevertheless, vaccines that are effective against cutaneous anthrax may not be so...

  11. Conservative rigid body dynamics by convected base vectors with implicit constraints

    DEFF Research Database (Denmark)

    Krenk, Steen; Nielsen, Martin Bjerre

    2014-01-01

    of the base vectors. Orthogonality and unit length of the base vectors are imposed by constraining the equivalent Green strain components, and the kinetic energy is represented corresponding to rigid body motion. The equations of motion are obtained via Hamilton’s equations including the zero......A conservative time integration formulation is developed for rigid bodies based on a convected set of orthonormal base vectors. The base vectors are represented in terms of their absolute coordinates, and thus the formulation makes use of three translation components, plus nine components......-strain conditions as well as external constraints via Lagrange multipliers. Subsequently, the Lagrange multipliers associated with the internal zero-strain constraints are eliminated by use of a set of orthogonality conditions between the generalized displacements and the momentum vector, leaving a set...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction ......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....

  13. 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.

  14. Agent-based modeling of malaria vectors: the importance of spatial simulation

    OpenAIRE

    Bomblies, Arne

    2014-01-01

    Background The modeling of malaria vector mosquito populations yields great insight into drivers of malaria transmission at the village scale. Simulation of individual mosquitoes as “agents” in a distributed, dynamic model domain may be greatly beneficial for simulation of spatial relationships of vectors and hosts. Methods In this study, an agent-based model is used to simulate the life cycle and movement of individual malaria vector mosquitoes in a Niger Sahel village, with individual simul...

  15. Model Based Defect Detection in Multi-Dimensional Vector Spaces

    Science.gov (United States)

    Honda, Toshifumi; Obara, Kenji; Harada, Minoru; Igarashi, Hajime

    A highly sensitive inspection algorithm is proposed that extracts defects in multidimensional vector spaces from multiple images. The proposed algorithm projects subtraction vectors calculated from test and reference images to control the noise by reducing the dimensionality of vector spaces. The linear projection vectors are optimized using a physical defect model, and the noise distribution is calculated from the images. Because the noise distribution varies with the intensity or texture of the pixels, the target image is divided into small regions and the noise distribution of the subtraction images are calculated for each divided region. The bidirectional local perturbation pattern matching (BD-LPPM) which is an enhanced version of the LPPM, is proposed to increase the sensitivity when calculating the subtraction vectors, especially when the reference image contains more high-frequency components than the test image. The proposed algorithm is evaluated using defect samples for three different scanning electron microscopy images. The results reveal that the proposed algorithm increases the signal-to-noise ratio by a factor of 1.32 relative to that obtained using the Mahalanobis distance algorithm.

  16. The use of layered double hydroxides as DNA vaccine delivery vector for enhancement of anti-melanoma immune response.

    Science.gov (United States)

    Li, Ang; Qin, Lili; Wang, Wenrui; Zhu, Rongrong; Yu, Yongchun; Liu, Hui; Wang, Shilong

    2011-01-01

    Our previous studies have shown that Mg:Al 1:1 layered double hydroxides (LDH(R1)) nanoparticles could be taken up by the MDDCs effectively and had an adjuvant activity for DC maturation. Furthermore, these LDH(R1) nanoparticles could up-regulate the expression of CCR7 and augment the migration of DCs in response to CCL21. In current study, we have evaluated whether LDH(R1) as DNA vaccine delivery carrier can augment the efficacy of DNA vaccine immunization in vivo. Firstly, we found that LDH(R1) was efficient in combining DNA and formed LDH(R1)/DNA complex with an average diameter of about 80-120 nm. Its high transfection efficiency in vivo delivered with a GFP expression plasmid was also observed. After delivery of pcDNA(3)-OVA/LDH(R1) complex by intradermal immunization in C57BL/6 mice, the LDH(R1) induced an enhanced serum antibody response much greater than naked DNA vaccine. Using B16-OVA melanoma as tumor model, we demonstrated that pcDNA(3)-OVA/LDH(R1) complex enhanced immune priming and protection from tumor challenge in vivo. Furthermore, we showed that LDH(R1) induced dramatically more effective CTL activation and skewed T helper polarization to Th1. Collectively, these findings demonstrate that this LDH(R1)/DNA plasmid complex should be a new and promising way in vaccination against tumor. PMID:20934217

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

    Science.gov (United States)

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

    2016-01-01

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

  18. 76 FR 3075 - Availability of an Environmental Assessment for Field Testing Feline Leukemia Vaccine, Live...

    Science.gov (United States)

    2011-01-19

    ... Feline Leukemia Vaccine, Live Canarypox Vector AGENCY: Animal and Plant Health Inspection Service, USDA... testing, and then to field test, an unlicensed Feline Leukemia Vaccine, Live Canarypox Vector. The.... Product: Feline Leukemia Vaccine, Live Canarypox Vector. Field Test Locations: Alabama,...

  19. Design of nanomaterial based systems for novel vaccine development.

    Science.gov (United States)

    Yang, Liu; Li, Wen; Kirberger, Michael; Liao, Wenzhen; Ren, Jiaoyan

    2016-05-26

    With lower cell toxicity and higher specificity, novel vaccines have been greatly developed and applied to emerging infectious and chronic diseases. However, due to problems associated with low immunogenicity and complicated processing steps, the development of novel vaccines has been limited. With the rapid development of bio-technologies and material sciences, nanomaterials are playing essential roles in novel vaccine design. Incorporation of nanomaterials is expected to improve delivery efficiency, to increase immunogenicity, and to reduce the administration dosage. The purpose of this review is to discuss the employment of nanomaterials, including polymeric nanoparticles, liposomes, virus-like particles, peptide amphiphiles micelles, peptide nanofibers and microneedle arrays, in vaccine design. Compared to traditional methods, vaccines made from nanomaterials display many appealing benefits, including precise stimulation of immune responses, effective targeting to certain tissue or cells, and desirable biocompatibility. Current research suggests that nanomaterials may improve our approach to the design and delivery of novel vaccines.

  20. Design of nanomaterial based systems for novel vaccine development.

    Science.gov (United States)

    Yang, Liu; Li, Wen; Kirberger, Michael; Liao, Wenzhen; Ren, Jiaoyan

    2016-05-26

    With lower cell toxicity and higher specificity, novel vaccines have been greatly developed and applied to emerging infectious and chronic diseases. However, due to problems associated with low immunogenicity and complicated processing steps, the development of novel vaccines has been limited. With the rapid development of bio-technologies and material sciences, nanomaterials are playing essential roles in novel vaccine design. Incorporation of nanomaterials is expected to improve delivery efficiency, to increase immunogenicity, and to reduce the administration dosage. The purpose of this review is to discuss the employment of nanomaterials, including polymeric nanoparticles, liposomes, virus-like particles, peptide amphiphiles micelles, peptide nanofibers and microneedle arrays, in vaccine design. Compared to traditional methods, vaccines made from nanomaterials display many appealing benefits, including precise stimulation of immune responses, effective targeting to certain tissue or cells, and desirable biocompatibility. Current research suggests that nanomaterials may improve our approach to the design and delivery of novel vaccines. PMID:26891972

  1. Vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing CS of Plasmodium.

    Directory of Open Access Journals (Sweden)

    Dolores Rodríguez

    Full Text Available With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs carrying the CD8(+ T cell epitope (SYVPSAEQI of the circumsporozoite (CS protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS, and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8(+ T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV vectors from the Western Reserve (WR and modified virus Ankara (MVA strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.

  2. A Vector-based Cellular Automata Model for Simulating Urban Land Use Change

    Institute of Scientific and Technical Information of China (English)

    LU Yi; CAO Min; ZHANG Lei

    2015-01-01

    Cellular Automata (CA) is widely used for the simulation of land use changes.This study applied a vector-based CA model to simulate land use change in order to minimize or eliminate the scale sensitivity in traditional raster-based CA model.The cells of vector-based CA model are presented according to the shapes and attributes of geographic entities,and the transition rules of vector-based CA model are improved by taking spatial variables of the study area into consideration.The vector-based CA model is applied to simulate land use changes in downtown of Qidong City,Jiangsu Province,China and its validation is confirmed by the methods of visual assessment and spatial accuracy.The simulation result of vector-based CA model reveals that nearly 75% of newly increased urban cells are located in the northwest and southwest parts of the study area from 2002 to 2007,which is in consistent with real land use map.In addition,the simulation results of the vector-based and raster-based CA models are compared to real land use data and their spatial accuracies are found to be 84.0% and 81.9%,respectively.In conclusion,results from this study indicate that the vector-based CA model is a practical and applicable method for the simulation of urbanization processes.

  3. Cell culture based production of avian influenza vaccines

    OpenAIRE

    Wielink, van, P.

    2012-01-01

    Vaccination of poultry can be used as a tool to control outbreaks of avian influenza, including that of highly pathogenic H5 and H7 strains. Influenza vaccines are traditionally produced in embryonated chicken eggs. Continuous cell lines have been suggested as an alternative substrate to produce influenza vaccines, as they are more robust and lack the long lead times associated with the production of large quantities of embryonated eggs. In the study that is described in this thesis, the prod...

  4. Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Chad E Mire

    Full Text Available The filoviruses, Marburg virus (MARV and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV that expresses individual filovirus glycoproteins (GPs in place of the VSV glycoprotein (G. These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.

  5. Exploring the potential of novel multivalent DNA-based vaccines

    OpenAIRE

    Fissolo, Nicolas Miguel

    2005-01-01

    In this dissertation, we exploited the DNA vaccination approach to test in the mouse some aspects relevant for the design of optimal CTL-stimulating, multiepitope vaccines. We have used three different ways to prime multispecific CD8+ T cell responses: 1) We have cloned a polytope DNA vaccine that encodes 10 epitopes binding MHC class I molecules encoded by the K, D or L locus (of H-2d, H-2b and H-2k haplotype mice). Vaccination of different mouse strains showed that Ld-restricted CD8+ T cell...

  6. Malaria vaccine based on self-assembling protein nanoparticles.

    Science.gov (United States)

    Burkhard, Peter; Lanar, David E

    2015-01-01

    Despite recent progress with GSK's RTS,S malaria vaccine, there remains a desperate need for an efficient malaria vaccine. We have used a repetitive antigen display technology to display malaria specific B cell and T cell epitopes in an effort to design a vaccine against Plasmodium falciparum malaria. Our protein sequence when assembled into a nanoparticle induces strong, long-lived and protective immune responses against infection with the parasite. We are confident that the clinical trials with our most developed vaccine candidate will show good protection in a controlled human malaria infection trial.

  7. Evaluation of the efficacy of a new oil-based adjuvant ISA 61 VG FMD vaccine as a potential vaccine for cattle.

    Science.gov (United States)

    Khorasani, A; Madadgar, O; Soleimanjahi, H; Keyvanfar, H; Mahravani, H

    2016-01-01

    Foot-and-mouth disease is an important viral disease of cloven-hoofed animals. Inactivated whole particle virus vaccines are still widely used in prophylactic vaccination campaigns. The choice of adjuvant is a very important factor in enhancing immune responses and the efficacy of inactivated vaccines. Montanide ISA 61 VG is a new ready-to-use mineral oil-based adjuvant developed by SEPPIC Inc. (SEPPIC, France) with high-potential immune responses needed for clinical protection against FMD infection. In this study, we compared the efficacy of two FMD vaccines either formulated with the new oil-based adjuvant ISA 61 VG and saponin, or with aluminum hydroxide gel and saponin. Both vaccines contained the same antigen payloads of O2010/IR. Two groups of 15 naive cattle received a single vaccination with different doses (full dose, 1/3 dose and 1/9 dose) to calculate their PD50 (50% protective dose) after being challenged with the homologous virulent virus. The mean neutralizing antibody titer was determined at 0, 7, 14 and 21 days after vaccination, measured by a micro neutralization test. The new vaccine improved humoral immune responses by 19%, while inducing a higher geometric mean. The titer for neutralizing antibodies was 2.91 log10 compared to the alum-gel based adjuvant vaccine which was 2.44 log10 (P-value=0.1782). The new vaccine showed a PD50 value of 10.05 as compared to a PD50 value of 4.171, respectively. According to the results, the FMD vaccine formulated with the new oil adjuvant, ISA 61 VG, shows potential as an alternative vaccine for routine and emergency vaccinations in the FMD enzootic region. PMID:27656222

  8. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer.

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-14

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  9. Arthropod vaccines.

    Science.gov (United States)

    Lee, R; Opdebeeck, J P

    1999-03-01

    Antigens located in the midgut of the tick are hidden from the host's immune system. Egg production of ticks can be reduced when ticks are fed on animals vaccinated with midgut antigens of the tick, and a subunit vaccine formulated with the recombinant antigen Bm86 is now available that can reduce the number of ticks infesting cattle grazing on pasture. Midgut antigens used in vaccines against insects that transmit pathogenic organisms to humans have not been as effective in reducing insect fecundity and an alternative approach may be necessary. Transmission-blocking vaccines directed at interfering with the vector-pathogen interaction could result in loss of vector competence and block the spread of disease-causing organisms. PMID:10198800

  10. ELABORATION OF A VECTOR BASED SEMANTIC CLASSIFICATION OVER THE WORDS AND NOTIONS OF THE NATURAL LANGUAGE

    OpenAIRE

    Safonov, K.; Lichargin, D.

    2009-01-01

    The problem of vector-based semantic classification over the words and notions of the natural language is discussed. A set of generative grammar rules is offered for generating the semantic classification vector. Examples of the classification application and a theorem of optional formal classification incompleteness are presented. The principles of assigning the meaningful phrases functions over the classification word groups are analyzed.

  11. A Novel Coding Method Based on Fuzzy Vector Quantization for Noised Image

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this paper a novel coding method based on fuzzy vector quantization for noised image with Gaussian white-noise pollution is presented. By restraining the high frequency subbands of wavelet image the noise is significantly removed and coded with fuzzy vector quantization. The experimental result shows that the method can not only achieve high compression ratio but also remove noise dramatically.

  12. New Iterative Learning Control Algorithms Based on Vector Plots Analysis1)

    Institute of Scientific and Technical Information of China (English)

    XIESheng-Li; TIANSen-Ping; XIEZhen-Dong

    2004-01-01

    Based on vector plots analysis, this paper researches the geometric frame of iterativelearning control method. New structure of iterative learning algorithms is obtained by analyzingthe vector plots of some general algorithms. The structure of the new algorithm is different fromthose of the present algorithms. It is of faster convergence speed and higher accuracy. Simulationspresented here illustrate the effectiveness and advantage of the new algorithm.

  13. [Approaches and problems in vaccine development against leishmaniasis].

    Science.gov (United States)

    Allahverdiyev, Adil; Bağirova, Melahat; Cakir Koç, Rabia; Oztel, Olga Nehir; Elçıçek, Serhat; Ateş, Sezen Canım; Karaca, Tuğçe Deniz

    2010-01-01

    Leishmaniasis is a major public health problem of the world and Turkey. Recently there has been increasing interest in vaccine studies among strategies for control of leishmaniasis. Recently the increase of interest in vaccine studies among leishmaniasis control strategies makes the subject more up to date. So the aim of this review is to present information about recent vaccine studies, problems and new strategies for vaccine development studies. There are 3 generations of vaccine against leishmaniasis. First-generation vaccines are killed or live attenuated parasites; second-generation vaccines are recombinant or native antigens and live genetically modified parasites (knock out and suicidal cassettes), third generation vaccines are DNA vaccines. Also vector salivary proteins, dendritic cells and non-pathogenic L. tarentolae have been used as vaccine candidates. However there is still no effective vaccine against leishmaniasis. Since polymer conjugates considerably increase immunogenicity, polymer based vaccine studies have gained importance in recent years. However, there has not been such a study for an antileishmanial vaccine yet. LPG, surface antigen of Leishmania promastigotes, and polymer conjugates may be promising in antileishmanial vaccine studies so we are carrying out a TUBITAK Project on this subject which has been given the number, 1085170SBAG-4007. PMID:20597059

  14. Enhanced immunity against classical swine fever in pigs induced by prime-boost immunization using an alphavirus replicon-vectored DNA vaccine and a recombinant adenovirus.

    Science.gov (United States)

    Sun, Yuan; Li, Na; Li, Hong-Yu; Li, Miao; Qiu, Hua-Ji

    2010-09-15

    Classical swine fever (CSF) - caused by the classical swine fever virus (CSFV) - is a fatal disease of pigs that is responsible for extensive losses to the swine industry worldwide. We had demonstrated previously that a prime-boost vaccination strategy using an alphavirus (Semliki Forest virus, SFV) replicon-vectored DNA vaccine (pSFV1CS-E2) and a recombinant adenovirus (rAdV-E2) expressing the E2 glycoprotein of CSFV induced enhanced immune responses in a mouse model. In this study, we evaluated further the efficacy of the heterologous prime-boost immunization approach in pigs, the natural host of CSFV. The results showed that the pigs (n=5) receiving pSFV1CS-E2/rAdV-E2 heterologous prime-boost immunization developed significantly higher titers of CSFV-specific neutralizing antibodies and comparable CD4(+) and CD8(+) T-cell proliferation, compared to the pigs receiving double immunizations with rAdV-E2 alone. When challenged with virulent CSFV Shimen strain, the pigs of the heterologous prime-boost group did not show clinical symptoms or viremia, which were observed in one of the 5 pigs immunized with rAdV-E2 alone and all the 5 control pigs immunized with an empty adenovirus. The results demonstrate that the heterologous DNA prime and recombinant adenovirus boost strategy can induce solid protective immunity.

  15. Genetic stability of a recombinant adenovirus vaccine vector seed library expressing human papillomavirus type 16 E6 and E7 proteins

    Science.gov (United States)

    WU, JIE; CHEN, KE-DA; GAO, MENG; CHEN, GANG; JIN, SU-FENG; ZHUANG, FANG-CHENG; WU, XIAO-HONG; JIANG, YUN-SHUI; LI, JIAN-BO

    2015-01-01

    The aim of the present study was to understand the genetic stability of a master seed bank (MSB) and a working seed bank (WSB) of an adenovirus vector vaccine expressing the human papillomavirus (HPV) type 16 E6 and E7 fusion proteins (Ad-HPV16E6E7). Microscopic examination and viral infectious efficacy were used to measure the infectious titers of the Ad-HPV16E6E7 MSB and WSB. Polymerase chain reaction was used to analyze the stability of the Ad-HPV16E6E7 target gene insertion, while western blot analysis and immunofluorescence were used to assess the expression levels of the Ad-HPV16E6E7 target protein. A C57BL/6 mouse TC-1 tumor cell growth inhibition model was used to evaluate the biological effect of Ad-HPV16E6E7 administration. The infectious titers of the Ad-HPV16E6E7 MSB and WSB were 6.31×109 IU/ml and 3.0×109 IU/ml, respectively. In addition, the expression levels of the inserted target genes and target proteins were found to be stable. In the mouse TC-1 tumor inhibition analysis, when the virus titers of the Ad-HPV16E6E7 MSB and WSB were 109 IU/ml, the tumor inhibition rate was 100%, which was significantly different when compared with the control group (χ2MSB=20.00 and χ2WSB=20.00; P<0.01). Therefore, the Ad-HPV16E6E7 vaccine seed bank is genetically stable and meets the requirements for vaccine development. PMID:25780403

  16. Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine.

    Science.gov (United States)

    Yang, Chin-Fen; Wang, C Kathy; Malkin, Elissa; Schickli, Jeanne H; Shambaugh, Cindy; Zuo, Fengrong; Galinski, Mark S; Dubovsky, Filip; Tang, Roderick S

    2013-06-10

    MEDI-534 is the first live vectored RSV vaccine candidate to be evaluated in seronegative children. It consists of the bovine parainfluenza virus type 3 (PIV3) genome with substituted human PIV3 F and HN glycoproteins engineered to express RSV F protein. A Phase 1 study of 49 healthy RSV and PIV3 seronegative children 6 to <24 months of age demonstrated an acceptable safety profile at the following doses: 10(4), 10(5) and 10(6)TCID50. After 3 doses of MEDI-534 at 10(6)TCID50, administered at 0, 2 and 4 month intervals, 100% of subjects seroresponded to PIV3, whereas only 50% seroresponded to RSV. To investigate the discordance in seroresponse rates, the RSV F transgene and its flanking non-coding nucleotides were sequenced from shed virus recovered from the nasal washes of 24 MEDI-534-vaccinated children. Eleven out of 24 samples contained no nucleotide changes in the analyzed region. The other 13 samples contained mixtures of variant subpopulations. Fifty-five percent exhibited changes in the transcription termination poly A gene sequences of the upstream bPIV3N gene while 21% had variant subpopulations in the RSV F open reading frame that resulted in pre-mature stop codons. Both types of changes are expected to reduce RSV F expression. Evaluation of the administered vaccine by dual immunofluorescence staining showed ~2.5% variants with low or no RSV F expression while single nucleotide primer extension detected ~1% variation at nucleotide 2045 that resulted in a pre-mature translational termination at codon 85. An association between shedding of variants and lower RSV F serological response was observed but it was not possible to establish a definitive clinical significance due to the small number of subjects in this study.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  18. Development of an Acid-Resistant Salmonella Typhi Ty21a Attenuated Vector For Improved Oral Vaccine Delivery

    Science.gov (United States)

    Feuille, Catherine M.; Starke, Carly Elizabeth C.; Bhagwat, Arvind A.; Stibitz, Scott; Kopecko, Dennis J.

    2016-01-01

    The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella enterica serovar Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, Ty21a is acid-labile and, for effective oral immunization, stomach acidity has to be either neutralized with buffer or by-passed with Ty21a in an enteric-coated capsule (ECC). Several studies have shown that efficacy is reduced when Ty21a is administered in an ECC versus as a buffered liquid formulation, the former limiting exposure to GI tract lymphoid tissues. However, the ECC was selected as a more practical delivery format for both packaging/shipping and vaccine administration ease. We have sought to increase Ty21a acid-resistance to allow for removal from the ECC and immune enhancement. To improve Ty21a acid-resistance, glutamate-dependent acid resistance genes (GAD; responsible for Shigella spp. survival at very low pH) were cloned on a multi-copy plasmid (pGad) under a controllable arabinose-inducible promoter. pGad enhanced acid survival of Ty21a by 5 logs after 3 hours at pH 2.5, when cells were pre-grown in arabinose and under conditions that promote an acid-tolerance response (ATR). For genetically 100% stable expression, we inserted the gad genes into the Ty21a chromosome, using a method that allowed for subsequent removal of a selectable antibiotic resistance marker. Further, both bacterial growth curves and survival assays in cultured human monocytes/macrophages suggest that neither the genetic methods employed nor the resulting acid-resistance conferred by expression of the Gad proteins in Ty21a had any effect on the existing attenuation of this vaccine strain. PMID:27673328

  19. Classification of Regional Ionospheric Disturbances Based on Support Vector Machines

    Science.gov (United States)

    Begüm Terzi, Merve; Arikan, Feza; Arikan, Orhan; Karatay, Secil

    2016-07-01

    Ionosphere is an anisotropic, inhomogeneous, time varying and spatio-temporally dispersive medium whose parameters can be estimated almost always by using indirect measurements. Geomagnetic, gravitational, solar or seismic activities cause variations of ionosphere at various spatial and temporal scales. This complex spatio-temporal variability is challenging to be identified due to extensive scales in period, duration, amplitude and frequency of disturbances. Since geomagnetic and solar indices such as Disturbance storm time (Dst), F10.7 solar flux, Sun Spot Number (SSN), Auroral Electrojet (AE), Kp and W-index provide information about variability on a global scale, identification and classification of regional disturbances poses a challenge. The main aim of this study is to classify the regional effects of global geomagnetic storms and classify them according to their risk levels. For this purpose, Total Electron Content (TEC) estimated from GPS receivers, which is one of the major parameters of ionosphere, will be used to model the regional and local variability that differs from global activity along with solar and geomagnetic indices. In this work, for the automated classification of the regional disturbances, a classification technique based on a robust machine learning technique that have found wide spread use, Support Vector Machine (SVM) is proposed. SVM is a supervised learning model used for classification with associated learning algorithm that analyze the data and recognize patterns. In addition to performing linear classification, SVM can efficiently perform nonlinear classification by embedding data into higher dimensional feature spaces. Performance of the developed classification technique is demonstrated for midlatitude ionosphere over Anatolia using TEC estimates generated from the GPS data provided by Turkish National Permanent GPS Network (TNPGN-Active) for solar maximum year of 2011. As a result of implementing the developed classification

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

    Directory of Open Access Journals (Sweden)

    Paolo Pellegrino

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

  1. Acute Disseminated Encephalomyelitis Onset: Evaluation Based on Vaccine Adverse Events Reporting Systems

    Science.gov (United States)

    Perrone, Valentina; Pozzi, Marco; Antoniazzi, Stefania; Clementi, Emilio; Radice, Sonia

    2013-01-01

    Objective To evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM) by considering data from different pharmacovigilance surveillance systems. Methods The Vaccine Adverse Event Reporting System (VAERS) database and the EudraVigilance post-authorisation module (EVPM) were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed. Results We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40±21.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines. Conclusions This study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reaction. PMID:24147076

  2. [Conflicts and vector-borne diseases

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian

    2010-01-01

    Based on literature and personal experiences, vector-borne diseases and conflicts are reviewed. Simple rapid diagnostic tests for three important parasitoses are available. Resort is often made to case definitions and to presumptive treatment. Resistance is an emerging problem. Vaccines are still...

  3. A versatile system for USER cloning-based assembly of expression vectors for mammalian cell engineering.

    Directory of Open Access Journals (Sweden)

    Anne Mathilde Lund

    Full Text Available A new versatile mammalian vector system for protein production, cell biology analyses, and cell factory engineering was developed. The vector system applies the ligation-free uracil-excision based technique--USER cloning--to rapidly construct mammalian expression vectors of multiple DNA fragments and with maximum flexibility, both for choice of vector backbone and cargo. The vector system includes a set of basic vectors and a toolbox containing a multitude of DNA building blocks including promoters, terminators, selectable marker- and reporter genes, and sequences encoding an internal ribosome entry site, cellular localization signals and epitope- and purification tags. Building blocks in the toolbox can be easily combined as they contain defined and tested Flexible Assembly Sequence Tags, FASTs. USER cloning with FASTs allows rapid swaps of gene, promoter or selection marker in existing plasmids and simple construction of vectors encoding proteins, which are fused to fluorescence-, purification-, localization-, or epitope tags. The mammalian expression vector assembly platform currently allows for the assembly of up to seven fragments in a single cloning step with correct directionality and with a cloning efficiency above 90%. The functionality of basic vectors for FAST assembly was tested and validated by transient expression of fluorescent model proteins in CHO, U-2-OS and HEK293 cell lines. In this test, we included many of the most common vector elements for heterologous gene expression in mammalian cells, in addition the system is fully extendable by other users. The vector system is designed to facilitate high-throughput genome-scale studies of mammalian cells, such as the newly sequenced CHO cell lines, through the ability to rapidly generate high-fidelity assembly of customizable gene expression vectors.

  4. DSP Based Direct Torque Control of Permanent Magnet Synchronous Motor (PMSM) using Space Vector Modulation (DTC-SVM)

    DEFF Research Database (Denmark)

    Swierczynski, Dariusz; Kazmierkowski, Marian P.; Blaabjerg, Frede

    2002-01-01

    DSP Based Direct Torque Control of Permanent Magnet Synchronous Motor (PMSM) using Space Vector Modulation (DTC-SVM)......DSP Based Direct Torque Control of Permanent Magnet Synchronous Motor (PMSM) using Space Vector Modulation (DTC-SVM)...

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

    Directory of Open Access Journals (Sweden)

    Jones Christopher

    2005-01-01

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

  6. Integrated control of Boophilus microplus ticks in Cuba based on vaccination with the anti-tick vaccine Gavac.

    Science.gov (United States)

    Valle, Manuel Rodriguez; Mèndez, Luis; Valdez, Mario; Redondo, Miguel; Espinosa, Carlos Montero; Vargas, Milagro; Cruz, Ricardo Lleonart; Barrios, Humberto Perez; Seoane, Guillermo; Ramirez, Emerio Serrano; Boue, Oscar; Vigil, Jorge Lodos; Machado, Héctor; Nordelo, Carlos Borroto; Piñeiro, Marisdania Joglar

    2004-01-01

    Boophilus microplus has developed resistance against a range of chemical acaricides which has stimulated the development of alternative methods such as vaccination against ticks. In Cuba, the Bm86-based recombinant vaccine Gavac has been successfully used in a number of controlled laboratory and field trials in cattle against B. microplus. In this paper, we have evaluated Gavac in a large scale field trial wherein 588,573 dairy cattle were vaccinated with the aim to reduce the number of acaricidal treatments. It was found that the number of acaricidal treatments could be reduced by 87% over a period of 8 years (1995--2003). Prior to the introduction of the vaccine, 54 clinical cases of babesiosis and six fatal cases were reported per 1000 animals. Six years later, the incidence of babesiosis was reduced to 1.9 cases per 1000 cattle and mortality reduced to 0.18 per 1000. The national consumption of acaricides in Cuba could be reduced by 82% after the implementation of the integrated anti-B. microplus control program. PMID:15651533

  7. Research on Matrix Converter Based on Space Vector Modulation

    Directory of Open Access Journals (Sweden)

    Zhanjun Qiao

    2013-09-01

    Full Text Available In this study, we study the control strategy for matrix converter. Through absorbing ideas about virtual rectification put forward by P.D.Ziogas, the common control idea of AC-DC-AC convertor is introduced into control of matrix converter; SPWM modulation strategy and space vector modulation strategy for matrix converter are studied respectively. In terms of SPWM modulation strategy, it has some advantages: for example, main circuit structure is simple; control program is simple; control switch function does not need complex mathematical derivation and calculation. In terms of space vector modulation strategy, it has advantages as follows: the physical conception is clear; input power factor can be adjusted; output voltage and current sine degree are high. In this chapter, an in-depth analysis will be conducted for this control method

  8. Poly ICLC increases the potency of a replication-defective human adenovirus vectored foot-and-mouth disease vaccine

    Science.gov (United States)

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have previously demonstrated that a replication-defective human adenovirus 5 vector carrying the FMDV capsid coding region of serotype A24 Cruzeiro (Ad5-CI-A24-2B) protects swine and cattle against FM...

  9. Rigid Body Time Integration by Convected Base Vectors with Implicit Constraints

    OpenAIRE

    Krenk, Steen; Nielsen, Martin Bjerre

    2013-01-01

    A conservative time integration algorithm based on a convected set of orthonormal base vectors is presented. The equations of motion are derived from an extended Hamiltonian formulation, combining the components of the three base vectors with a set of orthonormality constraints. The particular form of the kinetic energy used in the present formulation is deliberately chosen to correspond to a rigid body rotation, and the orthonormality constraints are introduced via the equivalent Green strai...

  10. Support vector regression-based internal model control

    Institute of Scientific and Technical Information of China (English)

    HUANG Yan-wei; PENG Tie-gen

    2007-01-01

    This paper proposes a design of internal model control systems for process with delay by using support vector regression (SVR). The proposed system fully uses the excellent nonlinear estimation performance of SVR with the structural risk minimization principle. Closed-system stability and steady error are analyzed for the existence of modeling errors. The simulations show that the proposed control systems have the better control performance than that by neural networks in the cases of the training samples with small size and noises.

  11. Wireless Localization Based on RSSI Fingerprint Feature Vector

    OpenAIRE

    Aiguo Zhang; Ying Yuan; Qunyong Wu; Shunzhi Zhu; Jian Deng

    2015-01-01

    RSSI wireless signal is a reference information that is widely used in indoor positioning. However, due to the wireless multipath influence, the value of the received RSSI will have large fluctuations and cause large distance error when RSSI is fitted to distance. But experimental data showed that, being affected by the combined factors of the environment, the received RSSI feature vector which is formed by lots of RSSI values from different APs is a certain stability. Therefore, the paper pr...

  12. Research on Matrix Converter Based on Space Vector Modulation

    OpenAIRE

    Zhanjun Qiao; Wei Xu

    2013-01-01

    In this study, we study the control strategy for matrix converter. Through absorbing ideas about virtual rectification put forward by P.D.Ziogas, the common control idea of AC-DC-AC convertor is introduced into control of matrix converter; SPWM modulation strategy and space vector modulation strategy for matrix converter are studied respectively. In terms of SPWM modulation strategy, it has some advantages: for example, main circuit structure is simple; control program is simple; control swit...

  13. Window-Based Example Selection in Learning Vector Quantization

    OpenAIRE

    Witoelar, A. W.; Ghosh, Anarta; De Vries, J.J.G.; Hammer, B; Biehl, M.

    2010-01-01

    A variety of modifications have been employed to learning vector quantization (LVQ) algorithms using either crisp or soft windows for selection of data. Although these schemes have been shown in practice to improve performance, a theoretical study on the influence of windows has so far been limited. Here we rigorously analyze the influence of windows in a controlled environment of gaussian mixtures in high dimensions. Concepts from statistical physics and the theory of online learning allow a...

  14. Chord Recognition Based on Temporal Correlation Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Zhongyang Rao

    2016-05-01

    Full Text Available In this paper, we propose a method called temporal correlation support vector machine (TCSVM for automatic major-minor chord recognition in audio music. We first use robust principal component analysis to separate the singing voice from the music to reduce the influence of the singing voice and consider the temporal correlations of the chord features. Using robust principal component analysis, we expect the low-rank component of the spectrogram matrix to contain the musical accompaniment and the sparse component to contain the vocal signals. Then, we extract a new logarithmic pitch class profile (LPCP feature called enhanced LPCP from the low-rank part. To exploit the temporal correlation among the LPCP features of chords, we propose an improved support vector machine algorithm called TCSVM. We perform this study using the MIREX’09 (Music Information Retrieval Evaluation eXchange Audio Chord Estimation dataset. Furthermore, we conduct comprehensive experiments using different pitch class profile feature vectors to examine the performance of TCSVM. The results of our method are comparable to the state-of-the-art methods that entered the MIREX in 2013 and 2014 for the MIREX’09 Audio Chord Estimation task dataset.

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

    Science.gov (United States)

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

    2015-02-01

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

  16. Vaccines and immunization strategies for dengue prevention.

    Science.gov (United States)

    Liu, Yang; Liu, Jianying; Cheng, Gong

    2016-01-01

    Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future. PMID:27436365

  17. Genetic vaccination against acute viral disease

    OpenAIRE

    Fleeton, Marina N

    1999-01-01

    This thesis describes the development of recombinant vaccines based on the Semliki Forest virus (SFV) expression system. Immunisation of mice with recombinant virus particles, a layered DNA/RNA plasmid vector, and recombinant self-replicating RNA were carried out and the protective effect of these recombinant vaccines against viral challenge were examined. The construction of a full-length infectious clone formed the basis for the SFV expression system which has previous...

  18. Establishment of a Bovine Herpesvirus 4 based vector expressing a secreted form of the Bovine Viral Diarrhoea Virus structural glycoprotein E2 for immunization purposes

    Directory of Open Access Journals (Sweden)

    Donofrio Gaetano

    2007-10-01

    Full Text Available Abstract Background The biological characteristics of BoHV-4 make it a good candidate as a gene delivery vector for vaccination purposes. These characteristics include little or no pathogenicity, unlikely oncogenicity, the capability to accommodate large amounts of foreign genetic material, the ability to infect several cell types from different animal species, and the ability to maintain transgene expression in both undifferentiated and differentiated cells. Results A recombinant bovine herpesvirus 4 (BoHV-4CMV-IgKE2-14ΔTK expressing an enhanced secreted form of the bovine viral diarrhea virus (BVDV structural glycoprotein E2 (gE2-14, obtained by the removal of the putative transmembrane domain and addition of a 14 amino acids peptide at its carboxyl terminal and an immunoglobulin K signal peptide to the amino terminal, was successfully constructed using a Recombineering (recombination -mediated genetic engineering approach on BoHV-4 cloned as bacterial artificial chromosome. The galactokinase – based recombineering system was modified by the introduction of a kanamycin expression cassette and a kanamycin selection step that allowed a significant reduction of the untargeted background clones. BoHV-4CMV-IgKE2-14ΔTK infected cell lines highly expressed gE2-14, which maintained native antigenic properties in a serum neutralization inhibition test. When rabbits and sheep were immunized with BoHV-4CMV-IgKE2-14ΔTK, high levels of serum neutralized antibodies against BVDV were generated. Conclusion This work highlights the engineerization of BoHV-4 genome as a vector for vaccine purposes and may provide the basis for BVDV vaccination exploiting the BoHV-4- based vector that delivers an improved secreted version of the BVDV structural glycoprotein E2.

  19. A new method for comparing scanpaths based on vectors and dimensions

    OpenAIRE

    Dewhurst, Richard; Jarodzka, Halszka; Holmqvist, Kenneth; Foulsham, Tom; Nyström, Marcus

    2011-01-01

    Dewhurst, R., Jarodzka, H., Holmqvist, K., Foulsham, T., & Nyström, M. (2011, May). A new method for comparing scanpaths based on vectors and dimensions. Vision Sciences Society 2011, Naples, Florida.

  20. Rigid Body Time Integration by Convected Base Vectors with Implicit Constraints

    DEFF Research Database (Denmark)

    Krenk, Steen; Nielsen, Martin Bjerre

    2013-01-01

    of orthogonality relations between the base vector components and their conjugate momentum components. These orthogonality relations permit explicit elimination of the Lagrange multipliers associated with the constraints, leading to a projected form of the dynamic equation without explicit algebraic constraints...

  1. An evidence-based vector control strategy for military deployments: the British Army experience.

    Science.gov (United States)

    Croft, A M; Baker, D; von Bertele, M J

    2001-01-01

    We describe the British Army's current strategy for controlling arthropod vectors of disease during overseas deployments. Military commanders and medical officers have different, but complementary responsibilities in achieving vector control. In this paper we define a hierarchy of evidence-based vector control guidelines. Field guidelines must be based on the best available research evidence, preferably that derived from pragmatic randomised controlled trials (RCTs), and from systematic reviews of trials. Assessing the effectiveness of different vector control measures involves a trade-off between the relative benefits and harm of different technology options. There is compelling scientific evidence that bed nets and screens treated with a pyrethroid insecticide are highly effective in protecting against nocturnally active, anthropophilic arthropods (including ectoparasites), and will reduce the incidence of malaria, leishmaniasis, lymphatic filariasis and Chagas' disease. Etofenprox and deltamethrin are the safest pyrethroids, and permethrin the least safe. Vector control strategies of probable effectiveness are the use of insecticide-treated clothing, the wearing of protective clothing, and the correct use of DEET-based topical insect repellents. Aerosol insecticides are of debatable effectiveness. Other effective vector control measures, of limited usefulness during deployments, include electric fans, mosquito coils/vaporising mats, and smoke. "Biological" vector control measures, and insect buzzers/electrocuters are ineffective. Practical insect avoidance measures, based on an understanding of vector biology, complete the military vector-control arsenal. We conclude that practical insect avoidance measures, combined with pyrethroid-treated nets and clothing, and DEET-based topical repellents, can achieve almost 100% protection against biting arthropods. PMID:11584666

  2. Bethe vectors for models based on the super-Yangian $Y(\\mathfrak{gl}(m|n))$

    CERN Document Server

    Pakuliak, S Z; Slavnov, N A

    2016-01-01

    We study Bethe vectors of integrable models based on the super-Yangian $Y(\\mathfrak{gl}(m|n))$. Starting from the super-trace formula, we exhibit recursion relations for these vectors in the case of $Y(\\mathfrak{gl}(2|1))$ and $Y(\\mathfrak{gl}(1|2))$. These recursion relations allow to get explicit expressions for the Bethe vectors. Using an antimorphism of the super-Yangian $Y(\\mathfrak{gl}(m|n))$, we also construct a super-trace formula for dual Bethe vectors, and, for $Y(\\mathfrak{gl}(2|1))$ and $Y(\\mathfrak{gl}(1|2))$ super-Yangians, show recursion relations for them. Again, the latter allow us to get explicit expressions for dual Bethe vectors.

  3. Fast encoding algorithm for vector quantization based on subvector L2-norm

    Institute of Scientific and Technical Information of China (English)

    Chen Shanxue; Li Fangwei; Zhu Weile

    2008-01-01

    A fast encoding algorithm based on the mean square error (MSE) distortion for vector quantization is introduced. The vector, which is effectively constructed with wavelet transform (WT) coefficients of images, can simplify the realization of the non-linear interpolated vector quantization (NLIVQ) technique and make the partial distance search (PDS) algorithm more efficient. Utilizing the relationship of vector L2-norm and its Euclidean distance, some conditions of eliminating unnecessary codewords are obtained. Further, using inequality constructed by the subvector L2-norm, more unnecessary codewords are eliminated. During the search process for code, mostly unlikely codewords can be rejected by the proposed algorithm combined with the non-linear interpolated vector quantization technique and the partial distance search technique. The experimental results show that the reduction of computation is outstanding in the encoding time and complexity against the full search method.

  4. Real-time traffic information extraction based on compressed video with interframe motion vector

    Institute of Scientific and Technical Information of China (English)

    黄庆明; 王聪

    2003-01-01

    Extraction of traffic information from image or video sequence is a hot research topic in intelligenttransportation system and computer vision. A real-time traffic information extraction method based on com-pressed video with interframe motion vectors for speed, density and flow detection, has been proposed for ex-traction of traffic information under fixed camera setting and well-defined environment. The motion vectors arefirst separated from the compressed video streams, and then filtered to eliminate incorrect and noisy vectors u-sing the well-defined environmental knowledge. By applying the projective transform and using the filtered mo-tion vectors, speed can be calculated from motion vector statistics, density can be estimated using the motionvector occupancy, and flow can be detected using the combination of speed and density. The embodiment of aprototype system for sky camera traffic monitoring using the MPEG video has been implemented, and experi-mental results proved the effectiveness of the method proposed.

  5. Automatic SIMD vectorization of SSA-based control flow graphs

    CERN Document Server

    Karrenberg, Ralf

    2015-01-01

    Ralf Karrenberg presents Whole-Function Vectorization (WFV), an approach that allows a compiler to automatically create code that exploits data-parallelism using SIMD instructions. Data-parallel applications such as particle simulations, stock option price estimation or video decoding require the same computations to be performed on huge amounts of data. Without WFV, one processor core executes a single instance of a data-parallel function. WFV transforms the function to execute multiple instances at once using SIMD instructions. The author describes an advanced WFV algorithm that includes a v

  6. Emotional Vector Distance Based Sentiment Analysis of Wakamono Kotoba

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    In this paper, we propose a method for estimating emotion in Wakamono Kotoba that were not registered in the system, by using Wakamono Kotoba example sentences as features. The pro- posed method applies Earth Mover's Distance (EMD) to vector of words. As a result of the evaluation ex- periment using 14 440 sentences, higher estimation accuracy is obtained by considering emotional dis- tance between words - an approach that had not been used in the conventional research - than by using only word importance value.

  7. Digital Simulation of Space Vector Modulation Based Induction Motor Drive

    Directory of Open Access Journals (Sweden)

    G.V. Siva Krishna Rao and T.S. Surendra

    2011-04-01

    Full Text Available This study deals with simulation of Space vector modulated inverter fed induction motor drive. The drive system is modeled using matlab simulink and the results are presented. This drive has advantages like reduced harmonics and heating. Fixed AC is converted into DC and this DC is converted into variable voltage and variable frequency AC using SVM inverter. The output of SVM is applied to the stator of induction motor. The simulation results are compared with the analytical results. The FFT analysis shows that the current spectrum has reduced harmonics compared to the conventional system.

  8. Sagnac Interferometer Based Generation of Controllable Cylindrical Vector Beams

    Directory of Open Access Journals (Sweden)

    Cristian Acevedo

    2016-01-01

    Full Text Available We report on a novel experimental geometry to generate cylindrical vector beams in a very robust manner. Continuous control of beams’ properties is obtained using an optically addressable spatial light modulator incorporated into a Sagnac interferometer. Forked computer-generated holograms allow introducing different topological charges while orthogonally polarized beams within the interferometer permit encoding the spatial distribution of polarization. We also demonstrate the generation of complex waveforms obtained by combining two orthogonal beams having both radial modulations and azimuthal dislocations.

  9. Development and Evaluation of the Protective Efficacy of Novel Marek's Disease Virus Rispens Vector Vaccines Against Infectious Bursal Disease.

    Science.gov (United States)

    Ishihara, Yukari; Esaki, Motoyuki; Saitoh, Shuji; Sato, Takanori; Yasuda, Atsushi

    2016-09-01

    Infectious bursal disease (IBD) is a major disease affecting the poultry industry and is caused by infection with IBD virus (IBDV). To develop a novel vaccine to prevent IBD in chickens, recombinant Marek's disease virus Rispens viruses carrying the VP2 gene of IBDV driven by five different promoters (Rispens/IBD) were constructed using homologous recombination and a bacterial artificial chromosome (BAC). Rispens/IBD driven by the chicken beta-actin (Bac) promoter (Rispens/Bac-IBD), Rous sarcoma virus promoter, or simian virus 40 promoter were administered to 1-day-old SPF chicks, and the protective efficacy against IBDV was evaluated by challenging chicks with virulent IBDV. As a result, Rispens/Bac-IBD showed the best protection (87%). Next, we constructed the virus driven by the Bac-derived Coa5 promoter (Rispens/Coa5-IBD) for a secondary in vivo trial using commercial layer chickens since Rispens/Bac-IBD was thought to be genetically unstable. Rispens/Coa5-IBD showed stability in vitro and exhibited better antibody production and protection during challenge against virulent IBDV at both 5 (95%) and 7 wk of age (91%) compared with that of Rispens/Bac-IBD (90% at 5 wk of age and 84% at 7 wk of age). Thus, Rispens/Coa5-IBD may be a novel promising vaccine against IBD and virulent Marek's disease. PMID:27610721

  10. Inertial Vector Based Attitude Stabilization of Rigid Body Without Angular Velocity Measurements

    OpenAIRE

    Benziane, L.; Benallegue, A.; Chitour, Y.; Tayebi, A.

    2015-01-01

    We address the problem of attitude stabilization of a rigid body, in which neither the angular velocity nor the instantaneous measurements of the attitude are used in the feedback, only body vector measurements are needed. The design of the controller is based on an angular velocity observer-like system, where a first order linear auxiliary system based directly on vector measurements is introduced. The introduction of gain matrices provides more tuning flexibility and better results compared...

  11. Formulation of 2D Graphene Deformation Based on Chiral-Tube Base Vectors

    Directory of Open Access Journals (Sweden)

    Bohua Sun

    2010-01-01

    Full Text Available The intrinsic feature of graphene honeycomb lattice is defined by its chiral index (n,m, which can be taken into account when using molecular dynamics. However, how to introduce the index into the continuum model of graphene is still an open problem. The present manuscript adopts the continuum shell model with single director to describe the mechanical behaviors of graphene. In order to consider the intrinsic features of the graphene honeycomb lattice—chiral index (n,m, the chiral-tube vectors of graphene in real space have been used for construction of reference unit base vectors of the shell model; therefore, the formulations will contain the chiral index automatically, or in an explicit form in physical components. The results are quite useful for future studies of graphene mechanics.

  12. Web-based GIS: the vector-borne disease airline importation risk (VBD-AIR tool

    Directory of Open Access Journals (Sweden)

    Huang Zhuojie

    2012-08-01

    Full Text Available Abstract Background Over the past century, the size and complexity of the air travel network has increased dramatically. Nowadays, there are 29.6 million scheduled flights per year and around 2.7 billion passengers are transported annually. The rapid expansion of the network increasingly connects regions of endemic vector-borne disease with the rest of the world, resulting in challenges to health systems worldwide in terms of vector-borne pathogen importation and disease vector invasion events. Here we describe the development of a user-friendly Web-based GIS tool: the Vector-Borne Disease Airline Importation Risk Tool (VBD-AIR, to help better define the roles of airports and airlines in the transmission and spread of vector-borne diseases. Methods Spatial datasets on modeled global disease and vector distributions, as well as climatic and air network traffic data were assembled. These were combined to derive relative risk metrics via air travel for imported infections, imported vectors and onward transmission, and incorporated into a three-tier server architecture in a Model-View-Controller framework with distributed GIS components. A user-friendly web-portal was built that enables dynamic querying of the spatial databases to provide relevant information. Results The VBD-AIR tool constructed enables the user to explore the interrelationships among modeled global distributions of vector-borne infectious diseases (malaria. dengue, yellow fever and chikungunya and international air service routes to quantify seasonally changing risks of vector and vector-borne disease importation and spread by air travel, forming an evidence base to help plan mitigation strategies. The VBD-AIR tool is available at http://www.vbd-air.com. Conclusions VBD-AIR supports a data flow that generates analytical results from disparate but complementary datasets into an organized cartographical presentation on a web map for the assessment of vector-borne disease movements

  13. What you always needed to know about electroporation based DNA vaccines

    DEFF Research Database (Denmark)

    Gothelf, Anita Birgitte; Gehl, Julie

    2012-01-01

    Vaccinations are increasingly used to fight infectious disease, and DNA vaccines offer considerable advantages, including broader possibilities for vaccination and lack of need for cold storage. It has been amply demonstrated, that electroporation augments uptake of DNA in both skin and muscle......, and it is foreseen that future DNA vaccination may to a large extent be coupled with and dependent upon electroporation based delivery. Understanding the basic science of electroporation and exploiting knowledge obtained on optimization of DNA electrotransfer to muscle and skin, may greatly augment efforts...... on vaccine development. The purpose of this review is to give a succinct but comprehensive overview of electroporation as a delivery modality including electrotransfer to skin and muscle. As well, this review will speculate and discuss future uses for this powerful electrotransfer technology....

  14. Vaccination against Bm86 Homologues in Rabbits Does Not Impair Ixodes ricinus Feeding or Oviposition

    OpenAIRE

    Jeroen Coumou; Alex Wagemakers; Trentelman, Jos J.; Nijhof, Ard M; Hovius, Joppe W.

    2015-01-01

    Human tick-borne diseases that are transmitted by Ixodes ricinus, such as Lyme borreliosis and tick borne encephalitis, are on the rise in Europe. Diminishing I. ricinus populations in nature can reduce tick exposure to humans, and one way to do so is by developing an anti-vector vaccine against tick antigens. Currently, there is only one anti-vector vaccine available against ticks, which is a veterinary vaccine based on the tick antigen Bm86 in the gut of Rhipicephalus microplus. Bm86 vaccin...

  15. High-base vector beam encoding/decoding for visible-light communications.

    Science.gov (United States)

    Zhao, Yifan; Wang, Jian

    2015-11-01

    Polarization is a basic property of light. Different from well-known linear, circular, and elliptical polarizations, which are spatially homogeneous, a vector light beam with spatially variant polarization states has received increasing interest for its expanded functionalities. In this Letter, we present a visible-light communication link exploiting high-base vector beam encoding/decoding. Using a single phase-only spatial light modulator, we generate 16 states of vector beams representing hexadecimal numbers. In the visible-light communication link experiment, we transmit a random high-base number sequence with 10,000 hexadecimal numbers and a 64×64 pixel Lena gray image with 8192 hexadecimal numbers. The bit error rate is evaluated, and zero error among all received hexadecimal numbers is achieved, showing favorable link communication performance using the high-base vector beam encoding/decoding. PMID:26512464

  16. Mass detection algorithm based on support vector machine and relevance feedback

    Institute of Scientific and Technical Information of China (English)

    Ying WANG; Xinbo GAO

    2008-01-01

    To improve the detection of mass with appearance that borders on the similarity between mass and density tissues in the breast,an support vector machine classifier based on typical features iS designed to classify the region of interest(ROI).Furthermore,relevance feedback is introduced to improve the performance of support vector machines.A new mass detection scheme based on the support vector machine and the relevance feedback is proposed.Simulation experiments on mammograms illustrate that the novel support vector machine classifier based on typical features can improve the detection performance of the featureless classifier by 5%,while the introduction of relevance feedback can further improve the detection performance to about 90%.

  17. Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases.

    Directory of Open Access Journals (Sweden)

    Kenichi W Okamoto

    2016-03-01

    Full Text Available Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted. We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences-consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even

  18. Vaccination against ticks (Boophilus spp.): the experience with the Bm86-based vaccine Gavac.

    Science.gov (United States)

    de la Fuente, J; Rodríguez, M; Montero, C; Redondo, M; García-García, J C; Méndez, L; Serrano, E; Valdés, M; Enríquez, A; Canales, M; Ramos, E; Boué, O; Machado, H; Lleonart, R

    1999-11-01

    The control of tick infestations and the transmission of tick-borne diseases remain a challenge for the cattle industry in tropical and subtropical areas of the world. Traditional control methods have been only partially successful and the parasites continue to result in significant losses for the cattle industry. Recently, vaccines containing the recombinant B. microplus gut antigen Bm86 have been developed. Our vaccine formulation (Gavac, Heber Biotec S.A., Havana, Cuba) has been registered and is commercially available in Cuba, Colombia, Dominican Republic, Brazil and Mexico. In controlled pen trials, Gavac has been effective for the control of artificial infestations of B. annulatus, B. decoloratus and chemical-sensitive and resistant B. microplus strains from Australia, Africa, America and Iran. In controlled field trials in Cuba, Brazil, Argentina and Mexico, Gavac has shown a 55-100% efficacy in the control of B. microplus infestations in grazing cattle 12-36 weeks after the first vaccination. Field trials under production conditions have been conducted in Cuba, Colombia, Brazil and Mexico in pure and cross-bred cattle herds. The application of Gavac has increased the time between acaricide treatments by an average of 32 /-21 days (P = 0.0005) resulting in important savings for the cattle industry. In Cuba, a cost-effectiveness analysis was conducted in more than 260000 animals. The cost-effectiveness analysis showed a 60% reduction in the number of acaricide treatments, together with the control of tick infestations and transmission of babesiosis, which resulted in savings of 23.4 dollars animal(-1) year (-1). These results clearly demonstrate the advantage of vaccination and support the application of Gavac for the control of Boophilus spp. infestations. PMID:10596754

  19. A commercial PCV2a-based vaccine significantly reduces PCV2b transmission in experimental conditions.

    Science.gov (United States)

    Rose, N; Andraud, M; Bigault, L; Jestin, A; Grasland, B

    2016-07-19

    Transmission characteristics of PCV2 have been compared between vaccinated and non-vaccinated pigs in experimental conditions. Twenty-four Specific Pathogen Free (SPF) piglets, vaccinated against PCV2 at 3weeks of age (PCV2a recombinant CAP protein-based vaccine), were inoculated at 15days post-vaccination with a PCV2b inoculum (6⋅10(5) TCID50), and put in contact with 24 vaccinated SPF piglets during 42days post-inoculation. Those piglets were shared in six replicates of a contact trial involving 4 inoculated piglets mingled with 4 susceptible SPF piglets. Two replicates of a similar contact trial were made with non-vaccinated pigs. Non vaccinated animals received a placebo at vaccination time and were inoculated the same way and at the same time as the vaccinated group. All the animals were monitored twice weekly using quantitative real-time PCR and ELISA for serology until 42days post-inoculation. The frequency of infection and the PCV2 genome load in sera of the vaccinated pigs were significantly reduced compared to the non-vaccinated animals. The duration of infectiousness was significantly different between vaccinated and non-vaccinated groups (16.6days [14.7;18.4] and 26.6days [22.9;30.4] respectively). The transmission rate was also considerably decreased in vaccinated pigs (β=0.09 [0.05-0.14] compared to β=0.19 [0.11-0.32] in non-vaccinated pigs). This led to an estimated reproduction ratio of 1.5 [95% CI 0.8 - 2.2] in vaccinated animals versus 5.1 [95% CI 2.5 - 8.2] in non-vaccinated pigs when merging data of this experiment with previous trials carried out in same conditions. PMID:27318416

  20. Vaccines for viral diseases with dermatologic manifestations.

    Science.gov (United States)

    Brentjens, Mathijs H; Yeung-Yue, Kimberly A; Lee, Patricia C; Tyring, Stephen K

    2003-04-01

    Vaccines against infectious diseases have been available since the 1800s, when an immunization strategy against smallpox developed by Jenner gained wide acceptance. Until recently, the only vaccination strategies available involved the use of protein-based, whole killed, and attenuated live virus vaccines. These strategies have led to the development of effective vaccines against a variety of diseases with primary or prominent cutaneous manifestations. Effective and safe vaccines now used worldwide include those directed against measles and rubella (now commonly used together with a mumps vaccine as the trivalent MMR), chickenpox, and hepatitis B. The eradication of naturally occurring smallpox remains one of the greatest successes in the history of modern medicine, but stockpiles of live smallpox exist in the United States and Russia. Renewed interest in the smallpox vaccine reflects concerns about a possible bioterrorist threat using this virus. Yellow fever is a hemorrhagic virus endemic to tropical areas of South America and Africa. An effective vaccine for this virus has existed since 1937, and it is used widely in endemic areas of South America, and to a lesser extent in Africa. This vaccine is recommended once every 10 years for people who are traveling to endemic areas. Advances in immunology have led to a greater understanding of immune system function in viral diseases. Progress in genetics and molecular biology has allowed researchers to design vaccines with novel mechanisms of action (eg, DNA, vector, and VLP vaccines). Vaccines have also been designed to specifically target particular viral components, allowing for stimulation of various arms of the immune system as desired. Ongoing research shows promise in prophylactic and therapeutic vaccination for viral infections with cutaneous manifestations. Further studies are necessary before vaccines for HSV, HPV, and HIV become commercially available. PMID:12757257

  1. Farming of Plant-Based Veterinary Vaccines and Their Applications for Disease Prevention in Animals

    Directory of Open Access Journals (Sweden)

    Pit Sze Liew

    2015-01-01

    Full Text Available Plants have been studied for the production of pharmaceutical compounds for more than two decades now. Ever since the plant-made poultry vaccine against Newcastle disease virus made a breakthrough and went all the way to obtain regulatory approval, research to use plants for expression and delivery of vaccine proteins for animals was intensified. Indeed, in view of the high production costs of veterinary vaccines, plants represent attractive biofactories and offer many promising advantages in the production of recombinant vaccine proteins. Furthermore, the possibility of conducting immunogenicity and challenge studies in target animals has greatly exaggerated the progress. Although there are no edible plant-produced animal vaccines in the market, plant-based vaccine technology has great potentials. In this review, development, uses, and advantages of plant-based recombinant protein production in various expression platforms are discussed. In addition, examples of plant-based veterinary vaccines showing strong indication in terms of efficacy in animal disease prevention are also described.

  2. Clinical development of Ebola vaccines.

    Science.gov (United States)

    Sridhar, Saranya

    2015-09-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines.

  3. Clinical development of Ebola vaccines.

    Science.gov (United States)

    Sridhar, Saranya

    2015-09-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  4. Parental education and text messaging reminders as effective community based tools to increase HPV vaccination rates among Mexican American children

    Directory of Open Access Journals (Sweden)

    Abraham Aragones

    2015-01-01

    Conclusions: Parental text messaging plus education, implemented in a community based setting, was strongly associated with vaccine completion rates among vaccine-eligible Mexican American children. Although pilot in nature, the study achieved an 88% series completion rate in the children of those who received the text messages, significantly higher than current vaccination levels.

  5. Development of novel AAV serotype 6 based vectors with selective tropism for human cancer cells.

    Science.gov (United States)

    Sayroo, R; Nolasco, D; Yin, Z; Colon-Cortes, Y; Pandya, M; Ling, C; Aslanidi, G

    2016-01-01

    Viral vectors-based gene therapy is an attractive alternative to common anti-cancer treatments. In the present studies, AAV serotype 6 vectors were identified to be particularly effective in the transduction of human prostate (PC3), breast (T47D) and liver (Huh7) cancer cells. Next, we developed chimeric AAV vectors with Arg-Gly-Asp (RGD) peptide incorporated into the viral capsid to enable specific targeting of integrin-overexpressing malignant cells. These AAV6-RGD vectors improved transduction efficiency approximately 3-fold compared with wild-type AAV6 vectors by enhancing the viral entry into the cells. We also observed that transduction efficiency significantly improved, up to approximately 5-fold, by the mutagenesis of surface-exposed tyrosine and threonine residues involved in the intracellular trafficking of AAV vectors. Therefore, in our study, the AAV6-Y705-731F+T492V vector was identified as the most efficient. The combination of RGD peptide, tyrosine and threonine mutations on the same AAV6 capsid further increased the transduction efficiency, approximately 8-fold in vitro. In addition, we mutated lysine (K531E) to impair the affinity of AAV6 vectors to heparan sulfate proteoglycan. Finally, we showed a significant increase in both specificity and efficiency of AAV6-RGD-Y705-731F+T492V+K531E vectors in a xenograft animal model in vivo. In summary, the approach described here can lead to the development of AAV vectors with selective tropism to human cancer cells.

  6. GET POKED: Comparing an Incentive-Based Flu Campaign with Vaccinate-or-Mask Policies to Boost Influenza Vaccination Rates Among Healthcare Workers.

    Science.gov (United States)

    Marwaha, Seema; Lorv, Bailey; Henseleit, Susanne; Iroanyah, Ngozi

    2016-01-01

    The median influenza vaccination rate for Toronto acute care facilities in 2013/14 was only 44%, well below the target rate of 90%. While many Toronto hospitals adopted a vaccinate-or-mask policy, Trillium Health Partners (THP) opted to create a multimodal incentives-based flu campaign entitled GET POKED. This campaign, which required significant additional resourcing, only increased our vaccination rate by 10%. While having some modest success, we believe it is unlikely that non-policy based interventions will efficiently and sustainably raise flu vaccine rates. Vaccinate-or-mask policies, while having some inherent challenges, may be worth exploring as part of THP's larger flu-prevention strategy. PMID:27009712

  7. Adenovirus-Vectored Drug-Vaccine Duo as a Rapid-Response Tool for Conferring Seamless Protection against Influenza

    OpenAIRE

    Jianfeng Zhang; E Bart Tarbet; Tsungwei Feng; Zhongkai Shi; Van Kampen, Kent R; Tang, De-chu C

    2011-01-01

    Few other diseases exert such a huge toll of suffering as influenza. We report here that intranasal (i.n.) administration of E1/E3-defective (ΔE1E3) adenovirus serotype 5 (Ad5) particles rapidly induced an anti-influenza state as a means of prophylactic therapy which persisted for several weeks in mice. By encoding an influenza virus (IFV) hemagglutinin (HA) HA1 domain, an Ad5-HA1 vector conferred rapid protection as a prophylactic drug followed by elicitation of sustained protective immunity...

  8. An Even Grid Based Lattice Vector Quantization Algorithm for Mobile Audio Coding

    Directory of Open Access Journals (Sweden)

    Bo Hang

    2011-06-01

    Full Text Available This paper proposed an even grid based lattice vector quantization method for audio coding. The method uses energy priority, with basic code book and the ball-type expansion, which is applicable to the low rate of the variable-rate vector quantization coding. The method uses the lattice characteristics to resolve rapid index distribution problem, as well as the compression of the basic code book. The experiment results show that the proposed method is as good as vector quantization method in ITU-T standard G729.1 in quality, with lower storage cost and computational complexity.

  9. The seam offset identification based on support vector regression machines

    Institute of Scientific and Technical Information of China (English)

    Zeng Songsheng; Shi Yonghua; Wang Guorong; Huang Guoxing

    2009-01-01

    The principle of the support vector regression machine(SVR) is first analysed. Then the new data-dependent kernel function is constructed from information geometry perspective. The current waveforms change regularly in accordance with the different horizontal offset when the rotational frequency of the high speed rotational arc sensor is in the range from 15 Hz to 30 Hz. The welding current data is pretreated by wavelet filtering, mean filtering and normalization treatment. The SVR model is constructed by making use of the evolvement laws, the decision function can be achieved by training the SVR and the seam offset can be identified. The experimental results show that the precision of the offset identification can be greatly improved by modifying the SVR and applying mean filtering from the longitudinal direction.

  10. A local technique based on vectorized surfaces for craniofacial reconstruction.

    Science.gov (United States)

    Tilotta, Françoise M; Glaunès, Joan A; Richard, Frédéric J P; Rozenholc, Yves

    2010-07-15

    In this paper, we focus on the automation of facial reconstruction. Since they consider the whole head as the object of interest, usual reconstruction techniques are global and involve a large number of parameters to be estimated. We present a local technique which aims at reaching a good trade-off between bias and variance following the paradigm of non-parametric statistics. The estimation is localized on patches delimited by surface geodesics between anatomical points of the skull. The technique relies on a continuous representation of the individual surfaces embedded in the vectorial space of extended normal vector fields. This allows to compute deformations and averages of surfaces. It consists in estimating the soft-tissue surface over patches. Using a homogeneous database described in [31], we obtain results on the chin and nasal regions with an average error below 1mm, outperforming the global reconstruction techniques.

  11. Aero-Engine Condition Monitoring Based on Support Vector Machine

    Science.gov (United States)

    Zhang, Chunxiao; Wang, Nan

    The maintenance and management of civil aero-engine require advanced monitor approaches to estimate aero-engine performance and health in order to increase life of aero-engine and reduce maintenance costs. In this paper, we adopted support vector machine (SVM) regression approach to monitor an aero-engine health and condition by building monitoring models of main aero-engine performance parameters(EGT, N1, N2 and FF). The accuracy of nonlinear baseline models of performance parameters is tested and the maximum relative error does not exceed ±0.3%, which meets the engineering requirements. The results show that SVM nonlinear regression is an effective method in aero-engine monitoring.

  12. Improved Production Efficiency of Virus-Like Particles by the Baculovirus Expression Vector System

    OpenAIRE

    López-Vidal, Javier; Gómez-Sebastián, Silvia; Bárcena, Juan; Nuñez, Maria del Carmen; Martínez-Alonso, Diego; Dudognon, Benoit; Guijarro, Eva; José M Escribano

    2015-01-01

    Vaccines based on virus-like particles (VLPs) have proven effective in humans and animals. In this regard, the baculovirus expression vector system (BEVS) is one of the technologies of choice to generate such highly immunogenic vaccines. The extended use of these vaccines for human and animal populations is constrained because of high production costs, therefore a significant improvement in productivity is crucial to ensure their commercial viability. Here we describe the use of the previousl...

  13. A Novel M2e Based Flu Vaccine Formulation for Dogs

    Science.gov (United States)

    Leclerc, Denis; Rivest, Marie; Babin, Cindy; López-Macias, Constantino; Savard, Pierre

    2013-01-01

    Background The USA 2004 influenza virus outbreak H3N8 in dogs heralded the emergence of a new disease in this species. A new inactivated H3N8 vaccine was developed to control the spread of the disease but, as in humans and swine, it is anticipated that the virus will mutate shift and drift in the dog population. Therefore, there is a need for a vaccine that can trigger a broad protection to prevent the spread of the virus and the emergence of new strains. Methodology and Principal Findings The universal M2e peptide is identical in almost all the H3N8 influenza strains sequenced to date and known to infect dogs. This epitope is therefore a good choice for development of a vaccine to provide broad protection. Malva mosaic virus (MaMV) nanoparticles were chosen as a vaccine platform to improve the stability of the M2e peptide and increase its immunogenicity in animals. The addition of an adjuvant (OmpC) purified from Salmonella typhi membrane in the vaccine formulation increased the immune response directed to the M2e peptide significantly and enlarged the protection to include the heterosubtypic strain of influenza in a mouse model. An optimal vaccine formulation was also shown to be immunogenic in dogs. Conclusions and Significance The MaMV vaccine platform triggered an improved immune response directed towards the universal M2e peptide. The adjuvant OmpC increased the immune response to the M2e peptide and protection to a heterosubtypic influenza strain that harbors a different M2e peptide in a mouse model. Antibodies generated by the vaccine formulation showed cross-reactivity with M2e peptides derived from influenza strains H9N2, H5N1 and H1N1. The vaccine formulation shows a potential for commercialization of a new M2e based vaccine in dogs. PMID:24098576

  14. HPV vaccination syndrome. A questionnaire-based study.

    Science.gov (United States)

    Martínez-Lavín, Manuel; Martínez-Martínez, Laura-Aline; Reyes-Loyola, Paola

    2015-11-01

    Isolated cases and small series have described the development of complex regional pain syndrome, postural orthostatic tachycardia, and fibromyalgia after human papillomavirus (HPV) vaccination. These illnesses are difficult to diagnose and have overlapping clinical features. Small fiber neuropathy and dysautonomia may play a major role in the pathogenesis of these entities. We used the following validated questionnaires to appraise the chronic illness that might appear after HPV vaccination: The 2010 American College of Rheumatology Fibromyalgia Diagnostic Criteria, COMPASS 31 dysautonomia questionnaire, and S-LANSS neuropathic pain form. These questionnaires and a "present illness" survey were e-mailed to persons who had the onset of a chronic ailment soon after HPV vaccination. Forty-five filled questionnaires from individuals living in 13 different countries were collected in a month's period. Mean (±SD) age at vaccination time was 14 ± 5 years. Twenty-nine percent of the cases had immediate (within 24 h) post-vaccination illness onset. The most common presenting complaints were musculoskeletal pain (66%), fatigue (57%), headache (57%), dizziness/vertigo (43%), and paresthesias/allodynia (36%). Fifty-three percent of affected individuals fulfill the fibromyalgia criteria. COMPASS-31 score was 43 ± 21, implying advanced autonomic dysfunction. Eighty-three percent of the patients who had ongoing pain displayed S-LANSS values >12, suggesting a neuropathic component in their pain experience. After a mean period of 4.2 ± 2.5 years post-vaccination, 93% of patients continue to have incapacitating symptoms and remain unable to attend school or work. In conclusion, a disabling syndrome of chronic neuropathic pain, fatigue, and autonomic dysfunction may appear after HPV vaccination.

  15. Support vector machine based on chaos particle swarm optimization for fault diagnosis of rotating machine

    Institute of Scientific and Technical Information of China (English)

    TANG Xian-lun; ZHUANG Ling; QIU Guo-qing; CAI Jun

    2009-01-01

    The performance of the support vector machine models depends on a proper setting of its parameters to a great extent. A novel method of searching the optimal parameters of support vector machine based on chaos particle swarm optimization is proposed. A multi-fault classification model based on SVM optimized by chaos particle swarm optimization is established and applied to the fault diagnosis of rotating machines. The results show that the proposed fault classification model outperforms the neural network trained by chaos particle swarm optimization and least squares support vector machine, and the precision and reliability of the fault classification results can meet the requirement of practical application. It indicates that chaos particle swarm optimization is a suitable method for searching the optimal parameters of support vector machine.

  16. The electronic image stabilization technology research based on improved optical-flow motion vector estimation

    Science.gov (United States)

    Wang, Chao; Ji, Ming; Zhang, Ying; Jiang, Wentao; Lu, Xiaoyan; Wang, Jiaoying; Yang, Heng

    2016-01-01

    The electronic image stabilization technology based on improved optical-flow motion vector estimation technique can effectively improve the non normal shift, such as jitter, rotation and so on. Firstly, the ORB features are extracted from the image, a set of regions are built on these features; Secondly, the optical-flow vector is computed in the feature regions, in order to reduce the computational complexity, the multi resolution strategy of Pyramid is used to calculate the motion vector of the frame; Finally, qualitative and quantitative analysis of the effect of the algorithm is carried out. The results show that the proposed algorithm has better stability compared with image stabilization based on the traditional optical-flow motion vector estimation method.

  17. A sight on the current nanoparticle-based gene delivery vectors

    Science.gov (United States)

    Dizaj, Solmaz Maleki; Jafari, Samira; Khosroushahi, Ahmad Yari

    2014-05-01

    Nowadays, gene delivery for therapeutic objects is considered one of the most promising strategies to cure both the genetic and acquired diseases of human. The design of efficient gene delivery vectors possessing the high transfection efficiencies and low cytotoxicity is considered the major challenge for delivering a target gene to specific tissues or cells. On this base, the investigations on non-viral gene vectors with the ability to overcome physiological barriers are increasing. Among the non-viral vectors, nanoparticles showed remarkable properties regarding gene delivery such as the ability to target the specific tissue or cells, protect target gene against nuclease degradation, improve DNA stability, and increase the transformation efficiency or safety. This review attempts to represent a current nanoparticle based on its lipid, polymer, hybrid, and inorganic properties. Among them, hybrids, as efficient vectors, are utilized in gene delivery in terms of materials (synthetic or natural), design, and in vitro/ in vivo transformation efficiency.

  18. Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients.

    Science.gov (United States)

    Odunsi, Kunle; Matsuzaki, Junko; Karbach, Julia; Neumann, Antje; Mhawech-Fauceglia, Paulette; Miller, Austin; Beck, Amy; Morrison, Carl D; Ritter, Gerd; Godoy, Heidi; Lele, Shashikant; duPont, Nefertiti; Edwards, Robert; Shrikant, Protul; Old, Lloyd J; Gnjatic, Sacha; Jäger, Elke

    2012-04-10

    Recombinant poxviruses (vaccinia and fowlpox) expressing tumor-associated antigens are currently being evaluated in clinical trials as cancer vaccines to induce tumor-specific immune responses that will improve clinical outcome. To test whether a diversified prime and boost regimen targeting NY-ESO-1 will result in clinical benefit, we conducted two parallel phase II clinical trials of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations with recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in 25 melanoma and 22 epithelial ovarian cancer (EOC) patients with advanced disease who were at high risk for recurrence/progression. Integrated NY-ESO-1-specific antibody and CD4(+) and CD8(+) T cells were induced in a high proportion of melanoma and EOC patients. In melanoma patients, objective response rate [complete and partial response (CR+PR)] was 14%, mixed response was 5%, and disease stabilization was 52%, amounting to a clinical benefit rate (CBR) of 72% in melanoma patients. The median PFS in the melanoma patients was 9 mo (range, 0-84 mo) and the median OS was 48 mo (range, 3-106 mo). In EOC patients, the median PFS was 21 mo (95% CI, 16-29 mo), and median OS was 48 mo (CI, not estimable). CD8(+) T cells derived from vaccinated patients were shown to lyse NY-ESO-1-expressing tumor targets. These data provide preliminary evidence of clinically meaningful benefit for diversified prime and boost recombinant pox-viral-based vaccines in melanoma and ovarian cancer and support further evaluation of this approach in these patient populations.

  19. Immunogenicity of DNA and Recombinant Sendai Virus Vaccines Expressing the HIV-1 gag Gene

    Institute of Scientific and Technical Information of China (English)

    Xia FENG; Shuang-qing YU; Tsugumine Shu; Tetsuro Matano; Mamoru Hasegawa; Xiao-li WANG; Hong-tao MA; Hong-xia LI; Yi ZENG

    2008-01-01

    Combinations of DNA and recombinant-viral-vector based vaccines are promising AIDS vaccine methods because of their potential for inducing cellular immune responses. It was found that Gag-specific cytotoxic lymphocyte (CTL) responses were associated with lowering viremia in an untreated HIV-1 infected cohort. The main objectives of our studies were the construction of DNA and recombinant Sendal virus vector (rSeV) vaccines containing a gag gene from the prevalent Thailand subtype B strain in China and trying to use these vaccines for therapeutic and prophylactic vaccines. The candidate plasmid DNA vaccine pcDNA3.1(+)-gag and recombinant Sendai virus vaccine (rSeV-gag) were constructed separately. It was verified by Western blotting analysis that both DNA and rSeV-gag vaccines expressed the HIV-1 Gag protein correctly and efficiently. Balb/c mice were immunized with these two vaccines in different administration schemes. HIV-1 Gag-specific CTL responses and antibody levels were detected by intracellular cytokine staining assay and enzyme-linked immunosorbant assay (ELISA) respectively. Combined vaccines in a DNA prime/rSeV-gag boost vaccination regimen induced the strongest and most long-lasting Gag-specific CTL and antibody responses. It maintained relatively high levels even 9 weeks post immunization. This data indicated that the prime-boost regimen with DNA and rSeV-gag vaccines may offer promising HIV vaccine regimens.

  20. Gene-based vaccine development for improving animal production in developing countries

    International Nuclear Information System (INIS)

    Full text: The cloning and expression of microbial genes in alternate hosts to enhance production of antigens for animal vaccines against all disease is theoretically achievable. It is essential, however, that antigens expressed in this way are known to be protective. Many years of costly research usually precedes the identification of such antigens or combinations of antigens. Thus, while conventional vaccines based on living, attenuated or inactivated microorganisms may be effective, the protective components contained in them i.e. the candidates for cloning, have yet to be found. The principal protective antigen in vaccines against foot rot of sheep and goats is fimbrial protein of Dichelobacter nodosus. Recombinant vaccines against this infection are ineffective if the protein subunits are not assembled and presented to the host in a manner morphologically indistinguishable from those of the natural fimbriae. Availability of recombinant antigen does not necessarily avoid the need for the use of adjuvants to potentiate response. Oil emulsion vaccines, while enhancing immune response, almost inevitably cause a marked reaction at the site of injection. Livestock owners in developing countries are as likely as those elsewhere to object to these reactions. The need to find an acceptable and effective formulation adds to the cost of recombinant vaccines and their application in countries with limited resources for disease control. Another costly feature of recombinant vaccines has been the patenting of processes involving gene technology and licencing agreements for production under the protection of these patents. In some systems antigenic competition between similar and disparate antigens limits the usefulness of even recombinant antigens that, administered individually, are highly potent. In the case of programs for the control and eventual eradication of footrot in sheep and goats in Nepal this problem was overcome by the prior identification of causal serotypes

  1. Classification of a set of vectors using self-organizing map- and rule-based technique

    Science.gov (United States)

    Ae, Tadashi; Okaniwa, Kaishirou; Nosaka, Kenzaburou

    2005-02-01

    There exist various objects, such as pictures, music, texts, etc., around our environment. We have a view for these objects by looking, reading or listening. Our view is concerned with our behaviors deeply, and is very important to understand our behaviors. We have a view for an object, and decide the next action (data selection, etc.) with our view. Such a series of actions constructs a sequence. Therefore, we propose a method which acquires a view as a vector from several words for a view, and apply the vector to sequence generation. We focus on sequences of the data of which a user selects from a multimedia database containing pictures, music, movie, etc... These data cannot be stereotyped because user's view for them changes by each user. Therefore, we represent the structure of the multimedia database as the vector representing user's view and the stereotyped vector, and acquire sequences containing the structure as elements. Such a vector can be classified by SOM (Self-Organizing Map). Hidden Markov Model (HMM) is a method to generate sequences. Therefore, we use HMM of which a state corresponds to the representative vector of user's view, and acquire sequences containing the change of user's view. We call it Vector-state Markov Model (VMM). We introduce the rough set theory as a rule-base technique, which plays a role of classifying the sets of data such as the sets of "Tour".

  2. Progress and challenges in the vaccine-based treatment of head and neck cancers

    Directory of Open Access Journals (Sweden)

    Venuti Aldo

    2009-05-01

    Full Text Available Abstract Head and neck (HN cancer represents one of the most challenging diseases because the mortality remains high despite advances in early diagnosis and treatment. Although vaccine-based approaches for the treatment of advanced squamous cell carcinoma of the head and neck have achieved limited clinical success, advances in cancer immunology provide a strong foundation and powerful new tools to guide current attempts to develop effective cancer vaccines. This article reviews what has to be rather what has been done in the field for the development of future vaccines in HN tumours.

  3. Designing Peptide-Based HIV Vaccine for Chinese

    Directory of Open Access Journals (Sweden)

    Jiayi Shu

    2014-01-01

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

  4. Safety and tolerability of conserved region vaccines vectored by plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind phase I trial.

    Directory of Open Access Journals (Sweden)

    Emma-Jo Hayton

    Full Text Available TRIAL DESIGN: HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported. METHODS: Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination. RESULTS: Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1 and predominantly transient (<48 hours. Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range of 633 (231-1533 post-vaccination, which is of no safety concern. CONCLUSIONS: These data demonstrate

  5. Adenovirus vaccine vectors expressing hepatitis B surface antigen: importance of regulatory elements in the adenovirus major late intron.

    Science.gov (United States)

    Mason, B B; Davis, A R; Bhat, B M; Chengalvala, M; Lubeck, M D; Zandle, G; Kostek, B; Cholodofsky, S; Dheer, S; Molnar-Kimber, K

    1990-08-01

    Adenovirus types 4 and 7 are currently used as live oral vaccines for prevention of acute respiratory disease caused by these adenovirus serotypes. To investigate the concept of producing live recombinant vaccines using these serotypes, adenovirus types 4 (Ad4) and 7 (Ad7) were constructed that produce HBsAg upon infection of cell cultures. Ad4 recombinants were constructed that express HBsAg from a cassette inserted 135 bp from the right-hand terminus of the viral genome. The cassette contained the Ad4 major late promoter followed by leader 1 of the tripartite leader, the first intervening sequence between leaders 1 and 2, leaders 2 and 3, the HBsAg gene, and tandem polyadenylation signals from the Ad4 E3B and hexon genes. Using this same cassette, a series of Ad4 recombinants expressing HBsAg were constructed with deletions in the intervening sequence between leaders 1 and 2 to evaluate the contribution of the downstream control elements more precisely. Inclusion of regions located between +82 and +148 as well as +148 and +232 resulted in increases in expression levels of HBsAg in A549-infected cells by 22-fold and 44-fold, respectively, over the levels attained by an adenovirus recombinant retaining only sequences from +1 to +82, showing the importance of these elements in the activation of the major late promoter during the course of a natural Ad4 viral infection. Parallel increases were also observed in steady-state levels of cytoplasmic HBsAg-specific mRNA. When similar Ad7 recombinant viruses were constructed, these viruses also expressed 20-fold more HBsAg due to the presence of the intron. All Ad4 and Ad7 recombinants produced HBsAg particles containing gp27 and p24 which were secreted in the medium. When dogs were immunized intratracheally with one of these Ad7 recombinants, they seroconverted to both Ad7 and HBsAg to a high level. PMID:2371766

  6. Two initial vaccinations with the Bm86-based Gavacplus vaccine against Rhipicephalus (Boophilus microplus induce similar reproductive suppression to three initial vaccinations under production conditions

    Directory of Open Access Journals (Sweden)

    Fernández Erlinda

    2010-09-01

    Full Text Available Abstract Background The cattle tick, Rhipicephalus (Boophilus microplus, affects livestock production in many regions of the world. Up to now, the widespread use of chemical acaricides has led to the selection of acaricide-resistant ticks and to environmental contamination. Gavacplus is a subunit vaccine based on the recombinant Bm86 tick antigen expressed in yeast, capable to control infestations of R. microplus under controlled and production conditions. The vaccine constitutes the core element of broad control programs against this ectoparasite, in which acquired immunity in cattle to Bm86 is combined with a rational use of acaricides. At present, the conventional vaccine scheme consists of three doses that should be administered at weeks 0, 4 and 7, followed by a booster every six months. Results In this study we assayed a reduction in the number of the initial doses of Gavacplus, evaluated the time course and the level of bovine anti-Bm86 antibodies elicited, and analyzed the vaccine effect on ticks engorging on immunized cattle under production conditions. Following three different immunization schemes, the bovines developed a strong and specific immune response characterized by elevated anti-Bm86 IgG titers. A reduction in the weight of engorging female ticks, in the weight of the eggs laid and also in R. microplus viable eggs percentage was obtained by using only two doses of Gavacplus administered at weeks 0 and 4, followed by a booster six months later. This reduction did not differ from the results obtained on ticks engorging on cattle immunized at weeks 0, 4 and 7. It was also demonstrated that anti-Bm86 antibody titers over 1:640, measured in bovines immunized at weeks 0 and 4, were sufficient to affect weight and reproductive potential of female ticks as compared with ticks engorging on unvaccinated animals. In addition, no statistically significant differences were detected in the average weight of eggs laid by ticks engorged on

  7. Future directions for the development of Chlamydomonas-based vaccines.

    Science.gov (United States)

    Rosales-Mendoza, Sergio

    2013-09-01

    Besides serving as a valuable model in biological sciences, Chamydomonas reinhardtii has been used during the last decade in the biotechnology arena to establish models for the low cost production of vaccines. Antigens from various pathogens including Plasmodium falciparum, foot and mouth disease virus, Staphylococcus aureus, classical swine fever virus (CSFV) as well as some auto-antigens, have been produced in C. reinhardtii. Although some of them have been functionally characterized with promising results, this review identifies future directions for the advancement in the exploitation of this robust and safe vaccine production platform. The present analysis reflects that important immunological implications exist for this system and remain unexplored, including the possible adjuvant effects of algae biomolecules, the effect of bioencapsulation on immunogenicity and the possible development of whole-cell vaccines as an approach to trigger cytotoxic immune responses. Recently described molecular strategies that aim to optimize the expression of nuclear-encoded target antigens are also discussed. PMID:24053395

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

    Directory of Open Access Journals (Sweden)

    Seybolt LM

    2012-06-01

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

  9. Provider dismissal policies and clustering of vaccine-hesitant families: an agent-based modeling approach.

    Science.gov (United States)

    Buttenheim, Alison M; Cherng, Sarah T; Asch, David A

    2013-08-01

    Many pediatric practices have adopted vaccine policies that require parents who refuse to vaccinate according to the ACIP schedule to find another health care provider. Such policies may inadvertently cluster unvaccinated patients into practices that tolerate non vaccination or alternative schedules, turning them into risky pockets of low herd immunity. The objective of this study was to assess the effect of provider zero-tolerance vaccination policies on the clustering of intentionally unvaccinated children. We developed an agent-based model of parental vaccine hesitancy, provider non-vaccination tolerance, and selection of patients into pediatric practices. We ran 84 experiments across a range of parental hesitancy and provider tolerance scenarios. When the model is initialized, all providers accommodate refusals and intentionally unvaccinated children are evenly distributed across providers. As provider tolerance decreases, hesitant children become more clustered in a smaller number of practices and eventually are not able to find a practice that will accept them. Each of these effects becomes more pronounced as the level of hesitancy in the population rises. Heterogeneity in practice tolerance to vaccine-hesitant parents has the unintended result of concentrating susceptible individuals within a small number of tolerant practices, while providing little if any compensatory protection to adherent individuals. These externalities suggest an agenda for stricter policy regulation of individual practice decisions.

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

    Science.gov (United States)

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

    2016-08-01

    Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families. PMID:27405928

  11. The case for a rational genome-based vaccine against malaria

    Directory of Open Access Journals (Sweden)

    Carla eProietti

    2015-01-01

    Full Text Available Historically, vaccines have been designed to mimic the immunity induced by natural exposure to the target pathogen, but this approach has not been effective for any parasitic pathogens of humans or complex pathogens that cause chronic disease in humans, such as Plasmodium. Despite intense efforts by many laboratories around the world on different aspects of Plasmodium spp. molecular and cell biology, epidemiology and immunology, progress towards the goal of an effective malaria vaccine has been disappointing. The premise of rational vaccine design is to induce the desired immune response against the key pathogen antigens or epitopes targeted by protective immune responses. We advocate that development of an optimally efficacious malaria vaccine will need to improve on nature, and that this can be accomplished by rational vaccine design facilitated by mining genomic, proteomic and transcriptomic datasets in the context of relevant biological function. In our opinion, modern genome-based rational vaccine design offers enormous potential above and beyond that of whole-organism vaccines approaches established over 200 years ago where immunity is likely suboptimal due to the many genetic and immunological host-parasite adaptations evolved to allow the Plasmodium parasite to coexist in the human host, and which are associated with logistic and regulatory hurdles for production and delivery.

  12. Vaccination with an adenoviral vector encoding the tumor antigen directly linked to invariant chain induces potent CD4(+) T-cell-independent CD8(+) T-cell-mediated tumor control

    DEFF Research Database (Denmark)

    Sorensen, Maria R; Holst, Peter J; Pircher, Hanspeter;

    2009-01-01

    of the vaccine antigen to invariant chain (Ii). To evaluate this strategy we used a mouse model, in which an immunodominant epitope (GP33) of the LCMV glycoprotein (GP) represents the tumor-associated neoantigen. Prophylactic vaccination of C57BL/6 mice with a replication-deficient human adenovirus 5 vector...... vaccination with adenovirus expressing GP alone (Ad-GP), or GP and Ii unlinked (Ad-GP+Ii). Ad-Ii-GP- induced tumor control depended on an improved generation of the tumor-associated neoantigen-specific CD8(+) T-cell response and was independent of CD4(+) T cells. IFN-gamma was shown to be a key player during...

  13. Direct power control of DFIG based on discrete space vector modulation

    Energy Technology Data Exchange (ETDEWEB)

    Verij Kazemi, Mohammad; Sadeghi Yazdankhah, Ahmad; Madadi Kojabadi, Hossein [Electrical Engineering Department, Sahand University of Technology, Tabriz (Iran)

    2010-05-15

    This paper presents a new direct power control (DPC) strategy for a double fed induction generator (DFIG) based wind energy generation system. Switching vectors for rotor side converter were selected from the optimal switching table using the estimated stator flux position and the errors of the active and reactive power. A few number of voltage vectors may cause undesired power and stator current ripple. In this paper the increased number of voltage vectors with application of the Discrete Space Vector Modulation (DSVM) will be presented. Then a new switching table in supersynchronous and subsynchronous frames will be proposed. Simulation results of a 2 MW DFIG system demonstrate the effectiveness and robustness of the proposed control strategy during variations of active and reactive power, machine parameters, and wind speed. (author)

  14. A versatile bacterial expression vector based on the synthetic biology plasmid pSB1.

    Science.gov (United States)

    Skrlj, Nives; Erculj, Nina; Dolinar, Marko

    2009-04-01

    We have developed an Escherichia coli expression vector that is particularly useful for construction and production of fusion proteins. Based on the synthetic biology pSB1C3 platform, the resulting vector offers a combination of useful features: the strong T7 promoter combined with lac operator, OmpA signal sequence, a selection of cloning sites located at convenient positions and a 3'-terminal His-10 tag. Each of these regions is flanked by a restriction site that allows for easy vector modification, including removal of the signal sequence without perturbation of the reading frame. All the elements were assembled by stepwise addition of three cassettes for which the design was made de novo. To prove the efficiency of the new vector, named pMD204, we successfully produced a cysteine proteinase inhibitor variant in the periplasm and in the cytoplasm of E. coli, in both cases as a soluble and active protein. PMID:19027858

  15. Characterization of the immune response induced by pertussis OMVs-based vaccine.

    Science.gov (United States)

    Bottero, D; Gaillard, M E; Zurita, E; Moreno, G; Martinez, D Sabater; Bartel, E; Bravo, S; Carriquiriborde, F; Errea, A; Castuma, C; Rumbo, M; Hozbor, D

    2016-06-14

    For the development of a third generation of pertussis vaccine that could improve the control of the disease, it was proposed that the immune responses induced by the classic whole cell vaccine (wP) or after infection should be used as a reference point. We have recently identified a vaccine candidate based on outer membrane vesicles (OMVs) derived from the disease etiologic agent that have been shown to be safe and protective in mice model of infection. Here we characterized OMVs-mediated immunity and the safety of our new candidate. We also deepen the knowledge of the induced humoral response contribution in pertussis protection. Regarding the safety of the OMVs based vaccine (TdapOMVsBp,) the in vitro whole blood human assay here performed, showed that the low toxicity of OMVs-based vaccine previously detected in mice could be extended to human samples. Stimulation of splenocytes from immunized mice evidenced the presence of IFN-γ and IL-17-producing cells, indicated that OMVs induces both Th1 and Th17 response. Interestingly TdapOMVsBp-raised antibodies such as those induced by wP and commercial acellular vaccines (aP) which contribute to induce protection against Bordetella pertussis infection. As occurs with wP-induced antibodies, the TdapOMVsBp-induced serum antibodies efficiently opsonized B. pertussis. All the data here obtained shows that OMVs based vaccine is able to induce Th1/Th17 and Th2 mixed profile with robust humoral response involved in protection, positioning this candidate among the different possibilities to constitute the third generation of anti-pertussis vaccines.

  16. A replication competent lentivirus (RCL) assay for equine infectious anaemia virus (EIAV)-based lentiviral vectors.

    Science.gov (United States)

    Miskin, J; Chipchase, D; Rohll, J; Beard, G; Wardell, T; Angell, D; Roehl, H; Jolly, D; Kingsman, S; Mitrophanous, K

    2006-02-01

    Lentiviral vectors are being developed to satisfy a wide range of currently unmet medical needs. Vectors destined for clinical evaluation have been rendered multiply defective by deletion of all viral coding sequences and nonessential cis-acting sequences from the transfer genome. The viral envelope and accessory proteins are excluded from the production system. The vectors are produced from separate expression plasmids that are designed to minimize the potential for homologous recombination. These features ensure that the regeneration of the starting virus is impossible. It is a regulatory requirement to confirm the absence of any replication competent virus, so we describe here the development and validation of a replication competent lentivirus (RCL) assay for equine infectious anaemia virus (EIAV)-based vectors. The assay is based on the guidelines developed for testing retroviral vectors, and uses the F-PERT (fluorescent-product enhanced reverse transcriptase) assay to test for the presence of a transmissible reverse transcriptase. We have empirically modelled the replication kinetics of an EIAV-like entity in human cells and devised an amplification protocol by comparison with a replication competent MLV. The RCL assay has been validated at the 20 litre manufacturing scale, during which no RCL was detected. The assay is theoretically applicable to any lentiviral vector and pseudotype combination. PMID:16208418

  17. Vector perturbation based adaptive distributed precoding scheme with limited feedback for CoMP systems

    Directory of Open Access Journals (Sweden)

    Cuthbert Laurie

    2011-01-01

    Full Text Available Abstract A downlink adaptive distributed precoding scheme is proposed for coordinated multi-point (CoMP transmission systems. The serving base station (BS obtains the optimal precoding vector via user feedback. Meanwhile, the precoding vector of each coordinated BS is determined by adaptive gradient iteration according to the perturbation vector and the adjustment factor based on the vector perturbation method. In each transmission frame, the CoMP user feeds the precoding matrix index back to the serving BS, and feeds back the adjustment factor index to the coordinated BSs, which can reduce the uplink feedback overhead. The selected adjustment factor for each coordinated BS is obtained via the precoding vector of the coordinated BS used in the previous frame and the preferred precoding vector of the serving BS in this frame. The proposed scheme takes advantage of the spatial non-correlation and temporal correlation of the distributed MIMO channel. The design of the adjustment factor set is given and the channel feedback delay is considered. The system performance of the proposed scheme is verified with and without feedback delay respectively and the system feedback overhead is analyzed. Simulation results show that the proposed scheme has a good trade-off between system performance and the system control information overhead on feedback.

  18. Space vector-based analysis of overmodulation in triangle-comparison based PWM for voltage source inverter

    Indian Academy of Sciences (India)

    Manoj Kumar Modi; S Venugopal; G Narayanan

    2013-06-01

    The equivalence of triangle-comparison-based pulse width modulation (TCPWM) and space vector based PWM (SVPWM) during linear modulation is well-known. This paper analyses triangle-comparison based PWM techniques (TCPWM) such as sine-triangle PWM (SPWM) and common-mode voltage injection PWM during overmodulation from a space vector point of view. The average voltage vector produced by TCPWM during overmodulation is studied in the stationary (a–b) reference frame. This is compared and contrasted with the average voltage vector corresponding to the well-known standard two-zone algorithm for space vector modulated inverters. It is shown that the two-zone overmodulation algorithm itself can be derived from the variation of average voltage vector with TCPWM. The average voltage vector is further studied in a synchronously revolving (d-q) reference frame. The RMS value of low-order voltage ripple can be estimated, and can be used to compare harmonic distortion due to different PWM methods during overmodulation. The measured values of the total harmonic distortion (THD) in the line currents are presented at various fundamental frequencies. The relative values of measured current THD pertaining to different PWM methods tally with those of analytically evaluated RMS voltage ripple.

  19. Cloning and stable maintenance of DNA fragments over 300 kb in Escherichia coli with conventional plasmid-based vectors.

    OpenAIRE

    Tao, Q.; Zhang, H. B.

    1998-01-01

    Bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) systems were previously developed for cloning of very large eukaryotic DNA fragments in bacteria. We report the feasibility of cloning very large fragments of eukaryotic DNA in bacteria using conventional plasmid-based vectors. One conventional plasmid vector (pGEM11), one conventional binary plasmid vector (pSLJ1711) and one conventional binary cosmid vector (pCLD04541) were investigated using the widely used BA...

  20. Opportunities for Improved Chagas Disease Vector Control Based on Knowledge, Attitudes and Practices of Communities in the Yucatan Peninsula, Mexico

    OpenAIRE

    Kathryn Rosecrans; Gabriela Cruz-Martin; Ashley King; Eric Dumonteil

    2014-01-01

    BACKGROUND: Chagas disease is a vector-borne parasitic disease of major public health importance. Current prevention efforts are based on triatomine vector control to reduce transmission to humans. Success of vector control interventions depends on their acceptability and value to affected communities. We aimed to identify opportunities for and barriers to improved vector control strategies in the Yucatan peninsula, Mexico. METHODOLOGY/PRINCIPAL FINDINGS: We employed a sequence of qualitative...

  1. DNA vaccine: the miniature miracle

    Directory of Open Access Journals (Sweden)

    Karthik Kaliaperumal

    2013-08-01

    Full Text Available DNA, the essential part of the life is making way in to new vaccine technology. Plasmid vectors from the bacteria have revolutionized the world of vaccine design by its new technology – DNA vaccines. Small portion of the nucleotides from the pathogen held under the control of promoter in a plasmid vector can be used as a vaccine. DNA vaccines alleviate the odds of the other vaccines by having good hold on both the faces of the immunity. The key to the success of DNA vaccine lies in the route of administration of the vaccine which can be done in many ways. Prime boost strategy is an approach used to boost the action of DNA vaccine. To date there are only four DNA vaccine available in the market. [Vet World 2013; 6(4.000: 228-232

  2. Research of universal influenza virus vaccine conjugated human papillomavirus 16 LI as a vector%以人乳头瘤病毒16 L1为载体的流感通用疫苗初步研究

    Institute of Scientific and Technical Information of China (English)

    刘蕊; 李志奎; 王希良; 罗德炎; 颜艳; 陈中伟; 花艳红

    2008-01-01

    Objective To construct a universal influenza virus vaccine Baemid containing M2 extracellular domain(M2e) of influenza virus which conjugated human papillomavirus(HPV)16 L1 as a vector and expressed the protein in insect baeulovirus system. Methods HPV16 L1 gene was amplified by PCR with the primers contained M2e gene. The conjugated genes were inserted into pFast HTA vector to recombine in DHI0Bac. The recombinant baemid was transfected into sf9 insect cells by liposome to produce baculovirus contained M2e-HPVI6 L1. Protein was determined by SDS-PAGE, immunofluorescence and electronmicroseope. Results The universal influenza virus vaccine Bacmid containing M2e of influenza virus which conjugated HPV16 L1 as a vector was successfully constructed. The recombinant protein wasexpressed in insect cells. Conclusions The recombinant protein was expressed in insect cells in the form of virus-like particles through the baculovirus system,which was a base of the universal influenza virus vaccine development.%目的 构建以人乳头瘤病毒(human papillomavirus,HPV)16 L1为载体的甲型流感病毒M2基因胞外区(M2e)通用疫苗杆粒,利用昆虫细胞杆状病毒表达系统,进行初步的蛋白表达.方法 利用PCR技术将甲型流感病毒M2e基因序列与HPVl6 L1相连.经酶切、酶联将融合基因插入pFastBacHTA载体,在DH10Bac细胞中进行同源重组,经测序鉴定后构建M2e-HPV16 L1杆粒,脂质体转染sf9昆虫细胞,收获并扩增含有M2e-HPV16 L1的杆状病毒,经扩增后获得高效价的重组杆状病毒,用SDS-PAGE、免疫荧光法和电镜检测目的蛋白的表达.结果 构建了以HPV16 L1为载体的M2e通用疫苗杆粒,通过转染sf9昆虫细胞得到初步M2e-HPV16 L1融合蛋白表达.结论 成功构建了HPV16 L1与甲型流感病毒M2e融合蛋白的病毒样颗粒,为流感通用疫苗的研制奠定了基础.

  3. Feasibilty of oral immunisation with LTB-based edible vaccines

    NARCIS (Netherlands)

    Lauterslager, Tosca Genevieve Maria

    2003-01-01

    This thesis describes the research to explore the feasibility of plants for oral vaccination. The research focussed on a model of LTB produced in potato tubers or ovalbumin (OVA) as antigen and tested in mice. A general introduction into the backgrounds of oral immunisation is given in Chapter 1. Th

  4. Recent advances in recombinant protein-based malaria vaccines

    DEFF Research Database (Denmark)

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

    2015-01-01

    Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito...

  5. Fc-based delivery system enhances immunogenicity of a tuberculosis subunit vaccine candidate consisting of the ESAT-6:CFP-10 complex.

    Science.gov (United States)

    Farsiani, Hadi; Mosavat, Arman; Soleimanpour, Saman; Sadeghian, Hamid; Akbari Eydgahi, Mohammad Reza; Ghazvini, Kiarash; Sankian, Mojtaba; Aryan, Ehsan; Jamehdar, Saeid Amel; Rezaee, Seyed Abdolrahim

    2016-06-21

    Tuberculosis (TB) remains a major global health threat despite chemotherapy and Bacilli Calmette-Guérin (BCG) vaccination. Therefore, a safer and more effective vaccine against TB is urgently needed. This study evaluated the immunogenicity of a recombinant fusion protein consisting of early secreted antigenic target protein 6 kDa (ESAT-6), culture filtrate protein 10 kDa (CFP-10) and the Fc-domain of mouse IgG2a as a novel subunit vaccine. The recombinant expression vectors (pPICZαA-ESAT-6:CFP-10:Fcγ2a and pPICZαA-ESAT-6:CFP-10:His) were transferred into Pichia pastoris. After SDS-PAGE and immunoblotting, the immunogenicity of the recombinant proteins was evaluated in mice. When both recombinant proteins (ESAT-6:CFP-10:Fcγ2a and ESAT-6:CFP-10:His) were used for vaccination, Th1-type cellular responses were induced producing high levels of IFN-γ and IL-12. However, the Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a small increase in IL-4 as compared to the BCG and ESAT-6:CFP-10:His groups. Moreover, mice primed with BCG and then supplemented with ESAT-6:CFP-10:Fcγ2a produced the highest levels of IFN-γ and IL-12 in immunized groups. The findings indicate that when Fcγ2a is fused to the ESAT-6:CFP-10 complex, as a delivery vehicle, there could be an increase in the immunogenicity of this type of subunit vaccine. Therefore, additional investigations are necessary for the development of appropriate Fc-based tuberculosis vaccines. PMID:27138226

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

    Directory of Open Access Journals (Sweden)

    Shu Ki Tsoi

    2015-01-01

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

  7. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines

    Science.gov (United States)

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela

    2016-01-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  8. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines.

    Science.gov (United States)

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela; Van Der Wielen, Marie

    2016-07-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  9. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines.

    Science.gov (United States)

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela; Van Der Wielen, Marie

    2016-07-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  10. The generation of arbitrary vector beams using a division of a wavefront-based setup

    Science.gov (United States)

    Kalita, Ranjan; Gaffar, Md; Boruah, Bosanta R.

    2016-07-01

    In this paper, we introduce an arbitrary vector-beam-forming scheme using a simple arrangement involving only one liquid crystal spatial light modulator. An arbitrary vector beam can be obtained by overlapping two orthogonally polarized beams. In most of the existing vector-beam-forming schemes the two orthogonally polarized beams are essentially copies of a single incident wavefront. However, in the proposed scheme the two orthogonally polarized beams correspond to two separated parts of a single incident wavefront. Taking a cue from the two-beam interference phenomenon, the present scheme can be referred to as a division of a wavefront-based scheme. The proposed setup offers certain important advantages and is more suitable for the generation of higher average-power vector beams. We demonstrate the working of the vector-beam-forming scheme by generating various vector beams such as radially polarized, azimuthally polarized, and Bessel-Gauss beams and also a boat-shaped beam in the focal volume of a low-numerical-aperture focusing lens. The boat-shaped beam comprises a dark center surrounded by intense light from all but one direction. The beam is realized at the focus of an azimuthally polarized beam in the presence of a moderate amount of coma in the beam. The experimental results obtained using the proposed setup are verified by comparing them with the theoretical results.

  11. Small-time scale network traffic prediction based on a local support vector machine regression model

    Institute of Scientific and Technical Information of China (English)

    Meng Qing-Fang; Chen Yue-Hui; Peng Yu-Hua

    2009-01-01

    In this paper we apply the nonlinear time series analysis method to small-time scale traffic measurement data. The prediction-based method is used to determine the embedding dimension of the traffic data. Based on the reconstructed phase space, the local support vector machine prediction method is used to predict the traffic measurement data, and the BIC-based neighbouring point selection method is used to choose the number of the nearest neighbouring points for the local support vector machine regression model. The experimental results show that the local support vector machine prediction method whose neighbouring points are optimized can effectively predict the small-time scale traffic measurement data and can reproduce the statistical features of real traffic measurements.

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

    Science.gov (United States)

    Banik, Sukalyani; Mansour, Ahd Ahmed; Suresh, Ragavan Varadharajan; Wykoff-Clary, Sherri; Malik, Meenakshi; McCormick, Alison A; Bakshi, Chandra Shekhar

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sukalyani Banik

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

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

    Directory of Open Access Journals (Sweden)

    Signe Tandrup Schmidt

    2016-03-01

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

  15. Acceptability and uptake of HPV vaccine in Argentina before its inclusion in the immunization program: a population-based survey.

    Science.gov (United States)

    Arrossi, Silvina; Maceira, Veronica; Paolino, Melisa; Sankaranarayanan, Rengaswamy

    2012-03-23

    In Argentina, human papillomavirus (HPV) vaccination was approved in 2006, but not included in the National Immunization Program. In 2008 a mass media campaign was carried out by a cancer Non-Governmental Organization (NGO), but it was stopped due to criticisms about the publicity. In October 2011 the Ministry of Health (MoH) has introduced HPV vaccination in the National Immunization Program. In this context, to assure high HPV vaccine coverage, evidence is needed on factors both associated to vaccine acceptability and uptake. In 2009-2010 we carried out a population-based survey among a representative sample of 1200 women aged 18-49 years from the Metropolitan Area of Buenos Aires. The objective was twofold: first to analyze socio-demographic determinants of women's knowledge on HPV vaccine and secondly, determinants of actual HPV vaccine uptake and acceptability in Argentina after the above-mentioned vaccine advertising shown in mass media in the year 2008. We analyzed vaccine uptake/acceptability separately for women and for their daughters aged 9-15, and willingness to vaccinate one's daughter younger than 9 to receive future HPV vaccination. Results of the 1200 women interviewed, 438 women (36.5%) knew the HPV vaccine and 303 (25%) remembered the mass media advertisement about HPV vaccination. When asked whether she would get vaccinated after having seen/heard the advertisement, around 75% (n=226) of women answered surely/probably yes. No significant differences in socio-demographic characteristics were found among women who would or not get vaccinated. When surveyed, 6 women had been vaccinated. Main reasons for non-vaccination were: "Doctor did not mention/recommend it" (34.1%) and "Vaccine is too expensive" (15.7%). No woman had had their 9-15 year-old daughter vaccinated. Among women who only had at least one daughter under 9 (n=278), 74% answered that they would get their daughter vaccinated if they were pre-adolescents. The conclusion is that, in

  16. A Novel CSR-Based Sparse Matrix-Vector Multiplication on GPUs

    OpenAIRE

    Guixia He; Jiaquan Gao

    2016-01-01

    Sparse matrix-vector multiplication (SpMV) is an important operation in scientific computations. Compressed sparse row (CSR) is the most frequently used format to store sparse matrices. However, CSR-based SpMVs on graphic processing units (GPUs), for example, CSR-scalar and CSR-vector, usually have poor performance due to irregular memory access patterns. This motivates us to propose a perfect CSR-based SpMV on the GPU that is called PCSR. PCSR involves two kernels and accesses CSR arrays in ...

  17. Development of a Simulink/RTW-Based Realtime Control System for an Induction Motor Vector Control

    Energy Technology Data Exchange (ETDEWEB)

    Kang, M. H. [Sunmoon University, Chonan (Korea)

    2001-03-01

    In this research a Simulink/RTW-based realtime control system was developed for an induction motor vector control. On the Simulink window, the control system is designed in the form of block diagrams, program codes are produced automatically with the RTW(Real Time Workshop), then an DSP c compiles the program codes. With this automatic program producing method rapid prototyping is realized with the least time-consuming manual programming procedures. To show effectiveness of the proposed system designing scheme a DSP-based induction motor vector controller was constructed and implemented. (author). 10 refs., 15 figs., 2 tabs.

  18. Gear Fault Diagnosis Based on Rough Set and Support Vector Machine

    Institute of Scientific and Technical Information of China (English)

    TIAN Huifang; SUN Shanxia

    2006-01-01

    By introducing Rough Set Theory and the principle of Support vector machine, a gear fault diagnosis method based on them is proposed. Firstly, diagnostic decision-making is reduced based on rough set theory, and the noise and redundancy in the sample are removed, then, according to the chosen reduction, a support vector machine multi-classifier is designed for gear fault diagnosis. Therefore, SVM' training data can be reduced and running speed can quicken. Test shows its accuracy and efficiency of gear fault diagnosis.

  19. Model based wind vector field reconstruction from lidar data

    OpenAIRE

    Schlipf, David; Rettenmeier, Andreas; Haizmann, Florian; Hofsäß, Martin; Courtney, Mike; Cheng, Po Wen

    2012-01-01

    In recent years lidar technology found its way into wind energy for resource assessment and control. For both fields of application it is crucial to reconstruct the wind field from the limited information provided by a lidar system. For lidar assisted wind turbine control model based wind field reconstruction is used to obtain signals from wind characteristics such as wind speed, direction and shears in a high temporal resolution. This work shows how these methods can be used for lidar based ...

  20. Quadrivalent HPV vaccine effectiveness against high-grade cervical lesions by age at vaccination: A population-based study.

    Science.gov (United States)

    Herweijer, Eva; Sundström, Karin; Ploner, Alexander; Uhnoo, Ingrid; Sparén, Pär; Arnheim-Dahlström, Lisen

    2016-06-15

    Human papillomavirus (HPV) types 16/18, included in HPV vaccines, contribute to the majority of cervical cancer, and a substantial proportion of cervical intraepithelial neoplasia (CIN) grades 2/3 or worse (CIN2+/CIN3+) including adenocarcinoma in situ or worse. The aim of this study was to quantify the effect of quadrivalent HPV (qHPV) vaccination on incidence of CIN2+ and CIN3+. A nationwide cohort of girls and young women resident in Sweden 2006-2013 and aged 13-29 (n = 1,333,691) was followed for vaccination and histologically confirmed high-grade cervical lesions. Data were collected using the Swedish nationwide healthcare registers. Poisson regression was used to calculate incidence rate ratios (IRRs) and vaccine effectiveness [(1-IRR)x100%] comparing fully vaccinated with unvaccinated individuals. IRRs were adjusted for attained age and parental education, and stratified on vaccination initiation age. Effectiveness against CIN2+ was 75% (IRR = 0.25, 95%CI = 0.18-0.35) for those initiating vaccination before age 17, and 46% (IRR = 0.54, 95%CI = 0.46-0.64) and 22% (IRR = 0.78, 95%CI = 0.65-0.93) for those initiating vaccination at ages 17-19, and at ages 20-29, respectively. Vaccine effectiveness against CIN3+ was similar to vaccine effectiveness against CIN2+. Results were robust for both women participating to the organized screening program and for women at prescreening ages. We show high effectiveness of qHPV vaccination on CIN2+ and CIN3+ lesions, with greater effectiveness observed in girls younger at vaccination initiation. Continued monitoring of impact of HPV vaccination in the population is needed in order to evaluate both long-term vaccine effectiveness and to evaluate whether the vaccination program achieves anticipated effects in prevention of invasive cervical cancer.

  1. Hybrid Asymmetric Space Vector Modulation for inverter based direct torque control induction motor drive

    Directory of Open Access Journals (Sweden)

    Nandakumar Sundararaju

    2014-05-01

    Full Text Available This paper proposes novel hybrid asymmetric space vector modulation technique for inverter operated direct torque control induction motor drive. The hybridization process is performed by the combination of continuous asymmetric space vector modulation pulse width technique (ASVPWM and fuzzy operated discontinuous ASVPWM technique. Combination process is based on pulse mismatching technique. Pulse mismatching technique helps to reduce the active region of the switch. Finally, optimal pulses are applied to control the inverter. The optimal hybrid pulse condense switching losses of the inverter and also improves the operating performance of the direct torque control (DTC based drive system like smooth dynamic response in speed reversal, minimum torque error, settling time of speed. Simulation results of proposed hybrid asymmetric space vector pulse width modulation technique to direct torque control (HASVPWM-DTC approach has been carried out by using Matlab-Simulink environment.

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

    Directory of Open Access Journals (Sweden)

    Peter M Ferguson

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. A New Strategy Based on Smrho Protein Loaded Chitosan Nanoparticles as a Candidate Oral Vaccine against Schistosomiasis

    OpenAIRE

    Oliveira, Carolina R.; Rezende, Cíntia M. F.; Silva, Marina R.; Ana Paula Pêgo; Olga Borges; Alfredo M. Goes

    2012-01-01

    BACKGROUND: Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticl...

  5. TAA Polyepitope DNA-Based Vaccines: A Potential Tool for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Roberto Bei

    2010-01-01

    Full Text Available DNA-based cancer vaccines represent an attractive strategy for inducing immunity to tumor associated antigens (TAAs in cancer patients. The demonstration that the delivery of a recombinant plasmid encoding epitopes can lead to epitope production, processing, and presentation to CD8+ T-lymphocytes, and the advantage of using a single DNA construct encoding multiple epitopes of one or more TAAs to elicit a broad spectrum of cytotoxic T-lymphocytes has encouraged the development of a variety of strategies aimed at increasing immunogenicity of TAA polyepitope DNA-based vaccines. The polyepitope DNA-based cancer vaccine approach can (a circumvent the variability of peptide presentation by tumor cells, (b allow the introduction in the plasmid construct of multiple immunogenic epitopes including heteroclitic epitope versions, and (c permit to enroll patients with different major histocompatibility complex (MHC haplotypes. This review will discuss the rationale for using the TAA polyepitope DNA-based vaccination strategy and recent results corroborating the usefulness of DNA encoding polyepitope vaccines as a potential tool for cancer therapy.

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

    Directory of Open Access Journals (Sweden)

    Soledad eMac Keon

    2015-05-01

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

  7. Status of vaccine research and development of vaccines for leishmaniasis.

    Science.gov (United States)

    Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena

    2016-06-01

    A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies. PMID:26973063

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

    Science.gov (United States)

    Vogel, B.; Reuter, S.; Taverna, M.; Fischer, M. R.; Schelling, J.

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Vogel, B.

    2016-02-01

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

  10. Production, purification and titration of a lentivirus-based vector for gene delivery purposes.

    Science.gov (United States)

    Nasri, Masoud; Karimi, Ali; Allahbakhshian Farsani, Mehdi

    2014-12-01

    Viral vectors are valuable tools to deliver genetic materials into cells. Vectors derived from human immunodeficiency virus type 1 are being widely used for gene delivery, mainly because they are able to transduce both dividing and non-dividing cells which leads to stable and long term gene expression. In addition, these types of vectors are safe, with low toxicity, high stability and cell type specificity. Therefore, this work was aimed to produce lentivirus-based vector using a three-plasmid system. To produce this system, the eGFP marker gene was cloned into the plasmid pWPXLd. Subsequently, this vector plasmid, along with packaging plasmids, psPAX2 and envelope plasmid, pMD2.G, was co-transfected into packaging cell line (293T) using calcium phosphate method. 48 h post transfection, the constructed viral vector was harvested, purified and concentrated and stored at -80 °C for next experiments. The titration of the vector was carried out, using ELISA, flowcytometry, and fluorescent microscopy. Finally, transduction of HEK-293T, CHO, HepG2, MCF-7, MEFs and Jurkat cell lines was carried out with indicated cell numbers and multiplicities of infections of the vector in the presence of polybrene. Using this system, high titer lentivirus at titers of up to 2 × 10(8) transducing units/ml (TU/ml) was successfully generated and its transduction efficacy was improved by seven to over 20-fold in various cell types. We demonstrate the applicability of this vector for the efficient transduction of dividing and non-dividing cells, including HEK-293T, CHO, HepG2, MCF-7, MEFs and Jurkat cell line. Transduction efficiency yielded titers of (6.3 ± 1.2) 10(5) TU/ml. Furthermore, lentivirus transferred transgene was expressed at high level in the target cells and expression was followed until 90 days after transduction. Thus, the vector generated in this work, might be able to deliver the transgene into a wide range of mammalian cells.

  11. Acoustic Event Detection Based on MRMR Selected Feature Vectors

    OpenAIRE

    VOZARIKOVA Eva; Juhar, Jozef; CIZMAR Anton

    2012-01-01

    This paper is focused on the detection of potentially dangerous acoustic events such as gun shots and breaking glass in the urban environment. Various feature extraction methods can be used forrepresenting the sound in the detection system based on Hidden Markov Models of acoustic events. Mel – frequency cepstral coefficients, low - level descriptors defined in MPEG-7 standard and another time andspectral features were considered in the system. For the selection of final subset of features Mi...

  12. Image Replica Detection based on Binary Support Vector Classifier

    OpenAIRE

    Maret, Y.; Dufaux, F.; Ebrahimi, T.

    2005-01-01

    In this paper, we present a system for image replica detection. More specifically, the technique is based on the extraction of 162 features corresponding to texture, color and gray-level characteristics. These features are then weighted and statistically normalized. To improve training and performances, the features space dimensionality is reduced. Lastly, a decision function is generated to classify the test image as replica or non-replica of a given reference image. Experimental results sho...

  13. A Vector Network Analyzer Based on Pulse Generators

    Directory of Open Access Journals (Sweden)

    B. Schulte

    2005-01-01

    Full Text Available A fast four channel network analyzer is introduced to measure S-parameters in a frequency range from 10MHz to 3GHz. The signal generation for this kind of analyzer is based on pulse generators, which are realized with bipolar transistors. The output signal of the transistor is differentiated and two short pulses, a slow and a fast one, with opposite polarities are generated. The slow pulse is suppressed with a clipping network. Thus the generation of very short electrical pulses with a duration of about 100ps is possible. The structure of the following network analyzer is similar to the structure of a conventional four channel network analyzer. All four pulses, which contain the high frequency information of the device under test, are evaluated after the digitalization of intermediate frequencies. These intermediate frequencies are generated with sampling mixers. The recorded data is evaluated with a special analysis technique, which is based on a Fourier transformation. The calibration techniques used are the same as for conventional four channel network analyzers, no new calibration techniques need to be developed.

  14. Support vector machine based on adaptive acceleration particle swarm optimization.

    Science.gov (United States)

    Abdulameer, Mohammed Hasan; Sheikh Abdullah, Siti Norul Huda; Othman, Zulaiha Ali

    2014-01-01

    Existing face recognition methods utilize particle swarm optimizer (PSO) and opposition based particle swarm optimizer (OPSO) to optimize the parameters of SVM. However, the utilization of random values in the velocity calculation decreases the performance of these techniques; that is, during the velocity computation, we normally use random values for the acceleration coefficients and this creates randomness in the solution. To address this problem, an adaptive acceleration particle swarm optimization (AAPSO) technique is proposed. To evaluate our proposed method, we employ both face and iris recognition based on AAPSO with SVM (AAPSO-SVM). In the face and iris recognition systems, performance is evaluated using two human face databases, YALE and CASIA, and the UBiris dataset. In this method, we initially perform feature extraction and then recognition on the extracted features. In the recognition process, the extracted features are used for SVM training and testing. During the training and testing, the SVM parameters are optimized with the AAPSO technique, and in AAPSO, the acceleration coefficients are computed using the particle fitness values. The parameters in SVM, which are optimized by AAPSO, perform efficiently for both face and iris recognition. A comparative analysis between our proposed AAPSO-SVM and the PSO-SVM technique is presented. PMID:24790584

  15. Support Vector Machine Based on Adaptive Acceleration Particle Swarm Optimization

    Directory of Open Access Journals (Sweden)

    Mohammed Hasan Abdulameer

    2014-01-01

    Full Text Available Existing face recognition methods utilize particle swarm optimizer (PSO and opposition based particle swarm optimizer (OPSO to optimize the parameters of SVM. However, the utilization of random values in the velocity calculation decreases the performance of these techniques; that is, during the velocity computation, we normally use random values for the acceleration coefficients and this creates randomness in the solution. To address this problem, an adaptive acceleration particle swarm optimization (AAPSO technique is proposed. To evaluate our proposed method, we employ both face and iris recognition based on AAPSO with SVM (AAPSO-SVM. In the face and iris recognition systems, performance is evaluated using two human face databases, YALE and CASIA, and the UBiris dataset. In this method, we initially perform feature extraction and then recognition on the extracted features. In the recognition process, the extracted features are used for SVM training and testing. During the training and testing, the SVM parameters are optimized with the AAPSO technique, and in AAPSO, the acceleration coefficients are computed using the particle fitness values. The parameters in SVM, which are optimized by AAPSO, perform efficiently for both face and iris recognition. A comparative analysis between our proposed AAPSO-SVM and the PSO-SVM technique is presented.

  16. Predicting population coverage of T-cell epitope-based diagnostics and vaccines

    Directory of Open Access Journals (Sweden)

    Newman Mark J

    2006-03-01

    Full Text Available Abstract Background T cells recognize a complex between a specific major histocompatibility complex (MHC molecule and a particular pathogen-derived epitope. A given epitope will elicit a response only in individuals that express an MHC molecule capable of binding that particular epitope. MHC molecules are extremely polymorphic and over a thousand different human MHC (HLA alleles are known. A disproportionate amount of MHC polymorphism occurs in positions constituting the peptide-binding region, and as a result, MHC molecules exhibit a widely varying binding specificity. In the design of peptide-based vaccines and diagnostics, the issue of population coverage in relation to MHC polymorphism is further complicated by the fact that different HLA types are expressed at dramatically different frequencies in different ethnicities. Thus, without careful consideration, a vaccine or diagnostic with ethnically biased population coverage could result. Results To address this issue, an algorithm was developed to calculate, on the basis of HLA genotypic frequencies, the fraction of individuals expected to respond to a given epitope set, diagnostic or vaccine. The population coverage estimates are based on MHC binding and/or T cell restriction data, although the tool can be utilized in a more general fashion. The algorithm was implemented as a web-application available at http://epitope.liai.org:8080/tools/population. Conclusion We have developed a web-based tool to predict population coverage of T-cell epitope-based diagnostics and vaccines based on MHC binding and/or T cell restriction data. Accordingly, epitope-based vaccines or diagnostics can be designed to maximize population coverage, while minimizing complexity (that is, the number of different epitopes included in the diagnostic or vaccine, and also minimizing the variability of coverage obtained or projected in different ethnic groups.

  17. Yeast recombination-based cloning as an efficient way of constructing vectors for Zymoseptoria tritici

    OpenAIRE

    Kilaru, S.; Steinberg, G.

    2015-01-01

    Highlights • Yeast recombination-based cloning (YRBC) is a reliable and inexpensive way of generating plasmids. • We provide 4 vectors for YRBC that a cover different resistance genes. • Using this technique promises rapid generation of molecular tools to study Z. tritici.

  18. Scale-Invariance of Support Vector Machines based on the Triangular Kernel

    OpenAIRE

    Sahbi, Hichem; Fleuret, François

    2002-01-01

    This report focuses on the scale-invariance and the good performances of Support Vector Machines based on the triangular kernel. After a mathematica- l analysis of the scale-invariance of learning with that kernel, we illustrate its behavior with a simple 2D classification problem and compare its performances to those of a Gaussian kernel on face detection and handwritten character recognition

  19. Enhanced transduction of mouse salivary glands with AAV5-based vectors

    NARCIS (Netherlands)

    H. Katano; M.R. Kok; A.P. Cotrim; S. Yamano; M. Schmidt; S. Afione; B.J. Baum; J.A. Chiorini

    2006-01-01

    We previously demonstrated that recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in salivary gland cells in vitro and in vivo. However, it is not known how other rAAV serotypes perform when infused into salivary glands. The capsids of serotypes 4

  20. Factors Affecting Learning of Vector Math from Computer-Based Practice: Feedback Complexity and Prior Knowledge

    Science.gov (United States)

    Heckler, Andrew F.; Mikula, Brendon D.

    2016-01-01

    In experiments including over 450 university-level students, we studied the effectiveness and time efficiency of several levels of feedback complexity in simple, computer-based training utilizing static question sequences. The learning domain was simple vector math, an essential skill in introductory physics. In a unique full factorial design, we…