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Sample records for hemagglutinin-based virus-like particles

  1. Single Dose of Consensus Hemagglutinin-Based Virus-Like Particles Vaccine Protects Chickens against Divergent H5 Subtype Influenza Viruses

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    Peipei Wu

    2017-11-01

    Full Text Available The H5 subtype highly pathogenic avian influenza (HPAI virus is one of the greatest threats to global poultry industry. To develop broadly protective H5 subunit vaccine, a recombinant consensus HA sequence (rHA was constructed and expressed in virus-like particles (rHA VLPs in the baculovirus-insect cell system. The efficacy of the rHA VLPs vaccine with or without immunopotentiator (CVCVA5 was assessed in chickens. Compared to the commercial Re6 or Re6-CVCVA5 vaccines, single dose immunization of chickens with rHA VLPs or rHA-CVCVA5 vaccines induced higher levels of serum hemagglutinin inhibition titers and neutralization titers, mucosal antibodies, IFN-γ and IL-4 cytokines in sera, and cytotoxic T lymphocyte responses. The rHA VLPs vaccine was superior to the commercial Re6 vaccine in conferring cross-protection against different clades of H5 subtype viruses. This study reports that H5 subtype consensus HA VLP single dose vaccination provides broad protection against HPAI virus in chickens.

  2. Virus-like particles as nanovaccine candidates

    International Nuclear Information System (INIS)

    Guillen, G; Aguilar, J C; Dueñas, S; Hermida, L; Iglesias, E; Penton, E; Lobaina, Y; Lopez, M; Mussachio, A; Falcon, V; Alvarez, L; Martinez, G; Gil, L; Valdes, I; Izquierdo, A; Lazo, L; Marcos, E; Guzman, G; Muzio, V; Herrera, L

    2013-01-01

    The existing vaccines are mainly limited to the microorganisms we are able to culture and produce and/or to those whose killing is mediated by humoral response (antibody mediated). It has been more difficult to develop vaccines capable of inducing a functional cellular response needed to prevent or cure chronic diseases. New strategies should be taken into account in the improvement of cell-based immune responses in order to prevent and control the infections and eventually clear the virus. Preclinical and clinical results with vaccine candidates developed as a vaccine platform based on virus-like particles (VLPs) evidenced their ability to stimulate mucosal as well as systemic immunity. Particles based on envelope, membrane or nucleocapsid microbial proteins induce a strong immune response after nasal or parenteral administration in mice, non-human primates and humans. In addition, the immune response obtained was modulated in a Th1 sense. The VLPs were also able to immunoenhance the humoral and cellular immune responses against several viral pathogens. Studies in animals and humans with nasal and systemic formulations evidenced that it is possible to induce functional immune response against HBV, HCV, HIV and dengue virus. (paper)

  3. Characterization of chikungunya virus-like particles.

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    Nitchakarn Noranate

    Full Text Available Chikungunya virus (CHIKV is becoming a global concern due to the increasing number of outbreaks throughout the world and the absence of any CHIKV-specific vaccine or treatment. Virus-like particles (VLPs are multistructured proteins that mimic the organization and conformation of native viruses but lack the viral genome. They are noninfectious and potentially safer vaccine candidates. Recent studies demonstrated that the yield of CHIKV VLPs varies depending on the strains, despite the 95% amino acid similarity of the strains. This might be due to the codon usage, since protein expression is differently controlled by different organisms. We optimized the region encoding CHIKV structural proteins, C-E3-E2-6k-E1, inserted it into a mammalian expression vector, and used the resulting construct to transfect 293 cells. We detected 50-kDa proteins corresponding to E1 and/or E2 in the cell lysate and the supernatant. Transmission electron microscopy revealed spherical particles with a 50- to 60-nm diameter in the supernatant that resembled the native CHIKV virions. The buoyant density of the VLPs was 1.23 g/mL, and the yield was 20 µg purified VLPs per 108 cells. The VLPs aggregated when mixed with convalescent sera from chikungunya patients, indicating that their antigenicity is similar to that of native CHIKV. Antibodies elicited with the VLPs were capable of detecting native CHIKV, demonstrating that the VLPs retain immunogenicity similar to that of the native virion. These results indicated that CHIKV VLPs are morphologically, antigenically, and immunologically similar to the native CHIKV, suggesting that they have potential for use in chikungunya vaccines.

  4. Enveloped virus-like particles as vaccines against pathogenic arboviruses

    NARCIS (Netherlands)

    Pijlman, G.P.

    2015-01-01

    Arthropod-borne arboviruses form a continuous threat to human and animal health, but few arboviral vaccines are currently available. Advances in expression technology for complex, enveloped virus-like particles (eVLPs) create new opportunities to develop potent vaccines against pathogenic

  5. Vaccine potential of Nipah virus-like particles.

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    Pramila Walpita

    2011-04-01

    Full Text Available Nipah virus (NiV was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease.

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

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

    2017-01-01

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

  7. Virus-Like Particles That Can Deliver Proteins and RNA | NCI Technology Transfer Center | TTC

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    The present invention describes novel virus-like particles (VLPs) that are capable of binding to and replicating within a target mammalian cell, including human cells. The claimed VLPs are safer than viral delivery because they are incapable of re-infecting target cells. The National Cancer Institute's Protein Expression Laboratory seeks parties interested in licensing the novel delivery of RNA to mammalian cells using virus-like particles.

  8. Feasibility of Cowpea chlorotic mottle virus-like particles as scaffold for epitope presentations

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    Hassani-Mehraban, A.; Creutzburg, S.; Heereveld, van L.; Kormelink, R.J.M.

    2015-01-01

    Within the last decade Virus-Like Particles (VLPs) have increasingly received attention from scientists for their use as a carrier of (peptide) molecules or as scaffold to present epitopes for use in subunit vaccines. To test the feasibility of Cowpea chlorotic mottle virus (CCMV) particles as a

  9. Towards the directed evolution of virus-like particles derived from polyomaviruses

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    Teunissen, E.A.

    2014-01-01

    Virus-like particles (VLPs) are assemblies of viral structural proteins. These particles resemble the native viral capsid in structure, tropism, and transduction efficiency, but do not contain any viral genetic material. This makes them a safer alternative to viral vectors for gene therapy, and

  10. Oligonucleotide Length-Dependent Formation of Virus-Like Particles.

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    Maassen, Stan J; de Ruiter, Mark V; Lindhoud, Saskia; Cornelissen, Jeroen J L M

    2018-05-23

    Understanding the assembly pathway of viruses can contribute to creating monodisperse virus-based materials. In this study, the cowpea chlorotic mottle virus (CCMV) is used to determine the interactions between the capsid proteins of viruses and their cargo. The assembly of the capsid proteins in the presence of different lengths of short, single-stranded (ss) DNA is studied at neutral pH, at which the protein-protein interactions are weak. Chromatography, electrophoresis, microscopy, and light scattering data show that the assembly efficiency and speed of the particles increase with increasing length of oligonucleotides. The minimal length required for assembly under the conditions used herein is 14 nucleotides. Assembly of particles containing such short strands of ssDNA can take almost a month. This slow assembly process enabled the study of intermediate states, which confirmed a low cooperative assembly for CCMV and allowed for further expansion of current assembly theories. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Exploiting Fluorescent Polymers To Probe the Self-Assembly of Virus-like Particles

    DEFF Research Database (Denmark)

    Caden-Nava, Ruben D.; Hu, Yufang; Garmann, Rees F.

    2011-01-01

    , for example, poly(styrene sulfonate) (PSS), forming virus-like particles (VLPs). We have demonstrated recently that the VLPs formed from cowpea chlorotic mottle virus (CCMV) capsid protein increase in size (from T = 2 to T = 3 structures) upon increase in PSS molecular weight (from 400 kDa to 3.4MDa...

  12. Virus-like particles suppress growth of the red-tide-forming marine dinoflagellate Gymnodinium mikimotoi.

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    Onji, Masashi; Nakano, Shin-ichi; Suzuki, Satoru

    2003-01-01

    We isolated 2 virus-like agents that suppressed growth of Gymnodinium mikimotoi from coastal waters of the Uwa Sea, Japan. The agents found in the flagellate cells, named GM6 and GM7, were filterable in a 0.22-microm-pore filter with approximately 100-nm shapes. Electron microscopic observation showed the presence of virus-like particles in severely damaged G. mikimotoi cells infected by GM6. The growth-suppression activity of the agents (GM6 or GM7) was lost by heating at 50 degrees C, with treatments of DNase and protease, and filtration through a 0.05-microm filter. Our results suggest that the agents are DNA viruses infectious to and virulent for G. mikimotoi. This is the first report of a virus-like agent specific to G. mikimotoi.

  13. Hantavirus Gn and Gc glycoproteins self-assemble into virus-like particles.

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    Acuña, Rodrigo; Cifuentes-Muñoz, Nicolás; Márquez, Chantal L; Bulling, Manuela; Klingström, Jonas; Mancini, Roberta; Lozach, Pierre-Yves; Tischler, Nicole D

    2014-02-01

    How hantaviruses assemble and exit infected cells remains largely unknown. Here, we show that the expression of Andes (ANDV) and Puumala (PUUV) hantavirus Gn and Gc envelope glycoproteins lead to their self-assembly into virus-like particles (VLPs) which were released to cell supernatants. The viral nucleoprotein was not required for particle formation. Further, a Gc endodomain deletion mutant did not abrogate VLP formation. The VLPs were pleomorphic, exposed protrusions and reacted with patient sera.

  14. Particle size effects on protein and virus-like particle adsorption on perfusion chromatography media.

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    Wu, Yige; Abraham, Dicky; Carta, Giorgio

    2015-01-02

    The resin structure, chromatographic behavior, and adsorption kinetics of proteins and virus-like-particles (VLPs) are studied for POROS HS 20 and POROS HS 50 (23 and 52 μm mean diameter, respectively) to determine the effects of particle size on perfusion chromatography and to determine the predictive ability of available models. Transmission electron microscopy (TEM) and inverse size-exclusion chromatography (iSEC) show similar structures for the two resins, both containing 200-1000 nm pores that transect a network of much smaller pores. For non-binding conditions, trends of the height equivalent to a theoretical plate (HETP) as a function of reduced velocity are consistent with perfusion. The estimated intraparticle flow fractions for these conditions are 0.0018 and 0.00063 for POROS HS 20 and HS 50, respectively. For strong binding conditions, confocal laser scanning microscopy (CLSM) shows asymmetrical intraparticle concentrations profiles and enhanced rates of IgG adsorption on POROS HS 20 at 1000 cm/h. The corresponding effective diffusivity under flow is 2-3 times larger than for non-flow conditions and much larger than observed for POROS HS 50, consistent with available models. For VLPs, however, adsorption is confined to a thin layer near the particle surface for both resins, suggesting that the bound VLPs block the pores. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Three-dimensional visualization of forming Hepatitis C virus-like particles by electron-tomography

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    Badia-Martinez, Daniel; Peralta, Bibiana [Structural Biology Unit, CIC bioGUNE, CIBERehd, 48160 Derio (Spain); Andres, German; Guerra, Milagros [Electron Microscopy Unit, Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, Campus Cantoblanco, 28049 Madrid (Spain); Gil-Carton, David [Structural Biology Unit, CIC bioGUNE, CIBERehd, 48160 Derio (Spain); Abrescia, Nicola G.A., E-mail: nabrescia@cicbiogune.es [Structural Biology Unit, CIC bioGUNE, CIBERehd, 48160 Derio (Spain); IKERBASQUE, Basque Foundation for Science, 48011 Bilbao (Spain)

    2012-09-01

    Hepatitis C virus infects almost 170 million people per year but its assembly pathway, architecture and the structures of its envelope proteins are poorly understood. Using electron tomography of plastic-embedded sections of insect cells, we have visualized the morphogenesis of recombinant Hepatitis C virus-like particles. Our data provide a three-dimensional sketch of viral assembly at the endoplasmic reticulum showing different budding stages and contiguity of buds. This latter phenomenon could play an important role during the assembly of wt-HCV and explain the size-heterogeneity of its particles.

  16. Three-dimensional visualization of forming Hepatitis C virus-like particles by electron-tomography

    International Nuclear Information System (INIS)

    Badia-Martinez, Daniel; Peralta, Bibiana; Andrés, German; Guerra, Milagros; Gil-Carton, David; Abrescia, Nicola G.A.

    2012-01-01

    Hepatitis C virus infects almost 170 million people per year but its assembly pathway, architecture and the structures of its envelope proteins are poorly understood. Using electron tomography of plastic-embedded sections of insect cells, we have visualized the morphogenesis of recombinant Hepatitis C virus-like particles. Our data provide a three-dimensional sketch of viral assembly at the endoplasmic reticulum showing different budding stages and contiguity of buds. This latter phenomenon could play an important role during the assembly of wt-HCV and explain the size-heterogeneity of its particles.

  17. Stability and assembly in vitro of bacteriophage PP7 virus-like particles

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    Peabody David S

    2007-11-01

    Full Text Available Abstract Background The stability of a virus-like particle (VLP is an important consideration for its use in nanobiotechnology. The icosahedral capsid of the RNA bacteriophage PP7 is cross-linked by disulfide bonds between coat protein dimers at its 5-fold and quasi-6-fold symmetry axes. This work determined the effects of these disulfides on the VLP's thermal stability. Results Measurements of the thermal denaturation behavior of PP7 VLPs in the presence and absence of a reducing agent show that disulfide cross-links substantially stabilize them against thermal denaturation. Although dimers in the capsid are linked to one another by disulfides, the two subunits of dimers themselves are held together only by non-covalent interactions. In an effort to confer even greater stability a new cross-link was introduced by genetically fusing two coat protein monomers, thus producing a "single-chain dimer" that assembles normally into a completely cross-linked VLP. However, subunit fusion failed to increase the thermal stability of the particles, even though it stabilized the isolated dimer. As a step toward gaining control of the internal composition of the capsid, conditions that promote the assembly of PP7 coat protein dimers into virus-like particles in vitro were established. Conclusion The presence of inter-dimer disulfide bonds greatly stabilizes the PP7 virus-like particle against thermal denaturation. Covalently cross-linking the subunits of the dimers themselves by genetically fusing them through a dipeptide linker sequence, offers no further stabilization of the VLP, although it does stabilize the dimer. PP7 capsids readily assemble in vitro in a reaction that requires RNA.

  18. High-yield production of canine parvovirus virus-like particles in a baculovirus expression system.

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    Jin, Hongli; Xia, Xiaohong; Liu, Bing; Fu, Yu; Chen, Xianping; Wang, Huihui; Xia, Zhenqiang

    2016-03-01

    An optimized VP2 gene from the current prevalent CPV strain (new CPV-2a) in China was expressed in a baculovirus expression system. It was found that the VP2 proteins assembled into virus-like particles (VLPs) with antigenic properties similar to those of natural CPV and with an especially high hemagglutination (HA) titer (1:2(20)). Dogs intramuscularly or orally immunized with VLPs produced antibodies against CPV with >1:80 hemagglutination inhibition (HI) units for at least 3 months. The CPV VLPs could be considered for use as a vaccine against CPV or as a platform for research on chimeric VLP vaccines against other diseases.

  19. Crystallization and preliminary X-ray diffraction analysis of recombinant hepatitis E virus-like particle

    International Nuclear Information System (INIS)

    Wang, Che-Yen; Miyazaki, Naoyuki; Yamashita, Tetsuo; Higashiura, Akifumi; Nakagawa, Atsushi; Li, Tian-Cheng; Takeda, Naokazu; Xing, Li; Hjalmarsson, Erik; Friberg, Claes; Liou, Der-Ming; Sung, Yen-Jen; Tsukihara, Tomitake; Matsuura, Yoshiharu; Miyamura, Tatsuo; Cheng, R. Holland

    2008-01-01

    A recombinant virus-like particle that is a potential oral hepatitis E vaccine was crystallized. Diffraction data were collected to 8.3 Å resolution and the X-ray structure was phased with the aid of a low-resolution density map determined using cryo-electron microscopy data. Hepatitis E virus (HEV) accounts for the majority of enterically transmitted hepatitis infections worldwide. Currently, there is no specific treatment for or vaccine against HEV. The major structural protein is derived from open reading frame (ORF) 2 of the viral genome. A potential oral vaccine is provided by the virus-like particles formed by a protein construct of partial ORF3 protein (residue 70–123) fused to the N-terminus of the ORF2 protein (residues 112–608). Single crystals obtained by the hanging-drop vapour-diffusion method at 293 K diffract X-rays to 8.3 Å resolution. The crystals belong to space group P2 1 2 1 2 1 , with unit-cell parameters a = 337, b = 343, c = 346 Å, α = β = γ = 90°, and contain one particle per asymmetric unit

  20. Self-assembly of virus-like particles of canine parvovirus capsid protein expressed from Escherichia coli and application as virus-like particle vaccine.

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    Xu, Jin; Guo, Hui-Chen; Wei, Yan-Quan; Dong, Hu; Han, Shi-Chong; Ao, Da; Sun, De-Hui; Wang, Hai-Ming; Cao, Sui-Zhong; Sun, Shi-Qi

    2014-04-01

    Canine parvovirus disease is an acute infectious disease caused by canine parvovirus (CPV). Current commercial vaccines are mainly attenuated and inactivated; as such, problems concerning safety may occur. To resolve this problem, researchers developed virus-like particles (VLPs) as biological nanoparticles resembling natural virions and showing high bio-safety. This property allows the use of VLPs for vaccine development and mechanism studies of viral infections. Tissue-specific drug delivery also employs VLPs as biological nanomaterials. Therefore, VLPs derived from CPV have a great potential in medicine and diagnostics. In this study, small ubiquitin-like modifier (SUMO) fusion motif was utilized to express a whole, naturalVP2 protein of CPV in Escherichia coli. After the cleavage of the fusion motif, the CPV VP2 protein has self-assembled into VLPs. The VLPs had a size and shape that resembled the authentic virus capsid. However, the self-assembly efficiency of VLPs can be affected by different pH levels and ionic strengths. The mice vaccinated subcutaneously with CPV VLPs and CPV-specific immune responses were compared with those immunized with the natural virus. This result showed that VLPs can effectively induce anti-CPV specific antibody and lymphocyte proliferation as a whole virus. This result further suggested that the antigen epitope of CPV was correctly present on VLPs, thereby showing the potential application of a VLP-based CPV vaccine.

  1. Molecular and structural characterization of fluorescent human parvovirus B19 virus-like particles

    International Nuclear Information System (INIS)

    Gilbert, Leona; Toivola, Jouni; White, Daniel; Ihalainen, Teemu; Smith, Wesley; Lindholm, Laura; Vuento, Matti; Oker-Blom, Christian

    2005-01-01

    Although sharing a T = 1 icosahedral symmetry with other members of the Parvoviridae family, it has been suggested that the fivefold channel of the human parvovirus B19 VP2 capsids is closed at its outside end. To investigate the possibility of placing a relatively large protein moiety at this site of B19, fluorescent virus-like particles (fVLPs) of B19 were developed. The enhanced green fluorescent protein (EGFP) was inserted at the N-terminus of the structural protein VP2 and assembly of fVLPs from this fusion protein was obtained. Electron microscopy revealed that these fluorescent protein complexes were very similar in size when compared to wild-type B19 virus. Further, fluorescence correlation spectroscopy showed that an average of nine EGFP domains were associated with these virus-like structures. Atomic force microscopy and immunoprecipitation studies showed that EGFP was displayed on the surface of these fVLPs. Confocal imaging indicated that these chimeric complexes were targeted to late endosomes when expressed in insect cells. The fVLPs were able to efficiently enter cancer cells and traffic to the nucleus via the microtubulus network. Finally, immunoglobulins present in human parvovirus B19 acute and past-immunity serum samples were able to detect antigenic epitopes present in these fVLPs. In summary, we have developed fluorescent virus-like nanoparticles displaying a large heterologous entity that should be of help to elucidate the mechanisms of infection and pathogenesis of human parvovirus B19. In addition, these B19 nanoparticles serve as a model in the development of targetable vehicles designed for delivery of biomolecules

  2. An efficient plant viral expression system generating orally immunogenic Norwalk virus-like particles.

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    Santi, Luca; Batchelor, Lance; Huang, Zhong; Hjelm, Brooke; Kilbourne, Jacquelyn; Arntzen, Charles J; Chen, Qiang; Mason, Hugh S

    2008-03-28

    Virus-like particles (VLPs) derived from enteric pathogens like Norwalk virus (NV) are well suited to study oral immunization. We previously described stable transgenic plants that accumulate recombinant NV-like particles (rNVs) that were orally immunogenic in mice and humans. The transgenic approach suffers from long generation time and modest level of antigen accumulation. We now overcome these constraints with an efficient tobacco mosaic virus (TMV)-derived transient expression system using leaves of Nicotiana benthamiana. We produced properly assembled rNV at 0.8 mg/g leaf 12 days post-infection (dpi). Oral immunization of CD1 mice with 100 or 250 microg/dose of partially purified rNV elicited systemic and mucosal immune responses. We conclude that the plant viral transient expression system provides a robust research tool to generate abundant quantities of rNV as enriched, concentrated VLP preparations that are orally immunogenic.

  3. RNA packaging of MRFV virus-like particles: The interplay between RNA pools and capsid coat protein

    Science.gov (United States)

    Virus-like particles (VLPs) can be produced through self-assembly of capsid protein (CP) into particles with discrete shapes and sizes and containing different types of RNA molecules. The general principle that governs particle assembly and RNA packaging is determined by unique interactions between ...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  5. Promising MS2 mediated virus-like particle vaccine against foot-and-mouth disease.

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    Dong, Yan-mei; Zhang, Guo-guang; Huang, Xiao-jun; Chen, Liang; Chen, Hao-tai

    2015-05-01

    Foot-and-mouth disease (FMD) has caused severe economic losses to millions of farmers worldwide. In this work, the coding genes of 141-160 epitope peptide (EP141-160) of VP1 were inserted into the coat protein (CP) genes of MS2 in prokaryotic expression vector, and the recombinant protein self-assembled into virus-like particles (VLP). Results showed that the CP-EP141-160 VLP had a strong immunoreaction with the FMD virus (FMDV) antigen in vitro, and also had an effective immune response in mice. Further virus challenge tests were carried out on guinea pigs and swine, high-titer neutralizing antibodies were produced and the CP-EP141-160 VLP vaccine could protect most of the animals against FMDV. Copyright © 2015. Published by Elsevier B.V.

  6. An optimized formulation of a thermostable spray dried virus-like particles vaccine against human papillomavirus

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    Saboo, Sugandha; Tumban, Ebenezer; Peabody, Julianne; Wafula, Denis; Peabody, David S.; Chackerian, Bryce; Muttil, Pavan

    2016-01-01

    Existing vaccines against human papillomavirus (HPV) require continuous cold-chain storage. Previously, we developed a bacteriophage virus-like particle (VLP) based vaccine for Human Papillomavirus (HPV) infection, which elicits broadly neutralizing antibodies against diverse HPV types. Here, we formulated these VLPs into a thermostable dry powder using a multi-component excipient system and by optimizing the spray drying parameters using a half-factorial design approach. Dry powder VLPs were stable after spray drying and after long-term storage at elevated temperatures. Immunization of mice with a single dose of reconstituted dry powder VLPs that were stored at 37°C for more than a year elicited high anti-L2 IgG antibody titers. Spray dried thermostable, broadly protective L2 bacteriophage VLPs vaccine could be accessible to remote regions of the world (where ~84% of cervical cancer patients reside) by eliminating the cold-chain requirement during transportation and storage. PMID:27019231

  7. Characterization of virus-like particles by atomic force microscopy in ambient conditions

    International Nuclear Information System (INIS)

    Oropesa, Reinier; Ramos, Jorge R; Falcón, Viviana; Felipe, Ariel

    2013-01-01

    Recombinant virus-like particles (VLPs) are attractive candidates for vaccine design since they resemble native viroids in size and morphology, but they are non-infectious due to the absence of a viral genome. The visualization of surface morphologies and structures can be used to deepen the understanding of physical, chemical, and biological phenomena. Atomic force microscopy (AFM) is a useful tool for the visualization of soft biological samples in a nanoscale resolution. In this work we have investigated the morphology of recombinant surface antigens of hepatitis B (rHBsAg) VLPs from Cuban vaccine against hepatitis B. The rHBsAg VLPs sizes estimated by AFM between 15 and 30 nm are similar to those reported on previous transmission electron microscopy (TEM) studies. (paper)

  8. Effective chikungunya virus-like particle vaccine produced in insect cells.

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    Stefan W Metz

    Full Text Available The emerging arthritogenic, mosquito-borne chikungunya virus (CHIKV causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present. This study describes for the first time the successful production of CHIKV virus-like particles (VLPs in insect cells using recombinant baculoviruses. This well-established expression system is rapidly scalable to volumes required for epidemic responses and proved well suited for processing of CHIKV glycoproteins and production of enveloped VLPs. Herein we show that a single immunization with 1 µg of non-adjuvanted CHIKV VLPs induced high titer neutralizing antibody responses and provided complete protection against viraemia and joint inflammation upon challenge with the Réunion Island CHIKV strain in an adult wild-type mouse model of CHIKV disease. CHIKV VLPs produced in insect cells using recombinant baculoviruses thus represents as a new, safe, non-replicating and effective vaccine candidate against CHIKV infections.

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

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    Andrea Jegerlehner

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

  10. Virus-like particles in venom of Meteorus pulchricornis induce host hemocyte apoptosis.

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    Suzuki, M; Tanaka, T

    2006-06-01

    Ultrastructural studies on the reproductive tract and venom apparatus of a female braconid, Meteorus pulchricornis, revealed that the parasitoid lacks the calyx region in its oviduct, but possesses a venom gland with two venom gland filaments and a venom reservoir filled with white and cloudy fluid. Its venom gland cell is concaved and has a lumen filled with numerous granules. Transmisson electron microscopic (TEM) observation revealed that virus-like particles (VLPs) were produced in venom gland cells. The virus-like particle observed in M. pulchricornis (MpVLP) is composed of membranous envelopes with two different parts: a high-density core and a whitish low-density part. The VLPs of M. pulchricornis is also found assembling ultimately in the lumen of venom gland cell. Microvilli were found thrusting into the lumen of the venom gland cell and seem to aid in driving the matured MpVLPs to the common duct of the venom gland filament. Injection of MpVLPs into non-parasitized Pseudaletia separata hosts induced apoptosis in hemocytes, particularly granulocytes (GRs). Rate of apoptosis induced in GRs peaked 48h after VLP injection. While a large part of the GR population collapsed due to apoptosis caused by MpVLPs, the plasmatocyte population was minimally affected. The capacity of MpVLPs to cause apoptosis in host's hemocytes was further demonstrated by a decrease ( approximately 10-fold) in ability of host hemocytes to encapsulate fluorescent latex beads when MpVLPs were present. Apparently, the reduced encapsulation ability was due to a decrease in the GR population resulting from MpVLP-induced apoptosis.

  11. Thermal Stability of RNA Phage Virus-Like Particles Displaying Foreign Peptides

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    Peabody David S

    2011-05-01

    Full Text Available Abstract Background To be useful for genetic display of foreign peptides a viral coat protein must tolerate peptide insertions without major disruption of subunit folding and capsid assembly. The folding of the coat protein of RNA phage MS2 does not normally tolerate insertions in its AB-loop, but an engineered single-chain dimer readily accepts them as long as they are restricted to one of its two halves. Results Here we characterize the effects of peptide insertions on the thermal stabilities of MS2 virus-like particles (VLPs displaying a variety of different peptides in one AB-loop of the coat protein single-chain dimer. These particles typically denature at temperatures around 5-10°C lower than unmodified VLPs. Even so, they are generally stable up to about 50°C. VLPs of the related RNA phage PP7 are cross-linked with intersubunit disulfide bonds and are therefore significantly more stable. An AB-loop insertion also reduces the stability of PP7 VLPs, but they only begin to denature above about 70°C. Conclusions VLPs assembled from MS2 single-chain dimer coat proteins with peptide insertions in one of their AB-loops are somewhat less stable than the wild-type particle, but still resist heating up to about 50°C. Because they possess disulfide cross-links, PP7-derived VLPs provide an alternate platform with even higher stability.

  12. Maize rayado fino virus capsid proteins assemble into virus-like particles in Escherichia coli.

    Science.gov (United States)

    Hammond, Rosemarie W; Hammond, John

    2010-02-01

    Maize rayado fino virus (MRFV; genus Marafivirus; family Tymoviridae) is an isometric plant virus of 30 nm containing two components: empty shells and complete virus particles (encapsidating the 6.3 kb genomic RNA). Both particles are composed of two serologically related, carboxy co-terminal, coat proteins (CP) of apparent molecular mass 21-22 kDa (CP2) and 24-28 kDa (CP1) in a molar ratio of 3:1, respectively; CP1 contains a 37 amino acid amino terminal extension of CP2. In our study, expression of CP1 or CP2 in Escherichia coli resulted in assembly of each capsid protein into virus-like particles (VLPs), appearing in electron microscopy as stain-permeable (CP2) or stain-impermeable particles (CP1). CP1 VLPs encapsidated bacterial 16S ribosomal RNA, but not CP mRNA, while CP2 VLPs encapsidated neither CP mRNA nor 16S ribosomal RNA. Expression of CP1 and CP2 in E. coli using a co-expression vector resulted in the assembly of VLPs which were stain-impermeable and encapsidated CP mRNA. These results suggest that the N-terminal 37 amino acid residues of CP1, although not required for particle formation, may be involved in the assembly of complete virions and that the presence of both CP1 and CP2 in the particle is required for specific encapsidation of MRFV CP mRNA. (c) 2009 Elsevier B.V. All rights reserved.

  13. Dengue virus-like particles mimic the antigenic properties of the infectious dengue virus envelope.

    Science.gov (United States)

    Metz, Stefan W; Thomas, Ashlie; White, Laura; Stoops, Mark; Corten, Markus; Hannemann, Holger; de Silva, Aravinda M

    2018-04-02

    The 4 dengue serotypes (DENV) are mosquito-borne pathogens that are associated with severe hemorrhagic disease. DENV particles have a lipid bilayer envelope that anchors two membrane glycoproteins prM and E. Two E-protein monomers form head-to-tail homodimers and three E-dimers align to form "rafts" that cover the viral surface. Some human antibodies that strongly neutralize DENV bind to quaternary structure epitopes displayed on E protein dimers or higher order structures forming the infectious virus. Expression of prM and E in cell culture leads to the formation of DENV virus-like particles (VLPs) which are smaller than wildtype virus particles and replication defective due to the absence of a viral genome. There is no data available that describes the antigenic landscape on the surface of flavivirus VLPs in comparison to the better studied infectious virion. A large panel of well characterized antibodies that recognize epitope of ranging complexity were used in biochemical analytics to obtain a comparative antigenic surface view of VLPs in respect to virus particles. DENV patient serum depletions were performed the show the potential of VLPs in serological diagnostics. VLPs were confirmed to be heterogeneous in size morphology and maturation state. Yet, we show that many highly conformational and quaternary structure-dependent antibody epitopes found on virus particles are efficiently displayed on DENV1-4 VLP surfaces as well. Additionally, DENV VLPs can efficiently be used as antigens to deplete DENV patient sera from serotype specific antibody populations. This study aids in further understanding epitopic landscape of DENV VLPs and presents a comparative antigenic surface view of VLPs in respect to virus particles. We propose the use VLPs as a safe and practical alternative to infectious virus as a vaccine and diagnostic antigen.

  14. 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.

  15. Rotavirus Virus-Like Particles as Surrogates in Environmental Persistence and Inactivation Studies

    Science.gov (United States)

    Caballero, Santiago; Abad, F. Xavier; Loisy, Fabienne; Le Guyader, Françoise S.; Cohen, Jean; Pintó, Rosa M.; Bosch, Albert

    2004-01-01

    Virus-like particles (VLPs) with the full-length VP2 and VP6 rotavirus capsid proteins, produced in the baculovirus expression system, have been evaluated as surrogates of human rotavirus in different environmental scenarios. Green fluorescent protein-labeled VLPs (GFP-VLPs) and particles enclosing a heterologous RNA (pseudoviruses), whose stability may be monitored by flow cytometry and antigen capture reverse transcription-PCR, respectively, were used. After 1 month in seawater at 20°C, no significant differences were observed between the behaviors of GFP-VLPs and of infectious rotavirus, whereas pseudovirus particles showed a higher decay rate. In the presence of 1 mg of free chlorine (FC)/liter both tracers persisted longer in freshwater at 20°C than infectious viruses, whereas in the presence of 0.2 mg of FC/liter no differences were observed between tracers and infectious rotavirus at short contact times. However, from 30 min of contact with FC onward, the decay of infectious rotavirus was higher than that of recombinant particles. The predicted Ct value for a 90% reduction of GFP-VLPs or pseudoviruses induces a 99.99% inactivation of infectious rotavirus. Both tracers were more resistant to UV light irradiation than infectious rotavirus in fresh and marine water. The effect of UV exposure was more pronounced on pseudovirus than in GFP-VLPs. In all types of water, the UV dose to induce a 90% reduction of pseudovirus ensures a 99.99% inactivation of infectious rotavirus. Recombinant virus surrogates open new possibilities for the systematic validation of virus removal practices in actual field situations where pathogenic agents cannot be introduced. PMID:15240262

  16. Protein-based polymers that bond to DNA : design of virus-like particles and supramolecular nanostructures

    NARCIS (Netherlands)

    Hernandez Garcia, A.

    2014-01-01

    In this thesis it is demonstrated that it is possible to use Protein-based Polymers (PbPs) as synthetic binders of DNA (or any other negatively charged polyelectrolyte). The PbPs co-assemble with their DNA templates to form highly organized virus-like particles and supramolecular structures. A

  17. A novel recombinant virus-like particle vaccine for prevention of porcine parvovirus-induced reproductive failure

    NARCIS (Netherlands)

    Antonis, A.F.G.; Bruschke, C.J.M.; Rueda, P.; Maranga, L.; Casal, J.; Vela, C.; Hilgers, L.A.T.; Belt, P.B.G.M.; Weerdmeester, K.; Carrondo, M.J.; Langeveld, J.P.M.

    2006-01-01

    A novel vaccine against porcine parvovirus (PPV), composed of recombinant virus-like particles (PPV-VLPs) produced with the baculovirus expression vector system (BEVS) at industrial scale, was tested for its immunogenicity and protective potency. A formulation of submicrogram amounts of PPV-VLPs in

  18. Virus-like particle nanoreactors: programmed en capsulation of the thermostable CelB glycosidase inside the P22 capsid

    NARCIS (Netherlands)

    Patterson, D.P.; Schwarz, B.; El-Boubbou, K.; Oost, van der J.; Prevelige, P.E.; Douglas, T.

    2012-01-01

    Self-assembling biological systems hold great potential for the synthetic construction of new active soft nanomaterials. Here we demonstrate the hierarchical bottom-up assembly of bacteriophage P22 virus-like particles (VLPs) that encapsulate the thermostable CelB glycosidase creating catalytically

  19. Human transbodies to VP40 inhibit cellular egress of Ebola virus-like particles

    International Nuclear Information System (INIS)

    Teimoori, Salma; Seesuay, Watee; Jittavisutthikul, Surasak; Chaisri, Urai; Sookrung, Nitat; Densumite, Jaslan; Saelim, Nawannaporn; Chulanetra, Monrat; Maneewatch, Santi; Chaicumpa, Wanpen

    2016-01-01

    A direct acting anti-Ebola agent is needed. VP40, a conserved protein across Ebolavirus (EBOV) species has several pivotal roles in the virus life cycle. Inhibition of VP40 functions would lessen the virion integrity and interfere with the viral assembly, budding, and spread. In this study, cell penetrable human scFvs (HuscFvs) that bound to EBOV VP40 were produced by phage display technology. Gene sequences coding for VP40-bound-HuscFvs were subcloned from phagemids into protein expression plasmids downstream to a gene of cell penetrating peptide, i.e., nonaarginine (R9). By electron microscopy, transbodies from three clones effectively inhibited egress of the Ebola virus-like particles from human hepatic cells transduced with pseudo-typed-Lentivirus particles carrying EBOV VP40 and GP genes. Computerized simulation indicated that the effective HuscFvs bound to multiple basic residues in the cationic patch of VP40 C-terminal domain which are important in membrane-binding for viral matrix assembly and virus budding. The transbodies bound also to VP40 N-terminal domain and L domain peptide encompassed the PTAPPEY (WW binding) motif, suggesting that they might confer VP40 function inhibition through additional mechanism(s). The generated transbodies are worthwhile tested with authentic EBOV before developing to direct acting anti-Ebola agent for preclinical and clinical trials. - Highlights: • Cell penetrable human scFvs (transbodies) to Ebolavirus (EBOV) VP40 were produced. • The transbodies inhibited egress of EBOV-like particles (VLPs) from human hepatocytes. • They interacted with VP40 CTD basic residues important for plasma membrane binding. • And hence interfere with viral matrix assembly and viral progeny budding. • This is the first report on human antibodies that target intracellular EBOV VP40.

  20. Production of FMDV virus-like particles by a SUMO fusion protein approach in Escherichia coli

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    Liang Shu-Mei

    2009-08-01

    Full Text Available Abstract Virus-like particles (VLPs are formed by the self-assembly of envelope and/or capsid proteins from many viruses. Some VLPs have been proven successful as vaccines, and others have recently found applications as carriers for foreign antigens or as scaffolds in nanoparticle biotechnology. However, production of VLP was usually impeded due to low water-solubility of recombinant virus capsid proteins. Previous studies revealed that virus capsid and envelope proteins were often posttranslationally modified by SUMO in vivo, leading into a hypothesis that SUMO modification might be a common mechanism for virus proteins to retain water-solubility or prevent improper self-aggregation before virus assembly. We then propose a simple approach to produce VLPs of viruses, e.g., foot-and-mouth disease virus (FMDV. An improved SUMO fusion protein system we developed recently was applied to the simultaneous expression of three capsid proteins of FMDV in E. coli. The three SUMO fusion proteins formed a stable heterotrimeric complex. Proteolytic removal of SUMO moieties from the ternary complexes resulted in VLPs with size and shape resembling the authentic FMDV. The method described here can also apply to produce capsid/envelope protein complexes or VLPs of other disease-causing viruses.

  1. Immunogenicity of virus-like particles containing modified goose parvovirus VP2 protein.

    Science.gov (United States)

    Chen, Zongyan; Li, Chuanfeng; Zhu, Yingqi; Wang, Binbin; Meng, Chunchun; Liu, Guangqing

    2012-10-01

    The major capsid protein VP2 of goose parvovirus (GPV) expressed using a baculovirus expression system (BES) assembles into virus-like particles (VLPs). To optimize VP2 gene expression in Sf9 cells, we converted wild-type VP2 (VP2) codons into codons that are more common in insect genes. This change greatly increased VP2 protein production in Sf9 cells. The protein generated from the codon-optimized VP2 (optVP2) was detected by immunoblotting and an indirect immunofluorescence assay (IFA). Transmission electron microscopy analysis revealed the formation of VLPs. These findings indicate that optVP2 yielded stable and high-quality VLPs. Immunogenicity assays revealed that the VLPs are highly immunogenic, elicit a high level of neutralizing antibodies and provide protection against lethal challenge. The antibody levels appeared to be directly related to the number of GP-Ag-positive hepatocytes. The variation trends for GP-Ag-positive hepatocytes were similar in the vaccine groups. In comparison with the control group, the optVP2 VLPs groups exhibited obviously better responses. These data indicate that the VLPs retained immunoreactivity and had strong immunogenicity in susceptible geese. Thus, GPV optVP2 appears to be a good candidate for the vaccination of goslings. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Robust production of virus-like particles and monoclonal antibodies with geminiviral replicon vectors in lettuce

    Science.gov (United States)

    Lai, Huafang; He, Junyun; Engle, Michael; Diamond, Michael S.; Chen, Qiang

    2011-01-01

    Summary Pharmaceutical protein production in plants has been greatly promoted by the development of viral-based vectors and transient expression systems. Tobacco and related Nicotiana species are currently the most common host plants for generation of plant-made pharmaceutical proteins (PMPs). Downstream processing of target PMPs from these plants, however, is hindered by potential technical and regulatory difficulties due to the presence of high levels of phenolics and toxic alkaloids. Here, we explored the use of lettuce, which grows quickly yet produces low levels of secondary metabolites, and viral vector-based transient expression systems to develop a robust PMP production platform. Our results showed that a geminiviral replicon system based on the bean yellow dwarf virus permits high-level expression in lettuce of virus-like particles (VLP) derived from the Norwalk virus capsid protein and therapeutic monoclonal antibodies (mAbs) against Ebola and West Nile viruses. These vaccine and therapeutic candidates can be readily purified from lettuce leaves with scalable processing methods while fully retaining functional activity. Furthermore, this study also demonstrated the feasibility of using commercially produced lettuce for high-level PMP production. This allows our production system to have access to unlimited quantities of inexpensive plant material for large-scale production. These results establish a new production platform for biological pharmaceutical agents that is effective, safe, low-cost, and amenable to large-scale manufacturing. PMID:21883868

  3. Homologous and Heterologous Protection of Nonhuman Primates by Ebola and Sudan Virus-Like Particles

    Science.gov (United States)

    Warfield, Kelly L.; Dye, John M.; Wells, Jay B.; Unfer, Robert C.; Holtsberg, Frederick W.; Shulenin, Sergey; Vu, Hong; Swenson, Dana L.; Bavari, Sina; Aman, M. Javad

    2015-01-01

    Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components. PMID:25793502

  4. Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.

    Directory of Open Access Journals (Sweden)

    Kelly L Warfield

    Full Text Available Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV and Marburg virus (MARV following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system and then demonstrate protection against Sudan virus (SUDV and Taï Forest virus (TAFV. Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components.

  5. Virus-Like Particle Engineering: From Rational Design to Versatile Applications.

    Science.gov (United States)

    Ding, Xuanwei; Liu, Dong; Booth, George; Gao, Wei; Lu, Yuan

    2018-05-01

    As mimicking natural virus structures, virus-like particles (VLPs) have evolved to become a widely accepted technology used for humans which are safe, highly efficacious, and profitable. Several remarkable advantages have been achieved to revolutionize the molecule delivery for diverse applications in nanotechnology, biotechnology, and medicine. Here, the rational structure design, manufacturing process, functionalization strategy, and emerging applications of VLPs is reviewed. The situation and challenges in the VLP engineering, the key development orientation, and future applications have been discussed. To develop a good VLP design concept, the virus/VLP-host interactions need to be examined and the screening methods of the VLP stabilization factors need to be established. The functionalization toolbox can be expanded to fabricate smart, robust, and multifunctional VLPs. Novel robust VLP manufacturing platforms are required to deliver vaccines in resource-poor regions with a significant reduction in the production time and cost. The future applications of VLPs are always driven by the development of emerging technologies and new requirements of modern life. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Effects of adjuvants on IgG subclasses elicited by virus-like Particles

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    Visciano Maria Luisa

    2012-01-01

    Full Text Available Abstract Background Virus-Like Particles (VLPs represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C adjuvants, has been evaluated in an animal model. Results Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3, with poly(I:C more potent than CpG ODN1826. Conclusions The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.

  7. Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice

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    Zhang Quanfu

    2011-06-01

    Full Text Available Abstract Background The incidence of dengue, an infectious disease caused by dengue virus (DENV, has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated. Results By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses. Conclusions Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.

  8. Expression and characterization of human group C rotavirus virus-like particles in insect cells

    International Nuclear Information System (INIS)

    Clark, Kristina B.; Lin, S.-C.; Humphrey, Charles; Foytich, Kimberly; Esona, Mathew; Wang Yuhuan; Liu, Merry; Jiang Baoming

    2009-01-01

    Group C rotavirus (GpC RV) is a causative agent of acute gastroenteritis in children and adults. We expressed the three major capsid proteins VP2, VP6 and VP7 of human GpC RV in baculovirus and demonstrated the self-assembly of VP2/6/7 or VP6/7 virus-like particles (VLPs) in insect cells. We examined a number of parameters, including the kinetics of protein synthesis in different cell lines and media, to optimize the most favorable conditions for the synthesis of recombinant viral proteins and the production of VLPs in Sf9 cells. Hyperimmune serum to VP2/6/7 and VP6/7 VLPs recognized individual recombinant proteins of human GpC RV by Western blot analysis. This serum also showed specific reactivities with the corresponding GpC VLPs but not GpA RV by using immune electron microscopy (IEM) and enzyme immunoassay (EIA). The ability to produce an unlimited amount of GpC RV antigen and the availability of high quality antibody will allow us to develop sensitive and specific diagnostic assays to better determine the epidemiology and disease burden of GpC RV in humans.

  9. Preclinical Development and Production of Virus-Like Particles As Vaccine Candidates for Hepatitis C

    Directory of Open Access Journals (Sweden)

    Makutiro Ghislain Masavuli

    2017-12-01

    Full Text Available Hepatitis C Virus (HCV infects 2% of the world’s population and is the leading cause of liver disease and liver transplantation. It poses a serious and growing worldwide public health problem that will only be partially addressed with the introduction of new antiviral therapies. However, these treatments will not prevent re-infection particularly in high risk populations. The introduction of a HCV vaccine has been predicted, using simulation models in a high risk population, to have a significant effect on reducing the incidence of HCV. A vaccine with 50 to 80% efficacy targeted to high-risk intravenous drug users could dramatically reduce HCV incidence in this population. Virus like particles (VLPs are composed of viral structural proteins which self-assemble into non-infectious particles that lack genetic material and resemble native viruses. Thus, VLPs represent a safe and highly immunogenic vaccine delivery platform able to induce potent adaptive immune responses. Currently, many VLP-based vaccines have entered clinical trials, while licensed VLP vaccines for hepatitis B virus (HBV and human papilloma virus (HPV have been in use for many years. The HCV core, E1 and E2 proteins can self-assemble into immunogenic VLPs while inclusion of HCV antigens into heterogenous (chimeric VLPs is also a promising approach. These VLPs are produced using different expression systems such as bacterial, yeast, mammalian, plant, or insect cells. Here, this paper will review HCV VLP-based vaccines and their immunogenicity in animal models as well as the different expression systems used in their production.

  10. An enhanced heterologous virus-like particle for human papillomavirus type 16 tumour immunotherapy.

    Directory of Open Access Journals (Sweden)

    Khairunadwa Jemon

    Full Text Available Cervical cancer is caused by high-risk, cancer-causing human papillomaviruses (HPV and is the second highest cause of cancer deaths in women globally. The majority of cervical cancers express well-characterized HPV oncogenes, which are potential targets for immunotherapeutic vaccination. Here we develop a rabbit haemorrhagic disease virus (RHDV virus-like particle (VLP-based vaccine designed for immunotherapy against HPV16 positive tumours. An RHDV-VLP, modified to contain the universal helper T cell epitope PADRE and decorated with an MHC I-restricted peptide (aa 48-57 from the HPV16 E6, was tested for its immunotherapeutic efficacy against the TC-1 HPV16 E6 and E7-expressing tumour in mice. The E6-RHDV-VLP-PADRE was administered therapeutically for the treatment of a pre-existing TC-1 tumour and was delivered with antibodies either to deplete regulatory T cells (anti-CD25 or to block T cell suppression mediated through CTLA-4. As a result, the tumour burden was reduced by around 50% and the median survival time of mice to the humane endpoint was almost doubled the compared to controls. The incorporation of PADRE into the RHDV-VLP was necessary for an E6-specific enhancement of the anti-tumour response and the co-administration of the immune modifying antibodies contributed to the overall efficacy of the immunotherapy. The E6-RHDV-VLP-PADRE shows immunotherapeutic efficacy, prolonging survival for HPV tumour-bearing mice. This was enhanced by the systemic administration of immune-modifying antibodies that are commercially available for use in humans. There is potential to further modify these particles for even greater efficacy in the path to development of an immunotherapeutic treatment for HPV precancerous and cancer stages.

  11. Evidences of Changes in Surface Electrostatic Charge Distribution during Stabilization of HPV16 Virus-Like Particles.

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    Juan F Vega

    Full Text Available The stabilization of human papillomavirus type 16 virus-like particles has been examined by means of different techniques including dynamic and static light scattering, transmission electron microscopy and electrophoretic mobility. All these techniques provide different and often complementary perspectives about the aggregation process and generation of stabilized virus-like particles after a period of time of 48 hours at a temperature of 298 K. Interestingly, static light scattering results point towards a clear colloidal instability in the initial systems, as suggested by a negative value of the second virial coefficient. This is likely related to small repulsive electrostatic interactions among the particles, and in agreement with relatively small absolute values of the electrophoretic mobility and, hence, of the net surface charges. At this initial stage the small repulsive interactions are not able to compensate binding interactions, which tend to aggregate the particles. As time proceeds, an increase of the size of the particles is accompanied by strong increases, in absolute values, of the electrophoretic mobility and net surface charge, suggesting enhanced repulsive electrostatic interactions and, consequently, a stabilized colloidal system. These results show that electrophoretic mobility is a useful methodology that can be applied to screen the stabilization factors for virus-like particles during vaccine development.

  12. Application of virus-like particles (VLP) to NMR characterization of viral membrane protein interactions

    Energy Technology Data Exchange (ETDEWEB)

    Antanasijevic, Aleksandar; Kingsley, Carolyn [University of Illinois at Chicago, Department of Biochemistry and Molecular Genetics (United States); Basu, Arnab; Bowlin, Terry L. [Microbiotix Inc. (United States); Rong, Lijun [University of Illinois at Chicago, Department of Microbiology and Immunology (United States); Caffrey, Michael, E-mail: caffrey@uic.edu [University of Illinois at Chicago, Department of Biochemistry and Molecular Genetics (United States)

    2016-03-15

    The membrane proteins of viruses play critical roles in the virus life cycle and are attractive targets for therapeutic intervention. Virus-like particles (VLP) present the possibility to study the biochemical and biophysical properties of viral membrane proteins in their native environment. Specifically, the VLP constructs contain the entire protein sequence and are comprised of native membrane components including lipids, cholesterol, carbohydrates and cellular proteins. In this study we prepare VLP containing full-length hemagglutinin (HA) or neuraminidase (NA) from influenza and characterize their interactions with small molecule inhibitors. Using HA-VLP, we first show that VLP samples prepared using the standard sucrose gradient purification scheme contain significant amounts of serum proteins, which exhibit high potential for non-specific interactions, thereby complicating NMR studies of ligand-target interactions. We then show that the serum contaminants may be largely removed with the addition of a gel filtration chromatography step. Next, using HA-VLP we demonstrate that WaterLOGSY NMR is significantly more sensitive than Saturation Transfer Difference (STD) NMR for the study of ligand interactions with membrane bound targets. In addition, we compare the ligand orientation to HA embedded in VLP with that of recombinant HA by STD NMR. In a subsequent step, using NA-VLP we characterize the kinetic and binding properties of substrate analogs and inhibitors of NA, including study of the H274Y-NA mutant, which leads to wide spread resistance to current influenza antivirals. In summary, our work suggests that VLP have high potential to become standard tools in biochemical and biophysical studies of viral membrane proteins, particularly when VLP are highly purified and combined with control VLP containing native membrane proteins.

  13. Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles

    International Nuclear Information System (INIS)

    Guo Lizheng; Lu Xiaoyan; Kang, S.-M.; Chen Changyi; Compans, Richard W.; Yao Qizhi

    2003-01-01

    To enhance mucosal immune responses using simian/human immunodeficiency virus-like particles (SHIV VLPs), we have produced novel phenotypically mixed chimeric influenza HA/SHIV VLPs and used them to immunize C57BL/6J mice intranasally. Antibody and cytotoxic T-cell (CTL) responses as well as cytokine production in both systemic and mucosal sites were compared after immunization with SHIV VLPs or chimeric HA/SHIV VLPs. By using enzyme-linked immunosorbent assay (ELISA), the levels of serum IgG and mucosal IgA to the HIV envelope protein (Env) were found to be highest in the group immunized with chimeric HA/SHIV VLPs. Furthermore, the highest titer of serum neutralizing antibody against HIV Env was found with the group immunized with chimeric HA/SHIV VLPs. Analysis of the IgG1/IgG2a ratio indicated that a T H 1-oriented immune response resulted from these VLP immunizations. HA/SHIV VLP-immunized mice also showed significantly higher CTL responses than those observed in SHIV VLP-immunized mice. Moreover, a MHC class I restricted T-cell activation ELISPOT assay showed a mixed type of T H 1/T H 2 cytokines in the HA/SHIV VLP-immunized mice, indicating that the chimeric VLPs can enhance both humoral and cellular immune responses to the HIV Env protein at multiple mucosal and systemic sites. The results indicate that incorporation of influenza HA into heterotypic VLPs may be highly effective for targeting vaccines to mucosal surfaces

  14. [Expression, purification and immunogenicity of human papillomavirus type 11 virus-like particles from Escherichia coli].

    Science.gov (United States)

    Yan, Chunyan; Li, Shaowei; Wang, Jin; Wei, Minxi; Huang, Bo; Zhuang, Yudi; Li, Zhongyi; Pan, Huirong; Zhang, Jun; Xia, Ningshao

    2009-11-01

    To produce human papillomavirus type 11 virus-like particles (HPV11 VLPs) from Escherichia coli and to investigate its immunogenicity and type cross neutralization nature. We expressed the major capsid protein of HPV11 (HPV11-L1) in Escherichia coli ER2566 in non fusion fashion and purified by amino sulfate precipitation, ion-exchange chromatography and hydrophobic interaction chromatography, sequentially. Then we removed the reductant DTT to have the purified HPV11-L1 self-assemble into VLPs in vitro. We investigated the morphology of these VLPs with dynamic light scattering and transmission electron microscopy. We assayed the immunogenicity of the resultant HPV11 VLPs by vaccinations on mice and evaluated by HPV6/11/16/18 pseudovirion neutralization cell models. We expressed HPV11 L1 in Escherichia coli with two forms, soluble and inclusion body. The soluble HPV11 L1 with over 95% purity can self assemble to VLPs in high efficiency. Morphologically, these VLPs were globular, homogeneous and with a diameter of - 50 nm, which is quite similar with native HPV11 virions. The half effective dosage (ED50) of HPV11 VLPs is 0.031 microg, and the maximum titer of neutralizing antibody elicited is averaged to 10(6). The cross neutralization activity (against HPV6/16/18) of the anti-HPV11 serum was found to have exact correlation to the inter-type homology in amino acid alignment. We can provide HPV11 VLPs with highly immunogenicity from prokaryote expression system, which may pave a new way for research and development of prophylactic vaccine for HPV11.

  15. ESCRT-independent budding of HIV-1 gag virus-like particles from Saccharomyces cerevisiae spheroplasts.

    Directory of Open Access Journals (Sweden)

    Andrew P Norgan

    Full Text Available Heterologous expression of HIV-1 Gag in a variety of host cells results in its packaging into virus-like particles (VLPs that are subsequently released into the extracellular milieu. This phenomenon represents a useful tool for probing cellular factors required for viral budding and has contributed to the discovery of roles for ubiquitin ligases and the endosomal sorting complexes required for transport (ESCRTs in viral budding. These factors are highly conserved throughout eukaryotes and have been studied extensively in the yeast Saccharomyces cerevisiae, a model eukaryote previously utilized as a host for the production of VLPs. We used heterologous expression of HIV Gag in yeast spheroplasts to examine the role of ESCRTs and associated factors (Rsp5, a HECT ubiquitin ligase of the Nedd4 family; Bro1, a homolog of Alix; and Vps4, the AAA-ATPase required for ESCRT function in all contexts/organisms investigated in the generation of VLPs. Our data reveal: 1 characterized Gag-ESCRT interaction motifs (late domains are not required for VLP budding, 2 loss of function alleles of the essential HECT ubiquitin ligase Rsp5 do not display defects in VLP formation, and 3 ESCRT function is not required for VLP formation from spheroplasts. These results suggest that the egress of HIV Gag from yeast cells is distinct from the most commonly described mode of exit from mammalian cells, instead mimicking ESCRT-independent VLP formation observed in a subset of mammalian cells. As such, budding of Gag from yeast cells appears to represent ESCRT-independent budding relevant to viral replication in at least some situations. Thus the myriad of genetic and biochemical tools available in the yeast system may be of utility in the study of this aspect of viral budding.

  16. Characterizing Enterovirus 71 and Coxsackievirus A16 virus-like particles production in insect cells.

    Science.gov (United States)

    Somasundaram, Balaji; Chang, Cindy; Fan, Yuan Y; Lim, Pei-Yin; Cardosa, Jane; Lua, Linda

    2016-02-15

    Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are two viruses commonly responsible for hand, foot and mouth disease (HFMD) in children. The lack of prophylactic or therapeutic measures against HFMD is a major public health concern. Insect cell-based EV71 and CVA16 virus-like particles (VLPs) are promising vaccine candidates against HFMD and are currently under development. In this paper, the influence of insect cell line, incubation temperature, and serial passaging effect and stability of budded virus (BV) stocks on EV71 and CVA16 VLP production was investigated. Enhanced EV71 and CVA16 VLP production was observed in Sf9 cells compared to High Five™ cells. Lowering the incubation temperature from the standard 27°C to 21°C increased the production of both VLPs in Sf9 cells. Serial passaging of CVA16 BV stocks in cell culture had a detrimental effect on the productivity of the structural proteins and the effect was observed with only 5 passages of BV stocks. A 2.7× higher production yield was achieved with EV71 compared to CVA16. High-resolution asymmetric flow field-flow fractionation couple with multi-angle light scattering (AF4-MALS) was used for the first time to characterize EV71 and CVA16 VLPs, displaying an average root mean square radius of 15±1nm and 15.3±5.8 nm respectively. This study highlights the need for different approaches in the design of production process to develop a bivalent EV71 and CVA16 vaccine. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Human immunodeficiency virus-like particles activate multiple types of immune cells

    International Nuclear Information System (INIS)

    Sailaja, Gangadhara; Skountzou, Ioanna; Quan, Fu-Shi; Compans, Richard W.; Kang, Sang-Moo

    2007-01-01

    The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down-regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses

  18. Negative chromatography of hepatitis B virus-like particle: Comparative study of different adsorbent designs.

    Science.gov (United States)

    Lee, Micky Fu Xiang; Chan, Eng Seng; Tan, Wen Siang; Tam, Kam Chiu; Tey, Beng Ti

    2016-05-06

    Purification of virus-like particles (VLPs) in bind-and-elute mode has reached a bottleneck. Negative chromatography has emerged as the alternative solution; however, benchmark of negative chromatography media and their respective optimized conditions are absent. Hence, this study was carried out to compare the performance of different negative chromatography media for the purification of hepatitis B VLPs (HB-VLPs) from clarified Escherichia coli feedstock. The modified anion exchange media, core-shell adsorbents (InertShell and InertLayer 1000) and polymer grafted adsorbents (SQ) were compared. The results of chromatography from packed bed column of core-shell adsorbents showed that there is a trade-off between the purity and recovery of HB-VLPs in the flowthrough fraction due to the shell thickness. Atomic force microscopic analysis revealed funnel-shaped pore channels in the shell layer which may contribute to the entrapment of HB-VLPs. A longer residence time at a lower feed flow rate (0.5ml/min) improved slightly the HB-VLPs purity in all modified adsorbents, but the recovery in InertShell reduced substantially. The preheat-treatment is not recommended for the negative chromatography as the thermal-induced co-aggregation of HCPs and HB-VLPs would flow along with HB-VLPs and thus reduced the HB-VLPs purity in the flowthrough. Further reduction in the feedstock concentration enhanced the purity of HB-VLPs especially in InertLayer 1000 but reduced substantially the recovery of HB-VLPs. In general, the polymer grafted adsorbent, SQ, performed better than the core-shell adsorbents in handling a higher feedstock concentration. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Biomedical and Catalytic Opportunities of Virus-Like Particles in Nanotechnology.

    Science.gov (United States)

    Schwarz, B; Uchida, M; Douglas, T

    2017-01-01

    Within biology, molecules are arranged in hierarchical structures that coordinate and control the many processes that allow for complex organisms to exist. Proteins and other functional macromolecules are often studied outside their natural nanostructural context because it remains difficult to create controlled arrangements of proteins at this size scale. Viruses are elegantly simple nanosystems that exist at the interface of living organisms and nonliving biological machines. Studied and viewed primarily as pathogens to be combatted, viruses have emerged as models of structural efficiency at the nanoscale and have spurred the development of biomimetic nanoparticle systems. Virus-like particles (VLPs) are noninfectious protein cages derived from viruses or other cage-forming systems. VLPs provide incredibly regular scaffolds for building at the nanoscale. Composed of self-assembling protein subunits, VLPs provide both a model for studying materials' assembly at the nanoscale and useful building blocks for materials design. The robustness and degree of understanding of many VLP structures allow for the ready use of these systems as versatile nanoparticle platforms for the conjugation of active molecules or as scaffolds for the structural organization of chemical processes. Lastly the prevalence of viruses in all domains of life has led to unique activities of VLPs in biological systems most notably the immune system. Here we discuss recent efforts to apply VLPs in a wide variety of applications with the aim of highlighting how the common structural elements of VLPs have led to their emergence as paradigms for the understanding and design of biological nanomaterials. © 2017 Elsevier Inc. All rights reserved.

  20. Evaluation of the stability of enterovirus 71 virus-like particle.

    Science.gov (United States)

    Lin, Shih-Yeh; Chung, Yao-Chi; Chiu, Hsin-Yi; Chi, Wei-Kuang; Chiang, Bor-Luen; Hu, Yu-Chen

    2014-03-01

    Enterovirus 71 (EV71) is responsible for the outbreaks of hand-foot-and-mouth disease that caused significant mortality in children, but no vaccine is available yet. EV71 virus-like particle (VLP) is the empty capsid consisting of viral structural proteins but can elicit potent immune responses, rendering VLP a promising EV71 vaccine candidate. To evaluate whether VLP remains stable after long-term storage, which is crucial for advancing the VLP vaccine to the clinical setting, we evaluated the effects of NaCl concentration, buffers and temperatures on the VLP stability. We first validated the use of dynamic light scattering (DLS) for measuring the hydrodynamic diameter (≈30-35 nm) of VLP, which was close to the VLP diameter (≈25-27 nm) as measured by transmission electron microscopy (TEM). Using these techniques, we found that EV71 VLP remained stable for 5 months in sodium phosphate (NaPi) buffers with various NaCl concentrations. EV71 VLP also remained morphologically stable in NaPi, citrate and TE(+) buffers for 5 months, yet the enzyme-linked immunosorbent assay (ELISA) revealed that the VLP stored in citrate and TE(+) buffers partially lost the immunogenicity after 5 months. In contrast, the VLP stored in the NaPi buffer at 4°C remained stable macroscopically and microscopically for 5 months, as judged from the DLS, TEM and ELISA. The VLP stored at 25°C and 37°C also retained stability for 1 month, which would obviate the need of a cold chain during the shipping. These data altogether proved the stability of EV71 VLP and suggested that the VLP is amenable to bioprocessing and storage. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles

    OpenAIRE

    Bárcena, Juan; Guerra, Beatriz; Angulo, Iván; González, Julia; Valcárcel, Félix; Mata, Carlos P.; Castón, José R.; Blanco, Esther; Alejo, Alí

    2015-01-01

    International audience; In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particl...

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

    Directory of Open Access Journals (Sweden)

    Bettina Huber

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

  3. Effect of HIV-1 envelope cytoplasmic tail on adenovirus primed virus encoded virus-like particle immunizations

    DEFF Research Database (Denmark)

    Andersson, Anne Marie C; Ragonnaud, Emeline; Seaton, Kelly E.

    2016-01-01

    were found between the different priming regimens as both induced high titered tier 1 neutralizing antibodies, but no tier 2 antibodies, possibly reflecting the similar presentation of trimer specific antibody epitopes. The described vaccine regimens provide insight into the effects of the HIV-1 Env......The low number of envelope (Env) spikes presented on native HIV-1 particles is a major impediment for HIV-1 prophylactic vaccine development. We designed virus-like particle encoding adenoviral vectors utilizing SIVmac239 Gag as an anchor for full length and truncated HIV-1 M consensus Env...

  4. A molecular assembly system for presentation of antigens on the surface of HBc virus-like particles

    Energy Technology Data Exchange (ETDEWEB)

    Blokhina, Elena A.; Kuprianov, Victor V. [Centre ' Bioengineering' , Russian Academy of Sciences, 117312 Prosp. 60-letya Oktyabrya 7-1, Moscow (Russian Federation); Stepanova, Ludmila A.; Tsybalova, Ludmila M. [Research Institute of Influenza, Russian Federation Ministry of Health and Social Development, St. Petersburg (Russian Federation); Kiselev, Oleg I. [Research Institute of Influenza, Russian Federation Ministry of Health and Social Development, St. Petersburg (Russian Federation); GenNanotech Ltd, St. Petersburg (Russian Federation); Ravin, Nikolai V., E-mail: nravin@biengi.ac.ru [Centre ' Bioengineering' , Russian Academy of Sciences, 117312 Prosp. 60-letya Oktyabrya 7-1, Moscow (Russian Federation); GenNanotech Ltd, St. Petersburg (Russian Federation); Skryabin, Konstantin G. [Centre ' Bioengineering' , Russian Academy of Sciences, 117312 Prosp. 60-letya Oktyabrya 7-1, Moscow (Russian Federation); GenNanotech Ltd, St. Petersburg (Russian Federation)

    2013-01-20

    Hepatitis B virus-like particles, icosahedral structures formed by multiple core protein dimers, are promising immune-enhancing vaccine carriers for foreign antigens. Insertions into the surface-exposed immunodominant loop are especially immunogenic. However, the need to conserve the particulate structure to ensure high immunogenicity imposes restraints on the nature of the heterologous sequence that can be inserted. We propose a new approach to constructing HBc particles linked to the target epitopes that relies on non-covalent interactions between the epitope and pre-assembled unmodified HBc particles. Interaction was enabled by fusion of the epitope to the GSLLGRMKGA peptide, binding to the spike tips. This peptide may be used as a 'binding tag' allowing in vitro construction of HBc particles carrying the target peptide. Such virus-like particles carrying multiple copies of the extracellular domain of the M2 protein of different influenza strains appeared to be highly immunogenic and protected immunised mice against a lethal influenza challenge.

  5. A molecular assembly system for presentation of antigens on the surface of HBc virus-like particles

    International Nuclear Information System (INIS)

    Blokhina, Elena A.; Kuprianov, Victor V.; Stepanova, Ludmila A.; Tsybalova, Ludmila M.; Kiselev, Oleg I.; Ravin, Nikolai V.; Skryabin, Konstantin G.

    2013-01-01

    Hepatitis B virus-like particles, icosahedral structures formed by multiple core protein dimers, are promising immune-enhancing vaccine carriers for foreign antigens. Insertions into the surface-exposed immunodominant loop are especially immunogenic. However, the need to conserve the particulate structure to ensure high immunogenicity imposes restraints on the nature of the heterologous sequence that can be inserted. We propose a new approach to constructing HBc particles linked to the target epitopes that relies on non-covalent interactions between the epitope and pre-assembled unmodified HBc particles. Interaction was enabled by fusion of the epitope to the GSLLGRMKGA peptide, binding to the spike tips. This peptide may be used as a “binding tag” allowing in vitro construction of HBc particles carrying the target peptide. Such virus-like particles carrying multiple copies of the extracellular domain of the M2 protein of different influenza strains appeared to be highly immunogenic and protected immunised mice against a lethal influenza challenge.

  6. Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Stoiber, Heribert; Nchinda, Godwin; Floto, Anja; Franz, Monika; Sauermann, Ulrike; Bredl, Simon; Deml, Ludwig; Ignatius, Ralf; Norley, Steve; Racz, Paul; Tenner-Racz, Klara; Steinman, Ralph M.; Wagner, Ralf; Uberla, Klaus

    2006-01-01

    Vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (VLP) has generally failed to provide sufficient protection in animal models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein (VSV-G), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. Therefore, we pseudotyped noninfectious immunodeficiency virus-like particles with VSV-G and carried out a preliminary screen of their immunogenicity and vaccination efficacy. Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers to HIV-1 Gag and enhancement of T cell responses in mice. Repeated vaccination of rhesus monkeys for 65 weeks with VSV-G pseudotyped simian immunodeficiency virus (SIV)-like particles (VLP[G]) provided initial evidence for efficient suppression of viral load after mucosal challenge with the SIVmac239 virus. Challenge of monkeys after a 28 week vaccination regimen with VLP[G] led to a reduction in peak viremia, but persistent suppression of viral load was not achieved. Due to limitations in the number of animals available for this study, improved efficacy of VSV-G pseudotyped VLPs in nonhuman primates could not be demonstrated. However, mouse experiments revealed that pseudotyping of VLPs with fusion-competent VSV-G clearly improves their immunogenicity. Additional strategies, particularly adjuvants, should be considered to provide greater protection against a challenge with pathogenic immunodeficiency virus

  7. Production of Novel Ebola Virus-Like Particles from cDNAs: an Alternative to Ebola Virus Generation by Reverse Genetics

    OpenAIRE

    Watanabe, Shinji; Watanabe, Tokiko; Noda, Takeshi; Takada, Ayato; Feldmann, Heinz; Jasenosky, Luke D.; Kawaoka, Yoshihiro

    2004-01-01

    We established a plasmid-based system for generating infectious Ebola virus-like particles (VLPs), which contain an Ebola virus-like minigenome consisting of a negative-sense copy of the green fluorescent protein gene. This system produced nearly 103 infectious particles per ml of supernatant, equivalent to the titer of Ebola virus generated by a reverse genetics system. Interestingly, infectious Ebola VLPs were generated, even without expression of VP24. Transmission and scanning electron mi...

  8. Oral Immunization with Recombinant Norwalk Virus-Like Particles Induces a Systemic and Mucosal Immune Response in Mice

    OpenAIRE

    Ball, Judith M.; Hardy, Michele E.; Atmar, Robert L.; Conner, Margaret E.; Estes, Mary K.

    1998-01-01

    Recombinant Norwalk virus-like particles (rNV VLPs) produced in insect cells were evaluated as an oral immunogen in CD1 and BALB/c mice by monitoring rNV-specific serum total and subclass immunoglobulin G (IgG) and intestinal IgA responses. Dose and kinetics of response were evaluated in the presence and absence of the mucosal adjuvant cholera toxin (CT). rNV-specific serum IgG and intestinal IgA were detected in the absence of CT, and the number of responders was not significantly different ...

  9. Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles.

    Science.gov (United States)

    Bárcena, Juan; Guerra, Beatriz; Angulo, Iván; González, Julia; Valcárcel, Félix; Mata, Carlos P; Castón, José R; Blanco, Esther; Alejo, Alí

    2015-09-24

    In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particles (VLPs). Our results further confirmed the differential antigenic properties exhibited by RHDV and RHDV2, highlighting the need of using RHDV2-specific diagnostic assays to monitor the spread of this new virus.

  10. Synthetic virus-like particles target dendritic cell lipid rafts for rapid endocytosis primarily but not exclusively by macropinocytosis.

    Directory of Open Access Journals (Sweden)

    Rajni Sharma

    Full Text Available DC employ several endocytic routes for processing antigens, driving forward adaptive immunity. Recent advances in synthetic biology have created small (20-30 nm virus-like particles based on lipopeptides containing a virus-derived coiled coil sequence coupled to synthetic B- and T-cell epitope mimetics. These self-assembling SVLP efficiently induce adaptive immunity without requirement for adjuvant. We hypothesized that the characteristics of DC interaction with SVLP would elaborate on the roles of cell membrane and intracellular compartments in the handling of a virus-like entity known for its efficacy as a vaccine. DC rapidly bind SVLP within min, co-localised with CTB and CD9, but not caveolin-1. In contrast, internalisation is a relatively slow process, delivering SVLP into the cell periphery where they are maintained for a number of hrs in association with microtubules. Although there is early association with clathrin, this is no longer seen after 10 min. Association with EEA-1(+ early endosomes is also early, but proteolytic processing appears slow, the SVLP-vesicles remaining peripheral. Association with transferrin occurs rarely, and only in the periphery, possibly signifying translocation of some SVLP for delivery to B-lymphocytes. Most SVLP co-localise with high molecular weight dextran. Uptake of both is impaired with mature DC, but there remains a residual uptake of SVLP. These results imply that DC use multiple endocytic routes for SVLP uptake, dominated by caveolin-independent, lipid raft-mediated macropinocytosis. With most SVLP-containing vesicles being retained in the periphery, not always interacting with early endosomes, this relates to slow proteolytic degradation and antigen retention by DC. The present characterization allows for a definition of how DC handle virus-like particles showing efficacious immunogenicity, elements valuable for novel vaccine design in the future.

  11. Synthetic Virus-Like Particles Target Dendritic Cell Lipid Rafts for Rapid Endocytosis Primarily but Not Exclusively by Macropinocytosis

    Science.gov (United States)

    Sharma, Rajni; Ghasparian, Arin; Robinson, John A.; McCullough, Kenneth C.

    2012-01-01

    DC employ several endocytic routes for processing antigens, driving forward adaptive immunity. Recent advances in synthetic biology have created small (20–30 nm) virus-like particles based on lipopeptides containing a virus-derived coiled coil sequence coupled to synthetic B- and T-cell epitope mimetics. These self-assembling SVLP efficiently induce adaptive immunity without requirement for adjuvant. We hypothesized that the characteristics of DC interaction with SVLP would elaborate on the roles of cell membrane and intracellular compartments in the handling of a virus-like entity known for its efficacy as a vaccine. DC rapidly bind SVLP within min, co-localised with CTB and CD9, but not caveolin-1. In contrast, internalisation is a relatively slow process, delivering SVLP into the cell periphery where they are maintained for a number of hrs in association with microtubules. Although there is early association with clathrin, this is no longer seen after 10 min. Association with EEA-1+ early endosomes is also early, but proteolytic processing appears slow, the SVLP-vesicles remaining peripheral. Association with transferrin occurs rarely, and only in the periphery, possibly signifying translocation of some SVLP for delivery to B-lymphocytes. Most SVLP co-localise with high molecular weight dextran. Uptake of both is impaired with mature DC, but there remains a residual uptake of SVLP. These results imply that DC use multiple endocytic routes for SVLP uptake, dominated by caveolin-independent, lipid raft-mediated macropinocytosis. With most SVLP-containing vesicles being retained in the periphery, not always interacting with early endosomes, this relates to slow proteolytic degradation and antigen retention by DC. The present characterization allows for a definition of how DC handle virus-like particles showing efficacious immunogenicity, elements valuable for novel vaccine design in the future. PMID:22905240

  12. Inactivation and purification of cowpea mosaic virus-like particles displaying peptide antigens from Bacillus anthracis

    OpenAIRE

    Phelps, Jamie P.; Dang, Nghiep; Rasochova, Lada

    2007-01-01

    Chimeric cowpea mosaic virus (CPMV) particles displaying foreign peptide antigens on the particle surface are suitable for development of peptide-based vaccines. However, commonly used PEG precipitation-based purification methods are not sufficient for production of high quality vaccine candidates because they do not allow for separation of chimeric particles from cleaved contaminating species. Moreover, the purified particles remain infectious to plants. To advance the CPMV technology furthe...

  13. A novel recombinant virus-like particle vaccine for prevention of porcine parvovirus-induced reproductive failure.

    Science.gov (United States)

    Antonis, Adriaan F G; Bruschke, Christianne J M; Rueda, Paloma; Maranga, Luis; Casal, J Ignacio; Vela, Carmen; Hilgers, Luuk A Th; Belt, Peter B G M; Weerdmeester, Klaas; Carrondo, Manuel J T; Langeveld, Jan P M

    2006-06-29

    A novel vaccine against porcine parvovirus (PPV), composed of recombinant virus-like particles (PPV-VLPs) produced with the baculovirus expression vector system (BEVS) at industrial scale, was tested for its immunogenicity and protective potency. A formulation of submicrogram amounts of PPV-VLPs in a water-in-mineral oil adjuvant evoked high serum antibody titres in both guinea pigs, used as reference model, and target species, pigs. A single immunisation with 0.7microg of this antigen yielded complete foetal protection against PPV infection after challenge with a virulent strain of this virus. Furthermore, also in the presence of mild adjuvants the protective action of these PPV-VLPs is excellent. This recombinant subunit vaccine overcomes some of the drawbacks of classical PPV vaccines.

  14. Binding of Human GII.4 Norovirus Virus-Like Particles to Carbohydrates of Romaine Lettuce Leaf Cell Wall Materials

    Science.gov (United States)

    Esseili, Malak A.

    2012-01-01

    Norovirus (NoV) genogroup II genotype 4 (GII.4) strains are the dominant cause of the majority of food-borne outbreaks, including those that involve leafy greens, such as lettuce. Since human NoVs use carbohydrates of histo-blood group antigens as receptors/coreceptors, we examined the role of carbohydrates in the attachment of NoV to lettuce leaves by using virus-like particles (VLPs) of a human NoV/GII.4 strain. Immunofluorescence analysis showed that the VLPs attached to the leaf surface, especially to cut edges, stomata, and along minor veins. Binding was quantified using enzyme-linked immunosorbent assay (ELISA) performed on cell wall materials (CWM) from innermost younger leaves and outermost lamina of older leaves. The binding to CWM of older leaves was significantly (P lettuce CWM by utilizing multiple carbohydrate moieties. This binding may enhance virus persistence on the leaf surface and prevent effective decontamination. PMID:22138991

  15. Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

    Directory of Open Access Journals (Sweden)

    Dace Skrastina

    Full Text Available Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs formed by recombinant full-length Hepatitis B virus core (HBc protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.

  16. Two proteins with reverse transcriptase activities associated with hepatitis B virus-like particles

    International Nuclear Information System (INIS)

    Bavand, M.R.; Laub, O.

    1988-01-01

    Recent studies suggest that hepatitis B virus (HBV), despite being a DNA virus, replicates via an RNA intermediate. The HBV life cycle is therefore a permuted version of the RNA retroviral life cycle. Sequence homology between retroviral reverse transcriptase and the putative HBV polymerase gene product suggests the presence of an HBV reverse transcriptase. As yet, there has been no direct evidence that reverse transcriptase activity is present in the viral particle. The authors used activity gel analysis to detect the in situ catalytic activities of DNA polymerases after sodium dodecyl sulfate-polyacrylamide gel electrophorsis. These studies demonstrated that HBV-like particles secreted by a differentiated human hepatoma cell line tranfected with genomic HBV DNA contain two major polymerase activities which migrate as ∼90- and ∼70-kilodalton (kDa) proteins. This demonstrated, for the first time, that HBV-like particles contain a novel DNA polymerase-reverse transcriptase activity. Furthermore, they propose that the 70-kDa reverse transcriptase may be produced by proteolytic self-cleavage of the 90-kDa precursor protein

  17. Remarkable morphological diversity of viruses and virus-like particles in hot terrestrial environments.

    Science.gov (United States)

    Rachel, R; Bettstetter, M; Hedlund, B P; Häring, M; Kessler, A; Stetter, K O; Prangishvili, D

    2002-12-01

    Electron microscopic studies of the viruses in two hot springs (85 degrees C, pH 1.5-2.0, and 75-93 degrees C, pH 6.5) in Yellowstone National Park revealed particles with twelve different morphotypes. This diversity encompassed known viruses of hyperthermophilic archaea, filamentous Lipothrixviridae, rod-shaped Rudiviridae, and spindle-shaped Fuselloviridae, and novel morphotypes previously not observed in nature. Two virus types resembled head-and-tail bacteriophages from the families Siphoviridae and Podoviridae, and constituted the first observation of these viruses in a hydrothermal environment. Viral hosts in the acidic spring were members of the hyperthermophilic archaeal genus Acidianus.

  18. Selective flocculation and precipitation for the improvement of virus-like particle recovery from yeast homogenate

    DEFF Research Database (Denmark)

    Tsoka, S.; Ciniawskyj, O. C.; Thomas, Owen R. T.

    2000-01-01

    The purification of an intracellular product from a complex mixture of contaminants after cell disruption is a common problem in processes downstream of fermentation systems. This is particularly challenging for the recovery of particulate (80 nm in diameter) multimeric protein products, named vi...... the challenge of scale-up of solid-liquid separation stages for biological particle processing.......The purification of an intracellular product from a complex mixture of contaminants after cell disruption is a common problem in processes downstream of fermentation systems. This is particularly challenging for the recovery of particulate (80 nm in diameter) multimeric protein products, named...

  19. Molecular analysis of human papillomavirus virus-like particle activated Langerhans cells in vitro.

    Science.gov (United States)

    Woodham, Andrew W; Raff, Adam B; Da Silva, Diane M; Kast, W Martin

    2015-01-01

    Langerhans cells (LC) are the resident antigen-presenting cells in human epithelium, and are therefore responsible for initiating immune responses against human papillomaviruses (HPV) entering the epithelial and mucosal layers in vivo. Upon proper pathogenic stimulation, LC become activated causing an internal signaling cascade that results in the up-regulation of co-stimulatory molecules and the release of inflammatory cytokines. Activated LC then migrate to lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response. However, HPV manipulates LC in a suppressive manner that alters these normal maturation responses. Here, in vitro LC activation assays for the detection of phosphorylated signaling intermediates, the up-regulation of activation-associated surface markers, and the release of inflammatory cytokines in response to HPV particles are described.

  20. Recombinant norovirus-specific scFv inhibit virus-like particle binding to cellular ligands

    Directory of Open Access Journals (Sweden)

    Hardy Michele E

    2008-01-01

    Full Text Available Abstract Background Noroviruses cause epidemic outbreaks of gastrointestinal illness in all age-groups. The rapid onset and ease of person-to-person transmission suggest that inhibitors of the initial steps of virus binding to susceptible cells have value in limiting spread and outbreak persistence. We previously generated a monoclonal antibody (mAb 54.6 that blocks binding of recombinant norovirus-like particles (VLP to Caco-2 intestinal cells and inhibits VLP-mediated hemagglutination. In this study, we engineered the antigen binding domains of mAb 54.6 into a single chain variable fragment (scFv and tested whether these scFv could function as cell binding inhibitors, similar to the parent mAb. Results The scFv54.6 construct was engineered to encode the light (VL and heavy (VH variable domains of mAb 54.6 separated by a flexible peptide linker, and this recombinant protein was expressed in Pichia pastoris. Purified scFv54.6 recognized native VLPs by immunoblot, inhibited VLP-mediated hemagglutination, and blocked VLP binding to H carbohydrate antigen expressed on the surface of a CHO cell line stably transfected to express α 1,2-fucosyltransferase. Conclusion scFv54.6 retained the functional properties of the parent mAb with respect to inhibiting norovirus particle interactions with cells. With further engineering into a form deliverable to the gut mucosa, norovirus neutralizing antibodies represent a prophylactic strategy that would be valuable in outbreak settings.

  1. Ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies

    International Nuclear Information System (INIS)

    Ye Ling; Lin Jianguo; Sun Yuliang; Bennouna, Soumaya; Lo, Michael; Wu Qingyang; Bu Zhigao; Pulendran, Bali; Compans, Richard W.; Yang Chinglai

    2006-01-01

    Recombinant baculoviruses (rBV) expressing Ebola virus VP40 (rBV-VP40) or GP (rBV-GP) proteins were generated. Infection of Sf9 insect cells by rBV-VP40 led to assembly and budding of filamentous particles from the cell surface as shown by electron microscopy. Ebola virus-like particles (VLPs) were produced by coinfection of Sf9 cells with rBV-VP40 and rBV-GP, and incorporation of Ebola GP into VLPs was demonstrated by SDS-PAGE and Western blot analysis. Recombinant baculovirus infection of insect cells yielded high levels of VLPs, which were shown to stimulate cytokine secretion from human dendritic cells similar to VLPs produced in mammalian cells. The immunogenicity of Ebola VLPs produced in insect cells was evaluated by immunization of mice. Analysis of antibody responses showed that most of the GP-specific antibodies were of the IgG2a subtype, while no significant level of IgG1 subtype antibodies specific for GP was induced, indicating the induction of a Th1-biased immune response. Furthermore, sera from Ebola VLP immunized mice were able to block infection by Ebola GP pseudotyped HIV virus in a single round infection assay, indicating that a neutralizing antibody against the Ebola GP protein was induced. These results show that production of Ebola VLPs in insect cells using recombinant baculoviruses represents a promising approach for vaccine development against Ebola virus infection

  2. Antiviral Activity of Gold/Copper Sulfide Core/Shell Nanoparticles against Human Norovirus Virus-Like Particles.

    Directory of Open Access Journals (Sweden)

    Jessica Jenkins Broglie

    Full Text Available Human norovirus is a leading cause of acute gastroenteritis worldwide in a plethora of residential and commercial settings, including restaurants, schools, and hospitals. Methods for easily detecting the virus and for treating and preventing infection are critical to stopping norovirus outbreaks, and inactivation via nanoparticles (NPs is a more universal and attractive alternative to other physical and chemical approaches. Using norovirus GI.1 (Norwalk virus-like particles (VLPs as a model viral system, this study characterized the antiviral activity of Au/CuS core/shell nanoparticles (NPs against GI.1 VLPs for the rapid inactivation of HuNoV. Inactivation of VLPs (GI.1 by Au/CuS NPs evaluated using an absorbance-based ELISA indicated that treatment with 0.083 μM NPs for 10 min inactivated ~50% VLPs in a 0.37 μg/ml VLP solution and 0.83 μM NPs for 10 min completely inactivated the VLPs. Increasing nanoparticle concentration and/or VLP-NP contact time significantly increased the virucidal efficacy of Au/CuS NPs. Changes to the VLP particle morphology, size, and capsid protein were characterized using dynamic light scattering, transmission electron microscopy, and Western blot analysis. The strategy reported here provides the first reported proof-of-concept Au/CuS NPs-based virucide for rapidly inactivating human norovirus.

  3. Canine parvovirus VP2 protein expressed in silkworm pupae self-assembles into virus-like particles with high immunogenicity.

    Directory of Open Access Journals (Sweden)

    Hao Feng

    Full Text Available The VP2 structural protein of parvovirus can produce virus-like particles (VLPs by a self-assembly process in vitro, making VLPs attractive vaccine candidates. In this study, the VP2 protein of canine parvovirus (CPV was expressed using a baculovirus expression system and assembled into parvovirus-like particles in insect cells and pupae. Electron micrographs of VLPs showed that they were very similar in size and morphology when compared to the wild-type parvovirus. The immunogenicity of the VLPs was investigated in mice and dogs. Mice immunized intramuscularly with purified VLPs, in the absence of an adjuvant, elicited CD4(+ and CD8(+ T cell responses and were able to elicit a neutralizing antibody response against CPV, while the oral administration of raw homogenates containing VLPs to the dogs resulted in a systemic immune response and long-lasting immunity. These results demonstrate that the CPV-VLPs stimulate both cellular and humoral immune responses, and so CPV-VLPs may be a promising candidate vaccine for the prevention of CPV-associated disease.

  4. Canine parvovirus VP2 protein expressed in silkworm pupae self-assembles into virus-like particles with high immunogenicity.

    Science.gov (United States)

    Feng, Hao; Hu, Gui-qiu; Wang, Hua-lei; Liang, Meng; Liang, Hongru; Guo, He; Zhao, Pingsen; Yang, Yu-jiao; Zheng, Xue-xing; Zhang, Zhi-fang; Zhao, Yong-kun; Gao, Yu-wei; Yang, Song-tao; Xia, Xian-zhu

    2014-01-01

    The VP2 structural protein of parvovirus can produce virus-like particles (VLPs) by a self-assembly process in vitro, making VLPs attractive vaccine candidates. In this study, the VP2 protein of canine parvovirus (CPV) was expressed using a baculovirus expression system and assembled into parvovirus-like particles in insect cells and pupae. Electron micrographs of VLPs showed that they were very similar in size and morphology when compared to the wild-type parvovirus. The immunogenicity of the VLPs was investigated in mice and dogs. Mice immunized intramuscularly with purified VLPs, in the absence of an adjuvant, elicited CD4(+) and CD8(+) T cell responses and were able to elicit a neutralizing antibody response against CPV, while the oral administration of raw homogenates containing VLPs to the dogs resulted in a systemic immune response and long-lasting immunity. These results demonstrate that the CPV-VLPs stimulate both cellular and humoral immune responses, and so CPV-VLPs may be a promising candidate vaccine for the prevention of CPV-associated disease.

  5. Characterization of self-assembled virus-like particles of human polyomavirus BK generated by recombinant baculoviruses

    International Nuclear Information System (INIS)

    Li, T.-C.; Takeda, Naokazu; Kato, Kenzo; Nilsson, Josefina; Xing Li; Haag, Lars; Cheng, R. Holland; Miyamura, Tatsuo

    2003-01-01

    The major structural protein of the human polyomavirus BK (BKV), VP1, was expressed by using recombinant baculoviruses. A large amount of protein with a molecular mass of about 42 kDa was synthesized and identified by Western blotting. The protein was detected exclusively in the nuclei by immunofluorescent analysis and it was released into culture medium. The expressed BKV VP1 protein was self-assembled into virus-like particles (BK-VLPs) with two different sizes (50 and 26 nm in diameter), which migrated into four different bands in CsCl gradient with buoyant densities of 1.29, 1.30, 1.33, and 1.35 g/cm 3 . The immunological studies on the BK-VLPs suggested that they have similar antigenicity with those of authentic BKV particles. Cryoelectron microscopy and 3D image analysis further revealed that the larger BK-VLPs were composed of 72 capsomers which all were pentamers arranged in a T = 7 surface lattice. This system provides useful information for detailed studies of viral morphogenesis and the structural basis for the antigenicity of BKV

  6. Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents.

    Science.gov (United States)

    Sharma, S; Murai, F; Miyanohara, A; Friedmann, T

    1997-09-30

    Retrovirus packaging cell lines expressing the Moloney murine leukemia virus gag and pol genes but lacking virus envelope genes produce virus-like particles constitutively, whether or not they express a transcript from an integrated retroviral provirus. In the absence of a proviral transcript, the assembled particles contain processed gag and reverse transcriptase, and particles made by cells expressing an integrated lacZ provirus also contain viral RNA. The virus-like particles from both cell types are enveloped and are secreted/budded into the extracellular space but are noninfectious. Their physicochemical properties are similar to those of mature retroviral particles. The noninfectious gag pol RNA particles can readily be made infectious by the addition of lipofection reagents to produce preparations with titers of up to 10(5) colony-forming units per ml.

  7. Optimisation of secretion of recombinant HBsAg virus-like particles: Impact on the development of HIV-1/HBV bivalent vaccines

    NARCIS (Netherlands)

    Michel, Marie; Lone, Yu-Chun; Centlivre, Mireille; Roux, Pascal; Wain-Hobson, Simon; Sala, Monica

    2007-01-01

    The hepatitis B surface antigen (HBsAg) assembles into virus-like particles (VLPs) that can be used as carrier of immunogenic peptides for the development of bivalent vaccine candidates. It is shown here that by respecting certain qualitative features of mammalian preS1 and preS2 protein domains

  8. Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation

    NARCIS (Netherlands)

    de Witte, Lot; Zoughlami, Younes; Aengeneyndt, Birgit; David, Guido; van Kooyk, Yvette; Gissmann, Lutz; Geijtenbeek, Teunis B. H.

    2007-01-01

    Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs) induces a robust and effective immune response, which has recently resulted in the implementation of the HPV-L1 VLP vaccination in health programs. However, during infection, HPV can escape immune surveillance leading to

  9. Prevalence of virus-like particles within a staghorn scleractinian coral ( Acropora muricata) from the Great Barrier Reef

    Science.gov (United States)

    Patten, N. L.; Harrison, P. L.; Mitchell, J. G.

    2008-09-01

    Transmission electron microscopy (TEM) was used to determine whether Acropora muricata coral colonies from the Great Barrier Reef (GBR), Australia, harboured virus-like particles (VLPs). VLPs were present in all coral colonies sampled at Heron Island (southern GBR) and in tagged coral colonies sampled in at least two of the three sampling periods at Lizard Island (northern GBR). VLPs were observed within gastrodermal and epidermal tissues, and on rarer occasions, within the mesoglea. These VLPs had similar morphologies to known prokaryotic and eukaryotic viruses in other systems. Icosahedral VLPs were observed most frequently, however, filamentous VLPs (FVLPs) and phage were also noted. There were no clear differences in VLP size, morphology or location within the tissues with respect to sample date, coral health status or site. The most common VLP morphotype exhibited icosahedral symmetry, 120-150 nm in diameter, with an electron-dense core and an electronlucent membrane. Larger VLPs of similar morphology were also common. VLPs occurred as single entities, in groups, or in dense clusters, either as free particles within coral tissues, or within membrane-bound vacuoles. VLPs were commonly observed within the perinuclear region, with mitochondria, golgi apparatus and crescent-shaped particles frequently observed within close proximity. The host(s) of these observed VLPs was not clear; however, the different sizes and morphologies of VLPs observed within A. muricata tissues suggest that viruses are infecting either the coral animal, zooxanthellae, intracellular bacteria and/or other coral-associated microbiota, or that the one host is susceptible to infection from more than one type of virus. These results add to the limited but emerging body of evidence that viruses represent another potentially important component of the coral holobiont.

  10. Structure determination of feline calicivirus virus-like particles in the context of a pseudo-octahedral arrangement.

    Directory of Open Access Journals (Sweden)

    Wim P Burmeister

    Full Text Available The vesivirus feline calicivirus (FCV is a positive strand RNA virus encapsidated by an icosahedral T=3 shell formed by the viral VP1 protein. Upon its expression in the insect cell - baculovirus system in the context of vaccine development, two types of virus-like particles (VLPs were formed, a majority built of 60 subunits (T=1 and a minority probably built of 180 subunits (T=3. The structure of the small particles was determined by x-ray crystallography at 0.8 nm resolution helped by cryo-electron microscopy in order to understand their formation. Cubic crystals belonged to space group P213. Their self-rotation function showed the presence of an octahedral pseudo-symmetry similar to the one described previously by Agerbandje and co-workers for human parvovirus VLPs. The crystal structure could be solved starting from the published VP1 structure in the context of the T=3 viral capsid. In contrast to viral capsids, where the capsomers are interlocked by the exchange of the N-terminal arm (NTA domain, this domain is disordered in the T=1 capsid of the VLPs. Furthermore it is prone to proteolytic cleavage. The relative orientation of P (protrusion and S (shell domains is alerted so as to fit VP1 to the smaller T=1 particle whereas the intermolecular contacts around 2-fold, 3-fold and 5-fold axes are conserved. By consequence the surface of the VLP is very similar compared to the viral capsid and suggests a similar antigenicity. The knowledge of the structure of the VLPs will help to improve their stability, in respect to a use for vaccination.

  11. Energetic changes caused by antigenic module insertion in a virus-like particle revealed by experiment and molecular dynamics simulations.

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    Lin Zhang

    Full Text Available The success of recombinant virus-like particles (VLPs for human papillomavirus and hepatitis B demonstrates the potential of VLPs as safe and efficacious vaccines. With new modular designs emerging, the effects of antigen module insertion on the self-assembly and structural integrity of VLPs should be clarified so as to better enabling improved design. Previous work has revealed insights into the molecular energetics of a VLP subunit, capsomere, comparing energetics within various solution conditions known to drive or inhibit self-assembly. In the present study, molecular dynamics (MD simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA method were performed to examine the molecular interactions and energetics in a modular capsomere of a murine polyomavirus (MPV VLP designed to protect against influenza. Insertion of an influenza antigenic module is found to lower the binding energy within the capsomere, and a more active state is observed in Assembly Buffer as compared with that in Stabilization Buffer, which has been experimentally validated through measurements using differential scanning calorimetry. Further in-depth analysis based on free-energy decomposition indicates that destabilized binding can be attributed to electrostatic interaction induced by the chosen antigen module. These results provide molecular insights into the conformational stability of capsomeres and their abilities to be exploited for antigen presentation, and are expected to be beneficial for the biomolecular engineering of VLP vaccines.

  12. Production and immunogenicity of chimeric virus-like particles containing the spike glycoprotein of infectious bronchitis virus.

    Science.gov (United States)

    Lv, Lishan; Li, Xiaoming; Liu, Genmei; Li, Ran; Liu, Qiliang; Shen, Huifang; Wang, Wei; Xue, Chunyi; Cao, Yongchang

    2014-01-01

    Infectious bronchitis virus (IBV) poses a severe threat to the poultry industry and causes heavy economic losses worldwide. Vaccination is the most effective method of preventing infection and controlling the spread of IBV, but currently available inactivated and attenuated virus vaccines have some disadvantages. We developed a chimeric virus-like particle (VLP)-based candidate vaccine for IBV protection. The chimeric VLP was composed of matrix 1 protein from avian influenza H5N1 virus and a fusion protein neuraminidase (NA)/spike 1 (S1) that was generated by fusing IBV S1 protein to the cytoplasmic and transmembrane domains of NA protein of avian influenza H5N1 virus. The chimeric VLPs elicited significantly higher S1-specific antibody responses in intramuscularly immunized mice and chickens than inactivated IBV viruses. Furthermore, the chimeric VLPs induced significantly higher neutralization antibody levels than inactivated H120 virus in SPF chickens. Finally, the chimeric VLPs induced significantly higher IL-4 production in mice. These results demonstrate that chimeric VLPs have the potential for use in vaccines against IBV infection.

  13. Selective elimination of HIV-1-infected cells by Env-directed, HIV-1-based virus-like particles

    International Nuclear Information System (INIS)

    Peretti, Silvia; Schiavoni, Ilaria; Pugliese, Katherina; Federico, Maurizio

    2006-01-01

    We recently showed that both replicating and resting cells cultivated with ganciclovir (GCV) were killed when challenged with vesicular stomatitis virus G glycoprotein pseudotyped HIV-1-based virus-like particles (VLPs) carrying the Nef7 (i.e., an HIV-1 Nef mutant incorporating in virions at high levels)/herpes simplex virus-1 thymidine kinase (HSV-TK) fusion product. On this basis, a novel anti-HIV therapeutic approach based on Nef7/TK VLPs expressing X4 or R5 HIV cell receptor complexes has been attempted. We here report that (CD4-CXCR4) and (CD4-CCR5) Nef7-based VLPs efficiently enter cells infected by X4- or R5-tropic HIV-1 strains, respectively. Importantly, the delivery of the VLP-associated Nef7/TK led to cell death upon GCV treatment. Of interest, VLPs were effective also against non-replicating, HIV-1-infected primary human monocyte-derived macrophages. HIV-targeted VLPs represent a promising candidate for the treatment of persistently HIV-1-infected cells that are part of virus reservoirs resistant to HAART therapies

  14. Gene therapy for human glioblastoma using neurotropic JC virus-like particles as a gene delivery vector.

    Science.gov (United States)

    Chao, Chun-Nun; Yang, Yu-Hsuan; Wu, Mu-Sheng; Chou, Ming-Chieh; Fang, Chiung-Yao; Lin, Mien-Chun; Tai, Chien-Kuo; Shen, Cheng-Huang; Chen, Pei-Lain; Chang, Deching; Wang, Meilin

    2018-02-02

    Glioblastoma multiforme (GBM), the most common malignant brain tumor, has a short period of survival even with recent multimodality treatment. The neurotropic JC polyomavirus (JCPyV) infects glial cells and oligodendrocytes and causes fatal progressive multifocal leukoencephalopathy in patients with AIDS. In this study, a possible gene therapy strategy for GBM using JCPyV virus-like particles (VLPs) as a gene delivery vector was investigated. We found that JCPyV VLPs were able to deliver the GFP reporter gene into tumor cells (U87-MG) for expression. In an orthotopic xenograft model, nude mice implanted with U87 cells expressing the near-infrared fluorescent protein and then treated by intratumoral injection of JCPyV VLPs carrying the thymidine kinase suicide gene, combined with ganciclovir administration, exhibited significantly prolonged survival and less tumor fluorescence during the experiment compared with controls. Furthermore, JCPyV VLPs were able to protect and deliver a suicide gene to distal subcutaneously implanted U87 cells in nude mice via blood circulation and inhibit tumor growth. These findings show that metastatic brain tumors can be targeted by JCPyV VLPs carrying a therapeutic gene, thus demonstrating the potential of JCPyV VLPs to serve as a gene therapy vector for the far highly treatment-refractory GBM.

  15. Virus-Like Particles of Chimeric Recombinant Porcine Circovirus Type 2 as Antigen Vehicle Carrying Foreign Epitopes

    Directory of Open Access Journals (Sweden)

    Huawei Zhang

    2014-12-01

    Full Text Available Virus-like particles (VLPs of chimeric porcine circovirus type 2 (PCV2 were generated by replacing the nuclear localization signal (NLS; at 1–39 aa of PCV2 capsid protein (Cap with classical swine fever virus (CSFV T-cell epitope (1446–1460 aa, CSFV B-cell epitope (693–716 aa and CSFV T-cell epitope conjugated with B-cell epitope. The recombinant proteins were expressed using the baculovirus expression system and detected by immunoblotting and indirect immunofluorescence assay. The abilities to form PCV2 VLPs were confirmed by transmission electron microscopy. Immunogenicities of the three recombinant proteins were evaluated in mice. Our Results indicated that Cap protein NLS deletion or substitution with CSFV epitopes did not affect the VLPs assembly. Three chimeric Cap proteins could form VLPs and induce efficient humoral and cellular immunity against PCV2 and CSFV in mice. Results show that PCV2 VLPs can be used as an efficient antigen carrier for delivery of foreign epitopes, and a potential novel vaccine.

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

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    Shaoheng Chen

    2015-01-01

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

  17. In vitro assembly into virus-like particles is an intrinsic quality of Pichia pastoris derived HCV core protein

    International Nuclear Information System (INIS)

    Acosta-Rivero, Nelson; Rodriguez, Armando; Musacchio, Alexis; Falcon, Viviana; Suarez, Viana M.; Martinez, Gillian; Guerra, Ivis; Paz-Lago, Dalila; Morera, Yanelys; Rosa, Maria C. de la; Morales-Grillo, Juan; Duenas-Carrera, Santiago

    2004-01-01

    Different variants of hepatitis C virus core protein (HCcAg) have proved to self-assemble in vitro into virus-like particles (VLPs). However, difficulties in obtaining purified mature HCcAg have limited these studies. In this study, a high degree of monomeric HCcAg purification was accomplished using chromatographic procedures under denaturing conditions. Size exclusion chromatography and sucrose density gradient centrifugation of renatured HCcAg (in the absence of structured RNA) under reducing conditions suggested that it assembled into empty capsids. The electron microscopy analysis of renatured HCcAg showed the presence of spherical VLPs with irregular shapes and an average diameter of 35 nm. Data indicated that HCcAg monomers assembled in vitro into VLPs in the absence of structured RNA, suggesting that recombinant HCcAg used in this work contains all the information necessary for the assembly process. However, they also suggest that some cellular factors might be required for the proper in vitro assembly of capsids

  18. Oral Immunization with Recombinant Norwalk Virus-Like Particles Induces a Systemic and Mucosal Immune Response in Mice

    Science.gov (United States)

    Ball, Judith M.; Hardy, Michele E.; Atmar, Robert L.; Conner, Margaret E.; Estes, Mary K.

    1998-01-01

    Recombinant Norwalk virus-like particles (rNV VLPs) produced in insect cells were evaluated as an oral immunogen in CD1 and BALB/c mice by monitoring rNV-specific serum total and subclass immunoglobulin G (IgG) and intestinal IgA responses. Dose and kinetics of response were evaluated in the presence and absence of the mucosal adjuvant cholera toxin (CT). rNV-specific serum IgG and intestinal IgA were detected in the absence of CT, and the number of responders was not significantly different from that of mice administered VLPs with CT at most doses. The use of CT was associated with induction of higher levels of IgG in serum; this effect was greater at higher doses of VLPs. IgG in serum was detected in the majority of animals by 9 days postimmunization (dpi), and intestinal IgA responses were detected by 24 dpi. In the absence of CT, IgG2b was the dominant IgG subclass response in both mouse strains. Thus, nonreplicating rNV VLPs are immunogenic when administered orally in the absence of any delivery system or mucosal adjuvant. These studies demonstrate that rNV VLPs are an excellent model to study the oral delivery of antigen, and they are a potential mucosal vaccine for NV infections. PMID:9445035

  19. Generation of Recombinant Porcine Parvovirus Virus-Like Particles in Saccharomyces cerevisiae and Development of Virus-Specific Monoclonal Antibodies

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    Paulius Lukas Tamošiūnas

    2014-01-01

    Full Text Available Porcine parvovirus (PPV is a widespread infectious virus that causes serious reproductive diseases of swine and death of piglets. The gene coding for the major capsid protein VP2 of PPV was amplified using viral nucleic acid extract from swine serum and inserted into yeast Saccharomyces cerevisiae expression plasmid. Recombinant PPV VP2 protein was efficiently expressed in yeast and purified using density gradient centrifugation. Electron microscopy analysis of purified PPV VP2 protein revealed the self-assembly of virus-like particles (VLPs. Nine monoclonal antibodies (MAbs against the recombinant PPV VP2 protein were generated. The specificity of the newly generated MAbs was proven by immunofluorescence analysis of PPV-infected cells. Indirect IgG ELISA based on the recombinant VLPs for detection of PPV-specific antibodies in swine sera was developed and evaluated. The sensitivity and specificity of the new assay were found to be 93.4% and 97.4%, respectively. In conclusion, yeast S. cerevisiae represents a promising expression system for generating recombinant PPV VP2 protein VLPs of diagnostic relevance.

  20. Virus-like particle vaccine primes immune responses preventing inactivated-virus vaccine-enhanced disease against respiratory syncytial virus.

    Science.gov (United States)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Youri; Kwon, Young-Man; Kang, Sang-Moo

    2017-11-01

    Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia. Copyright © 2017. Published by Elsevier Inc.

  1. Virus-like particles vaccine containing Clonorchis sinensis tegumental protein induces partial protection against Clonorchis sinensis infection.

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    Lee, Dong-Hun; Kim, Ah-Ra; Lee, Su-Hwa; Quan, Fu-Shi

    2017-12-29

    Human clonorchiasis, caused by the infection of Clonorchis sinensis, is one of the major health problems in Southeast Asia. However, vaccine efficacy against C. sinensis infection remains largely unknown. In this study, for the first time, we generated virus-like particles (VLPs) vaccine containing the C. sinensis tegumental protein 22.3 kDa (CsTP 22.3) and the influenza matrix protein (M1) as a core protein, and investigated the vaccine efficacy in Sprague-Dawley rats. Intranasal immunization of VLPs vaccine induced C. sinensis-specific IgG, IgG2a and IgG2c in the sera and IgA responses in the feces and intestines. Notably, upon challenge infection with C. sinensis metacercariae, significantly lower adult worm loads (70.2%) were measured in the liver of rats immunized with VLPs, compared to those of naïve rats. Furthermore, VLPs immunization induced antibody secreting cells (ASC) responses and CD4+/CD8+ T cell responses in the spleen. Our results indicated that VLPs vaccine containing C. sinensis CsTP 22.3 kDa provided partial protection against C. sisnensis infection. Thus, VLPs could be a potential vaccine candidate against C. sinensis.

  2. Immunogenicity of plant-produced African horse sickness virus-like particles: implications for a novel vaccine.

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    Dennis, Susan J; Meyers, Ann E; Guthrie, Alan J; Hitzeroth, Inga I; Rybicki, Edward P

    2018-02-01

    African horse sickness (AHS) is a debilitating and often fatal viral disease affecting horses in much of Africa, caused by the dsRNA orbivirus African horse sickness virus (AHSV). Vaccination remains the single most effective weapon in combatting AHS, as there is no treatment for the disease apart from good animal husbandry. However, the only commercially available vaccine is a live-attenuated version of the virus (LAV). The threat of outbreaks of the disease outside its endemic region and the fact that the LAV is not licensed for use elsewhere in the world, have spurred attempts to develop an alternative safer, yet cost-effective recombinant vaccine. Here, we report the plant-based production of a virus-like particle (VLP) AHSV serotype five candidate vaccine by Agrobacterium tumefaciens-mediated transient expression of all four capsid proteins in Nicotiana benthamiana using the cowpea mosaic virus-based HyperTrans (CPMV-HT) and associated pEAQ plant expression vector system. The production process is fast and simple, scalable, economically viable, and most importantly, guinea pig antiserum raised against the vaccine was shown to neutralize live virus in cell-based assays. To our knowledge, this is the first report of AHSV VLPs produced in plants, which has important implications for the containment of, and fight against the spread of, this deadly disease. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  3. Studies towards the potential of poliovirus as a vector for the expression of HPV 16 virus-like-particles.

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    van Kuppeveld, Frank J M; de Jong, Arjan; Dijkman, Henri B P M; Andino, Raul; Melchers, Willem J G

    2002-11-15

    Development of human cervical carcinomas is associated with infection by certain human papillomavirus (HPV) types. Thus, protection against HPV infection through vaccination may prevent development of cervical cancer. The purpose of this study was to investigate the possibility of using a poliovirus recombinant vector to induce immunity against HPV. A poliovirus recombinant was constructed which contained the complete coding sequence of the HPV 16 major capsid protein L1, between the P1 and P2 region of the poliovirus polyprotein. A replication-competent virus was obtained after transfection of the recombinant RNA into tissue culture cells. Electron microscopically examination of cells infected with the poliovirus-HPV L1 recombinant indicated that HPV 16 L1 self-assembles into virus-like particles. To investigate the immunological response in vivo, susceptible transgenic mice carrying the poliovirus receptor were infected with the recombinant poliovirus. In all mice a modest but consistent immune response against HPV 16 was observed. Based on these results, the potential for picornavirus-derived vectors in vaccine development against HPV infection is discussed.

  4. Virus-like particles activate type I interferon pathways to facilitate post-exposure protection against Ebola virus infection.

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    Natarajan Ayithan

    Full Text Available Ebola virus (EBOV causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs in liver and spleen of wild type mice, but not in Ifnar-/- mice. Accordingly, EBOV infected Ifnar-/- mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar-/- mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host.

  5. Induction of long-term protective immune responses by influenza H5N1 virus-like particles.

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    Sang-Moo Kang

    Full Text Available Recurrent outbreaks of highly pathogenic H5N1 avian influenza virus pose a threat of eventually causing a pandemic. Early vaccination of the population would be the single most effective measure for the control of an emerging influenza pandemic.Influenza virus-like particles (VLPs produced in insect cell-culture substrates do not depend on the availability of fertile eggs for vaccine manufacturing. We produced VLPs containing influenza A/Viet Nam1203/04 (H5N1 hemagglutinin, neuraminidase, and matrix proteins, and investigated their preclinical immunogenicity and protective efficacy. Mice immunized intranasally with H5N1 VLPs developed high levels of H5N1 specific antibodies and were 100% protected against a high dose of homologous H5N1 virus infection at 30 weeks after immunization. Protection is likely to be correlated with humoral and cellular immunologic memory at systemic and mucosal sites as evidenced by rapid anamnestic responses to re-stimulation with viral antigen in vivo and in vitro.These results provide support for clinical evaluation of H5N1 VLP vaccination as a public health intervention to mitigate a possible pandemic of H5N1 influenza.

  6. Long-term protective immunity from an influenza virus-like particle vaccine administered with a microneedle patch.

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    Quan, Fu-Shi; Kim, Yeu-Chun; Song, Jae-Min; Hwang, Hye Suk; Compans, Richard W; Prausnitz, Mark R; Kang, Sang-Moo

    2013-09-01

    Skin vaccination with influenza virus-like particles (VLPs) using microneedles has been shown to induce protection similar to or better than that induced by intramuscular immunization. In this study, we examined the long-term protective efficacy of influenza (H1N1 A/PR/8/34) VLPs after skin vaccination using microneedle patches coated with the vaccine. Microneedle vaccination of mice in the skin induced 100% protection against lethal challenge infection with influenza A/PR/8/34 virus 14 months after a single vaccine dose. Influenza virus-specific total IgG response and hemagglutination inhibition (HAI) titers were maintained at high levels for over 1 year after microneedle vaccination. Microneedle vaccination also induced substantial levels of lung IgG and IgA antibody responses, and antibody-secreting plasma cells from spleen and bone marrow, as well as conferring effective control of lung viral loads, resulting in complete protection 14 months after vaccination. These strong and long-lasting immune responses were enabled in part by stabilization of the vaccine by formulation with trehalose during microneedle patch fabrication. Administration of the stabilized vaccine using microneedles was especially effective at enabling strong recall responses measured 4 days after lethal virus challenge, including increased HAI and antibody-secreting cells in the spleen and reduced viral titer and inflammatory response in the lung. The results in this study indicate that skin vaccination with VLP vaccine using a microneedle patch provides long-term protection against influenza in mice.

  7. Co-immunization with virus-like particle and DNA vaccines induces protection against respiratory syncytial virus infection and bronchiolitis

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    Hwang, Hye Suk; Kwon, Young-Man; Lee, Jong Seok; Yoo, Si-Eun; Lee, Yu-Na; Ko, Eun-Ju; Kim, Min-Chul; Cho, Min-Kyoung; Lee, Young-Tae; Jung, Yu-Jin; Lee, Ji-Yun; Li, Jian Dong; Kang, Sang-Moo

    2014-01-01

    This study demonstrates that immunization with non-replicating virus-like particle (FFG VLP) containing RSV F and G glycoproteins together with RSV F DNA induced T helper type 1 antibody responses to RSV F similar to live RSV infection. Upon RSV challenge 21 weeks after immunization, FFG VLP vaccination induced protection against RSV infection as shown by clearance of lung viral loads, and the absence of eosinophil infiltrates, and did not cause lung pathology. In contrast, formalin-inactivated RSV (FI-RSV) vaccination showed significant pulmonary eosinophilia, severe mucus production, and extensive histopathology resulting in a hallmark of pulmonary pathology. Substantial lung pathology was also observed in mice with RSV re-infections. High levels of systemic and local inflammatory cytokine-secreting cells were induced in mice with FI-RSV but not with FFG VLP immunization after RSV challenge. Therefore, the results provide evidence that recombinant RSV FFG VLP vaccine can confer long-term protection against RSV without causing lung pathology. PMID:25110201

  8. Self-assembly of virus-like particles of porcine circovirus type 2 capsid protein expressed from Escherichia coli

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    Cai Xuepeng

    2010-07-01

    Full Text Available Abstract Background Porcine circovirus 2 (PCV2 is a serious problem to the swine industry and can lead to significant negative impacts on profitability of pork production. Syndrome associated with PCV2 is known as porcine circovirus closely associated with post-weaning multisystemic wasting syndrome (PMWS. The capsid (Cap protein of PCV2 is a major candidate antigen for development of recombinant vaccine and serological diagnostic method. The recombinant Cap protein has the ability to self-assemble into virus-like particles (VLPs in vitro, it is particularly opportunity to develop the PV2 VLPs vaccine in Escherichia coli,(E.coli , because where the cost of the vaccine must be weighed against the value of the vaccinated pig, when it was to extend use the VLPs vaccine of PCV2. Results In this report, a highly soluble Cap-tag protein expressed in E.coli was constructed with a p-SMK expression vector with a fusion tag of small ubiquitin-like modifiers (SUMO. The recombinant Cap was purified using Ni2+ affinity resins, whereas the tag was used to remove the SUMO protease. Simultaneously, the whole native Cap protein was able to self-assemble into VLPs in vitro when viewed under an electron microscope. The Cap-like particles had a size and shape that resembled the authentic Cap. The result could also be applied in the large-scale production of VLPs of PCV2 and could be used as a diagnostic antigen or a potential VLP vaccine against PCV2 infection in pigs. Conclusion we have, for the first time, utilized the SUMO fusion motif to successfully express the entire authentic Cap protein of PCV2 in E. coli. After the cleavage of the fusion motif, the nCap protein has the ability to self-assemble into VLPs, which can be used as as a potential vaccine to protect pigs from PCV2-infection.

  9. Self-assembly of virus-like particles of porcine circovirus type 2 capsid protein expressed from Escherichia coli

    Science.gov (United States)

    2010-01-01

    Background Porcine circovirus 2 (PCV2) is a serious problem to the swine industry and can lead to significant negative impacts on profitability of pork production. Syndrome associated with PCV2 is known as porcine circovirus closely associated with post-weaning multisystemic wasting syndrome (PMWS). The capsid (Cap) protein of PCV2 is a major candidate antigen for development of recombinant vaccine and serological diagnostic method. The recombinant Cap protein has the ability to self-assemble into virus-like particles (VLPs) in vitro, it is particularly opportunity to develop the PV2 VLPs vaccine in Escherichia coli,(E.coli ), because where the cost of the vaccine must be weighed against the value of the vaccinated pig, when it was to extend use the VLPs vaccine of PCV2. Results In this report, a highly soluble Cap-tag protein expressed in E.coli was constructed with a p-SMK expression vector with a fusion tag of small ubiquitin-like modifiers (SUMO). The recombinant Cap was purified using Ni2+ affinity resins, whereas the tag was used to remove the SUMO protease. Simultaneously, the whole native Cap protein was able to self-assemble into VLPs in vitro when viewed under an electron microscope. The Cap-like particles had a size and shape that resembled the authentic Cap. The result could also be applied in the large-scale production of VLPs of PCV2 and could be used as a diagnostic antigen or a potential VLP vaccine against PCV2 infection in pigs. Conclusion we have, for the first time, utilized the SUMO fusion motif to successfully express the entire authentic Cap protein of PCV2 in E. coli. After the cleavage of the fusion motif, the nCap protein has the ability to self-assemble into VLPs, which can be used as as a potential vaccine to protect pigs from PCV2-infection. PMID:20646322

  10. Generation and characterization of a stable cell population releasing fluorescent HIV-1-based Virus Like Particles in an inducible way

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    Bosch Valerie

    2006-12-01

    Full Text Available Abstract Background The availability of cell lines releasing fluorescent viral particles can significantly support a variety of investigations, including the study of virus-cell interaction and the screening of antiviral compounds. Regarding HIV-1, the recovery of such biologic reagents represents a very hard challenge due to the intrinsic cytotoxicity of many HIV-1 products. We sought to overcome such a limitation by using a cell line releasing HIV-1 particles in an inducible way, and by exploiting the ability of a HIV-1 Nef mutant to be incorporated in virions at quite high levels. Results Here, we report the isolation and characterization of a HIV-1 packaging cell line, termed 18-4s, able to release valuable amounts of fluorescent HIV-1 based Virus-Like Particles (VLPs in an inducible way. 18-4s cells were recovered by constitutively expressing the HIV-1 NefG3C mutant fused with the enhanced-green fluorescent protein (NefG3C-GFP in a previously isolated inducible HIV-1 packaging cell line. The G3C mutation creates a palmitoylation site which results in NefG3C-GFP incorporation into virions greatly exceeding that of the wild type counterpart. Upon induction of 18-4s cells with ponasterone A and sodium butyrate, up to 4 μg/ml of VLPs, which had incorporated about 150 molecules of NefG3C-GFP per viral particle, were released into the culture supernatant. Due to their intrinsic strong fluorescence, the 18-4s VLPs were easily detectable by a novel cytofluorometric-based assay developed here. The treatment of target cells with fluorescent 18-4 VLPs pseudotyped with different glycoprotein receptors resulted in these becoming fluorescent as early as two hours post-challenge. Conclusion We created a stable cell line releasing fluorescent HIV-1 based VLPs upon induction useful for several applications including the study of virus-cell interactions and the screening of antiviral compounds.

  11. Characterization of self-assembled virus-like particles of dromedary camel hepatitis e virus generated by recombinant baculoviruses.

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    Zhou, Xianfeng; Kataoka, Michiyo; Liu, Zheng; Takeda, Naokazu; Wakita, Takaji; Li, Tian-Cheng

    2015-12-02

    Dromedary camel hepatitis E virus (DcHEV), a novel hepatitis E virus, has been identified in dromedary camels in Dubai, United Arab Emirates. The antigenicity, pathogenicity and epidemiology of this virus have been unclear. Here we first used a recombinant baculovirus expression system to express the 13 and 111 N-terminus amino-acid-truncated DcHEV ORF2 protein in insect Tn5 cells, and we obtained two types of virus-like particles (VLPs) with densities of 1.300 g/cm(3) and 1.285 g/cm(3), respectively. The small VLPs (Dc4sVLPs) were estimated to be 24 nm in diameter, and were assembled by a protein with the molecular mass 53 kDa. The large VLPs (Dc3nVLPs and Dc4nVLPs) were 35 nm in diameter, and were assembled by a 64-kDa protein. An antigenic analysis demonstrated that DcHEV was cross-reactive with G1, G3-G6, ferret and rat HEVs, and DcHEV showed a stronger cross-reactivity to G1 G3-G6 HEV than it did to rat and ferret HEV. In addition, the antibody against DcHEV-LPs neutralized G1 and G3 HEV in a cell culture system, suggesting that the serotypes of these HEVs are identical. We also found that the amino acid residue Met-358 affects the small DcHEV-LPs assembly. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Identifying SARS-CoV membrane protein amino acid residues linked to virus-like particle assembly.

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    Ying-Tzu Tseng

    Full Text Available Severe acute respiratory syndrome coronavirus (SARS-CoV membrane (M proteins are capable of self-assembly and release in the form of membrane-enveloped vesicles, and of forming virus-like particles (VLPs when coexpressed with SARS-CoV nucleocapsid (N protein. According to previous deletion analyses, M self-assembly involves multiple M sequence regions. To identify important M amino acid residues for VLP assembly, we coexpressed N with multiple M mutants containing substitution mutations at the amino-terminal ectodomain, carboxyl-terminal endodomain, or transmembrane segments. Our results indicate that a dileucine motif in the endodomain tail (218LL219 is required for efficient N packaging into VLPs. Results from cross-linking VLP analyses suggest that the cysteine residues 63, 85 and 158 are not in close proximity to the M dimer interface. We noted a significant reduction in M secretion due to serine replacement for C158, but not for C63 or C85. Further analysis suggests that C158 is involved in M-N interaction. In addition to mutations of the highly conserved 107-SWWSFNPE-114 motif, substitutions at codons W19, W57, P58, W91, Y94 or F95 all resulted in significantly reduced VLP yields, largely due to defective M secretion. VLP production was not significantly affected by a tryptophan replacement of Y94 or F95 or a phenylalanine replacement of W19, W57 or W91. Combined, these results indicate the involvement of specific M amino acids during SARS-CoV virus assembly, and suggest that aromatic residue retention at specific positions is critical for M function in terms of directing virus assembly.

  13. Sensitivity of immune response quality to influenza helix 190 antigen structure displayed on a modular virus-like particle.

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    Anggraeni, Melisa R; Connors, Natalie K; Wu, Yang; Chuan, Yap P; Lua, Linda H L; Middelberg, Anton P J

    2013-09-13

    Biomolecular engineering enables synthesis of improved proteins through synergistic fusion of modules from unrelated biomolecules. Modularization of peptide antigen from an unrelated pathogen for presentation on a modular virus-like particle (VLP) represents a new and promising approach to synthesize safe and efficacious vaccines. Addressing a key knowledge gap in modular VLP engineering, this study investigates the underlying fundamentals affecting the ability of induced antibodies to recognize the native pathogen. Specifically, this quality of immune response is correlated to the peptide antigen module structure. We modularized a helical peptide antigen element, helix 190 (H190) from the influenza hemagglutinin (HA) receptor binding region, for presentation on murine polyomavirus VLP, using two strategies aimed to promote H190 helicity on the VLP. In the first strategy, H190 was flanked by GCN4 structure-promoting elements within the antigen module; in the second, dual H190 copies were arrayed as tandem repeats in the module. Molecular dynamics simulation predicted that tandem repeat arraying would minimize secondary structural deviation of modularized H190 from its native conformation. In vivo testing supported this finding, showing that although both modularization strategies conferred high H190-specific immunogenicity, tandem repeat arraying of H190 led to a strikingly higher immune response quality, as measured by ability to generate antibodies recognizing a recombinant HA domain and split influenza virion. These findings provide new insights into the rational engineering of VLP vaccines, and could ultimately enable safe and efficacious vaccine design as an alternative to conventional approaches necessitating pathogen cultivation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Toll-like receptor agonist augments virus-like particle-mediated protection from Ebola virus with transient immune activation.

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    Karen A O Martins

    Full Text Available Identifying safe and effective adjuvants is critical for the advanced development of protein-based vaccines. Pattern recognition receptor (PRR agonists are increasingly being explored as potential adjuvants, but there is concern that the efficacy of these molecules may be dependent on potentially dangerous levels of non-specific immune activation. The filovirus virus-like particle (VLP vaccine protects mice, guinea pigs, and nonhuman primates from viral challenge. In this study, we explored the impact of a stabilized dsRNA mimic, polyICLC, on VLP vaccination of C57BL/6 mice and Hartley guinea pigs. We show that at dose levels as low as 100 ng, the adjuvant increased the efficacy of the vaccine in mice. Antigen-specific, polyfunctional CD4 and CD8 T cell responses and antibody responses increased significantly upon inclusion of adjuvant. To determine whether the efficacy of polyICLC correlated with systemic immune activation, we examined serum cytokine levels and cellular activation in the draining lymph node. PolyICLC administration was associated with increases in TNFα, IL6, MCP1, MIP1α, KC, and MIP1β levels in the periphery and with the activation of dendritic cells (DCs, NK cells, and B cells. However, this activation resolved within 24 to 72 hours at efficacious adjuvant dose levels. These studies are the first to examine the polyICLC-induced enhancement of antigen-specific immune responses in the context of non-specific immune activation, and they provide a framework from which to consider adjuvant dose levels.

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

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    Susan Thrane

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

  16. Disassembly and reassembly of human papillomavirus virus-like particles produces more virion-like antibody reactivity

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    Zhao Qinjian

    2012-02-01

    Full Text Available Abstract Background Human papillomavirus (HPV vaccines based on major capsid protein L1 are licensed in over 100 countries to prevent HPV infections. The yeast-derived recombinant quadrivalent HPV L1 vaccine, GARDASIL(R, has played an important role in reducing cancer and genital warts since its introduction in 2006. The L1 proteins self-assemble into virus-like particles (VLPs. Results VLPs were subjected to post-purification disassembly and reassembly (D/R treatment during bioprocessing to improve VLP immunoreactivity and stability. The post-D/R HPV16 VLPs and their complex with H16.V5 neutralizing antibody Fab fragments were visualized by cryo electron microscopy, showing VLPs densely decorated with antibody. Along with structural improvements, post-D/R VLPs showed markedly higher antigenicity to conformational and neutralizing monoclonal antibodies (mAbs H16.V5, H16.E70 and H263.A2, whereas binding to mAbs recognizing linear epitopes (H16.J4, H16.O7, and H16.H5 was greatly reduced. Strikingly, post-D/R VLPs showed no detectable binding to H16.H5, indicating that the H16.H5 epitope is not accessible in fully assembled VLPs. An atomic homology model of the entire HPV16 VLP was generated based on previously determined high-resolution structures of bovine papillomavirus and HPV16 L1 pentameric capsomeres. Conclusions D/R treatment of HPV16 L1 VLPs produces more homogeneous VLPs with more virion-like antibody reactivity. These effects can be attributed to a combination of more complete and regular assembly of the VLPs, better folding of L1, reduced non-specific disulfide-mediated aggregation and increased stability of the VLPs. Markedly different antigenicity of HPV16 VLPs was observed upon D/R treatment with a panel of monoclonal antibodies targeting neutralization sensitive epitopes. Multiple epitope-specific assays with a panel of mAbs with different properties and epitopes are required to gain a better understanding of the immunochemical

  17. Chimaeric Virus-Like Particles Derived from Consensus Genome Sequences of Human Rotavirus Strains Co-Circulating in Africa

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    Jere, Khuzwayo C.; O'Neill, Hester G.; Potgieter, A. Christiaan; van Dijk, Alberdina A.

    2014-01-01

    Rotavirus virus-like particles (RV-VLPs) are potential alternative non-live vaccine candidates due to their high immunogenicity. They mimic the natural conformation of native viral proteins but cannot replicate because they do not contain genomic material which makes them safe. To date, most RV-VLPs have been derived from cell culture adapted strains or common G1 and G3 rotaviruses that have been circulating in communities for some time. In this study, chimaeric RV-VLPs were generated from the consensus sequences of African rotaviruses (G2, G8, G9 or G12 strains associated with either P[4], P[6] or P[8] genotypes) characterised directly from human stool samples without prior adaptation of the wild type strains to cell culture. Codon-optimised sequences for insect cell expression of genome segments 2 (VP2), 4 (VP4), 6 (VP6) and 9 (VP7) were cloned into a modified pFASTBAC vector, which allowed simultaneous expression of up to four genes using the Bac-to-Bac Baculovirus Expression System (BEVS; Invitrogen). Several combinations of the genome segments originating from different field strains were cloned to produce double-layered RV-VLPs (dRV-VLP; VP2/6), triple-layered RV-VLPs (tRV-VLP; VP2/6/7 or VP2/6/7/4) and chimaeric tRV-VLPs. The RV-VLPs were produced by infecting Spodoptera frugiperda 9 and Trichoplusia ni cells with recombinant baculoviruses using multi-cistronic, dual co-infection and stepwise-infection expression strategies. The size and morphology of the RV-VLPs, as determined by transmission electron microscopy, revealed successful production of RV-VLPs. The novel approach of producing tRV-VLPs, by using the consensus insect cell codon-optimised nucleotide sequence derived from dsRNA extracted directly from clinical specimens, should speed-up vaccine research and development by by-passing the need to adapt rotaviruses to cell culture. Other problems associated with cell culture adaptation, such as possible changes in epitopes, can also be circumvented

  18. Enhanced stability of a chimeric hepatitis B core antigen virus-like-particle (HBcAg-VLP) by a C-terminal linker-hexahistidine-peptide.

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    Schumacher, Jens; Bacic, Tijana; Staritzbichler, René; Daneschdar, Matin; Klamp, Thorsten; Arnold, Philipp; Jägle, Sabrina; Türeci, Özlem; Markl, Jürgen; Sahin, Ugur

    2018-04-13

    Virus-like-particles (VLPs) are attractive nanoparticulate scaffolds for broad applications in material/biological sciences and medicine. Prior their functionalization, specific adaptations have to be carried out. These adjustments frequently lead to disordered particles, but the particle integrity is an essential factor for the VLP suitability. Therefore, major requirements for particle stabilization exist. The objective of this study was to evaluate novel stabilizing elements for functionalized chimeric hepatitis B virus core antigen virus-like particles (HBcAg-VLP), with beneficial characteristics for vaccine development, imaging or delivery. The effects of a carboxy-terminal polyhistidine-peptide and an intradimer disulfide-bridge on the stability of preclinically approved chimeric HBcAg-VLPs were assessed. We purified recombinant chimeric HBcAg-VLPs bearing different modified C-termini and compared their physical and chemical particle stability by quantitative protein-biochemical and biophysical techniques. We observed lower chemical resistance of T = 3- compared to T = 4-VLP (triangulation number) capsids and profound impairment of accessibility of hexahistidine-peptides in assembled VLPs. Histidines attached to the C-terminus were associated with superior mechanical and/or chemical particle stability depending on the number of histidine moieties. A molecular modeling approach based on cryo-electron microscopy and biolayer interferometry revealed the underlying structural mechanism for the strengthening of the integrity of VLPs. Interactions triggering capsid stabilization occur on a highly conserved residue on the basis of HBcAg-monomers as well as on hexahistidine-peptides of adjacent monomers. This new stabilization mechanism appears to mimic an evolutionary conserved stabilization concept for hepadnavirus core proteins. These findings establish the genetically simply transferable C-terminal polyhistidine-peptide as a general stabilizing element

  19. A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles

    Energy Technology Data Exchange (ETDEWEB)

    Meador, Lydia R. [Ira A. Fulton School of Engineering, Arizona State University, Tempe, AZ (United States); Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); Kessans, Sarah A. [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States); Kilbourne, Jacquelyn; Kibler, Karen V. [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); Pantaleo, Giuseppe [Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne (Switzerland); Swiss Vaccine Research Institute, Lausanne (Switzerland); Roderiguez, Mariano Esteban [Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia – CSIC, Madrid (Spain); Blattman, Joseph N. [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States); Jacobs, Bertram L., E-mail: bjacobs@asu.edu [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States); Mor, Tsafrir S., E-mail: tsafrir.mor@asu.edu [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States)

    2017-07-15

    Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1. - Highlights: • We devised a prime/boost anti HIV-1 vaccination strategy modeled after RV144. • We used plant-derived virus-like particles (VLPs) consisting of Gag and dgp41. • We used attenuated, replicating vaccinia virus vectors expressing the same antigens. • The immunogens elicited strong cellular and humoral immune responses.

  20. Detection of norovirus virus-like particles using a surface plasmon resonance-assisted fluoroimmunosensor optimized for quantum dot fluorescent labels.

    Science.gov (United States)

    Ashiba, Hiroki; Sugiyama, Yuki; Wang, Xiaomin; Shirato, Haruko; Higo-Moriguchi, Kyoko; Taniguchi, Koki; Ohki, Yoshimichi; Fujimaki, Makoto

    2017-07-15

    A highly sensitive biosensor to detect norovirus in environment is desired to prevent the spread of infection. In this study, we investigated a design of surface plasmon resonance (SPR)-assisted fluoroimmunosensor to increase its sensitivity and performed detection of norovirus virus-like particles (VLPs). A quantum dot fluorescent dye was employed because of its large Stokes shift. The sensor design was optimized for the CdSe-ZnS-based quantum dots. The optimal design was applied to a simple SPR-assisted fluoroimmunosensor that uses a sensor chip equipped with a V-shaped trench. Excitation efficiency of the quantum dots, degree of electric field enhancement by SPR, and intensity of autofluorescence of a substrate of the sensor chip were theoretically and experimentally evaluated to maximize the signal-to-noise ratio. As the result, an excitation wavelength of 390nm was selected to excite SPR on an Al film of the sensor chip. The sandwich assay of norovirus VLPs was performed using the designed sensor. Minimum detectable concentration of 0.01ng/mL, which corresponds to 100 virus-like particles included in the detection region of the V-trench, was demonstrated. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine

    Science.gov (United States)

    Hellerstein, Michael; Xu, Yongxian; Marino, Tracie; Lu, Shan; Yi, Hong; Wright, Elizabeth R.; Robinson, Harriet L.

    2012-01-01

    Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection. PMID:23111169

  2. Tandem fusion of hepatitis B core antigen allows assembly of virus-like particles in bacteria and plants with enhanced capacity to accommodate foreign proteins.

    Directory of Open Access Journals (Sweden)

    Hadrien Peyret

    Full Text Available The core protein of the hepatitis B virus, HBcAg, assembles into highly immunogenic virus-like particles (HBc VLPs when expressed in a variety of heterologous systems. Specifically, the major insertion region (MIR on the HBcAg protein allows the insertion of foreign sequences, which are then exposed on the tips of surface spike structures on the outside of the assembled particle. Here, we present a novel strategy which aids the display of whole proteins on the surface of HBc particles. This strategy, named tandem core, is based on the production of the HBcAg dimer as a single polypeptide chain by tandem fusion of two HBcAg open reading frames. This allows the insertion of large heterologous sequences in only one of the two MIRs in each spike, without compromising VLP formation. We present the use of tandem core technology in both plant and bacterial expression systems. The results show that tandem core particles can be produced with unmodified MIRs, or with one MIR in each tandem dimer modified to contain the entire sequence of GFP or of a camelid nanobody. Both inserted proteins are correctly folded and the nanobody fused to the surface of the tandem core particle (which we name tandibody retains the ability to bind to its cognate antigen. This technology paves the way for the display of natively folded proteins on the surface of HBc particles either through direct fusion or through non-covalent attachment via a nanobody.

  3. Affinity selection of Nipah and Hendra virus-related vaccine candidates from a complex random peptide library displayed on bacteriophage virus-like particles

    Energy Technology Data Exchange (ETDEWEB)

    Peabody, David S.; Chackerian, Bryce; Ashley, Carlee; Carnes, Eric; Negrete, Oscar

    2017-01-24

    The invention relates to virus-like particles of bacteriophage MS2 (MS2 VLPs) displaying peptide epitopes or peptide mimics of epitopes of Nipah Virus envelope glycoprotein that elicit an immune response against Nipah Virus upon vaccination of humans or animals. Affinity selection on Nipah Virus-neutralizing monoclonal antibodies using random sequence peptide libraries on MS2 VLPs selected peptides with sequence similarity to peptide sequences found within the envelope glycoprotein of Nipah itself, thus identifying the epitopes the antibodies recognize. The selected peptide sequences themselves are not necessarily identical in all respects to a sequence within Nipah Virus glycoprotein, and therefore may be referred to as epitope mimics VLPs displaying these epitope mimics can serve as vaccine. On the other hand, display of the corresponding wild-type sequence derived from Nipah Virus and corresponding to the epitope mapped by affinity selection, may also be used as a vaccine.

  4. Goose parvovirus structural proteins expressed by recombinant baculoviruses self-assemble into virus-like particles with strong immunogenicity in goose

    International Nuclear Information System (INIS)

    Ju, Huanyu; Wei, Na; Wang, Qian; Wang, Chunyuan; Jing, Zhiqiang; Guo, Lu; Liu, Dapeng; Gao, Mingchun; Ma, Bo; Wang, Junwei

    2011-01-01

    Highlights: → All three capsid proteins can be expressed in insect cells in baculovirus expression system. → All three recombinant proteins were spontaneously self-assemble into virus-like particles whose size and appearance were similar to those of native purified GPV virions. → The immunogenicity of GPV-VLPs was better than commercial inactivated vaccine and attenuated vaccine. -- Abstract: Goose parvovirus (GPV), a small non-enveloped ssDNA virus, can cause Derzsy's disease, and three capsid proteins of VP1, VP2, and VP3 are encoded by an overlapping nucleotide sequence. However, little is known on whether recombinant viral proteins (VPs) could spontaneously assemble into virus-like particles (VLPs) in insect cells and whether these VLPs could retain their immunoreactivity and immunogenicity in susceptible geese. To address these issues, genes for these GPV VPs were amplified by PCR, and the recombinant VPs proteins were expressed in insect cells using a baculovirus expression system for the characterization of their structures, immunoreactivity, and immunogenicity. The rVP1, rVP2, and rVP3 expressed in Sf9 cells were detected by anti-GPV sera, anti-VP3 sera, and anti-His antibodies, respectively. Electron microscopy revealed that these rVPs spontaneously assembled into VLPs in insect cells, similar to that of the purified wild-type GPV virions. In addition, vaccination with individual types of VLPs, particularly with the rVP2-VLPs, induced higher titers of antibodies and neutralized different strains of GPVs in primary goose and duck embryo fibroblast cells in vitro. These data indicated that these VLPs retained immunoreactivity and had strong immunogenicity in susceptible geese. Therefore, our findings may provide a framework for development of new vaccines for the prevention of Derzsy's disease and vehicles for the delivery of drugs.

  5. The virus-like particles of a braconid endoparasitoid wasp, Meteorus pulchricornis, inhibit hemocyte spreading in its noctuid host, Pseudaletia separata.

    Science.gov (United States)

    Suzuki, M; Miura, K; Tanaka, T

    2008-06-01

    We previously reported that the virus-like particles of Meteorus pulchricornis (MpVLPs) are capable of inducing apoptosis by around 6h in the hemocytes of the host, Pseudaletia separata [Suzuki, M., Tanaka, T., 2006. Virus-like particles in venom of Meteorus pulchricornis induce host hemocyte apoptosis. Journal of Insect Physiology 52, 602-611], thereby protecting the oviposited egg. In the present study, we focused on analyses of the earlier events caused by the MpVLPs upon the host immune response, namely their effects on hemocyte spreading. After recognition and attachment on foreign substance, the granulocytes and plasmatocytes assemble focal complexes and focal adhesions and spread by protruding filopodia/lamellipodia. The well-spread, cultured hemocytes were subjected to MpVLPs exposure, and the morphological changes were observed. The granulocytes lost the focal complexes/adhesions visualized as phosphotyrosine clusters and retracted the filopodia/lamellipodia within 30min after exposure, while the plasmatocytes exhibited similar but distinct responses. The two hemocyte species prepared from either parasitized or MpVLP-injected hosts lost the ability to form both filopodia/lamellipodia and phosphotyrosine clusters. A caspase inhibitor, Z-VAD-FMK, did not affect these MpVLP-induced morphological changes, indicating that these earlier changes found in the hemocytes precede apoptosis. The present study together with our previous data has established that the attenuation of host immune defense by the MpVLPs comprises at least two temporally distinguishable phases: immediate and early inhibition of hemocyte spreading and the eventual induction of hemocyte apoptosis.

  6. Goose parvovirus structural proteins expressed by recombinant baculoviruses self-assemble into virus-like particles with strong immunogenicity in goose

    Energy Technology Data Exchange (ETDEWEB)

    Ju, Huanyu; Wei, Na; Wang, Qian; Wang, Chunyuan; Jing, Zhiqiang; Guo, Lu; Liu, Dapeng; Gao, Mingchun; Ma, Bo [College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150030 (China); Wang, Junwei, E-mail: jwwang@neau.edu.cn [College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150030 (China)

    2011-05-27

    Highlights: {yields} All three capsid proteins can be expressed in insect cells in baculovirus expression system. {yields} All three recombinant proteins were spontaneously self-assemble into virus-like particles whose size and appearance were similar to those of native purified GPV virions. {yields} The immunogenicity of GPV-VLPs was better than commercial inactivated vaccine and attenuated vaccine. -- Abstract: Goose parvovirus (GPV), a small non-enveloped ssDNA virus, can cause Derzsy's disease, and three capsid proteins of VP1, VP2, and VP3 are encoded by an overlapping nucleotide sequence. However, little is known on whether recombinant viral proteins (VPs) could spontaneously assemble into virus-like particles (VLPs) in insect cells and whether these VLPs could retain their immunoreactivity and immunogenicity in susceptible geese. To address these issues, genes for these GPV VPs were amplified by PCR, and the recombinant VPs proteins were expressed in insect cells using a baculovirus expression system for the characterization of their structures, immunoreactivity, and immunogenicity. The rVP1, rVP2, and rVP3 expressed in Sf9 cells were detected by anti-GPV sera, anti-VP3 sera, and anti-His antibodies, respectively. Electron microscopy revealed that these rVPs spontaneously assembled into VLPs in insect cells, similar to that of the purified wild-type GPV virions. In addition, vaccination with individual types of VLPs, particularly with the rVP2-VLPs, induced higher titers of antibodies and neutralized different strains of GPVs in primary goose and duck embryo fibroblast cells in vitro. These data indicated that these VLPs retained immunoreactivity and had strong immunogenicity in susceptible geese. Therefore, our findings may provide a framework for development of new vaccines for the prevention of Derzsy's disease and vehicles for the delivery of drugs.

  7. Development and evaluation of a competitive ELISA using a monoclonal antibody for antibody detection after goose parvovirus virus-like particles (VLPs) and vaccine immunization in goose sera.

    Science.gov (United States)

    Wang, Qian; Ju, Huanyu; Li, Yanwei; Jing, Zhiqiang; Guo, Lu; Zhao, Yu; Ma, Bo; Gao, Mingchun; Zhang, Wenlong; Wang, Junwei

    2014-12-01

    An assay protocol based on a monoclonal antibody-based competitive enzyme-linked immunosorbent assay (MAb-based C-ELISA) for detecting antibodies against goose parvovirus (GPV) and its virus-like particles (VLPs) is described. The assay was developed using baculovirus-expressed recombinant VP2 virus-like particles (rVP2-VLPs) as antigens and a monoclonal antibody against GPV as the competitive antibody. Of the four anti-GPV MAbs that were screened, MAb 1G3 was selected as it was blocked by the GPV positive serum. Based on the distribution of percent inhibition (PI) of the known negative sera (n=225), a cut-off value was set at 36% inhibition. Using this cut-off value, the sensitivity of the assay was 93.3% and the specificity was 95.8%, as compared with the gold standard (virus neutralization assay). The rVP2-VLPs did not react with anti-sera to other goose pathogens, indicating that it is specific for the recognization of goose parvovirus antibodies. The assay was then validated with serum samples from goslings vaccinated with several VLPs (rVP1-VLPs, rVP2-VLPs, rVP3-VLPs, and rCGV-VLPs) and other vaccines (inactivated and attenuated). The C-ELISA described in this study is a sensitive and specific diagnostic test and should have wide applications for the sero-diagnosis and immunologic surveillance of GPV. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. 78 FR 18359 - Prospective Grant of Exclusive License: Papilloma Pseudovirus and Virus-Like Particles as a...

    Science.gov (United States)

    2013-03-26

    ... encapsulation technology for the treatment, diagnosis and imaging of cancer tumors and metastases as well as their respective pre-cursor dysplasia states. Licensee's proprietary nanosphere encapsulation technology...-derived nanoparticles to create particles targeted to solid tumors and distant metastases; and (2...

  9. Live attenuated measles vaccine expressing HIV-1 Gag virus like particles covered with gp160ΔV1V2 is strongly immunogenic

    International Nuclear Information System (INIS)

    Guerbois, Mathilde; Moris, Arnaud; Combredet, Chantal; Najburg, Valerie; Ruffie, Claude; Fevrier, Michele; Cayet, Nadege; Brandler, Samantha; Schwartz, Olivier; Tangy, Frederic

    2009-01-01

    Although a live attenuated HIV vaccine is not currently considered for safety reasons, a strategy inducing both T cells and neutralizing antibodies to native assembled HIV-1 particles expressed by a replicating virus might mimic the advantageous characteristics of live attenuated vaccine. To this aim, we generated a live attenuated recombinant measles vaccine expressing HIV-1 Gag virus-like particles (VLPs) covered with gp160ΔV1V2 Env protein. The measles-HIV virus replicated efficiently in cell culture and induced the intense budding of HIV particles covered with Env. In mice sensitive to MV infection, this recombinant vaccine stimulated high levels of cellular and humoral immunity to both MV and HIV with neutralizing activity. The measles-HIV virus infected human professional antigen-presenting cells, such as dendritic cells and B cells, and induced efficient presentation of HIV-1 epitopes and subsequent activation of human HIV-1 Gag-specific T cell clones. This candidate vaccine will be next tested in non-human primates. As a pediatric vaccine, it might protect children and adolescents simultaneously from measles and HIV.

  10. M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A.

    Directory of Open Access Journals (Sweden)

    Lorena Itatí Ibañez

    Full Text Available The ectodomain of influenza A matrix protein 2 (M2e is a candidate for a universal influenza A vaccine. We used recombinant Hepatitis B core antigen to produce virus-like particles presenting M2e (M2e-VLPs. We produced the VLPs with and without entrapped nucleic acids and compared their immunogenicity and protective efficacy. Immunization of BALB/c mice with M2e-VLPs containing nucleic acids induced a stronger, Th1-biased antibody response compared to particles lacking nucleic acids. The former also induced a stronger M2e-specific CD4(+ T cell response, as determined by ELISPOT. Mice vaccinated with alum-adjuvanted M2e-VLPs containing the nucleic acid-binding domain were better protected against influenza A virus challenge than mice vaccinated with similar particles lacking this domain, as deduced from the loss in body weight following challenge with X47 (H3N2 or PR/8 virus. Challenge of mice that had been immunized with M2e-VLPs with or without nucleic acids displayed significantly lower mortality, morbidity and lung virus titers than control-immunized groups. We conclude that nucleic acids present in M2e-VLPs correlate with improved immune protection.

  11. Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine.

    Science.gov (United States)

    Fan, Yi-Chin; Chen, Jo-Mei; Lin, Jen-Wei; Chen, Yi-Ying; Wu, Guan-Hong; Su, Kuan-Hsuan; Chiou, Ming-Tang; Wu, Shang-Rung; Yin, Ji-Hang; Liao, Jiunn-Wang; Chang, Gwong-Jen J; Chiou, Shyan-Song

    2018-05-10

    Swine are a critical amplifying host involved in human Japanese encephalitis (JE) outbreaks. Cross-genotypic immunogenicity and sterile protection are important for the current genotype III (GIII) virus-derived vaccines in swine, especially now that emerging genotype I (GI) JE virus (JEV) has replaced GIII virus as the dominant strain. Herein, we aimed to develop a system to generate GI JEV virus-like particles (VLPs) and evaluate the immunogenicity and protection of the GI vaccine candidate in mice and specific pathogen-free swine. A CHO-heparan sulfate-deficient (CHO-HS(-)) cell clone, named 51-10 clone, stably expressing GI-JEV VLP was selected and continually secreted GI VLPs without signs of cell fusion. 51-10 VLPs formed a homogeneously empty-particle morphology and exhibited similar antigenic activity as GI virus. GI VLP-immunized mice showed balanced cross-neutralizing antibody titers against GI to GIV viruses (50% focus-reduction micro-neutralization assay titers 71 to 240) as well as potent protection against GI or GIII virus infection. GI VLP-immunized swine challenged with GI or GIII viruses showed no fever, viremia, or viral RNA in tonsils, lymph nodes, and brains as compared with phosphate buffered saline-immunized swine. We thus conclude GI VLPs can provide sterile protection against GI and GIII viruses in swine.

  12. Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents

    Science.gov (United States)

    Sharma, Sanjai; Murai, Fukashi; Miyanohara, Atsushi; Friedmann, Theodore

    1997-01-01

    Retrovirus packaging cell lines expressing the Moloney murine leukemia virus gag and pol genes but lacking virus envelope genes produce virus-like particles constitutively, whether or not they express a transcript from an integrated retroviral provirus. In the absence of a proviral transcript, the assembled particles contain processed gag and reverse transcriptase, and particles made by cells expressing an integrated lacZ provirus also contain viral RNA. The virus-like particles from both cell types are enveloped and are secreted/budded into the extracellular space but are noninfectious. Their physicochemical properties are similar to those of mature retroviral particles. The noninfectious gag pol RNA particles can readily be made infectious by the addition of lipofection reagents to produce preparations with titers of up to 105 colony-forming units per ml. PMID:9380714

  13. Incorporation of membrane-anchored flagellin or Escherichia coli heat-labile enterotoxin B subunit enhances the immunogenicity of rabies virus-like particles in mice and dogs

    Directory of Open Access Journals (Sweden)

    Yinglin eQi

    2015-03-01

    Full Text Available Rabies remains an important worldwide public health threat, so safe, effective and affordable vaccines are still being sought. Virus-like particle (VLP-based vaccines targeting various viral pathogens have been successfully produced, licensed and commercialized. Here, we designed and constructed two chimeric rabies virus-like particles (cRVLPs containing rabies virus (RABV glycoprotein (G, matrix (M protein, and membrane-anchored flagellin (EVLP-F or Escherichia coli heat-labile enterotoxin B subunit (EVLP-L as molecular adjuvants to enhance the immune response against rabies. The immunogenicity and potential of cRVLPs as novel rabies vaccine were evaluated by intramuscular vaccination in mouse and dog models. Mouse studies demonstrated that both EVLP-F and EVLP-L induced faster and larger virus-neutralizing antibodies (VNA responses and elicited greater numbers of CD4+ and CD8+ T cells secreting IFN-γ or IL-4 compared with a standard rabies VLP (sRVLP containing only G and M. Moreover, cRVLPs recruited and/or activated more B cells and dendritic cells in inguinal lymph nodes. EVLP-F induced a strong, specific IgG2a response but not an IgG1 response, suggesting the activation of Th1 class immunity; in contrast, Th2 class immunity was observed with EVLP-L. The significantly enhanced humoral and cellular immune responses induced by cRVLPs provided complete protection against lethal challenge with RABV. Most importantly, dogs vaccinated with EVLP-F or EVLP-L exhibited increased VNA titers in sera and enhanced IFN-γ and IL-4 secretion from peripheral blood mononuclear cells. Taken together, these results illustrate that when incorporated into sRVLP, membrane-anchored flagellin and LTB possess strong adjuvant activity. EVLP-F and EVLP-L induce significantly enhanced RABV-specific humoral and cellular immune responses in both mouse and dog. Therefore, these cRVLPs may be developed as safe and more efficacious rabies vaccine candidate for animals.

  14. Heterologous prime-boost vaccination with DNA and MVA vaccines, expressing HIV-1 subtype C mosaic Gag virus-like particles, is highly immunogenic in mice.

    Directory of Open Access Journals (Sweden)

    Ros Chapman

    Full Text Available In an effort to make affordable vaccines suitable for the regions most affected by HIV-1, we have constructed stable vaccines that express an HIV-1 subtype C mosaic Gag immunogen (BCG-GagM, MVA-GagM and DNA-GagM. Mosaic immunogens have been designed to address the tremendous diversity of this virus. Here we have shown that GagM buds from cells infected and transfected with MVA-GagM and DNA-GagM respectively and forms virus-like particles. Previously we showed that a BCG-GagM prime MVA-GagM boost generated strong cellular immune responses in mice. In this study immune responses to the DNA-GagM and MVA-GagM vaccines were evaluated in homologous and heterologous prime-boost vaccinations. The DNA homologous prime boost vaccination elicited predominantly CD8+ T cells while the homologous MVA vaccination induced predominantly CD4+ T cells. A heterologous DNA-GagM prime MVA-GagM boost induced strong, more balanced Gag CD8+ and CD4+ T cell responses and that were predominantly of an effector memory phenotype. The immunogenicity of the mosaic Gag (GagM was compared to a naturally occurring subtype C Gag (GagN using a DNA homologous vaccination regimen. DNA-GagN expresses a natural Gag with a sequence that was closest to the consensus sequence of subtype C viruses sampled in South Africa. DNA-GagM homologous vaccination induced cumulative HIV-1 Gag-specific IFN-γ ELISPOT responses that were 6.5-fold higher than those induced by the DNA-GagN vaccination. Similarly, DNA-GagM vaccination generated 7-fold higher levels of cytokine-positive CD8+ T cells than DNA-GagN, indicating that this subtype C mosaic Gag elicits far more potent immune responses than a consensus-type Gag. Cells transfected and infected with DNA-GagM and MVA-GagM respectively, expressed high levels of GagM and produced budding virus-like particles. Our data indicates that a heterologous prime boost regimen using DNA and MVA vaccines expressing HIV-1 subtype C mosaic Gag is highly

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

    Directory of Open Access Journals (Sweden)

    Cashman Kathleen A

    2010-10-01

    Full Text Available Abstract Background Lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully utilized intravenous administration of ribavirin, a nucleotide analogue drug, but this is not an approved use; efficacy of oral administration has not been demonstrated. To date, several potential new vaccine platforms have been explored, but none have progressed toward clinical trials and commercialization. Therefore, the development of a robust vaccine platform that could be generated in sufficient quantities and at a low cost per dose could herald a subcontinent-wide vaccination program. This would move Lassa endemic areas toward the control and reduction of major outbreaks and endemic infections. To this end, we have employed efficient mammalian expression systems to generate a Lassa virus (LASV-like particle (VLP-based modular vaccine platform. Results A mammalian expression system that generated large quantities of LASV VLP in human cells at small scale settings was developed. These VLP contained the major immunological determinants of the virus: glycoprotein complex, nucleoprotein, and Z matrix protein, with known post-translational modifications. The viral proteins packaged into LASV VLP were characterized, including glycosylation profiles of glycoprotein subunits GP1 and GP2, and structural compartmentalization of each polypeptide. The host cell protein component of LASV VLP was also partially analyzed, namely glycoprotein incorporation, though the identity of these proteins remain unknown. All combinations of LASV Z, GPC, and NP proteins that generated VLP did not incorporate host cell ribosomes, a known component of native arenaviral particles, despite detection of small RNA species packaged into pseudoparticles. Although VLP did not contain the same host cell components as the native

  16. Influence of minor displacements in loops of the porcine parvovirus VP2 capsid on virus-like particles assembly and the induction of antibody responses.

    Science.gov (United States)

    Pan, Qunxing; He, Kongwang; Wang, Yongshan; Wang, Xiaoli; Ouyang, Wei

    2013-06-01

    An antigen-delivery system based on hybrid virus-like particles (VLPs) formed by the self-assembly of the capsid VP2 protein of porcine parvovirus (PPV) and expressing foreign peptides offers an alternative method for vaccination. In this study, the three-dimensional structure of the PPV capsid protein and surface loops deletion mutants were analyzed to define essential domains in PPV VP2 for the assembly of VLPs. Electron microscopic analysis and SDS-PAGE analysis confirmed the presence of abundant VLPs in a loop2 deletion mutant of expected size and appropriate morphology. Loop4 and loop2-loop4 deletion mutants, however, resulted in a lower number of particles and the morphology of the particles was not well preserved. Furthermore, the green fluorescent protein (gfp) gene was used as a model. GFP was observed at the same level in displacements mutants. However, GFP displacement mutants in loop2 construct allowed better adaptation for the fusion GFP to be further displayed on the surface of the capsid-like structure. Immunogenicity study showed that there is no obvious difference in mice inoculated with rAd-VP2(Δloop2), rAd-VP2(Δloop4), rAd-VP2(Δloop2-Δloop4), and PPV inactivated vaccine. The results suggested the possibility of inserting simultaneously B and T cell epitopes in the surface loop2 and the N-terminus. The combination of different types of epitopes (B, CD4+, and CD8+) in different positions of the PPV particles opens the way to the development of highly efficient vaccines, able to stimulate at the same time the different branches of the immune system.

  17. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like-particle vaccine in Latin American women.

    Science.gov (United States)

    Perez, Gonzalo; Lazcano-Ponce, Eduardo; Hernandez-Avila, Mauricio; García, Patricia J; Muñoz, Nubia; Villa, Luisa L; Bryan, Janine; Taddeo, Frank J; Lu, Shuang; Esser, Mark T; Vuocolo, Scott; Sattler, Carlos; Barr, Eliav

    2008-03-15

    The prevalence of HPV infection in Latin America is among the highest in the world. A quadrivalent (types 6/11/16/18) human papillomavirus L1 virus-like-particle vaccine has been shown to be 95-100% effective in preventing HPV 6/11/16/18-related cervical and genital disease in women naive to vaccine HPV types. A total of 6,004 female subjects aged 9-24 were recruited from Brazil, Mexico, Colombia, Costa Rica, Guatemala and Peru. Subjects were randomized to immunization with intramuscular (deltoid) injections of HPV vaccine or placebo at enrollment (day 1), month 2 and month 6. Among vaccinated subjects in the per-protocol population from Latin America, quadrivalent HPV vaccine was 92.8 and 100% effective in preventing cervical intraepithelial neoplasia and external genital lesions related to vaccine HPV types, respectively. These data support vaccination of adolescents and young adults in the region, which is expected to greatly reduce the burden of cervical and genital cancers, precancers and genital warts. (c) 2007 Wiley-Liss, Inc.

  18. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

    2016-07-15

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  19. Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

    International Nuclear Information System (INIS)

    Kawano, Masaaki; Morikawa, Katsuma; Suda, Tatsuya; Ohno, Naohito; Matsushita, Sho; Akatsuka, Toshitaka; Handa, Hiroshi; Matsui, Masanori

    2014-01-01

    Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A ⁎ 02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A ⁎ 02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: • We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. • Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. • Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. • Chimeric SV40-VLPs induce long-lasting memory CTLs. • Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties

  20. Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants.

    Science.gov (United States)

    Kawano, Masaaki; Morikawa, Katsuma; Suda, Tatsuya; Ohno, Naohito; Matsushita, Sho; Akatsuka, Toshitaka; Handa, Hiroshi; Matsui, Masanori

    2014-01-05

    Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A*02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A*02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. © 2013 Elsevier Inc. All rights reserved.

  1. Duck hepatitis A virus structural proteins expressed in insect cells self-assemble into virus-like particles with strong immunogenicity in ducklings.

    Science.gov (United States)

    Wang, Anping; Gu, Lingling; Wu, Shuang; Zhu, Shanyuan

    2018-02-01

    Duck hepatitis A virus (DHAV), a non-enveloped ssRNA virus, can cause a highly contagious disease in young ducklings. The three capsid proteins of VP0, VP1 and VP3 are translated within a single large open reading frame (ORF) and hydrolyzed by protease 3CD. However, little is known on whether the recombinant viral structural proteins (VPs) expressed in insect cells could spontaneously assemble into virus-like particles (VLPs) and whether these VLPs could induce protective immunity in young ducklings. To address these issues, the structural polyprotein precursor gene P1 and the protease gene 3CD were amplified by PCR, and the recombinant proteins were expressed in insect cells using a baculovirus expression system for the characterization of their structures and immunogenicity. The recombinant proteins expressed in Sf9 cells were detected by indirect immunofluorescence assay and Western blot analysis. Electron microscopy showed that the recombinant proteins spontaneously assembled into VLPs in insect cells. Western blot analysis of the purified VLPs revealed that the VLPs were composed with the three structural proteins. In addition, vaccination with the VLPs induced high humoral immune response and provided strong protection. Therefore, our findings may provide a framework for development of new vaccines for the prevention of duck viral hepatitis. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Murine polyomavirus virus-like particles carrying full-length human PSA protect BALB/c mice from outgrowth of a PSA expressing tumor.

    Directory of Open Access Journals (Sweden)

    Mathilda Eriksson

    Full Text Available Virus-like particles (VLPs consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV VLPs carrying the entire human Prostate Specific Antigen (PSA (PSA-MPyVLPs for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs. Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4(+ and CD8(+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4(+ and CD8(+ cells with a low induction of anti-VLP antibodies.

  3. Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges

    Directory of Open Access Journals (Sweden)

    John M. Dye

    2016-04-01

    Full Text Available Marburg virus (MARV was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. Previous studies demonstrated that MARV virus-like particles (VLPs containing the glycoprotein (GP, matrix protein VP40 and nucleoprotein (NP generated using a baculovirus/insect cell expression system could protect macaques from subcutaneous (SQ challenge with multiple species of marburgviruses. In the current study, the protective efficacy of the MARV VLPs in conjunction with two different adjuvants: QS-21, a saponin derivative, and poly I:C against homologous aerosol challenge was assessed in cynomolgus macaques. Antibody responses against the GP antigen were equivalent in all groups receiving MARV VLPs irrespective of the adjuvant; adjuvant only-vaccinated macaques did not demonstrate appreciable antibody responses. All macaques were subsequently challenged with lethal doses of MARV via aerosol or SQ as a positive control. All MARV VLP-vaccinated macaques survived either aerosol or SQ challenge while animals administered adjuvant only exhibited clinical signs and lesions consistent with MARV disease and were euthanized after meeting the predetermined criteria. Therefore, MARV VLPs induce IgG antibodies recognizing MARV GP and VP40 and protect cynomolgus macaques from an otherwise lethal aerosol exposure with MARV.

  4. Goose parvovirus structural proteins expressed by recombinant baculoviruses self-assemble into virus-like particles with strong immunogenicity in goose.

    Science.gov (United States)

    Ju, Huanyu; Wei, Na; Wang, Qian; Wang, Chunyuan; Jing, Zhiqiang; Guo, Lu; Liu, Dapeng; Gao, Mingchun; Ma, Bo; Wang, Junwei

    2011-05-27

    Goose parvovirus (GPV), a small non-enveloped ssDNA virus, can cause Derzsy's disease, and three capsid proteins of VP1, VP2, and VP3 are encoded by an overlapping nucleotide sequence. However, little is known on whether recombinant viral proteins (VPs) could spontaneously assemble into virus-like particles (VLPs) in insect cells and whether these VLPs could retain their immunoreactivity and immunogenicity in susceptible geese. To address these issues, genes for these GPV VPs were amplified by PCR, and the recombinant VPs proteins were expressed in insect cells using a baculovirus expression system for the characterization of their structures, immunoreactivity, and immunogenicity. The rVP1, rVP2, and rVP3 expressed in Sf9 cells were detected by anti-GPV sera, anti-VP3 sera, and anti-His antibodies, respectively. Electron microscopy revealed that these rVPs spontaneously assembled into VLPs in insect cells, similar to that of the purified wild-type GPV virions. In addition, vaccination with individual types of VLPs, particularly with the rVP2-VLPs, induced higher titers of antibodies and neutralized different strains of GPVs in primary goose and duck embryo fibroblast cells in vitro. These data indicated that these VLPs retained immunoreactivity and had strong immunogenicity in susceptible geese. Therefore, our findings may provide a framework for development of new vaccines for the prevention of Derzsy's disease and vehicles for the delivery of drugs. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Porcine parvovirus capsid protein expressed in Escherichia coli self-assembles into virus-like particles with high immunogenicity in mice and guinea pigs.

    Science.gov (United States)

    Ji, Pengchao; Liu, Yunchao; Chen, Yumei; Wang, Aiping; Jiang, Dawei; Zhao, Baolei; Wang, Jvcai; Chai, Shujun; Zhou, Enmin; Zhang, Gaiping

    2017-03-01

    Porcine parvovirus (PPV) is a causative agent of reproductive failure in pregnant sows. Classical inactivated vaccine is extensively used to control PPV infection, but problems concerning safety, such as incomplete inactivation may occur. In this study, a novel subunit vaccine against PPV based on virus-like particles (VLPs) formed from the complete PPV VP2 protein expressed in a prokaryotic system with co-expressed chaperones is reported. The VLPs have a similar size, shape, and hemagglutination property to the PPV. Immunization with these VLPs stimulated the neutralization antibody and hemagglutination inhibition (HI) antibody responses in mice and guinea pigs. The lymphocyte proliferation response and cytokine secretion was also induced in immunized guinea pigs comparable to those immunized with PPV inactivated vaccine. In addition, immunization with VLPs also significantly reduced the PPV content in the spleen of guinea pigs 14 days after the challenge with intact virus. These studies suggest that PPV VLPs created as described here could be a potential candidate for vaccine development. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. CCL28 induces mucosal homing of HIV-1-specific IgA-secreting plasma cells in mice immunized with HIV-1 virus-like particles.

    Directory of Open Access Journals (Sweden)

    Veronica Rainone

    Full Text Available Mucosae-associated epithelial chemokine (MEC or CCL28 binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASCs in the mucosal lamina propria. The ability of this chemokine to enhance migration of IgA-ASCs to mucosal sites was assessed in a mouse immunization model using HIV-1(IIIB Virus-like particles (VLPs. Mice receiving either HIV-1(IIIB VLPs alone, CCL28 alone, or the irrelevant CCL19 chemokine were used as controls. Results showed a significantly increased CCR3 and CCR10 expression on CD19(+ splenocytes of HIV-1(IIIB VPL-CCL28-treated mice. HIV-1 Env-specific IFN-γ, IL-4 and IL-5 production, total IgA, anti-Env IgA as well as gastro-intestinal mucosal IgA-secreting plasma cells were also significantly augmented in these mice. Notably, sera and vaginal secretions from HIV-1(IIIB VLP-CCL28-treated mice exhibited an enhanced neutralizing activity against both a HIV-1/B-subtype laboratory strain and a heterologous HIV-1/C-subtype primary isolate. These data suggest that CCL28 could be useful in enhancing the IgA immune response that will likely play a pivotal role in prophylactic HIV vaccines.

  7. Maize rayado fino virus virus-like particles expressed in tobacco plants: A new platform for cysteine selective bioconjugation peptide display.

    Science.gov (United States)

    Natilla, Angela; Hammond, Rosemarie W

    2011-12-01

    Maize rayado fino virus (MRFV) virus-like-particles (VLPs) produced in tobacco plants were examined for their ability to serve as a novel platform to which a variety of peptides can be covalently displayed when expressed through a Potato virus X (PVX)-based vector. To provide an anchor for chemical modifications, three Cys-MRFV-VLPs mutants were created by substituting several of the amino acids present on the shell of the wild-type MRFV-VLPs with cysteine residues. The mutant designated Cys 2-VLPs exhibited, under native conditions, cysteine thiol reactivity in bioconjugation reactions with a fluorescent dye. In addition, this Cys 2-VLPs was cross-linked by NHS-PEG4-Maleimide to 17 (F) and 8 (HN) amino acid long peptides, corresponding to neutralizing epitopes of Newcastle disease virus (NDV). The resulting Cys 2-VLPs-F and Cys 2-VLPs-HN were recognized in Western blots by antibodies to MRFV as well as to F and HN. The results demonstrated that plant-produced MRFV-VLPs have the ability to function as a novel platform for the multivalent display of surface ligands. Published by Elsevier B.V.

  8. A Rapid Screen for Host-Encoded miRNAs with Inhibitory Effects against Ebola Virus Using a Transcription- and Replication-Competent Virus-Like Particle System

    Directory of Open Access Journals (Sweden)

    Zhongyi Wang

    2018-05-01

    Full Text Available MicroRNAs (miRNAs may become efficient antiviral agents against the Ebola virus (EBOV targeting viral genomic RNAs or transcripts. We previously conducted a genome-wide search for differentially expressed miRNAs during viral replication and transcription. In this study, we established a rapid screen for miRNAs with inhibitory effects against EBOV using a tetracistronic transcription- and replication-competent virus-like particle (trVLP system. This system uses a minigenome comprising an EBOV leader region, luciferase reporter, VP40, GP, VP24, EBOV trailer region, and three noncoding regions from the EBOV genome and can be used to model the life cycle of EBOV under biosafety level (BSL 2 conditions. Informatic analysis was performed to select up-regulated miRNAs targeting the coding regions of the minigenome with the highest binding energy to perform inhibitory effect screening. Among these miRNAs, miR-150-3p had the most significant inhibitory effect. Reverse transcription polymerase chain reaction (RT-PCR, Western blot, and double fluorescence reporter experiments demonstrated that miR-150-3p inhibited the reproduction of trVLPs via the regulation of GP and VP40 expression by directly targeting the coding regions of GP and VP40. This novel, rapid, and convenient screening method will efficiently facilitate the exploration of miRNAs against EBOV under BSL-2 conditions.

  9. Murine Polyomavirus Virus-Like Particles Carrying Full-Length Human PSA Protect BALB/c Mice from Outgrowth of a PSA Expressing Tumor

    Science.gov (United States)

    Eriksson, Mathilda; Andreasson, Kalle; Weidmann, Joachim; Lundberg, Kajsa; Tegerstedt, Karin

    2011-01-01

    Virus-like particles (VLPs) consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV) VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs). Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4+ and CD8+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4+ and CD8+ cells with a low induction of anti-VLP antibodies. PMID:21858228

  10. Neutralizing antibodies induced by recombinant virus-like particles of enterovirus 71 genotype C4 inhibit infection at pre- and post-attachment steps.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Ku

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 is a major causative agent of hand, foot and mouth disease, which has been prevalent in Asia-Pacific regions, causing significant morbidity and mortality in young children. Antibodies elicited by experimental EV71 vaccines could neutralize infection in vitro and passively protect animal models from lethal challenge, indicating that neutralizing antibodies play an essential role in protection. However, how neutralizing antibodies inhibit infection in vitro remains unclear. METHODS/FINDINGS: In the present study, we explored the mechanisms of neutralization by antibodies against EV71 virus-like particles (VLPs. Recombinant VLPs of EV71 genotype C4 were produced in insect cells using baculovirus vectors. Immunization with the VLPs elicited a high-titer, EV71-specific antibody response in mice. Anti-VLP mouse sera potently neutralized EV71 infection in vitro. The neutralizing antibodies in the anti-VLP mouse sera were found to target mainly an extremely conserved epitope (FGEHKQEKDLEYGAC located at the GH loop of the VP1 protein. The neutralizing anti-VLP antisera were able to inhibit virus binding to target cells efficiently. In addition, post-attachment treatment of virus-bound cells with the anti-VLP antisera also neutralized virus infection, although the antibody concentration required was higher than that of the pre-attachment treatment. CONCLUSIONS: Collectively, our findings represent a valuable addition to the understanding of mechanisms of EV71 neutralization and have strong implications for EV71 vaccine development.

  11. Novel chimeric foot-and-mouth disease virus-like particles harboring serotype O VP1 protect guinea pigs against challenge.

    Science.gov (United States)

    Li, Haitao; Li, Zhiyong; Xie, Yinli; Qin, Xiaodong; Qi, Xingcai; Sun, Peng; Bai, Xingwen; Ma, Youji; Zhang, Zhidong

    2016-02-01

    Foot-and-mouth disease is a highly contagious, acute viral disease of cloven-hoofed animal species causing severe economic losses worldwide. Among the seven serotypes of foot-and-mouth disease virus (FMDV), serotype O is predominant, but its viral capsid is more acid sensitive than other serotypes, making it more difficult to produce empty serotype O VLPs in the low pH insect hemolymph. Therefore, a novel chimeric virus-like particle (VLP)-based candidate vaccine for serotype O FMDV was developed and characterized in the present study. The chimeric VLPs were composed of antigenic VP1 from serotype O and segments of viral capsid proteins from serotype Asia1. These VLPs elicited significantly higher FMDV-specific antibody levels in immunized mice than did the inactivated vaccine. Furthermore, the chimeric VLPs protected guinea pigs from FMDV challenge with an efficacy similar to that of the inactivated vaccine. These results suggest that chimeric VLPs have the potential for use in vaccines against serotype O FMDV infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

    Directory of Open Access Journals (Sweden)

    Nuriban Valero-Pacheco

    Full Text Available The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs, have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

  13. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    International Nuclear Information System (INIS)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

    2016-01-01

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  14. The cellular endosomal sorting complex required for transport pathway is not involved in avian metapneumovirus budding in a virus-like-particle expression system.

    Science.gov (United States)

    Weng, Yuejin; Lu, Wuxun; Harmon, Aaron; Xiang, Xiaoxiao; Deng, Qiji; Song, Minxun; Wang, Dan; Yu, Qingzhong; Li, Feng

    2011-05-01

    Avian metapneumovirus (AMPV) is a paramyxovirus that principally causes respiratory disease and egg production drops in turkeys and chickens. Together with its closely related human metapneumovirus (HMPV), they comprise the genus Metapneumovirus in the family Paramyxoviridae. Little is currently known about the mechanisms involved in the budding of metapneumovirus. By using AMPV as a model system, we showed that the matrix (M) protein by itself was insufficient to form virus-like-particles (VLPs). The incorporation of M into VLPs was shown to occur only when both the viral nucleoprotein (N) and the fusion (F) proteins were co-expressed. Furthermore, we provided evidence indicating that two YSKL and YAGL segments encoded within the M protein were not a functional late domain, and the endosomal sorting complex required for transport (ESCRT) machinery was not involved in metapneumovirus budding, consistent with a recent observation that human respiratory syncytial virus, closely related to HMPV, uses an ESCRT-independent budding mechanism. Taken together, these results suggest that metapneumovirus budding is independent of the ESCRT pathway and the minimal budding machinery described here will aid our future understanding of metapneumovirus assembly and egress.

  15. Modeling and simulation of anion-exchange membrane chromatography for purification of Sf9 insect cell-derived virus-like particles.

    Science.gov (United States)

    Ladd Effio, Christopher; Hahn, Tobias; Seiler, Julia; Oelmeier, Stefan A; Asen, Iris; Silberer, Christine; Villain, Louis; Hubbuch, Jürgen

    2016-01-15

    Recombinant protein-based virus-like particles (VLPs) are steadily gaining in importance as innovative vaccines against cancer and infectious diseases. Multiple VLPs are currently evaluated in clinical phases requiring a straightforward and rational process design. To date, there is no generic platform process available for the purification of VLPs. In order to accelerate and simplify VLP downstream processing, there is a demand for novel development approaches, technologies, and purification tools. Membrane adsorbers have been identified as promising stationary phases for the processing of bionanoparticles due to their large pore sizes. In this work, we present the potential of two strategies for designing VLP processes following the basic tenet of 'quality by design': High-throughput experimentation and process modeling of an anion-exchange membrane capture step. Automated membrane screenings allowed the identification of optimal VLP binding conditions yielding a dynamic binding capacity of 5.7 mg/mL for human B19 parvovirus-like particles derived from Spodoptera frugiperda Sf9 insect cells. A mechanistic approach was implemented for radial ion-exchange membrane chromatography using the lumped-rate model and stoichiometric displacement model for the in silico optimization of a VLP capture step. For the first time, process modeling enabled the in silico design of a selective, robust and scalable process with minimal experimental effort for a complex VLP feedstock. The optimized anion-exchange membrane chromatography process resulted in a protein purity of 81.5%, a DNA clearance of 99.2%, and a VLP recovery of 59%. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Cell wall biochemical alterations during Agrobacterium-mediated expression of haemagglutinin-based influenza virus-like vaccine particles in tobacco.

    Science.gov (United States)

    Le Mauff, François; Loutelier-Bourhis, Corinne; Bardor, Muriel; Berard, Caroline; Doucet, Alain; D'Aoust, Marc-André; Vezina, Louis-Philippe; Driouich, Azeddine; Couture, Manon M-J; Lerouge, Patrice

    2017-03-01

    Influenza virus-like particles (VLPs) have been shown to induce a safe and potent immune response through both humoral and cellular responses. They represent promising novel influenza vaccines. Plant-based biotechnology allows for the large-scale production of VLPs of biopharmaceutical interest using different model organisms, including Nicotiana benthamiana plants. Through this platform, influenza VLPs bud from the plasma membrane and accumulate between the membrane and the plant cell wall. To design and optimize efficient production processes, a better understanding of the plant cell wall composition of infiltrated tobacco leaves is a major interest for the plant biotechnology industry. In this study, we have investigated the alteration of the biochemical composition of the cell walls of N. benthamiana leaves subjected to abiotic and biotic stresses induced by the Agrobacterium-mediated transient transformation and the resulting high expression levels of influenza VLPs. Results show that abiotic stress due to vacuum infiltration without Agrobacterium did not induce any detectable modification of the leaf cell wall when compared to non infiltrated leaves. In contrast, various chemical changes of the leaf cell wall were observed post-Agrobacterium infiltration. Indeed, Agrobacterium infection induced deposition of callose and lignin, modified the pectin methylesterification and increased both arabinosylation of RG-I side chains and the expression of arabinogalactan proteins. Moreover, these modifications were slightly greater in plants expressing haemagglutinin-based VLP than in plants infiltrated with the Agrobacterium strain containing only the p19 suppressor of silencing. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  17. A single intranasal administration of virus-like particle vaccine induces an efficient protection for mice against human respiratory syncytial virus.

    Science.gov (United States)

    Jiao, Yue-Ying; Fu, Yuan-Hui; Yan, Yi-Fei; Hua, Ying; Ma, Yao; Zhang, Xiu-Juan; Song, Jing-Dong; Peng, Xiang-Lei; Huang, Jiaqiang; Hong, Tao; He, Jin-Sheng

    2017-08-01

    Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully. The resulting VLPs showed similar immunoreactivity and function to RSV virion in vitro. Moreover, Th1 polarized response, and effective mucosal virus-neutralizing antibody and CD8 + T-cell responses were induced by a single intranasal (i.n.) administration of RSV VLPs rather than intramuscular (i.m.) inoculation, although the comparable RSV F-specific serum IgG and long-lasting RSV-specific neutralizing antibody were detected in the mice immunized by both routes. Upon RSV challenge, VLP-immunized mice showed increased viral clearance but decreased signs of enhanced lung pathology and fewer eosinophils compared to mice immunized with formalin-inactivated RSV (FI-RSV). In addition, a single i.n. RSV VLP vaccine has the capability to induce RSV-specific long-lasting neutralizing antibody responses observable up to 15 months. Our results demonstrate that the long-term and memory immune responses in mice against RSV were induced by a single i.n. administration of RSV VLP vaccine, suggesting a successful approach of RSV VLPs as an effective and safe mucosal vaccine against RSV infection, and an applicable and qualified platform of FGAd-infected Vero cells for VLP production. Copyright © 2017. Published by Elsevier B.V.

  18. Virus-like particle of Macrobrachium rosenbergii nodavirus produced in Spodoptera frugiperda (Sf9) cells is distinctive from that produced in Escherichia coli.

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    Kueh, Chare Li; Yong, Chean Yeah; Masoomi Dezfooli, Seyedehsara; Bhassu, Subha; Tan, Soon Guan; Tan, Wen Siang

    2017-03-01

    Macrobrachium rosenbergii nodavirus (MrNV) is a virus native to giant freshwater prawn. Recombinant MrNV capsid protein has been produced in Escherichia coli, which self-assembled into virus-like particles (VLPs). However, this recombinant protein is unstable, degrading and forming heterogenous VLPs. In this study, MrNV capsid protein was produced in insect Spodoptera frugiperda (Sf9) cells through a baculovirus system. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed that the recombinant protein produced by the insect cells self-assembled into highly stable, homogenous VLPs each of approximately 40 nm in diameter. Enzyme-linked immunosorbent assay (ELISA) showed that the VLPs produced in Sf9 cells were highly antigenic and comparable to those produced in E. coli. In addition, the Sf9 produced VLPs were highly stable across a wide pH range (2-12). Interestingly, the Sf9 produced VLPs contained DNA of approximately 48 kilo base pairs and RNA molecules. This study is the first report on the production and characterization of MrNV VLPs produced in a eukaryotic system. The MrNV VLPs produced in Sf9 cells were about 10 nm bigger and had a uniform morphology compared with the VLPs produced in E. coli. The insect cell production system provides a good source of MrNV VLPs for structural and immunological studies as well as for host-pathogen interaction studies. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:549-557, 2017. © 2016 American Institute of Chemical Engineers.

  19. CD4+ and CD8+ T cells can act separately in tumour rejection after immunization with murine pneumotropic virus chimeric Her2/neu virus-like particles.

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    Kalle Andreasson

    Full Text Available BACKGROUND: Immunization with murine pneumotropic virus virus-like particles carrying Her2/neu (Her2MPtVLPs prevents tumour outgrowth in mice when given prophylactically, and therapeutically if combined with the adjuvant CpG. We investigated which components of the immune system are involved in tumour rejection, and whether long-term immunological memory can be obtained. METHODOLOGY AND RESULTS: During the effector phase in BALB/c mice, only depletion of CD4+ and CD8+ in combination, with or without NK cells, completely abrogated tumour protection. Depletion of single CD4+, CD8+ or NK cell populations only had minor effects. During the immunization/induction phase, combined depletion of CD4+ and CD8+ cells abolished protection, while depletion of each individual subset had no or negligible effect. When tumour rejection was studied in knock-out mice with a C57Bl/6 background, protection was lost in CD4-/-CD8-/- and CD4-/-, but not in CD8-/- mice. In contrast, when normal C57Bl/6 mice were depleted of different cell types, protection was lost irrespective of whether only CD4+, only CD8+, or CD4+ and CD8+ cells in combination were eradicated. No anti-Her2/neu antibodies were detected but a Her2/neu-specific IFNgamma response was seen. Studies of long-term memory showed that BALB/c mice could be protected against tumour development when immunized together with CpG as long as ten weeks before challenge. CONCLUSION: Her2MPtVLP immunization is efficient in stimulating several compartments of the immune system, and induces an efficient immune response including long-term memory. In addition, when depleting mice of isolated cellular compartments, tumour protection is not as efficiently abolished as when depleting several immune compartments together.

  20. Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice.

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    Wang, Chong; Zheng, Xuexing; Gai, Weiwei; Wong, Gary; Wang, Hualei; Jin, Hongli; Feng, Na; Zhao, Yongkun; Zhang, Weijiao; Li, Nan; Zhao, Guoxing; Li, Junfu; Yan, Jinghua; Gao, Yuwei; Hu, Guixue; Yang, Songtao; Xia, Xianzhu

    2017-04-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). sVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphology similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. sVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1: 320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Virus-Like Particle (VLP Plus Microcrystalline Tyrosine (MCT Adjuvants Enhance Vaccine Efficacy Improving T and B Cell Immunogenicity and Protection against Plasmodium berghei/vivax

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    Gustavo Cabral-Miranda

    2017-05-01

    Full Text Available Vaccination is the most effective prophylactic tool against infectious diseases. Despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. Microcrystalline tyrosine (MCT is a well described depot used in licensed allergy immunotherapy products and in clinical development. However, its proof of concept in prophylactic vaccines has only recently been explored. MCT has never been used in combination with virus-like particles (VLPs, which are considered to be one of the most potent inducers of cellular and humoral immune responses in mice and humans. In the current study we assessed the potential of MCT to serve as an adjuvant in the development of a vaccine against malaria either alone or combined with VLP using Plasmodium vivax thrombospondin-related adhesive protein (TRAP as a target antigen. We chemically coupled PvTRAP to VLPs derived from the cucumber mosaic virus fused to a universal T-cell epitope of the tetanus toxin (CMVtt, formulated with MCT and compared the induced immune responses to PvTRAP formulated in PBS or Alum. The protective capacity of the various formulations was assessed using Plasmodium berghei expressing PvTRAP. All vaccine formulations using adjuvants and/or VLP increased humoral immunogenicity for PvTRAP compared to the antigen alone. The most proficient responder was the group of mice immunized with the vaccine formulated with PvTRAP-VLP + MCT. The VLP-based vaccine formulated in MCT also induced the strongest T cell response and conferred best protection against challenge with recombinant Plasmodium berghei. Thus, the combination of VLP with MCT may take advantage of the properties of each component and appears to be an alternative biodegradable depot adjuvant for development of novel prophylactic vaccines.

  2. Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine.

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    Chuan, Yap P; Rivera-Hernandez, Tania; Wibowo, Nani; Connors, Natalie K; Wu, Yang; Hughes, Fiona K; Lua, Linda H L; Middelberg, Anton P J

    2013-09-01

    Modularization of a peptide antigen for presentation on a microbially synthesized murine polyomavirus (MuPyV) virus-like particle (VLP) offers a new alternative for rapid and low-cost vaccine delivery at a global scale. In this approach, heterologous modules containing peptide antigenic elements are fused to and displayed on the VLP carrier, allowing enhancement of peptide immunogenicity via ordered and densely repeated presentation of the modules. This study addresses two key engineering questions pertaining to this platform, exploring the effects of (i) pre-existing carrier-specific immunity on modular VLP vaccine effectiveness and (ii) increase in the antigenic element number per VLP on peptide-specific immune response. These effects were studied in a mouse model and with modular MuPyV VLPs presenting a group A streptococcus (GAS) peptide antigen, J8i. The data presented here demonstrate that immunization with a modular VLP could induce high levels of J8i-specific antibodies despite a strong pre-existing anti-carrier immune response. Doubling of the J8i antigenic element number per VLP did not enhance J8i immunogenicity at a constant peptide dose. However, the strategy, when used in conjunction with increased VLP dose, could effectively increase the peptide dose up to 10-fold, leading to a significantly higher J8i-specific antibody titer. This study further supports feasibility of the MuPyV modular VLP vaccine platform by showing that, in the absence of adjuvant, modularized GAS antigenic peptide at a dose as low as 150 ng was sufficient to raise a high level of peptide-specific IgGs indicative of bactericidal activity. Copyright © 2013 Wiley Periodicals, Inc.

  3. Overcoming antigen masking of anti-amyloidbeta antibodies reveals breaking of B cell tolerance by virus-like particles in amyloidbeta immunized amyloid precursor protein transgenic mice

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    Ugen Kenneth E

    2004-06-01

    Full Text Available Abstract Background In prior work we detected reduced anti-Aβ antibody titers in Aβ-vaccinated transgenic mice expressing the human amyloid precursor protein (APP compared to nontransgenic littermates. We investigated this observation further by vaccinating APP and nontransgenic mice with either the wild-type human Aβ peptide, an Aβ peptide containing the "Dutch Mutation", E22Q, or a wild-type Aβ peptide conjugated to papillomavirus virus-like particles (VLPs. Results Anti-Aβ antibody titers were lower in vaccinated APP than nontransgenic mice even when vaccinated with the highly immunogenic Aβ E22Q. One concern was that human Aβ derived from the APP transgene might mask anti-Aβ antibodies in APP mice. To test this possibility, we dissociated antigen-antibody complexes by incubation at low pH. The low pH incubation increased the anti-Aβ antibody titers 20–40 fold in APP mice but had no effect in sera from nontransgenic mice. However, even after dissociation, the anti-Aβ titers were still lower in transgenic mice vaccinated with wild-type Aβ or E22Q Aβ relative to non-transgenic mice. Importantly, the dissociated anti-Aβ titers were equivalent in nontransgenic and APP mice after VLP-based vaccination. Control experiments demonstrated that after acid-dissociation, the increased antibody titer did not cross react with bovine serum albumin nor alpha-synuclein, and addition of Aβ back to the dissociated serum blocked the increase in antibody titers. Conclusions Circulating human Aβ can interfere with ELISA assay measurements of anti-Aβ titers. The E22Q Aβ peptide vaccine is more immunogenic than the wild-type peptide. Unlike peptide vaccines, VLP-based vaccines against Aβ abrogate the effects of Aβ self-tolerance.

  4. The influence of ligand charge and length on the assembly of Brome mosaic virus derived virus-like particles with magnetic core

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    Mieloch, Adam A.; Krecisz, Monika; Rybka, Jakub D.; Strugała, Aleksander; Krupiński, Michał; Urbanowicz, Anna; Kozak, Maciej; Skalski, Bohdan; Figlerowicz, Marek; Giersig, Michael

    2018-03-01

    Virus-like particles (VLPs) have sparked a great interest in the field of nanobiotechnology and nanomedicine. The introduction of superparamagnetic nanoparticles (SPIONs) as a core, provides potential use of VLPs in the hyperthermia therapy, MRI contrast agents and magnetically-powered delivery agents. Magnetite NPs also provide a significant improvement in terms of VLPs stability. Moreover employing viral structural proteins as self-assembling units has opened a new paths for targeted therapy, drug delivery systems, vaccines design, and many more. In many cases, the self-assembly of a virus strongly depends on electrostatic interactions between positively charged groups of the capsid proteins and negatively charged nucleic acid. This phenomenon imposes the negative net charge as a key requirement for the core nanoparticle. In our experiments, Brome mosaic virus (BMV) capsid proteins isolated from infected plants Hordeum vulgare were used. Superparamagnetic iron oxide nanoparticles (Fe3O4) with 15 nm in diameter were synthesized by thermal decomposition and functionalized with COOH-PEG-PL polymer or dihexadecylphosphate (DHP) in order to provide water solubility and negative charge required for the assembly. Nanoparticles were characterized by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta Potential, Fourier Transformed Infrared Spectroscopy (FTIR) and Superconducting Quantum Interference Device (SQUID) magnetometry. TEM and DLS study were conducted to verify VLPs creation. This study demonstrates that the increase of negative surface charge is not a sufficient factor determining successful assembly. Additional steric interactions provided by longer ligands are crucial for the assembly of BMV SPION VLPs and may enhance the colloidal stability.

  5. The influence of ligand charge and length on the assembly of Brome mosaic virus derived virus-like particles with magnetic core

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    Adam A. Mieloch

    2018-03-01

    Full Text Available Virus-like particles (VLPs have sparked a great interest in the field of nanobiotechnology and nanomedicine. The introduction of superparamagnetic nanoparticles (SPIONs as a core, provides potential use of VLPs in the hyperthermia therapy, MRI contrast agents and magnetically-powered delivery agents. Magnetite NPs also provide a significant improvement in terms of VLPs stability. Moreover employing viral structural proteins as self-assembling units has opened a new paths for targeted therapy, drug delivery systems, vaccines design, and many more. In many cases, the self-assembly of a virus strongly depends on electrostatic interactions between positively charged groups of the capsid proteins and negatively charged nucleic acid. This phenomenon imposes the negative net charge as a key requirement for the core nanoparticle. In our experiments, Brome mosaic virus (BMV capsid proteins isolated from infected plants Hordeum vulgare were used. Superparamagnetic iron oxide nanoparticles (Fe3O4 with 15 nm in diameter were synthesized by thermal decomposition and functionalized with COOH-PEG-PL polymer or dihexadecylphosphate (DHP in order to provide water solubility and negative charge required for the assembly. Nanoparticles were characterized by Transmission Electron Microscopy (TEM, Dynamic Light Scattering (DLS, Zeta Potential, Fourier Transformed Infrared Spectroscopy (FTIR and Superconducting Quantum Interference Device (SQUID magnetometry. TEM and DLS study were conducted to verify VLPs creation. This study demonstrates that the increase of negative surface charge is not a sufficient factor determining successful assembly. Additional steric interactions provided by longer ligands are crucial for the assembly of BMV SPION VLPs and may enhance the colloidal stability.

  6. Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Masaaki [Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Morikawa, Katsuma [Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); Suda, Tatsuya [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Ohno, Naohito [Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Matsushita, Sho [Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Allergy Center, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Akatsuka, Toshitaka [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Handa, Hiroshi, E-mail: handa.h.aa@m.titech.ac.jp [Solutions Research Laboratory, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8503 (Japan); Matsui, Masanori, E-mail: mmatsui@saitama-med.ac.jp [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan)

    2014-01-05

    Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A{sup ⁎}02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A{sup ⁎}02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: • We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. • Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. • Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. • Chimeric SV40-VLPs induce long-lasting memory CTLs. • Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties.

  7. Novel recombinant chimeric virus-like particle is immunogenic and protective against both enterovirus 71 and coxsackievirus A16 in mice.

    Science.gov (United States)

    Zhao, Hui; Li, Hao-Yang; Han, Jian-Feng; Deng, Yong-Qiang; Zhu, Shun-Ya; Li, Xiao-Feng; Yang, Hui-Qin; Li, Yue-Xiang; Zhang, Yu; Qin, E-De; Chen, Rong; Qin, Cheng-Feng

    2015-01-19

    Hand-foot-and-mouth disease (HFMD) has been recognized as an important global public health issue, which is predominantly caused by enterovirus 71 (EV-A71) and coxsackievirus A16 (CVA16). There is no available vaccine against HFMD. An ideal HFMD vaccine should be bivalent against both EV-A71 and CVA16. Here, a novel strategy to produce bivalent HFMD vaccine based on chimeric EV-A71 virus-like particles (ChiEV-A71 VLPs) was proposed and illustrated. The neutralizing epitope SP70 within the capsid protein VP1 of EV-A71 was replaced with that of CVA16 in ChiEV-A71 VLPs. Structural modeling revealed that the replaced CVA16-SP70 epitope is well exposed on the surface of ChiEV-A71 VLPs. These VLPs produced in Saccharomyces cerevisiae exhibited similarity in both protein composition and morphology as naive EV-A71 VLPs. Immunization with ChiEV-A71 VLPs in mice elicited robust Th1/Th2 dependent immune responses against EV-A71 and CVA16. Furthermore, passive immunization with anti-ChiEV-A71 VLPs sera conferred full protection against lethal challenge of both EV-A71 and CVA16 infection in neonatal mice. These results suggested that this chimeric vaccine, ChiEV-A71 might have the potential to be further developed as a bivalent HFMD vaccine in the near future. Such chimeric enterovirus VLPs provide an alternative platform for bivalent HFMD vaccine development.

  8. A virus-like particle based bivalent vaccine confers dual protection against enterovirus 71 and coxsackievirus A16 infections in mice.

    Science.gov (United States)

    Ku, Zhiqiang; Liu, Qingwei; Ye, Xiaohua; Cai, Yicun; Wang, Xiaoli; Shi, Jinping; Li, Dapeng; Jin, Xia; An, Wenqi; Huang, Zhong

    2014-07-23

    Enterovirus 71(EV71) and coxsackievirus A16 (CA16) are responsible for hand, foot and mouth disease which has been prevalent in Asia-Pacific regions, causing significant morbidity and mortality in young children. Co-circulation of and co-infection by both viruses underscores the importance and urgency of developing vaccines against both viruses simultaneously. Here we report the immunogenicity and protective efficacy of a bivalent combination vaccine comprised of EV71 and CA16 virus-like particles (VLPs). We show that monovalent EV71- or CA16-VLPs-elicited serum antibodies exhibited potent neutralization effect on the homotypic virus but little or no effect on the heterotypic one, whereas the antisera against the bivalent vaccine formulation were able to efficiently neutralize both EV71 and CA16, indicating there is no immunological interference between the two antigens with respect to their ability to induce virus-specific neutralizing antibodies. Passive immunization with monovalent VLP vaccines protected mice against a homotypic virus challenge but not heterotypic infection. Surprisingly, antibody-dependent enhancement (ADE) of disease was observed in mice passively transferred with mono-specific anti-CA16 VLP sera and subsequently challenged with EV71. In contrast, the bivalent VLP vaccine conferred full protection against lethal challenge by either EV71 or CA16, thus eliminating the potential of ADE. Taken together, our results demonstrate for the first time that the bivalent VLP approach represents a safe and efficacious vaccine strategy for both EV71 and CA16. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Virus-like particle production with yeast: ultrastructural and immunocytochemical insights into Pichia pastoris producing high levels of the Hepatitis B surface antigen

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    Adnan Ahmad

    2011-06-01

    Full Text Available Abstract Background A protective immune response against Hepatitis B infection can be obtained through the administration of a single viral polypeptide, the Hepatitis B surface antigen (HBsAg. Thus, the Hepatitis B vaccine is generated through the utilization of recombinant DNA technology, preferentially by using yeast-based expression systems. However, the polypeptide needs to assemble into spherical particles, so-called virus-like particles (VLPs, to elicit the required protective immune response. So far, no clear evidence has been presented showing whether HBsAg assembles in vivo inside the yeast cell into VLPs or later in vitro during down-stream processing and purification. Results High level production of HBsAg was carried out with recombinant Pichia pastoris using the methanol inducible AOX1 expression system. The recombinant vaccine was isolated in form of VLPs after several down-stream steps from detergent-treated cell lysates. Search for the intracellular localization of the antigen using electron microscopic studies in combination with immunogold labeling revealed the presence of HBsAg in an extended endoplasmic reticulum where it was found to assemble into defined multi-layered, lamellar structures. The distance between two layers was determined as ~6 nm indicating that these lamellas represent monolayers of well-ordered HBsAg subunits. We did not find any evidence for the presence of VLPs within the endoplasmic reticulum or other parts of the yeast cell. Conclusions It is concluded that high level production and intrinsic slow HBsAg VLP assembly kinetics are leading to retention and accumulation of the antigen in the endoplasmic reticulum where it assembles at least partly into defined lamellar structures. Further transport of HBsAg to the Golgi apparatus is impaired thus leading to secretory pathway disfunction and the formation of an extended endoplasmic reticulum which bulges into irregular cloud-shaped formations. As VLPs were

  10. Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

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    Chao, Chun-Nun; Lin, Mien-Chun; Fang, Chiung-Yao; Chen, Pei-Lain; Chang, Deching; Shen, Cheng-Huang; Wang, Meilin

    2016-01-01

    Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B) has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV) infection. Therefore, we designed that the JCPyV virus-like particle (VLP) packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk) for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp) or thymidine kinase gene (pSPB-tk) under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV) were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549) and large cell carcinoma (H460) cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV), a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

  11. Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

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    Chun-Nun Chao

    Full Text Available Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV infection. Therefore, we designed that the JCPyV virus-like particle (VLP packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp or thymidine kinase gene (pSPB-tk under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549 and large cell carcinoma (H460 cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV, a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

  12. A chimeric 18L1-45RG1 virus-like particle vaccine cross-protects against oncogenic alpha-7 human papillomavirus types.

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    Bettina Huber

    Full Text Available Persistent infection with oncogenic human papillomaviruses (HPV types causes all cervical and a subset of other anogenital and oropharyngeal carcinomas. Four high-risk (hr mucosal types HPV16, 18, 45, or 59 cause almost all cervical adenocarcinomas (AC, a subset of cervical cancer (CxC. Although the incidence of cervical squamous cell carcinoma (SCC has dramatically decreased following introduction of Papanicolaou (PAP screening, the proportion of AC has relatively increased. Cervical SCC arise mainly from the ectocervix, whereas AC originate primarily from the endocervical canal, which is less accessible to obtain viable PAP smears. Licensed (bivalent and quadrivalent HPV vaccines comprise virus-like particles (VLP of the most important hr HPV16 and 18, self-assembled from the major capsid protein L1. Due to mainly type-restricted efficacy, both vaccines do not target 13 additional hr mucosal types causing 30% of CxC. The papillomavirus genus alpha species 7 (α7 includes a group of hr types of which HPV18, 45, 59 are proportionally overrepresented in cervical AC and only partially (HPV18 targeted by current vaccines. To target these types, we generated a chimeric vaccine antigen that consists of a cross-neutralizing epitope (homologue of HPV16 RG1 of the L2 minor capsid protein of HPV45 genetically inserted into a surface loop of HPV18 L1 VLP (18L1-45RG1. Vaccination of NZW rabbits with 18L1-45RG1 VLP plus alum-MPL adjuvant induced high-titer neutralizing antibodies against homologous HPV18, that cross-neutralized non-cognate hr α7 types HPV39, 45, 68, but not HPV59, and low risk HPV70 in vitro, and induced a robust L1-specific cellular immune response. Passive immunization protected mice against experimental vaginal challenge with pseudovirions of HPV18, 39, 45 and 68, but not HPV59 or the distantly related α9 type HPV16. 18L1-45RG1 VLP might be combined with our previously described 16L1-16RG1 VLP to develop a second generation bivalent

  13. Pichia pastoris-expressed dengue 2 envelope forms virus-like particles without pre-membrane protein and induces high titer neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Shailendra Mani

    Full Text Available Dengue is a mosquito-borne viral disease with a global prevalence. It is caused by four closely-related dengue viruses (DENVs 1-4. A dengue vaccine that can protect against all four viruses is an unmet public health need. Live attenuated vaccine development efforts have encountered unexpected interactions between the vaccine viruses, raising safety concerns. This has emphasized the need to explore non-replicating dengue vaccine options. Virus-like particles (VLPs which can elicit robust immunity in the absence of infection offer potential promise for the development of non-replicating dengue vaccine alternatives. We have used the methylotrophic yeast Pichia pastoris to develop DENV envelope (E protein-based VLPs. We designed a synthetic codon-optimized gene, encoding the N-terminal 395 amino acid residues of the DENV-2 E protein. It also included 5' pre-membrane-derived signal peptide-encoding sequences to ensure proper translational processing, and 3' 6× His tag-encoding sequences to facilitate purification of the expressed protein. This gene was integrated into the genome of P. pastoris host and expressed under the alcohol oxidase 1 promoter by methanol induction. Recombinant DENV-2 protein, which was present in the insoluble membrane fraction, was extracted and purified using Ni(2+-affinity chromatography under denaturing conditions. Amino terminal sequencing and detection of glycosylation indicated that DENV-2 E had undergone proper post-translational processing. Electron microscopy revealed the presence of discrete VLPs in the purified protein preparation after dialysis. The E protein present in these VLPs was recognized by two different conformation-sensitive monoclonal antibodies. Low doses of DENV-2 E VLPs formulated in alum were immunogenic in inbred and outbred mice eliciting virus neutralizing titers >1,1200 in flow cytometry based assays and protected AG129 mice against lethal challenge (p<0.05. The formation of immunogenic DENV-2 E

  14. Chimeric polyomavirus-derived virus-like particles: the immunogenicity of an inserted peptide applied without adjuvant to mice depends on its insertion site and its flanking linker sequence

    OpenAIRE

    Lawatscheck, R.; Aleksaite, E.; Schenk, J.A.; Micheel, B.; Jandrig, B.; Holland, G.; Sasnauskas, K.; Gedvilaite, A.; Ulrich, R.G.

    2007-01-01

    We inserted the sequence of the carcinoembryonic antigen-derived T cell epitope CAP-1-6D (CEA) into different positions of the hamster polyomavirus major capsid protein VP1. Independently from additional flanking linkers, yeast-expressed VP1 proteins harboring the CEA insertion between VP1 amino acid residues 80 and 89 (site 1) or 288 and 295 (site 4) or simultaneously at both positions assembled to chimeric virus-like particles (VLPs). BALB/c mice immunized with adjuvant-free VLPs developed ...

  15. Virus-Like-Vaccines against HIV.

    Science.gov (United States)

    Andersson, Anne-Marie C; Schwerdtfeger, Melanie; Holst, Peter J

    2018-02-11

    Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production, is a distinct advantage over live-attenuated vaccines that must balance safety and immunogenicity. Previous studies have delivered VLVs encoded in modified Vaccinia Ankara vectors and we have developed the concept into a single-reading adenovirus-based technology capable of eliciting robust CD8⁺ and CD4⁺ T cells responses and trimer binding antibody responses. Such vaccines offer the potential to display the naturally produced immunogen directly and induce an integrated humoral and cellular immune response.

  16. HIV-specific humoral and cellular immunity in rabbits vaccinated with recombinant human immunodeficiency virus-like gag-env particles

    International Nuclear Information System (INIS)

    Haffar, O.K.; Smithgall, M.D.; Moran, P.A.; Travis, B.M.; Zarling, J.M.; Hu, S.L.

    1991-01-01

    Recombinant human immunodeficiency virus type-1 (HIV-1)-like gag-env particles produced in mammalian cells were inoculated into two New Zealand white rabbits. In parallel, two control rabbits were inoculated with the homologous HIV-1 virions inactivated by ultraviolet light (uv) and psoralen treatments. The humoral and cellular immune responses to HIV-1 were evaluated for both groups of animals. Recombinant particles elicited humoral immunity that was specific for all the viral structural proteins. The antibodies recognized both denatured and nondenatured proteins. Moreover, the sera neutralized the in vitro infectivity of the homologous virus in CEM cells. Importantly, the recombinant particles also generated a T helper response by priming with the HIV proteins. Similar results were observed with inactivated virus immunization. Therefore, the authors results suggest that the recombinant HIV-like particles elicit functional humoral immunity as well as cellular immunity and represent a novel vaccine candidate for AIDS

  17. The Generation of Turnip Crinkle Virus-Like Particles in Plants by the Transient Expression of Wild-Type and Modified Forms of Its Coat Protein.

    Science.gov (United States)

    Saunders, Keith; Lomonossoff, George P

    2015-01-01

    Turnip crinkle virus (TCV), a member of the genus carmovirus of the Tombusviridae family, has a genome consisting of a single positive-sense RNA molecule that is encapsidated in an icosahedral particle composed of 180 copies of a single type of coat protein. We have employed the CPMV-HT transient expression system to investigate the formation of TCV-like particles following the expression of the wild-type coat protein or modified forms of it that contain either deletions and/or additions. Transient expression of the coat protein in plants results in the formation of capsid structures that morphologically resemble TCV virions (T = 3 structure) but encapsidate heterogeneous cellular RNAs, rather than the specific TCV coat protein messenger RNA. Expression of an amino-terminal deleted form of the coat protein resulted in the formation of smaller T = 1 structures that are free of RNA. The possibility of utilizing TCV as a carrier for the presentation of foreign proteins on the particle surface was also explored by fusing the sequence of GFP to the C-terminus of the coat protein. The expression of coat protein-GFP hybrids permitted the formation of VLPs but the yield of particles is diminished compared to the yield obtained with unmodified coat protein. Our results confirm the importance of the N-terminus of the coat protein for the encapsidation of RNA and show that the coat protein's exterior P domain plays a key role in particle formation.

  18. Virus-like-vaccines against HIV

    DEFF Research Database (Denmark)

    Andersson, Anne Marie C.; Schwerdtfeger, Melanie; Holst, Peter J.

    2018-01-01

    Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (......Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus...... of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production...

  19. A novel HPV 16 L1-based chimeric virus-like particle containing E6 and E7 seroreactive epitopes permits highly specific detection of antibodies in patients with CIN 1 and HPV-16 infection

    Directory of Open Access Journals (Sweden)

    Santiago-Osorio Edelmiro

    2011-02-01

    Full Text Available Abstract Background The presence of IgG antibodies to HPV-16 L1-virus like particles (VLPs in serum has been reported as a result of persistent exposure to the virus and as a marker of disease progression. However, detection of VLP-specific antibodies in sera does not always indicate a malignant lesion as positive results may also be due to a nonmalignant viral infection. Furthermore, malignant lesions are associated with an increased antibody titer for E6 and E7 proteins. The aim of this study was to develop an ELISA using a novel chimeric virus-like particle (cVLP encoding an L1 protein fused with a string of HPV-16 E6 and E7 seroreactive epitopes to its C-terminus to be used for detection of HPV-16 specific antibodies in patients with cervical intraepithelial lesion grade 1 (CIN 1. Results The sera of 30 patients with CIN 1 who also tested positive for HPV-16 DNA and of 30 age-matched normal donors negative for HPV infection were tested for the presence of IgG antibodies specific for either VLP-L1 (HPV-16 L1, gVLP (derived from Gardasil, or cVLP by ELISA. The cVLP-reactive sera yielded two distinct groups of results: (H reactivity levels that presented very strong cVLP-specific titers, and (L reactivity levels with significantly lower titers similar to those obtained with VLP-L1 and gVLP antigens. Additionally, the sera that presented the higher cVLP titers closely matched those that had significantly stronger reactivity to E6 and E7 epitopes. Interestingly, the samples with the highest titers corresponded to patients with the higher numbers of sexual partners and pregnancies. On the other hand only 4 out of the 12 sera that harbored antibodies with VLP neutralizing ability corresponded to the group with high cVLP antibody titers. Conclusion We report for the first time that chimeric particles containing HPV-16 L1 protein fused with E6 and E7 seroreactive epitopes enable much better detection of IgG antibodies in the sera of CIN 1 patients

  20. A C-terminal truncated hepatitis C virus core protein variant assembles in vitro into virus-like particles in the absence of structured nucleic acids

    International Nuclear Information System (INIS)

    Acosta-Rivero, Nelson; Rodriguez, Armando; Mussachio, Alexis; Poutu, Johana; Falcon, Viviana; Torres, Dinorah; Aguilar, Julio C.; Linares, Marbelis; Alonso, Mabel; Perez, Angel; Menendez, Ivon; Morales-Grillo, Juan; Marquez, Gabriel; Duenas-Carrera, Santiago

    2005-01-01

    Little is known about the assembly pathway or structure of the hepatitis C virus (HCV). In this work a truncated HCcAg variant covering the first 120 aa (HCcAg.120) with a 32 aa N-terminal fusion peptide (6x Histag-Xpress epitope) was purified as a monomer under strong denaturing conditions. In addition, minor HCcAg.120 peaks exhibiting little different molecular mass by SDS-PAGE which possibly represents alternative forms harboring the N-termini of HCcAg.120 were detected. Analysis using gel filtration chromatography showed that HCcAg.120 assembled into high molecular weight structures in vitro in the absence of structured nucleic acids. The negative-stain electron microscopy analysis revealed that these structures correspond with spherical VLPs of uniform morphology and size distribution. The diameters of these particles ranged from 20 to 43 nm with an average diameter of approximately 30 nm and were specifically immunolabelled with a mouse monoclonal antibody against the residues 5-35 of HCcAg. Results presented in this work showed that HCcAg.120 assembled in vitro into VLPs in the absence of structured nucleic acids with similar morphology and size distribution to those found in sera and hepatocytes from HCV-infected patients. Therefore, these VLPs would be important to elucidate the mechanisms behind the ability of HCcAg to assemble into a nucleocapsid structure

  1. Cellular immune responses to HPV-18, -31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles

    International Nuclear Information System (INIS)

    Pinto, Ligia A.; Viscidi, Raphael; Harro, Clayton D.; Kemp, Troy J.; Garcia-Pineres, Alfonso J.; Trivett, Matthew; Demuth, Franklin; Lowy, Douglas R.; Schiller, John T.; Berzofsky, Jay A.; Hildesheim, Allan

    2006-01-01

    Human papillomavirus-like particles (HPV VLP) are candidate vaccines that have shown to be efficacious in reducing infection and inducing robust antiviral immunity. Neutralizing antibodies generated by vaccination are largely type-specific, but little is known about the type-specificity of cellular immune responses to VLP vaccination. To determine whether vaccination with HPV-16 L1VLP induces cellular immunity to heterologous HPV types (HPV-18, HPV-31, and HPV-53), we examined proliferative and cytokine responses in vaccine (n = 11) and placebo (n = 5) recipients. Increased proliferative and cytokine responses to heterologous types were observed postvaccination in some individuals. The proportion of women responding to heterologous types postvaccination (36%-55%) was lower than that observed in response to HPV-16 (73%). Response to HPV-16 VLP predicted response to other types. The strongest correlations in response were observed between HPV-16 and HPV-31, consistent with their phylogenetic relatedness. In summary, PBMC from HPV-16 VLP vaccine recipients can respond to L1VLP from heterologous HPV types, suggesting the presence of conserved T cell epitopes

  2. A heterologous prime-boost Ebola virus vaccine regimen induces durable neutralizing antibody response and prevents Ebola virus-like particle entry in mice.

    Science.gov (United States)

    Chen, Tan; Li, Dapeng; Song, Yufeng; Yang, Xi; Liu, Qingwei; Jin, Xia; Zhou, Dongming; Huang, Zhong

    2017-09-01

    Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting. Mouse immunization studies showed that the AdC7-GP prime/GP1t boost vaccine regimen was more potent in eliciting neutralizing antibodies than either the AdC7-GP or GP1t alone. Neutralizing antibodies induced by the heterologous prime-boost regimen sustained at high titers for at least 18 weeks after immunization. Significantly, in vivo challenge studies revealed that the entry of reporter EBOV-like particles was efficiently blocked in mice receiving the heterologous prime-boost regimen even at 18 weeks after the final dose of immunization. These results suggest that this novel AdC7-GP prime/GP1t boost regimen represents an EBOV vaccine approach capable of establishing long-term protection, and therefore warrants further development. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Novel Epstein-Barr virus-like particles incorporating gH/gL-EBNA1 or gB-LMP2 induce high neutralizing antibody titers and EBV-specific T-cell responses in immunized mice.

    Science.gov (United States)

    Perez, Elizabeth M; Foley, Joslyn; Tison, Timelia; Silva, Rute; Ogembo, Javier Gordon

    2017-03-21

    Previous Epstein-Barr virus (EBV) prophylactic vaccines based on the major surface glycoprotein gp350/220 as an immunogen have failed to block viral infection in humans, suggesting a need to target other viral envelope glycoproteins. In this study, we reasoned that incorporating gH/gL or gB, critical glycoproteins for viral fusion and entry, on the surface of a virus-like particle (VLP) would be more immunogenic than gp350/220 for generating effective neutralizing antibodies to prevent viral infection of both epithelial and B cell lines. To boost the humoral response and trigger cell-mediated immunity, EBV nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2), intracellular latency proteins expressed in all EBV-infected cells, were also included as critical components of the polyvalent EBV VLP. gH/gL-EBNA1 and gB-LMP2 VLPs were efficiently produced in Chinese hamster ovary cells, an FDA-approved vehicle for mass-production of biologics. Immunization with gH/gL-EBNA1 and gB-LMP2 VLPs without adjuvant generated both high neutralizing antibody titers in vitro and EBV-specific T-cell responses in BALB/c mice. These data demonstrate that will be invaluable not only in preventing EBV infection, but importantly, in preventing and treating the 200,000 cases of EBV-associated cancers that occur globally every year.

  4. Development of high-throughput and high sensitivity capillary gel electrophoresis platform method for Western, Eastern, and Venezuelan equine encephalitis (WEVEE) virus like particles (VLPs) purity determination and characterization.

    Science.gov (United States)

    Gollapudi, Deepika; Wycuff, Diane L; Schwartz, Richard M; Cooper, Jonathan W; Cheng, K C

    2017-10-01

    In this paper, we describe development of a high-throughput, highly sensitive method based on Lab Chip CGE-SDS platform for purity determination and characterization of virus-like particle (VLP) vaccines. A capillary gel electrophoresis approach requiring about 41 s per sample for analysis and demonstrating sensitivity to protein initial concentrations as low as 20 μg/mL, this method has been used previously to evaluate monoclonal antibodies, but this application for lot release assay of VLPs using this platform is unique. The method was qualified and shown to be accurate for the quantitation of VLP purity. Assay repeatability was confirmed to be less than 2% relative standard deviation of the mean (% RSD) with interday precision less than 2% RSD. The assay can evaluate purified VLPs in a concentration range of 20-249 μg/mL for VEE and 20-250 μg/mL for EEE and WEE VLPs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Foot-and-mouth disease virus-like particles produced by a SUMO fusion protein system in Escherichia coli induce potent protective immune responses in guinea pigs, swine and cattle

    Science.gov (United States)

    2013-01-01

    Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. The format of FMD virus-like particles (VLP) as a non-replicating particulate vaccine candidate is a promising alternative to conventional inactivated FMDV vaccines. In this study, we explored a prokaryotic system to express and assemble the FMD VLP and validated the potential of VLP as an FMDV vaccine candidate. VLP composed entirely of FMDV (Asia1/Jiangsu/China/2005) capsid proteins (VP0, VP1 and VP3) were simultaneously produced as SUMO fusion proteins by an improved SUMO fusion protein system in E. coli. Proteolytic removal of the SUMO moiety from the fusion proteins resulted in the assembly of VLP with size and shape resembling the authentic FMDV. Immunization of guinea pigs, swine and cattle with FMD VLP by intramuscular inoculation stimulated the FMDV-specific antibody response, neutralizing antibody response, T-cell proliferation response and secretion of cytokine IFN-γ. In addition, immunization with one dose of the VLP resulted in complete protection of these animals from homologous FMDV challenge. The 50% protection dose (PD50) of FMD VLP in cattle is up to 6.34. These results suggest that FMD VLP expressed in E. coli are an effective vaccine in guinea pigs, swine and cattle and support further development of these VLP as a vaccine candidate for protection against FMDV. PMID:23826638

  6. Chikungunya virus-like particle vaccine

    NARCIS (Netherlands)

    Metz, S.W.H.

    2013-01-01

    Chikungunya virus (CHIKV) is an arthropod-borne alphavirus (family Togaviridae) and is the causative agent of chikungunya fever. This disease is characterised by the sudden onset of high fever and long-lasting arthritic disease. First identified in Tanzania in 1952,

  7. Crystal Structures of Yeast-Produced Enterovirus 71 and Enterovirus 71/Coxsackievirus A16 Chimeric Virus-Like Particles Provide the Structural Basis for Novel Vaccine Design against Hand-Foot-and-Mouth Disease.

    Science.gov (United States)

    Lyu, Ke; He, Ya-Ling; Li, Hao-Yang; Chen, Rong

    2015-06-01

    Human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two major causative agents for hand-foot-and-mouth disease (HFMD). Previously, we demonstrated that a virus-like particle (VLP) for EV71 produced from Saccharomyces cerevisiae is a potential vaccine candidate against EV71 infection, and an EV71/CVA16 chimeric VLP can elicit protective immune responses against both virus infections. Here, we presented the crystal structures of both VLPs, showing that both the linear and conformational neutralization epitopes identified in EV71 are mostly preserved on both VLPs. The replacement of only 4 residues in the VP1 GH loop converted strongly negatively charged surface patches formed by portions of the SP70 epitope in EV71 VLP into a relatively neutral surface in the chimeric VLP, which likely accounted for the additional neutralization capability of the chimeric VLP against CVA16 infection. Such local variations in the amino acid sequences and the surface charge potential are also present in different types of polioviruses. In comparison to EV71 VLP, the chimeric VLP exhibits structural changes at the local site of amino acid replacement and the surface loops of all capsid proteins. This is consistent with the observation that the VP1 GH loop located near the pseudo-3-fold junction is involved in extensive interactions with other capsid regions. Furthermore, portions of VP0 and VP1 in EV71 VLP are at least transiently exposed, revealing the structural flexibility of the VLP. Together, our structural analysis provided insights into the structural basis of enterovirus neutralization and novel vaccine design against HFMD and other enterovirus-associated diseases. Our previous studies demonstrated that the enterovirus 71 (EV71) virus-like particle (VLP) produced from yeast is a vaccine candidate against EV71 infection and that a chimeric EV71/coxsackievirus A16 (CVA16) VLP with the replacement of 4 amino acids in the VP1 GH loop can confer protection against both

  8. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial.

    Science.gov (United States)

    Harper, Diane M; Franco, Eduardo L; Wheeler, Cosette; Ferris, Daron G; Jenkins, David; Schuind, Anne; Zahaf, Toufik; Innis, Bruce; Naud, Paulo; De Carvalho, Newton S; Roteli-Martins, Cecilia M; Teixeira, Julio; Blatter, Mark M; Korn, Abner P; Quint, Wim; Dubin, Gary

    Vaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions. We randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity. In the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic. The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.

  9. Mutations in the alpha-helical region of the amino terminus of the Maize rayado fino virus capsid protein and CP:RNA ratios affect virus-like particle encapsidation of RNAs.

    Science.gov (United States)

    Natilla, Angela; Murphy, Charles; Hammond, Rosemarie W

    2015-01-22

    Viral-based nanoplatforms rely on balancing the delicate array of virus properties to optimally achieve encapsidation of foreign materials with various potential objectives. We investigated the use of Maize rayado fino virus (MRFV)-virus-like particles (VLPs) as a multifunctional nanoplatform and their potential application as protein cages. MRFV-VLPs are composed of two serologically related, carboxy co-terminal coat proteins (CP1 and CP2) which are capable of self-assembling in Nicotiana benthamiana plants into 30nm particles with T=3 symmetry. The N-terminus of CP1 was targeted for genetic modification to exploit the driving forces for VLP assembly, packaging and retention of RNA in vivo and in vitro. The N-terminus of MRFV-CP1 contains a peptide sequence of 37 amino acids which has been predicted to have an alpha-helical structure, is rich in hydrophobic amino acids, facilitates CP-RNA interactions, and is not required for self-assembly. Amino acid substitutions were introduced in the 37 amino acid N-terminus by site-directed mutagenesis and the mutant VLPs produced in plants by a Potato virus X (PVX)-based vector were tested for particle stability and RNA encapsidation. All mutant CPs resulted in production of VLPs which encapsidated non-viral RNAs, including PVX genomic and subgenomic (sg) RNAs, 18S rRNA and cellular and viral mRNAs. In addition, MRFV-VLPs encapsidated GFP mRNA when was expressed in plant cells from the pGD vector. These results suggest that RNA packaging in MRFV-VLPs is predominantly driven by electrostatic interactions between the N-terminal 37 amino acid extension of CP1 and RNA, and that the overall species concentration of RNA in the cellular pool may determine the abundance and species of the RNAs packaged into the VLPs. Furthermore, RNA encapsidation is not required for VLPs stability, VLPs formed from MRFV-CP1 were stable at temperatures up to 70°C, and can be disassembled into CP monomers, which can then reassemble in vitro into

  10. A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

    Science.gov (United States)

    Yang, Ji-Rong; Chen, Chih-Yuan; Kuo, Chuan-Yi; Cheng, Chieh-Yu; Lee, Min-Shiuh; Cheng, Ming-Chu; Yang, Yu-Chih; Wu, Chia-Ying; Wu, Ho-Sheng; Liu, Ming-Tsan; Hsiao, Pei-Wen

    2016-02-01

    Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. A tetravalent virus-like particle vaccine designed to display domain III of dengue envelope proteins induces multi-serotype neutralizing antibodies in mice and macaques which confer protection against antibody dependent enhancement in AG129 mice.

    Directory of Open Access Journals (Sweden)

    Viswanathan Ramasamy

    2018-01-01

    Full Text Available Dengue is one of the fastest spreading vector-borne diseases, caused by four antigenically distinct dengue viruses (DENVs. Antibodies against DENVs are responsible for both protection as well as pathogenesis. A vaccine that is safe for and efficacious in all people irrespective of their age and domicile is still an unmet need. It is becoming increasingly apparent that vaccine design must eliminate epitopes implicated in the induction of infection-enhancing antibodies.We report a Pichia pastoris-expressed dengue immunogen, DSV4, based on DENV envelope protein domain III (EDIII, which contains well-characterized serotype-specific and cross-reactive epitopes. In natural infection, <10% of the total neutralizing antibody response is EDIII-directed. Yet, this is a functionally relevant domain which interacts with the host cell surface receptor. DSV4 was designed by in-frame fusion of EDIII of all four DENV serotypes and hepatitis B surface (S antigen and co-expressed with unfused S antigen to form mosaic virus-like particles (VLPs. These VLPs displayed EDIIIs of all four DENV serotypes based on probing with a battery of serotype-specific anti-EDIII monoclonal antibodies. The DSV4 VLPs were highly immunogenic, inducing potent and durable neutralizing antibodies against all four DENV serotypes encompassing multiple genotypes, in mice and macaques. DSV4-induced murine antibodies suppressed viremia in AG129 mice and conferred protection against lethal DENV-4 virus challenge. Further, neither murine nor macaque anti-DSV4 antibodies promoted mortality or inflammatory cytokine production when passively transferred and tested in an in vivo dengue disease enhancement model of AG129 mice.Directing the immune response to a non-immunodominant but functionally relevant serotype-specific dengue epitope of the four DENV serotypes, displayed on a VLP platform, can help minimize the risk of inducing disease-enhancing antibodies while eliciting effective tetravalent

  12. The inhibition of assembly of HIV-1 virus-like particles by 3-O-(3',3'-dimethylsuccinyl betulinic acid (DSB is counteracted by Vif and requires its Zinc-binding domain

    Directory of Open Access Journals (Sweden)

    Bouaziz Serge

    2008-12-01

    Full Text Available Abstract Background DSB, the 3-O-(3',3'dimethylsuccinyl derivative of betulinic acid, blocks the last step of protease-mediated processing of HIV-1 Gag precursor (Pr55Gag, which leads to immature, noninfectious virions. When administered to Pr55Gag-expressing insect cells (Sf9, DSB inhibits the assembly and budding of membrane-enveloped virus-like particles (VLP. In order to explore the possibility that viral factors could modulate the susceptibility to DSB of the VLP assembly process, several viral proteins were coexpressed individually with Pr55Gag in DSB-treated cells, and VLP yields assayed in the extracellular medium. Results Wild-type Vif (Vifwt restored the VLP production in DSB-treated cells to levels observed in control, untreated cells. DSB-counteracting effect was also observed with Vif mutants defective in encapsidation into VLP, suggesting that packaging and anti-DSB effect were separate functions in Vif. The anti-DSB effect was abolished for VifC133S and VifS116V, two mutants which lacked the zinc binding domain (ZBD formed by the four H108C114C133H139 coordinates with a Zn atom. Electron microscopic analysis of cells coexpressing Pr55Gag and Vifwt showed that a large proportion of VLP budded into cytoplasmic vesicles and were released from Sf9 cells by exocytosis. However, in the presence of mutant VifC133S or VifS116V, most of the VLP assembled and budded at the plasma membrane, as in control cells expressing Pr55Gag alone. Conclusion The function of HIV-1 Vif protein which negated the DSB inhibition of VLP assembly was independent of its packaging capability, but depended on the integrity of ZBD. In the presence of Vifwt, but not with ZBD mutants VifC133S and VifS116V, VLP were redirected to a vesicular compartment and egressed via the exocytic pathway.

  13. Characterization of a Latent Virus-Like Infection of Symbiotic Zooxanthellae▿

    Science.gov (United States)

    Lohr, Jayme; Munn, Colin B.; Wilson, William H.

    2007-01-01

    A latent virus-like agent, which we designated zooxanthella filamentous virus 1 (ZFV1), was isolated from Symbiodinium sp. strain CCMP 2465 and characterized. Transmission electron microscopy and analytical flow cytometry revealed the presence of a new group of distinctive filamentous virus-like particles after exposure of the zooxanthellae to UV light. Examination of thin sections of the zooxanthellae revealed the formation and proliferation of filamentous virus-like particles in the UV-induced cells. Assessment of Symbiodinium sp. cultures was used here as a model to show the effects of UV irradiance and induction of potential latent viruses. The unique host-virus system described here provides insight into the role of latent infections in zooxanthellae through environmentally regulated viral induction mechanisms. PMID:17351090

  14. Characterization of a latent virus-like infection of symbiotic zooxanthellae.

    Science.gov (United States)

    Lohr, Jayme; Munn, Colin B; Wilson, William H

    2007-05-01

    A latent virus-like agent, which we designated zooxanthella filamentous virus 1 (ZFV1), was isolated from Symbiodinium sp. strain CCMP 2465 and characterized. Transmission electron microscopy and analytical flow cytometry revealed the presence of a new group of distinctive filamentous virus-like particles after exposure of the zooxanthellae to UV light. Examination of thin sections of the zooxanthellae revealed the formation and proliferation of filamentous virus-like particles in the UV-induced cells. Assessment of Symbiodinium sp. cultures was used here as a model to show the effects of UV irradiance and induction of potential latent viruses. The unique host-virus system described here provides insight into the role of latent infections in zooxanthellae through environmentally regulated viral induction mechanisms.

  15. Chimaera and its modern virus-like descendants.

    Science.gov (United States)

    Ulrich, R; Gerlich, W H; Krüger, D H

    1996-01-01

    Chimaera was a monster in ancient Greek mythology combining elements from different animal species in its body. Modern molecular biology enabled the generation of harmless but useful chimaeras consisting of elements from different nonrelated viruses. The objective is that the resulting chimaeras form highly immunogenic virus-like particles (VLPs). Such chimaeric VLPs can be used as highly efficient carriers for sequential and conformational B cell epitopes and T cell epitopes. Most VLPs are readily produced in heterologous hosts and are easy to purify. This article deals with various systems of VLPs described in this topical issue of Intervirology and makes comparisons with chimaeric replication-competent viruses, recombinant virus vectors expressing foreign proteins, and DNA vaccines.

  16. Analysis of the solvent accessibility of cysteine residues on Maize rayado fino virus virus-like particles produced in Nicotiana benthamiana plants and cross-linking of peptides to VLPs.

    Science.gov (United States)

    Natilla, Angela; Hammond, Rosemarie W

    2013-02-14

    Mimicking and exploiting virus properties and physicochemical and physical characteristics holds promise to provide solutions to some of the world's most pressing challenges. The sheer range and types of viruses coupled with their intriguing properties potentially give endless opportunities for applications in virus-based technologies. Viruses have the ability to self- assemble into particles with discrete shape and size, specificity of symmetry, polyvalence, and stable properties under a wide range of temperature and pH conditions. Not surprisingly, with such a remarkable range of properties, viruses are proposed for use in biomaterials, vaccines, electronic materials, chemical tools, and molecular electronic containers. In order to utilize viruses in nanotechnology, they must be modified from their natural forms to impart new functions. This challenging process can be performed through several mechanisms including genetic modification of the viral genome and chemically attaching foreign or desired molecules to the virus particle reactive groups. The ability to modify a virus primarily depends upon the physiochemical and physical properties of the virus. In addition, the genetic or physiochemical modifications need to be performed without adversely affecting the virus native structure and virus function. Maize rayado fino virus (MRFV) coat proteins self-assemble in Escherichia coli producing stable and empty VLPs that are stabilized by protein-protein interactions and that can be used in virus-based technologies applications. VLPs produced in tobacco plants were examined as a scaffold on which a variety of peptides can be covalently displayed. Here, we describe the steps to 1) determine which of the solvent-accessible cysteines in a virus capsid are available for modification, and 2) bioconjugate peptides to the modified capsids. By using native or mutationally-inserted amino acid residues and standard coupling technologies, a wide variety of materials have been

  17. Membrane fusion-competent virus-like proteoliposomes and proteinaceous supported bilayers made directly from cell plasma membranes.

    Science.gov (United States)

    Costello, Deirdre A; Hsia, Chih-Yun; Millet, Jean K; Porri, Teresa; Daniel, Susan

    2013-05-28

    Virus-like particles are useful materials for studying virus-host interactions in a safe manner. However, the standard production of pseudovirus based on the vesicular stomatitis virus (VSV) backbone is an intricate procedure that requires trained laboratory personnel. In this work, a new strategy for creating virus-like proteoliposomes (VLPLs) and virus-like supported bilayers (VLSBs) is presented. This strategy uses a cell blebbing technique to induce the formation of nanoscale vesicles from the plasma membrane of BHK cells expressing the hemagglutinin (HA) fusion protein of influenza X-31. These vesicles and supported bilayers contain HA and are used to carry out single particle membrane fusion events, monitored using total internal reflection fluorescence microscopy. The results of these studies show that the VLPLs and VLSBs contain HA proteins that are fully competent to carry out membrane fusion, including the formation of a fusion pore and the release of fluorophores loaded into vesicles. This new strategy for creating spherical and planar geometry virus-like membranes has many potential applications. VLPLs could be used to study fusion proteins of virulent viruses in a safe manner, or they could be used as therapeutic delivery particles to transport beneficial proteins coexpressed in the cells to a target cell. VLSBs could facilitate high throughput screening of antiviral drugs or pathogen-host cell interactions.

  18. A Virus-like disease of chinook salmon

    Science.gov (United States)

    Ross, A.J.; Pelnar, J.; Rucker, R.R.

    1960-01-01

    Consideration is given to a recurring disease of early feeding chinook salmon fingerlings at the Coleman, California, Federal Fish Cultural Station. The infection becomes manifest in the early spring months at low water temperatures and abates as the water temperature rises. Bacteriological studies have failed to yield the presence of a disease agent, either by cultural or staining procedures. The disease has been successfully transmitted from infected fish to healthy fish by the injection of bacteria-free filtrates prepared from diseased fish tissue. The causative agent is therefore believed to be a virus-like entity.

  19. [Construction of RNA-containing virus-like nanoparticles expression vector with cysteine residues on surface and fluorescent decoration].

    Science.gov (United States)

    Cheng, Yang-Jian; Liang, Ji-Xuan; Li, Qing-Ge

    2005-08-01

    Site-directed mutagenesis was performed at the codon 15 of the MS2 bacteriophage coat protein gene,which had been cloned to the virus-like particles expression vector containing non-self RNA fragment. The produced expression vector,termed pARSC, was transformed to E. coli DH5alpha. The positive clones were selected and proliferated. The harvested cells were treated with sonication and the supernatant was then subjected to linear sucrose density gradients centrifugation (15% to 60%) at 32000 r/min for 4 h at 4 degrees C. The virus-like particles, VLP-Cy, were collected at 35% sucrose density. The particles were examined by transmission electron microscopy and the spherical viral particles of approximately 27 nm in diameter were found. The thiolated VLP-Cy was then chemically modified with fluorescein -5'-maleimide. The covalent fluorescent labeling was confirmed by absorption analysis, SDS-PAGE and MALDI-TOF mass spectroscopy. This is the first report of preparation of RNA-containing natural fluorescent nanoparticles. The study highlight the versatility of MS2 bacteriophage capsids as building blocks for functional nanomaterials construction for a variety of application purposes.

  20. Silicified virus-like nanoparticles in an extreme thermal environment: implications for the preservation of viruses in the geological record.

    Science.gov (United States)

    Peng, X; Xu, H; Jones, B; Chen, S; Zhou, H

    2013-11-01

    Biofilms that grow around Gumingquan hot spring (T = 71 °C, pH = 9.2) in the Rehai geothermal area, Tengchong, China, are formed of various cyanobacteria, Firmicutes, Aquificae, Thermodesulfobacteria, Desulfurococcales, and Thermoproteales. Silicified virus-like nanoparticles, 40-200 nm in diameter, are common inside the microbial cells and the extracellular polymeric substances around the cells. These nanoparticles, which are formed of a core encased by a silica cortex, are morphologically akin to known viruses and directly comparable to silicified virus-like particles that were produced in biofilms cultured in the laboratory. The information obtained from examination of the natural and laboratory-produced samples suggests that viruses can be preserved by silicification, especially while they are still encased in their host cells. These results expand our views of virus-host mineral interaction in extreme thermal environments and imply that viruses can be potentially preserved and identified in the geological record. © 2013 John Wiley & Sons Ltd.

  1. Discovery of viruses and virus-like pathogens in pistachio using high-throughput sequencing

    Science.gov (United States)

    Pistachio (Pistacia vera L.) trees from the National Clonal Germplasm Repository (NCGR) and orchards in California were surveyed for viruses and virus-like agents by high-throughput sequencing (HTS). Analyses of 60 trees including clonal UCB-1 hybrid rootstock (P. atlantica × P. integerrima) identif...

  2. Novel adenovirus encoded virus-like particles displaying the placental malaria associated VAR2CSA antigen

    DEFF Research Database (Denmark)

    Andersson, Anne-Marie C; dos Santos Marques Resende, Mafalda; Salanti, Ali

    2017-01-01

    The malaria parasite Plasmodium falciparum presents antigens on the infected erythrocyte surface that bind human receptors expressed on the vascular endothelium. The VAR2CSA mediated binding to a distinct chondroitin sulphate A (CSA) is a crucial step in the pathophysiology of placental malaria a...

  3. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    Energy Technology Data Exchange (ETDEWEB)

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O. [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States); Tumpey, Terrence M. [Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA (United States); Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States)

    2016-01-15

    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  4. Virus-like particle display of HER2 induces potent anti-cancer responses

    DEFF Research Database (Denmark)

    Palladini, Arianna; Thrane, Susan; Janitzek, Christoph M

    2018-01-01

    Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20-30% of invasive breast cancers. Monoclonal antibody therapy is effective in treating HER2-driven mammary carcinomas, but its utility is limited by high costs, side effects and development of resistance. Active vaccinat...

  5. Low Temperature-Dependent Salmonid Alphavirus Glycoprotein Processing and Recombinant Virus-Like Particle Formation

    NARCIS (Netherlands)

    Metz, S.W.H.; Feenstra, F.; Villoing, S.; Hulten, van M.C.; Lent, van J.W.M.; Koumans, J.; Vlak, J.M.; Pijlman, G.P.

    2011-01-01

    Pancreas disease (PD) and sleeping disease (SD) are important viral scourges in aquaculture of Atlantic salmon and rainbow trout. The etiological agent of PD and SD is salmonid alphavirus (SAV), an unusual member of the Togaviridae (genus Alphavirus). SAV replicates at lower temperatures in fish.

  6. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    International Nuclear Information System (INIS)

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O.; Tumpey, Terrence M.; Pushko, Peter

    2016-01-01

    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  7. In Vitro Assembly of Virus-Like Particles of a Gammaretrovirus, the Murine Leukemia Virus XMRV

    Czech Academy of Sciences Publication Activity Database

    Hadravová, Romana; de Marco, A.; Ulbrich, P.; Štokrová, Jitka; Doležal, Michal; Pichová, Iva; Ruml, T.; Briggs, J. A. G.; Rumlová, Michaela

    2012-01-01

    Roč. 86, č. 3 (2012), s. 1297-1306 ISSN 0022-538X R&D Projects: GA ČR GA204/09/1388; GA MŠk 1M0508 Grant - others:GA MŠk(CZ) 1M0520 Program:1M Institutional research plan: CEZ:AV0Z40550506 Keywords : human-immunodeficiency-virus * Rous sarcoma virus * chronic-fatigue-syndrome * Pfizer monkey virus * N-terminal domain Subject RIV: CE - Biochemistry Impact factor: 5.076, year: 2012

  8. Molecular and structural characterization of fluorescent human parvovirus B19 virus-like particles

    NARCIS (Netherlands)

    Gilbert, L.; Toivola, J.; White, D.; Ihalainen, T.; Smith, W.; Lindholm, L.; Vuento, M.; Oker-Blom, C.

    2005-01-01

    Although sharing a T = 1 icosahedral symmetry with other members of the Parvoviridae family, it has been suggested that the fivefold channel of the human parvovirus B19 VP2 capsids is closed at its outside end. To investigate the possibility of placing a relatively large protein moiety at this site

  9. High pressure treatment of human norovirus virus-like particles: factors affecting destruction efficacy

    Science.gov (United States)

    Human norovirus (NoV) accounts for more than 90% of nonbacterial gastroenteritis. To date, the efficacy of human NoV inactivation interventions cannot be accurately evaluated because the virus is nonculturable. In this study, we aimed to estimate inactivation of human NoV by high pressure processing...

  10. [Virus-like inclusions in the myocytes of the skeletal muscle in lateral amyotrophic sclerosis].

    Science.gov (United States)

    Musaeva, L S; Sakharova, A V; Zavalishin, I A

    2004-01-01

    Microscopic examination of musculus gastrocnemius biopsies was made in four cases of sporadic lateral amyotrophic sclerosis (LAS). The validity of the clinical diagnosis was confirmed by detected neurotrophic atrophy of the muscular fibers typical for LAS. Electron microscopic study revealed virus-like inclusions 200-450 nm in size in sarcoplasm of myocytes of all the patients. The inclusions consist of lined cells of hexagonal shape at the distance of 37-41 nm from each other. The inclusions resemble enteroviruses but are not identical to them both by size and structure of their elements. There were also specific ultrastructural changes of myocytes corresponding to viral infection. The above virus-like inclusions should be considered as specific structures formed as a result of metabolic shifts caused by productive action on the cell of infective or unknown factor.

  11. Inheritance and molecular mapping of an allele providing resistance to Cowpea mild mottle virus-like symptoms in soybean

    Science.gov (United States)

    Damage to soybean [Glycine max (L.) Merr.] from Cowpea mild mottle virus-like (CPMMV-L) symptoms (family: Betaflexiviridae, genus: Carlavirus) has been of increasing concern in Argentina, Brazil, Mexico, and Puerto Rico. Soybean cultivars and lines differing in their reaction to the virus have been ...

  12. Characterization of the size distribution and aggregation of virus-like nanoparticles used as active ingredients of the HeberNasvac therapeutic vaccine against chronic hepatitis B

    Science.gov (United States)

    Lopez, Matilde; Rodriguez, Elias Nelson; Lobaina, Yadira; Musacchio, Alexis; Falcon, Viviana; Guillen, Gerardo; Aguilar, Julio C.

    2017-06-01

    The use of virus-like particles (VLPs) as antigens constitutes a well established strategy in preventive vaccination. These non-infective particles have a composition, size, and structure favoring their interaction and processing by the immune system. Recombinant viral nucleocapsids encapsulating bacterial nucleic acids result in potent Th1-driving immunogens. Several antigens have been coadministered with VLPs or conjugated to them to further increase their immunogenicity. In the present work we characterize the size distribution of two different recombinant VLPs obtained as components of HeberNasvac, a novel therapeutic vaccine recently registered to treat chronic hepatitis B. The vaccine ingredients, hepatitis B virus surface and nucleocapsid antigens (HBsAg and HBcAg, respectively) and the vaccine formulation, were evaluated using dynamic light scattering (DLS), transmission electron microscopy (TEM) and light obscuration technology. The results demonstrate that both antigens are nanoparticles with sizes ranging between 20-30 nm, in line with reports in the literature. In addition, DLS studies evidenced the capacity of both antigens to form homologous and heterologous aggregates, both as active ingredients as well as being part of the final product. The evaluation of subvisible particles in HeberNasvac formulation fulfills the requirements in terms of quantity and size established for parenteral pharmaceutical compositions. Invited talk at 8th Int. Workshop on Advanced Materials Science and Nanotechnology (IWAMSN2016) (Ha Long City, Vietnam, 8-12 November 2016)

  13. A population of giant tailed virus-like particles associated with heterotrophic flagellates in a lake-type reservoir

    Czech Academy of Sciences Publication Activity Database

    Weinbauer, M.G.; Dolan, J. R.; Šimek, Karel

    2015-01-01

    Roč. 76, č. 2 (2015), s. 111-116 ISSN 0948-3055 R&D Projects: GA ČR(CZ) GA13-00243S Institutional support: RVO:60077344 Keywords : viral infection * virus induced mortality * burst size * heterotrophic flagellates Subject RIV: EE - Microbiology, Virology Impact factor: 2.109, year: 2015

  14. A novel virus-like particle based vaccine platform displaying the placental malaria antigen VAR2CSA

    DEFF Research Database (Denmark)

    Thrane, Susan; Janitzek, Christoph M; Agerbæk, Mette Ø

    2015-01-01

    , this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of parasites to CSA. This study demonstrates that the described Avi-L1 VLP-platform may serve as a versatile system for facilitating optimal VLP......SA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however...

  15. Humoral immune responses of dengue fever patients using epitope-specific serotype-2 virus-like particle antigens.

    Directory of Open Access Journals (Sweden)

    Wayne D Crill

    Full Text Available Dengue virus (DENV is a serious mosquito-borne pathogen causing significant global disease burden, either as classic dengue fever (DF or in its most severe manifestation dengue hemorrhagic fever (DHF. Nearly half of the world's population is at risk of dengue disease and there are estimated to be millions of infections annually; a situation which will continue to worsen with increasing expansion of the mosquito vectors and epidemic DF/DHF. Currently there are no available licensed vaccines or antivirals for dengue, although significant effort has been directed toward the development of safe and efficacious dengue vaccines for over 30 years. Promising vaccine candidates are in development and testing phases, but a better understanding of immune responses to DENV infection and vaccination is needed. Humoral immune responses to DENV infection are complex and may exacerbate pathogenicity, yet are essential for immune protection. In this report, we develop DENV-2 envelope (E protein epitope-specific antigens and measure immunoglobulin responses to three distinct epitopes in DENV-2 infected human serum samples. Immunoglobulin responses to DENV-2 infection exhibited significant levels of individual variation. Antibody populations targeting broadly cross-reactive epitopes centered on the fusion peptide in structural domain II were large, highly variable, and greater in primary than in secondary DENV-2 infected sera. E protein domain III cross-reactive immunoglobulin populations were similarly variable and much larger in IgM than in IgG. DENV-2 specific domain III IgG formed a very small proportion of the antibody response yet was significantly correlated with DENV-2 neutralization, suggesting that the highly protective IgG recognizing this epitope in murine studies plays a role in humans as well. This report begins to tease apart complex humoral immune responses to DENV infection and is thus important for improving our understanding of dengue disease and immunological correlates of protection, relevant to DENV vaccine development and testing.

  16. Monovalent Virus-Like Particle Vaccine Protects Guinea Pigs and Nonhuman Primates Against Infection with Multiple Marburg Viruses

    National Research Council Canada - National Science Library

    Swenson, Dana L; Warfield, Kelly L; Larsen, Tom; Alves, D. A; Coberley, Sadie S; Bavari, Sina

    2008-01-01

    .... Guinea pigs vaccinated with marburgvirus (m)VLPs or inactivated MARV (iMARV) develop homologous humoral and T cell responses and are completely protected from a lethal homologous MARV challenge...

  17. Fabrication and characterization of gold nano-wires templated on virus-like arrays of tobacco mosaic virus coat proteins

    International Nuclear Information System (INIS)

    Wnęk, M; Stockley, P G; Górzny, M Ł; Evans, S D; Ward, M B; Brydson, R; Wälti, C; Davies, A G

    2013-01-01

    The rod-shaped plant virus tobacco mosaic virus (TMV) is widely used as a nano-fabrication template, and chimeric peptide expression on its major coat protein has extended its potential applications. Here we describe a simple bacterial expression system for production and rapid purification of recombinant chimeric TMV coat protein carrying C-terminal peptide tags. These proteins do not bind TMV RNA or form disks at pH 7. However, they retain the ability to self-assemble into virus-like arrays at acidic pH. C-terminal peptide tags in such arrays are exposed on the protein surface, allowing interaction with target species. We have utilized a C-terminal His-tag to create virus coat protein-templated nano-rods able to bind gold nanoparticles uniformly. These can be transformed into gold nano-wires by deposition of additional gold atoms from solution, followed by thermal annealing. The resistivity of a typical annealed wire created by this approach is significantly less than values reported for other nano-wires made using different bio-templates. This expression construct is therefore a useful additional tool for the creation of chimeric TMV-like nano-rods for bio-templating. (paper)

  18. Fabrication and characterization of gold nano-wires templated on virus-like arrays of tobacco mosaic virus coat proteins

    Science.gov (United States)

    Wnęk, M.; Górzny, M. Ł.; Ward, M. B.; Wälti, C.; Davies, A. G.; Brydson, R.; Evans, S. D.; Stockley, P. G.

    2013-01-01

    The rod-shaped plant virus tobacco mosaic virus (TMV) is widely used as a nano-fabrication template, and chimeric peptide expression on its major coat protein has extended its potential applications. Here we describe a simple bacterial expression system for production and rapid purification of recombinant chimeric TMV coat protein carrying C-terminal peptide tags. These proteins do not bind TMV RNA or form disks at pH 7. However, they retain the ability to self-assemble into virus-like arrays at acidic pH. C-terminal peptide tags in such arrays are exposed on the protein surface, allowing interaction with target species. We have utilized a C-terminal His-tag to create virus coat protein-templated nano-rods able to bind gold nanoparticles uniformly. These can be transformed into gold nano-wires by deposition of additional gold atoms from solution, followed by thermal annealing. The resistivity of a typical annealed wire created by this approach is significantly less than values reported for other nano-wires made using different bio-templates. This expression construct is therefore a useful additional tool for the creation of chimeric TMV-like nano-rods for bio-templating.

  19. Autoselection of cytoplasmic yeast virus like elements encoding toxin/antitoxin systems involves a nuclear barrier for immunity gene expression.

    Science.gov (United States)

    Kast, Alene; Voges, Raphael; Schroth, Michael; Schaffrath, Raffael; Klassen, Roland; Meinhardt, Friedhelm

    2015-05-01

    Cytoplasmic virus like elements (VLEs) from Kluyveromyces lactis (Kl), Pichia acaciae (Pa) and Debaryomyces robertsiae (Dr) are extremely A/T-rich (>75%) and encode toxic anticodon nucleases (ACNases) along with specific immunity proteins. Here we show that nuclear, not cytoplasmic expression of either immunity gene (PaORF4, KlORF3 or DrORF5) results in transcript fragmentation and is insufficient to establish immunity to the cognate ACNase. Since rapid amplification of 3' ends (RACE) as well as linker ligation of immunity transcripts expressed in the nucleus revealed polyadenylation to occur along with fragmentation, ORF-internal poly(A) site cleavage due to the high A/T content is likely to prevent functional expression of the immunity genes. Consistently, lowering the A/T content of PaORF4 to 55% and KlORF3 to 46% by gene synthesis entirely prevented transcript cleavage and permitted functional nuclear expression leading to full immunity against the respective ACNase toxin. Consistent with a specific adaptation of the immunity proteins to the cognate ACNases, cross-immunity to non-cognate ACNases is neither conferred by PaOrf4 nor KlOrf3. Thus, the high A/T content of cytoplasmic VLEs minimizes the potential of functional nuclear recruitment of VLE encoded genes, in particular those involved in autoselection of the VLEs via a toxin/antitoxin principle.

  20. Autoselection of cytoplasmic yeast virus like elements encoding toxin/antitoxin systems involves a nuclear barrier for immunity gene expression.

    Directory of Open Access Journals (Sweden)

    Alene Kast

    2015-05-01

    Full Text Available Cytoplasmic virus like elements (VLEs from Kluyveromyces lactis (Kl, Pichia acaciae (Pa and Debaryomyces robertsiae (Dr are extremely A/T-rich (>75% and encode toxic anticodon nucleases (ACNases along with specific immunity proteins. Here we show that nuclear, not cytoplasmic expression of either immunity gene (PaORF4, KlORF3 or DrORF5 results in transcript fragmentation and is insufficient to establish immunity to the cognate ACNase. Since rapid amplification of 3' ends (RACE as well as linker ligation of immunity transcripts expressed in the nucleus revealed polyadenylation to occur along with fragmentation, ORF-internal poly(A site cleavage due to the high A/T content is likely to prevent functional expression of the immunity genes. Consistently, lowering the A/T content of PaORF4 to 55% and KlORF3 to 46% by gene synthesis entirely prevented transcript cleavage and permitted functional nuclear expression leading to full immunity against the respective ACNase toxin. Consistent with a specific adaptation of the immunity proteins to the cognate ACNases, cross-immunity to non-cognate ACNases is neither conferred by PaOrf4 nor KlOrf3. Thus, the high A/T content of cytoplasmic VLEs minimizes the potential of functional nuclear recruitment of VLE encoded genes, in particular those involved in autoselection of the VLEs via a toxin/antitoxin principle.

  1. Coronavirus-like particles in laboratory rabbits with different syndromes in The Netherlands (Coronavirus-like particles in rabbits).

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); J.S. Teppema; G. van Steenis (Bert)

    1982-01-01

    textabstractVirus-like particles were identified from the plasma of rabbits which developed pleural effusion disease after inoculation with different strains of Treponema pallidum. These particles were considered coronavirus-like on the basis of their size, morphology, and buoyant density. Clinical

  2. Pichia pastoris-Expressed Bivalent Virus-Like Particulate Vaccine Induces Domain III-Focused Bivalent Neutralizing Antibodies without Antibody-Dependent Enhancement in Vivo

    Directory of Open Access Journals (Sweden)

    Rahul Shukla

    2018-01-01

    Full Text Available Dengue, a significant public health problem in several countries around the world, is caused by four different serotypes of mosquito-borne dengue viruses (DENV-1, -2, -3, and -4. Antibodies to any one DENV serotype which can protect against homotypic re-infection, do not offer heterotypic cross-protection. In fact, cross-reactive antibodies may augment heterotypic DENV infection through antibody-dependent enhancement (ADE. A recently launched live attenuated vaccine (LAV for dengue, which consists of a mixture of four chimeric yellow-fever/dengue vaccine viruses, may be linked to the induction of disease-enhancing antibodies. This is likely related to viral interference among the replicating viral strains, resulting in an unbalanced immune response, as well as to the fact that the LAV encodes prM, a DENV protein documented to elicit ADE-mediating antibodies. This makes it imperative to explore the feasibility of alternate ADE risk-free vaccine candidates. Our quest for a non-replicating vaccine centered on the DENV envelope (E protein which mediates virus entry into the host cell and serves as an important target of the immune response. Serotype-specific neutralizing epitopes and the host receptor recognition function map to E domain III (EDIII. Recently, we found that Pichia pastoris-expressed DENV E protein, of all four serotypes, self-assembled into virus-like particles (VLPs in the absence of prM. Significantly, these VLPs displayed EDIII and elicited EDIII-focused DENV-neutralizing antibodies in mice. We now report the creation and characterization of a novel non-replicating recombinant particulate vaccine candidate, produced by co-expressing the E proteins of DENV-1 and DENV-2 in P. pastoris. The two E proteins co-assembled into bivalent mosaic VLPs (mVLPs designated as mE1E2bv VLPs. The mVLP, which preserved the serotype-specific antigenic integrity of its two component proteins, elicited predominantly EDIII-focused homotypic virus

  3. Reconstruction of putative DNA virus from endogenous rice tungro bacilliform virus-like sequences in the rice genome: implications for integration and evolution

    Directory of Open Access Journals (Sweden)

    Kishima Yuji

    2004-10-01

    Full Text Available Abstract Background Plant genomes contain various kinds of repetitive sequences such as transposable elements, microsatellites, tandem repeats and virus-like sequences. Most of them, with the exception of virus-like sequences, do not allow us to trace their origins nor to follow the process of their integration into the host genome. Recent discoveries of virus-like sequences in plant genomes led us to set the objective of elucidating the origin of the repetitive sequences. Endogenous rice tungro bacilliform virus (RTBV-like sequences (ERTBVs have been found throughout the rice genome. Here, we reconstructed putative virus structures from RTBV-like sequences in the rice genome and characterized to understand evolutionary implication, integration manner and involvements of endogenous virus segments in the corresponding disease response. Results We have collected ERTBVs from the rice genomes. They contain rearranged structures and no intact ORFs. The identified ERTBV segments were shown to be phylogenetically divided into three clusters. For each phylogenetic cluster, we were able to make a consensus alignment for a circular virus-like structure carrying two complete ORFs. Comparisons of DNA and amino acid sequences suggested the closely relationship between ERTBV and RTBV. The Oryza AA-genome species vary in the ERTBV copy number. The species carrying low-copy-number of ERTBV segments have been reported to be extremely susceptible to RTBV. The DNA methylation state of the ERTBV sequences was correlated with their copy number in the genome. Conclusions These ERTBV segments are unlikely to have functional potential as a virus. However, these sequences facilitate to establish putative virus that provided information underlying virus integration and evolutionary relationship with existing virus. Comparison of ERTBV among the Oryza AA-genome species allowed us to speculate a possible role of endogenous virus segments against its related disease.

  4. Impact of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine in a sexually active population of North American women.

    Science.gov (United States)

    Barr, Eliav; Gause, Christine K; Bautista, Oliver M; Railkar, Radha A; Lupinacci, Lisa C; Insinga, Ralph P; Sings, Heather L; Haupt, Richard M

    2008-03-01

    The purpose of this study was to inform policy regarding human papillomavirus (HPV) vaccination in North America. We measured the clinical impact of HPV-6/-11/-16/-18 vaccination in North American women. The study enrolled 21,954 women, the majority aged 16-25, across 5 studies of a quadrivalent HPV vaccine or its HPV-16 vaccine prototype. The North American subjects (n = 5996) were pooled from these trials, and the prevalence of HPV-6/-11/-16/-18 exposure was measured. The impact of vaccination on the burden of anogenital HPV lesions in an intention-to-treat population (regardless of enrollment HPV status) was calculated. At enrollment, the median age was 20 years; 13% of the women had had a Papanicolaou test abnormality, and 76% of the women had negative tests results for all 4 vaccine HPV types. With approximately 3 years of follow-up evaluations in the intention-to-treat population (regardless of enrollment HPV status), vaccination reduced the rate of HPV-16- and -18-related precancers and HPV-6/-11/-16/-18-related genital lesions by 66.4% (95% CI, 42.7%-81.1%) and 57.7% (95% CI, 27.3%-76.3%), respectively. The administration of HPV vaccine to sexually active North American women reduced the burden of HPV-6/-11/-16/-18-related disease. Catch-up vaccination programs in this population are warranted.

  5. Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

    International Nuclear Information System (INIS)

    Pushko, Peter; Tretyakova, Irina; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tumpey, Terrence M.; Kapczynski, Darrell R.

    2017-01-01

    Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. - Highlights: •VLPs were prepared that co-localized H5, H7 and H9 subtypes in a VLP envelope. •VLPs were characterized including electron microscopy, HA assay and NA enzyme activity. •Experimental VLP vaccine was evaluated in an avian influenza challenge model. •VLPs induced immune responses against heterologous H5, H7 and H9 virus challenges.

  6. Transient expression of human papillomavirus type 16 virus-like particles in tobacco and tomato using a tobacco rattle virus expression vector

    Czech Academy of Sciences Publication Activity Database

    Šmídková, Markéta; Müller, M.; Thönes, N.; Piuko, K.; Angelisová, Pavla; Velemínský, Jiří; Angelis, Karel

    2010-01-01

    Roč. 54, č. 3 (2010), s. 451-460 ISSN 0006-3134 R&D Projects: GA ČR GA521/01/1418; GA ČR GA521/04/0971; GA AV ČR IAA6038201; GA AV ČR IBS5038304; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z50380511; CEZ:AV0Z50520514 Keywords : ELISA * Lycopersicon esculentum * Nicotiana benthamiana Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.582, year: 2010

  7. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant

    DEFF Research Database (Denmark)

    Pedersen, Court; Petaja, Tiina; Strauss, Gitte

    2007-01-01

    will require prophylactic vaccination against oncogenic HPV 16 and 18 before the onset of sexual activity in early adolescent girls. To establish the feasibility of vaccination in girls 10-14 years of age, we compared the immunogenicity and safety in early adolescent female individuals to those 15-25 years...... measured by enzyme-linked immunosorbent assay. Vaccine safety was assessed at 7 or 30 days after each dose; serious adverse events were recorded during the entire study period. RESULTS: Both age groups achieved 100% seroconversion for HPV 16 and 18. Participants in the group aged 10-14 years were not only......PURPOSE: In female individuals 15-25-years of age, the AS04-containing human papillomavirus (HPV)-16/18 vaccine is highly immunogenic and provides up to 100% protection against HPV-16/18 persistent infection and associated cervical lesions up to 4.5 years. Optimal cervical cancer prevention...

  8. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant.

    NARCIS (Netherlands)

    Pedersen, C.; Petaja, T.; Strauss, G.; Rumke, H.C.; Poder, A.; Richardus, J.H.; Spiessens, B.; Descamps, D.; Hardt, K.; Lehtinen, M.; Dubin, G.

    2007-01-01

    PURPOSE: In female individuals 15-25-years of age, the AS04-containing human papillomavirus (HPV)-16/18 vaccine is highly immunogenic and provides up to 100% protection against HPV-16/18 persistent infection and associated cervical lesions up to 4.5 years. Optimal cervical cancer prevention will

  9. The impact of a quadrivalent human papillomavirus (types 6, 11, 16, 18) virus-like particle vaccine in European women aged 16 to 24

    DEFF Research Database (Denmark)

    Majewski, S; Bosch, F X; Dillner, J

    2009-01-01

    -associated cervico-genital lesions in a broad population of sexually active European women. METHODS: Female subjects (N = 9265) aged 16-24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection...

  10. Development of a Liquid Chromatography High Resolution Mass Spectrometry (LC-HRMS) Method for the Quantitation of Viral Envelope Glycoprotein in Ebola Virus-Like Particle Vaccine Preparations

    Science.gov (United States)

    2016-09-05

    distribution is unlimited. UNCLASSIFIED Background: 92 Ebola is an extremely pathogenic virus that causes hemorrhagic fever and can result in 93... animals . 155 156 Materials and Methods: 157 Generation and Characterization of eVLPs. 158 TR-16-141 DISTRIBUTION STATEMENT A...measuring the optical density (OD) at 280 nm in 186 a spectrophotometer and assuming an extinction coefficient at 1% equal to 10 (under this 187

  11. Chikungunya virus-like particles are more immunogenic in a lethal AG129 mouse model compared to glycoprotein El or E2 subunits

    NARCIS (Netherlands)

    Metz, S.W.H.; Martina, B.E.; Doel, van den P.; Geertsema, C.; Osterhaus, A.D.; Vlak, J.M.; Pijlman, G.P.

    2013-01-01

    Chikungunya virus (CHIKV) causes acute illness characterized by fever and long-lasting arthritic symptoms. The need for a safe and effective vaccine against CHM/infections is on the rise due to on-going vector spread and increasing severity of clinical complications. Here we report the results of a

  12. Saccharomyces cerevisiae-derived virus-like particle parvovirus B19 vaccine elicits binding and neutralizing antibodies in a mouse model for sickle cell disease.

    Science.gov (United States)

    Penkert, Rhiannon R; Young, Neal S; Surman, Sherri L; Sealy, Robert E; Rosch, Jason; Dormitzer, Philip R; Settembre, Ethan C; Chandramouli, Sumana; Wong, Susan; Hankins, Jane S; Hurwitz, Julia L

    2017-06-22

    Parvovirus B19 infections are typically mild in healthy individuals, but can be life threatening in individuals with sickle cell disease (SCD). A Saccharomyces cerevisiae-derived B19 VLP vaccine, now in pre-clinical development, is immunogenic in wild type mice when administered with the adjuvant MF59. Because SCD alters the immune response, we evaluated the efficacy of this vaccine in a mouse model for SCD. Vaccinated mice with SCD demonstrated similar binding and neutralizing antibody responses to those of heterozygous littermate controls following a prime-boost-boost regimen. Due to the lack of a mouse parvovirus B19 challenge model, we employed a natural mouse pathogen, Sendai virus, to evaluate SCD respiratory tract responses to infection. Normal mucosal and systemic antibody responses were observed in these mice. Results demonstrate that mice with SCD can respond to a VLP vaccine and to a respiratory virus challenge, encouraging rapid development of the B19 vaccine for patients with SCD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. High pressure inactivation of human norovirus virus-like particles: evidence that the capsid of human norovirus is highly pressure resistant

    Science.gov (United States)

    Human norovirus (NoV) is the leading cause of non-bacterial acute gastroenteritis epidemics worldwide. High pressure processing (HPP) has been considered a promising non-thermal processing technology to inactivate food- and water-borne viral pathogens. Due to the lack of an effective cell culture fo...

  14. Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

    Energy Technology Data Exchange (ETDEWEB)

    Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Tretyakova, Irina; Hidajat, Rachmat [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Zsak, Aniko; Chrzastek, Klaudia [USDA SEPRL, 934 College Station Rd, Athens, GA (United States); Tumpey, Terrence M. [Influenza Division, CDC,1600 Clifton Road N.E., Atlanta, GA (United States); Kapczynski, Darrell R. [USDA SEPRL, 934 College Station Rd, Athens, GA (United States)

    2017-01-15

    Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. - Highlights: •VLPs were prepared that co-localized H5, H7 and H9 subtypes in a VLP envelope. •VLPs were characterized including electron microscopy, HA assay and NA enzyme activity. •Experimental VLP vaccine was evaluated in an avian influenza challenge model. •VLPs induced immune responses against heterologous H5, H7 and H9 virus challenges.

  15. Deep Sequencing Reveals the Complete Genome and Evidence for Transcriptional Activity of the First Virus-Like Sequences Identified in Aristotelia chilensis (Maqui Berry

    Directory of Open Access Journals (Sweden)

    Javier Villacreses

    2015-04-01

    Full Text Available Here, we report the genome sequence and evidence for transcriptional activity of a virus-like element in the native Chilean berry tree Aristotelia chilensis. We propose to name the endogenous sequence as Aristotelia chilensis Virus 1 (AcV1. High-throughput sequencing of the genome of this tree uncovered an endogenous viral element, with a size of 7122 bp, corresponding to the complete genome of AcV1. Its sequence contains three open reading frames (ORFs: ORFs 1 and 2 shares 66%–73% amino acid similarity with members of the Caulimoviridae virus family, especially the Petunia vein clearing virus (PVCV, Petuvirus genus. ORF1 encodes a movement protein (MP; ORF2 a Reverse Transcriptase (RT and a Ribonuclease H (RNase H domain; and ORF3 showed no amino acid sequence similarity with any other known virus proteins. Analogous to other known endogenous pararetrovirus sequences (EPRVs, AcV1 is integrated in the genome of Maqui Berry and showed low viral transcriptional activity, which was detected by deep sequencing technology (DNA and RNA-seq. Phylogenetic analysis of AcV1 and other pararetroviruses revealed a closer resemblance with Petuvirus. Overall, our data suggests that AcV1 could be a new member of Caulimoviridae family, genus Petuvirus, and the first evidence of this kind of virus in a fruit plant.

  16. Epstein–Barr virus particles induce centrosome amplification and chromosomal instability

    Science.gov (United States)

    Shumilov, Anatoliy; Tsai, Ming-Han; Schlosser, Yvonne T.; Kratz, Anne-Sophie; Bernhardt, Katharina; Fink, Susanne; Mizani, Tuba; Lin, Xiaochen; Jauch, Anna; Mautner, Josef; Kopp-Schneider, Annette; Feederle, Regina; Hoffmann, Ingrid; Delecluse, Henri-Jacques

    2017-01-01

    Infections with Epstein–Barr virus (EBV) are associated with cancer development, and EBV lytic replication (the process that generates virus progeny) is a strong risk factor for some cancer types. Here we report that EBV infection of B-lymphocytes (in vitro and in a mouse model) leads to an increased rate of centrosome amplification, associated with chromosomal instability. This effect can be reproduced with virus-like particles devoid of EBV DNA, but not with defective virus-like particles that cannot infect host cells. Viral protein BNRF1 induces centrosome amplification, and BNRF1-deficient viruses largely lose this property. These findings identify a new mechanism by which EBV particles can induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for development of tumours that do not necessarily carry the viral genome. PMID:28186092

  17. Rescue of Infectious Particles from Preassembled Alphavirus Nucleocapsid Cores▿†

    OpenAIRE

    Snyder, Jonathan E.; Azizgolshani, Odisse; Wu, Bingbing; He, Yingpei; Lee, Aih Cheun; Jose, Joyce; Suter, Daniel M.; Knobler, Charles M.; Gelbart, William M.; Kuhn, Richard J.

    2011-01-01

    Alphaviruses are small, spherical, enveloped, positive-sense, single-stranded, RNA viruses responsible for considerable human and animal disease. Using microinjection of preassembled cores as a tool, a system has been established to study the assembly and budding process of Sindbis virus, the type member of the alphaviruses. We demonstrate the release of infectious virus-like particles from cells expressing Sindbis virus envelope glycoproteins following microinjection of Sindbis virus nucleoc...

  18. Particle Pollution

    Science.gov (United States)

    ... Your Health Particle Pollution Public Health Issues Particle Pollution Recommend on Facebook Tweet Share Compartir Particle pollution — ... see them in the air. Where does particle pollution come from? Particle pollution can come from two ...

  19. DNA vaccines based on chimeric potyvirus-like particles carrying HPV16 E7 peptide (aa 44-60)

    Czech Academy of Sciences Publication Activity Database

    Pokorná, D.; Čeřovská, Noemi; Šmahel, M.; Moravec, Tomáš; Ludvíková, V.; Machková, J.; Synková, Helena; Dušková, M.; Hozák, P.; Velemínský, Jiří

    2005-01-01

    Roč. 14, č. 4 (2005), s. 1045-1053 ISSN 1021-335X R&D Projects: GA ČR GA310/00/0381 Grant - others:IGA MHCR NC7552-3/2003 Institutional research plan: CEZ:AV0Z50380511 Keywords : human papillomavirus * E7 * virus-like particles Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.572, year: 2005

  20. Polyomavirus EGFP-pseudocapsids:analysis of model particles for introduction of proteins and pepetides into mammalian cells

    Czech Academy of Sciences Publication Activity Database

    Bouřa, E.; Liebl, D.; Spíšek, R.; Frič, Jan; Marek, M.; Štokrová, Jitka; Holáň, Vladimír; Forstová, J.

    2005-01-01

    Roč. 579, č. 29 (2005), s. 6549-6558 ISSN 0014-5793 R&D Projects: GA MZd(CZ) NC6957; GA ČR(CZ) GA204/03/0593 Institutional research plan: CEZ:AV0Z50520514 Keywords : mouse polyomavirus * empty artificial virus-like particle * dendritic cell activation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.415, year: 2005

  1. Point mutation in calcium-binding domain of mouse polyomavirus VP1 protein does not prevent virus-like particle formation, but changes VP1 interactions with Saccharomyces cerevisiae cell structures

    Czech Academy of Sciences Publication Activity Database

    Adamec, T.; Palková, Zdena; Velková, K.; Štokrová, Jitka; Forstová, J.

    2005-01-01

    Roč. 5, 4-5 (2005), s. 331-340 ISSN 1567-1356 R&D Projects: GA ČR GA204/03/0593 Institutional research plan: CEZ:AV0Z5052915 Keywords : polyomavirus VP1 * Saccharomyces cerevisiae * heterologous expression Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.477, year: 2005

  2. Immunization with DNA plasmids coding for crimean-congo hemorrhagic fever virus capsid and envelope proteins and/or virus-like particles induces protection and survival in challenged mice

    DEFF Research Database (Denmark)

    Hinkula, Jorma; Devignot, Stéphanie; Åkerström, Sara

    2017-01-01

    , there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice...... with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type...

  3. Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

    DEFF Research Database (Denmark)

    Haupt, Richard M; Wheeler, Cosette M; Brown, Darron R

    2011-01-01

    The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2-3 or adenocarcinoma in situ (CIN2-3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six-hundred and twenty-two women aged 16-26 were.......9). These data suggest HPV vaccination neither reduces nor enhances progression to HPV16/18-related high grade cervical lesions, and cervical cytology screening and corresponding management should continue as per local recommendations. Ultimately, population-based surveillance of vaccinated individuals beyond...

  4. Dengue envelope-based 'four-in-one' virus-like particles produced using Pichia pastoris induce enhancement-lacking, domain III-directed tetravalent neutralising antibodies in mice.

    Science.gov (United States)

    Rajpoot, Ravi Kant; Shukla, Rahul; Arora, Upasana; Swaminathan, Sathyamangalam; Khanna, Navin

    2018-06-05

    Dengue is a significant public health problem worldwide, caused by four antigenically distinct mosquito-borne dengue virus (DENV) serotypes. Antibodies to any given DENV serotype which can afford protection against that serotype tend to enhance infection by other DENV serotypes, by a phenomenon termed antibody-dependent enhancement (ADE). Antibodies to the viral pre-membrane (prM) protein have been implicated in ADE. We show that co-expression of the envelope protein of all four DENV serotypes, in the yeast Pichia pastoris, leads to their co-assembly, in the absence of prM, into tetravalent mosaic VLPs (T-mVLPs), which retain the serotype-specific antigenic integrity and immunogenicity of all four types of their monomeric precursors. Following a three-dose immunisation schedule, the T-mVLPs elicited EDIII-directed antibodies in mice which could neutralise all four DENV serotypes. Importantly, anti-T-mVLP antibodies did not augment sub-lethal DENV-2 infection of dengue-sensitive AG129 mice, based on multiple parameters. The 'four-in-one' tetravalent T-mVLPs possess multiple desirable features which may potentially contribute to safety (non-viral, prM-lacking and ADE potential-lacking), immunogenicity (induction of virus-neutralising antibodies), and low cost (single tetravalent immunogen produced using P. pastoris, an expression system known for its high productivity using simple inexpensive media). These results strongly warrant further exploration of this vaccine candidate.

  5. Enhanced light microscopy visualization of virus particles from Zika virus to filamentous ebolaviruses.

    Directory of Open Access Journals (Sweden)

    George G Daaboul

    Full Text Available Light microscopy is a powerful tool in the detection and analysis of parasites, fungi, and prokaryotes, but has been challenging to use for the detection of individual virus particles. Unlabeled virus particles are too small to be visualized using standard visible light microscopy. Characterization of virus particles is typically performed using higher resolution approaches such as electron microscopy or atomic force microscopy. These approaches require purification of virions away from their normal millieu, requiring significant levels of expertise, and can only enumerate small numbers of particles per field of view. Here, we utilize a visible light imaging approach called Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS that allows automated counting and sizing of thousands of individual virions. Virions are captured directly from complex solutions onto a silicon chip and then detected using a reflectance interference imaging modality. We show that the use of different imaging wavelengths allows the visualization of a multitude of virus particles. Using Violet/UV illumination, the SP-IRIS technique is able to detect individual flavivirus particles (~40 nm, while green light illumination is capable of identifying and discriminating between vesicular stomatitis virus and vaccinia virus (~360 nm. Strikingly, the technology allows the clear identification of filamentous infectious ebolavirus particles and virus-like particles. The ability to differentiate and quantify unlabeled virus particles extends the usefulness of traditional light microscopy and can be embodied in a straightforward benchtop approach allowing widespread applications ranging from rapid detection in biological fluids to analysis of virus-like particles for vaccine development and production.

  6. Rare particles

    International Nuclear Information System (INIS)

    Kutschera, W.

    1984-01-01

    The use of Accelerator Mass Spectrometry (AMS) to search for hypothetical particles and known particles of rare processes is discussed. The hypothetical particles considered include fractionally charged particles, anomalously heavy isotopes, and superheavy elements. The known particles produced in rare processes discussed include doubly-charged negative ions, counting neutrino-produced atoms in detectors for solar neutrino detection, and the spontaneous emission of 14 C from 223 Ra. 35 references

  7. Particle detection

    International Nuclear Information System (INIS)

    Charpak, G.

    2000-01-01

    In this article G.Charpak presents the principles on which particle detection is based. Particle accelerators are becoming more and more powerful and require new detectors able to track the right particle in a huge flux of particles. The gigantic size of detectors in high energy physics is often due to the necessity of getting a long enough trajectory in a magnetic field in order to deduce from the curvature an accurate account of impulses in the reaction. (A.C.)

  8. Strange particles

    International Nuclear Information System (INIS)

    Chinowsky, W.

    1989-01-01

    Work done in the mid 1950s at Brookhaven National Laboratory on strange particles is described. Experiments were done on the Cosmotron. The author describes his own and others' work on neutral kaons, lambda and theta particles and points out the theoretical gap between predictions and experimental findings. By the end of the decade, the theory of strange particles was better understood. (UK)

  9. Biophysical analysis of HTLV-1 particles reveals novel insights into particle morphology and Gag stochiometry

    Directory of Open Access Journals (Sweden)

    Fogarty Keir H

    2010-09-01

    Full Text Available Abstract Background Human T-lymphotropic virus type 1 (HTLV-1 is an important human retrovirus that is a cause of adult T-cell leukemia/lymphoma. While an important human pathogen, the details regarding virus replication cycle, including the nature of HTLV-1 particles, remain largely unknown due to the difficulties in propagating the virus in tissue culture. In this study, we created a codon-optimized HTLV-1 Gag fused to an EYFP reporter as a model system to quantitatively analyze HTLV-1 particles released from producer cells. Results The codon-optimized Gag led to a dramatic and highly robust level of Gag expression as well as virus-like particle (VLP production. The robust level of particle production overcomes previous technical difficulties with authentic particles and allowed for detailed analysis of particle architecture using two novel methodologies. We quantitatively measured the diameter and morphology of HTLV-1 VLPs in their native, hydrated state using cryo-transmission electron microscopy (cryo-TEM. Furthermore, we were able to determine HTLV-1 Gag stoichiometry as well as particle size with the novel biophysical technique of fluorescence fluctuation spectroscopy (FFS. The average HTLV-1 particle diameter determined by cryo-TEM and FFS was 71 ± 20 nm and 75 ± 4 nm, respectively. These values are significantly smaller than previous estimates made of HTLV-1 particles by negative staining TEM. Furthermore, cryo-TEM reveals that the majority of HTLV-1 VLPs lacks an ordered structure of the Gag lattice, suggesting that the HTLV-1 Gag shell is very likely to be organized differently compared to that observed with HIV-1 Gag in immature particles. This conclusion is supported by our observation that the average copy number of HTLV-1 Gag per particle is estimated to be 510 based on FFS, which is significantly lower than that found for HIV-1 immature virions. Conclusions In summary, our studies represent the first quantitative biophysical

  10. Particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  11. Particle therapy

    International Nuclear Information System (INIS)

    Raju, M.R.

    1993-01-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics

  12. Particle cosmology

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    The understanding of the Universe at the largest and smallest scales traditionally has been the subject of cosmology and particle physics, respectively. Studying the evolution of the Universe connects today's large scales with the tiny scales in the very early Universe and provides the link between the physics of particles and of the cosmos. This series of five lectures aims at a modern and critical presentation of the basic ideas, methods, models and observations in today's particle cosmology.

  13. Particle physics

    International Nuclear Information System (INIS)

    Kamal, Anwar

    2014-01-01

    Provides step-by-step derivations. Contains numerous tables and diagrams. Supports learning and teaching with numerous worked examples, questions and problems with answers. Sketches also the historical development of the subject. This textbook teaches particle physics very didactically. It supports learning and teaching with numerous worked examples, questions and problems with answers. Numerous tables and diagrams lead to a better understanding of the explanations. The content of the book covers all important topics of particle physics: Elementary particles are classified from the point of view of the four fundamental interactions. The nomenclature used in particle physics is explained. The discoveries and properties of known elementary particles and resonances are given. The particles considered are positrons, muon, pions, anti-protons, strange particles, neutrino and hadrons. The conservation laws governing the interactions of elementary particles are given. The concepts of parity, spin, charge conjugation, time reversal and gauge invariance are explained. The quark theory is introduced to explain the hadron structure and strong interactions. The solar neutrino problem is considered. Weak interactions are classified into various types, and the selection rules are stated. Non-conservation of parity and the universality of the weak interactions are discussed. Neutral and charged currents, discovery of W and Z bosons and the early universe form important topics of the electroweak interactions. The principles of high energy accelerators including colliders are elaborately explained. Additionally, in the book detectors used in nuclear and particle physics are described. This book is on the upper undergraduate level.

  14. Magnetic particles

    Science.gov (United States)

    Chang, Manchium (Inventor); Colvin, Michael S. (Inventor)

    1989-01-01

    Magnetic polymer particles are formed by swelling porous, polymer particles and impregnating the particles with an aqueous solution of precursor magnetic metal salt such as an equimolar mixture of ferrous chloride and ferric chloride. On addition of a basic reagent such as dilute sodium hydroxide, the metal salts are converted to crystals of magnetite which are uniformly contained througout the pores of the polymer particle. The magnetite content can be increased and neutral buoyancy achieved by repetition of the impregnaton and neutralization steps to adjust the magnetite content to a desired level.

  15. Particle accelerator

    International Nuclear Information System (INIS)

    Ress, R.I.

    1976-01-01

    Charged particles are entrained in a predetermined direction, independent of their polarity, in a circular orbit by a magnetic field rotating at high speed about an axis in a closed cylindrical or toroidal vessel. The field may be generated by a cylindrical laser structure, whose beam is polygonally reflected from the walls of an excited cavity centered on the axis, or by high-frequency energization of a set of electromagnets perpendicular to the axis. In the latter case, a separate magnetostatic axial field limits the orbital radius of the particles. These rotating and stationary magnetic fields may be generated centrally or by individual magnets peripherally spaced along its circular orbit. Chemical or nuclear reactions can be induced by collisions between the orbiting particles and an injected reactant, or by diverting high-speed particles from one doughnut into the path of counterrotating particles in an adjoining doughnut

  16. Particle detectors

    CERN Document Server

    Hilke, Hans Jürgen

    1992-01-01

    We shall discuss the principles of the main techniques applied to particle detection (including front-end electronics), the construction and performance of some of the devices presently in operation and a few ideas on future developments.

  17. Auroral particles

    International Nuclear Information System (INIS)

    Evans, D.S.

    1987-01-01

    The problems concerning the aurora posed prior to the war are now either solved in principle or were restated in a more fundamental form. The pre-war hypothesis concerning the nature of the auroral particles and their energies was fully confirmed, with the exception that helium and oxygen ions were identified as participating in the auroral particle precipitation in addition to the protons. The nature of the near-Earth energization processes affecting auroral particles was clarified. Charged particle trajectories in various electric field geometries were modeled. The physical problems have now moved from determining the nature and geometry of the electric fields, which accelerate charged particles near the Earth, to accounting for the existence of these electric fields as a natural consequence of the solar wind's interaction with Earth. Ultimately the reward in continuing the work in auroral and magnetospheric particle dynamics will be a deeper understanding of the subtleties of classical electricity and magnetism as applied to situations not blessed with well-defined and invariant geometries

  18. Elementary particles and particle interactions

    International Nuclear Information System (INIS)

    Bethge, K.; Schroeder, U.E.

    1986-01-01

    This book is a textbook for an introductory course of elementary particle physics. After a general introduction the symmetry principles governing the interactions of elementary particles are discussed. Then the phenomenology of the electroweak and strong interactions are described together with a short introduction to the Weinberg-Salam theory respectively to quantum chromodynamics. Finally a short outlook is given to grand unification with special regards to SU(5) and cosmology in the framework of the current understanding of the fundamental principles of nature. In the appendix is a table of particle properties and physical constants. (HSI) [de

  19. Particle detectors

    CERN Document Server

    Hilke, Hans Jürgen; Joram, Christian; CERN. Geneva

    1991-01-01

    Lecture 5: Detector characteristics: ALEPH Experiment cut through the devices and events - Discuss the principles of the main techniques applied to particle detection ( including front-end electronics), the construction and performance of some of the devices presently in operartion and a few ideas on the future performance. Lecture 4-pt. b Following the Scintillators. Lecture 4-pt. a : Scintillators - Used for: -Timing (TOF, Trigger) - Energy Measurement (Calorimeters) - Tracking (Fibres) Basic scintillation processes- Inorganic Scintillators - Organic Scintil - Discuss the principles of the main techniques applied to particle detection ( including front-end electronics), the construction and performance of some of the devices presently in operation and a fiew ideas on future developpement session 3 - part. b Following Calorimeters lecture 3-pt. a Calorimeters - determine energy E by total absorption of charged or neutral particles - fraction of E is transformed into measurable quantities - try to acheive sig...

  20. Stable particles

    International Nuclear Information System (INIS)

    Samios, N.P.

    1993-01-01

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets. with a few more additions -- with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers-exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the forte of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc

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

    Science.gov (United States)

    Young, Kelly R; Ross, Ted M

    2003-06-01

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

  2. Particle physics

    CERN Document Server

    Martin, Brian R

    2017-01-01

    An accessible and carefully structured introduction to Particle Physics, including important coverage of the Higgs Boson and recent progress in neutrino physics. Fourth edition of this successful title in the Manchester Physics series. Includes information on recent key discoveries including : An account of the discovery of exotic hadrons, beyond the simple quark model; Expanded treatments of neutrino physics and CP violation in B-decays; An updated account of ‘physics beyond the standard model’, including the interaction of particle physics with cosmology; Additional problems in all chapters, with solutions to selected problems available on the book’s website; Advanced material appears in optional starred sections.

  3. Elementary particles

    International Nuclear Information System (INIS)

    Prasad, R.

    1984-01-01

    Two previous monographs report on investigations into the extent to which a unified field theory can satisfactorily describe physical reality. The first, Unified field Theory, showed that the paths within a non-Riemannian space are governed by eigenvalue equations. The second, Fundamental Constants, show that the field tensors satisfy sets of differential equations with solutions which represent the evolution of the fields along the paths of the space. The results from the first two monographs are used in this one to make progress on the theory of elementary particles. The five chapters are as follows - Quantum mechanics, gravitation and electromagnetism are aspects of the Unified theory; the fields inside the particle; the quadratic and linear theories; the calculation of the eigenvalues and elementary particles as stable configurations of interacting fields. It is shown that it is possible to construct an internal structure theory for elementary particles. The theory lies within the framework of Einstein's programme-to identify physical reality with a specified geometrical structure. (U.K.)

  4. Pinpointing particles

    International Nuclear Information System (INIS)

    Miller, David J.

    1987-01-01

    The Conference on Position-Sensitive Detectors held at London's University College from 7-11 September highlighted the importance and the growing applications of these precision devices in many branches of science, underlining once again the high spinoff potential for techniques developed inside particle physics

  5. Particle tracking

    International Nuclear Information System (INIS)

    Mais, H.; Ripken, G.; Wrulich, A.; Schmidt, F.

    1986-02-01

    After a brief description of typical applications of particle tracking in storage rings and after a short discussion of some limitations and problems related with tracking we summarize some concepts and methods developed in the qualitative theory of dynamical systems. We show how these concepts can be applied to the proton ring HERA. (orig.)

  6. Pinpointing particles

    Energy Technology Data Exchange (ETDEWEB)

    Miller, David J.

    1987-10-15

    The Conference on Position-Sensitive Detectors held at London's University College from 7-11 September highlighted the importance and the growing applications of these precision devices in many branches of science, underlining once again the high spinoff potential for techniques developed inside particle physics.

  7. Particle Physics

    CERN Multimedia

    2005-01-01

    While biomedicine and geoscience use grids to bring together many different sub-disciplines, particle physicists use grid computing to increase computing power and storage resources, and to access and analyze vast amounts of data collected from detectors at the world's most powerful accelerators (1 page)

  8. [Construction and immunogenicity of recombinant porcine parvovirus-like particles with somatostatin].

    Science.gov (United States)

    Zhang, Xuehua; Zheng, Qisheng; Chen, Jin; Xue, Gang; Hou, Hongyan; Hou, Jibo

    2010-08-01

    In order to obtain a virus-like particle vaccine both for porcine parvovirus (PPV) prevention and growth-promotion, VP2 gene of PPV NJ-a strain was amplified with PCR, and four copies of synthetic somatostatin gene were fused to the N-terminal of VP2 gene. The fused gene was cloned into pFast-HT A to construct the recombinant plasmid pFast-SS4-VP2, then the pFast-SS4-VP2 was transformed into DH10Bac competent cells and recombined with shuttle vector Bacmid, followed by identification with blue-white screening and PCR analysis for three cycles, and the positive recombinant was named as rBacmid-SS4-VP2. The positive Sf-9 cells were transfected with rBacmid-SS4-VP2 by Lipofectamine to produce recombinant baculovirus. When the cytopathic effect (CPE) was obvious, the transfected Sf-9 cell was harvested, and the positive recombinant virus was named as rBac-SS4-VP2. The insertion for the target gene into baculovirus genome was confirmed with PCR. SDS-PAGE and Western blotting revealed that the calculated protein of approximately 68 kDa was in the expressed in the insect cells. The Sf-9 cells infected with rBac-SS4-VP2 were stained positive against PPV antibody using the indirect immunofluorescence assay (IFA). Moreover, the virus particle self-assembly was observed under electron microscopy. 90 four-week-old mice were immunized by the recombinant protein coupled with different adjuvants alhydrogel, IMS and oil. VP2-specific ELISA antibodies, PPV-specific neutralizing antibody, somatostatin antibody and growth hormone levels were examined to evaluate the immunogenicity of this virus like particle. Results indicated that mice groups immunized rSS4-VP2 protein with alhydrogel and IMS developed similar humoral immune response comparing with inactived PPV vaccine. Mice group immunized with rSS4-VP2 generated higher level of SS antibody and growth hormone comparing with negative control, mice receiving rSS4-VP2 with alhydrogel developed the highest antibody titre than all

  9. Active particles

    CERN Document Server

    Degond, Pierre; Tadmor, Eitan

    2017-01-01

    This volume collects ten surveys on the modeling, simulation, and applications of active particles using methods ranging from mathematical kinetic theory to nonequilibrium statistical mechanics. The contributing authors are leading experts working in this challenging field, and each of their chapters provides a review of the most recent results in their areas and looks ahead to future research directions. The approaches to studying active matter are presented here from many different perspectives, such as individual-based models, evolutionary games, Brownian motion, and continuum theories, as well as various combinations of these. Applications covered include biological network formation and network theory; opinion formation and social systems; control theory of sparse systems; theory and applications of mean field games; population learning; dynamics of flocking systems; vehicular traffic flow; and stochastic particles and mean field approximation. Mathematicians and other members of the scientific commu...

  10. Hot particles

    International Nuclear Information System (INIS)

    Merwin, S.E.; Moeller, M.P.

    1989-01-01

    Nuclear Regulatory Commission (NRC) licensees are required to assess the dose to skin from a hot particle contamination event at a depth of skin of7mg/cm 2 over an area of 1 cm 2 and compare the value to the current dose limit for the skin. Although the resulting number is interesting from a comparative standpoint and can be used to predict local skin reactions, comparison of the number to existing limits based on uniform exposures is inappropriate. Most incidents that can be classified as overexposures based on this interpretation of dose actually have no effect on the health of the worker. As a result, resources are expended to reduce the likelihood that an overexposure event will occur when they could be directed toward eliminating the cause of the problem or enhancing existing programs such as contamination control. Furthermore, from a risk standpoint, this practice is not ALARA because some workers receive whole body doses in order to minimize the occurrence of hot particle skin contaminations. In this paper the authors suggest an alternative approach to controlling hot particle exposures

  11. New particles

    Energy Technology Data Exchange (ETDEWEB)

    Khare, A.

    1980-07-01

    Current state of art in the discovery of new elementary particles is reviewed. At present, quarks and mesons are accepted as the basic constituents of matter. The charmonium model (canti-c system), and the 'open charm' are discussed. Explanations are offered for the recent discovery of the heavy lepton tau. Quark states such as the beauty and taste are also dealt with at length. The properties of the tanti-t bound system are speculated. It is concluded that the understanding of canti-c and banti-b families is facilitated by the assumption of the quarkonium model. Implications at the astrophysical level are indicated.

  12. Particle Mechanics

    CERN Document Server

    Collinson, Chris

    1995-01-01

    * Assumes no prior knowledge* Adopts a modelling approach* Numerous tutorial problems, worked examples and exercises included* Elementary topics augmented by planetary motion and rotating framesThis text provides an invaluable introduction to mechanicsm confining attention to the motion of a particle. It begins with a full discussion of the foundations of the subject within the context of mathematical modelling before covering more advanced topics including the theory of planetary orbits and the use of rotating frames of reference. Truly introductory , the style adoped is perfect for those u

  13. Fermilab | Particle Physics Division

    Science.gov (United States)

    Diversity Education Safety Sustainability and Environment Contact Science Science Particle Physics Neutrinos Scientific Computing Research & Development Key Discoveries Benefits of Particle Physics Particle Superconducting Test Accelerator LHC and Future Accelerators Accelerators for Science and Society Particle Physics

  14. Rescue of Infectious Particles from Preassembled Alphavirus Nucleocapsid Cores▿†

    Science.gov (United States)

    Snyder, Jonathan E.; Azizgolshani, Odisse; Wu, Bingbing; He, Yingpei; Lee, Aih Cheun; Jose, Joyce; Suter, Daniel M.; Knobler, Charles M.; Gelbart, William M.; Kuhn, Richard J.

    2011-01-01

    Alphaviruses are small, spherical, enveloped, positive-sense, single-stranded, RNA viruses responsible for considerable human and animal disease. Using microinjection of preassembled cores as a tool, a system has been established to study the assembly and budding process of Sindbis virus, the type member of the alphaviruses. We demonstrate the release of infectious virus-like particles from cells expressing Sindbis virus envelope glycoproteins following microinjection of Sindbis virus nucleocapsids purified from the cytoplasm of infected cells. Furthermore, it is shown that nucleocapsids assembled in vitro mimic those isolated in the cytoplasm of infected cells with respect to their ability to be incorporated into enveloped virions following microinjection. This system allows for the study of the alphavirus budding process independent of an authentic infection and provides a platform to study viral and host requirements for budding. PMID:21471237

  15. Particle kickers

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    These devices are designed to provide a current pulse of 5000 Amps which will in turn generate a fast magnetic pulse that steers the incoming beam into the LHC. Today, the comprehensive upgrade of the LHC injection kicker system is entering its final stages. The upgraded system will ensure the LHC can be refilled without needing to wait for the kicker magnets to cool, thus enhancing the performance of the whole accelerator.   An upgraded kicker magnet in its vacuum tank, with an upgraded beam screen. The LHC is equipped with two kicker systems installed at the injection points (near points 2 and 8, see schematic diagram) where the particle beams coming from the SPS are injected into the accelerator’s orbit. Each system comprises four magnets and four pulse generators in which the field rises to 0.12 Tesla in less than 900 nanoseconds and for a duration of approximately 8 microseconds. Although the injection kickers only pulse 12 times to fill the LHC up with beam, the LHC beam circ...

  16. Expression, purification, crystallization and preliminary X-ray crystallographic studies of hepatitis B virus core fusion protein corresponding to octahedral particles

    International Nuclear Information System (INIS)

    Kikuchi, Masaki; Iwabuchi, Shinichiro; Kikkou, Tatsuhiko; Noguchi, Keiichi; Odaka, Masafumi; Yohda, Masafumi; Kawata, Masaaki; Sato, Chikara; Matsumoto, Osamu

    2013-01-01

    Novel hepatitis B virus-like particles of recombinant dimeric core–GFP fusion protein were expressed, purified and crystallized. The crystals diffracted to 2.15 Å resolution and belonged to space group F432, with unit-cell parameters a = b = c = 219.7 Å. Recombinant hepatitis B virus core proteins dimerize to form building blocks that are capable of self-assembly into a capsid. A core capsid protein dimer (CPD) linked to a green fluorescent protein variant, EGFP, at the C-terminus has been designed. The recombinant fusion CPD was expressed in Escherichia coli, assembled into virus-like particles (VLPs), purified and crystallized. The single crystal diffracted to 2.15 Å resolution and belonged to the cubic space group F432, with unit-cell parameters a = b = c = 219.7 Å. The fusion proteins assembled into icosahedral VLPs in aqueous solution, but were rearranged into octahedral symmetry through the crystal-packing process under the crystallization conditions

  17. Fermilab | Science | Particle Physics

    Science.gov (United States)

    Photos and videos Latest news For the media Particle Physics Neutrinos Fermilab and the LHC Dark matter initiatives Research and development Key discoveries Benefits of particle physics Particle Accelerators society Particle Physics 101 Science of matter, energy, space and time How particle physics discovery

  18. Particle theory and cosmology

    International Nuclear Information System (INIS)

    Gaisser, T.K.; Shafi, Q.; Barr, S.M.; Seckel, D.; Rusjan, E.; Fletcher, R.S.

    1991-01-01

    This report discusses research of professor at Bartol research institute in the following general areas: particle phenomenology and non-accelerator physics; particle physics and cosmology; theories with higher symmetry; and particle astrophysics and cosmology

  19. Transmission of HCV to a chimpanzee using virus particles produced in an RNA-transfected HepG2 cell culture.

    Science.gov (United States)

    Dash, S; Kalkeri, G; McClure, H M; Garry, R F; Clejan, S; Thung, S N; Murthy, K K

    2001-10-01

    It was demonstrated previously that HepG2 cells produce negative strand RNA and virus-like particles after transfection with RNA transcribed from a full-length hepatitis C virus (HCV) cDNA clone [Dash et al. (1997) American Journal of Pathology, 151:363-373]. To determine in vivo infectivity of these in vitro synthesized viral particles, a chimpanzee was inoculated intravenously with HCV derived from HepG2 cells. The infected chimpanzee was examined serially for elevation of liver enzymes, for the presence of HCV RNA in the serum by reverse transcription nested polymerase chain reaction (RT-PCR), anti-HCV antibodies in the serum, and inflammation in the liver. The chimpanzee developed elevated levels of liver enzymes after the second week, but the levels fluctuated over a 10-week period. HCV RNA was detected in the serum of the chimpanzee at the second, seventh and ninth weeks after inoculation, and remained positive up to 25 weeks. Liver biopsies at Weeks 18 and 19 revealed of mild inflammation. Nucleotide sequence analysis of HCV recovered from the infected chimpanzee at the second and ninth weeks showed 100% sequence homology with the clone used for transfection studies. Serum anti-HCV antibodies were not detected by EIA during the 25 weeks follow-up period. These results suggest that intravenous administration of the virus-like particles derived from RNA-transfected HepG2 cells are infectious, and therefore, the pMO9.6-T7 clone is an infectious clone. These results provide new information that in vitro synthesized HCV particles produced from full-length HCV clone can cause infection in a chimpanzee. This study will facilitate the use of innovative approaches to the study of assembly of HCV particles and mechanisms of virus infectivity in cell culture. Copyright 2001 Wiley-Liss, Inc.

  20. Rotavirus-Like Particles: A Novel Nanocarrier for the Gut

    Directory of Open Access Journals (Sweden)

    Naima G. Cortes-Perez

    2010-01-01

    Full Text Available The delivery of bioactive molecules directly to damaged tissues represents a technological challenge. We propose here a new system based on virus-like particles (VLP from rotavirus, with a marked tropism for the gut to deliver bio-active molecules to intestinal cells. For this, nonreplicative VLP nanoparticles were constructed using a baculovirus expression system and used to deliver an exogenous biomolecule, the green fluorescent protein (GFP, into either MA104 cells or intestinal cells from healthy and 2,4,6-trinitrobenzene sulfonic acid (TNBS-treated mice. Our results show that expression of rotavirus capsid proteins in baculovirus led to the auto assembly of VLP that display similar properties to rotavirus. In vitro experiments showed that VLP were able to enter into MA104 cells and deliver the reporter protein. Intragastric administration of fluorescent VLP in healthy and TNBS-treated mice resulted in the detection of GFP and viral proteins in intestinal samples. Our results demonstrate an efficient entry of non-replicative rotavirus VLP into the epithelial cell line MA104 and provide the first in vivo evidence of the potential of these nanoparticles as a promising safe candidate for drug delivery to intestinal cells.

  1. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years

    DEFF Research Database (Denmark)

    Brown, Darron R; Kjaer, Susanne K; Sigurdsson, Kristján

    2009-01-01

    BACKGROUND: Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. METHODS: We enrolled 17......,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotyping was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV...... types on day 1. Prespecified analyses included infection of 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. RESULTS: Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95...

  2. A simple fluorescence based assay for quantification of human immunodeficiency virus particle release

    Directory of Open Access Journals (Sweden)

    Heuser Anke-Mareil

    2010-04-01

    Full Text Available Abstract Background The assembly and release of human immunodeficiency virus (HIV particles from infected cells represent attractive, but not yet exploited targets for antiretroviral therapy. The availability of simple methods to measure the efficiency of these replication steps in tissue culture would facilitate the identification of host factors essential for these processes as well as the screening for lead compounds acting as specific inhibitors of particle formation. We describe here the development of a rapid cell based assay for quantification of human immunodeficiency virus type 1 (HIV-1 particle assembly and/or release. Results Using a fluorescently labelled HIV-derivative, which carries an eYFP domain within the main viral structural protein Gag in the complete viral protein context, the release of virus like particles could be monitored by directly measuring the fluorescence intensity of the tissue culture supernatant. Intracellular Gag was quantitated in parallel by direct fluorescence analysis of cell lysates, allowing us to normalize for Gag expression efficiency. The assay was validated by comparison with p24 capsid ELISA measurements, a standard method for quantifying HIV-1 particles. Optimization of conditions allowed the robust detection of particle amounts corresponding to 50 ng p24/ml in medium by fluorescence spectroscopy. Further adaptation to a multi-well format rendered the assay suitable for medium or high throughput screening of siRNA libraries to identify host cell factors involved in late stages of HIV replication, as well as for random screening approaches to search for potential inhibitors of HIV-1 assembly or release. Conclusions The fast and simple fluorescence based quantification of HIV particle release yielded reproducible results which were comparable to the well established ELISA measurements, while in addition allowing the parallel determination of intracellular Gag expression. The protocols described here

  3. The relations of particles

    International Nuclear Information System (INIS)

    Okun, L.B.

    1991-01-01

    This book presents papers on elementary particle physics, relations between various particles, and the connections between particle physics with other branches of physics. The papers include: Contemporary status and prospects of high-energy physics; Particle physics prospects; and High energy physics

  4. Particle adhesion and removal

    CERN Document Server

    Mittal, K L

    2015-01-01

    The book provides a comprehensive and easily accessible reference source covering all important aspects of particle adhesion and removal.  The core objective is to cover both fundamental and applied aspects of particle adhesion and removal with emphasis on recent developments.  Among the topics to be covered include: 1. Fundamentals of surface forces in particle adhesion and removal.2. Mechanisms of particle adhesion and removal.3. Experimental methods (e.g. AFM, SFA,SFM,IFM, etc.) to understand  particle-particle and particle-substrate interactions.4. Mechanics of adhesion of micro- and  n

  5. Review of particle properties. Particle Data Group

    International Nuclear Information System (INIS)

    1978-04-01

    This review of the properties of leptons, mesons, and baryons is an updating of Review of Particle Properties, Particle Data Group [Rev. Mod. Phys. 48 (1976) No. 2, Part II; and Supplement, Phys. Lett. 68B (1977) 1]. Data are evaluated, listed, averaged, and summarized in tables. Numerous tables, figures, and formulae of interest to particle physicists are also included. A data booklet is available

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

    Directory of Open Access Journals (Sweden)

    Dhanasooraj D

    2013-02-01

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

  7. [The true story and advantages of the famous Hepatitis B virus core particles: Outlook 2016].

    Science.gov (United States)

    Pumpens, P; Grens, E

    2016-01-01

    This review article is a continuation of the paper "Hepatitis B core particles as a universal display model: a structure-function basis for development" written by Pumpens P. and Grens E., ordered by Professor Lev Kisselev and published in FEBS Letters, 1999, 442, 1-6. The past 17 years have strengthened the paper's finding that the human hepatitis B virus core protein, along with other Hepadnaviridae family member core proteins, is a mysterious, multifunctional protein. The core gene of the Hepadnaviridae genome encodes five partially collinear proteins. The most important of these is the HBV core protein p21, or HBc. It can self-assemble by forming viral HBc particles, but also plays a crucial role in the regulation of viral replication. Since 1986, the HBc protein has been one of the first and the most successful tools of the virus-like particle (VLP) technology. Later, the woodchuck hepatitis virus core protein (WHc) was also used as a VLP carrier. The Hepadnaviridae core proteins remain favourite VLP candidates for the knowledge-based design of future vaccines, gene therapy vectors, specifically targeted nanocontainers, and other modern nanotechnological tools for prospective medical use.

  8. Structure, Immunogenicity, and Protective Mechanism of an Engineered Enterovirus 71-Like Particle Vaccine Mimicking 80S Empty Capsid.

    Science.gov (United States)

    Wang, Xiaoli; Ku, Zhiqiang; Zhang, Xiang; Ye, Xiaohua; Chen, Jinhuan; Liu, Qingwei; Zhang, Wei; Zhang, Chao; Fu, Zhenglin; Jin, Xia; Cong, Yao; Huang, Zhong

    2018-01-01

    Enterovirus 71 (EV71) is the major causative agent of severe hand, foot, and mouth disease, which affects millions of young children in the Asia-Pacific region annually. In this study, we engineered a novel EV71 virus-like particle (VLP) that lacks VP4 (therefore designated VLP ΔVP4 ) and investigated its structure, antigenicity, and vaccine potential. The cryo-electron microscopy (cryo-EM) structure of VLP ΔVP4 was reconstructed to 3.71-Å resolution. Results from structural and biochemical analyses revealed that VLP ΔVP4 resembles the end product of the viral uncoating process, the 80S empty capsid. VLP ΔVP4 is able to elicit high-titer neutralizing antibodies and to fully protect mice against lethal viral challenge. Mechanistic studies showed that, at the cellular level, the anti-VLP ΔVP4 sera exert neutralization effects at both pre- and postattachment stages by inhibiting both virus attachment and internalization, and at the molecular level, the antisera can block multiple interactions between EV71 and its key receptors. Our study gives a better understanding of EV71 capsid assembly and provides important information for the design and development of new-generation vaccines for EV71, and perhaps for other enteroviruses, as well. IMPORTANCE Enterovirus 71 (EV71) infection may lead to severe hand, foot, and mouth disease, with significant morbidity and mortality. Knowledge regarding EV71 particle assembly remains limited. Here, we report the generation and characterization of a novel EV71 virus-like particle that lacks the VP4 capsid subunit protein. This particle, termed VLP ΔVP4 , structurally mimics the 80S empty capsid, which is the end stage of EV71 uncoating. We further show that VLP ΔVP4 exhibits desirable immunogenicity and protective efficacy in proof-of-concept studies. In addition, the inhibitory mechanisms of the VLP ΔVP4 -induced antibodies are unraveled at both the cellular and molecular levels. Our work provides the first evidence of

  9. Accelerators of atomic particles

    International Nuclear Information System (INIS)

    Sarancev, V.

    1975-01-01

    A brief survey is presented of accelerators and methods of accelerating elementary particles. The principle of collective accelerating of elementary particles is clarified and the problems are discussed of its realization. (B.S.)

  10. Elementary particles and cosmology

    International Nuclear Information System (INIS)

    Audouze, J.; Paty, M.

    2000-01-01

    The universe is the most efficient laboratory of particle physics and the understanding of cosmological processes implies the knowledge of how elementary particles interact. This article recalls the mutual influences between on the one hand: astrophysics and cosmology and on the other hand: nuclear physics and particle physics. The big-bang theory relies on nuclear physics to explain the successive stages of nucleo-synthesis and the study of solar neutrinos has led to discover new aspects of this particle: it is likely that neutrinos undergo oscillations from one neutrino type to another. In some universe events such as the bursting of a super-nova, particles are released with a kinetic energy that would be impossible to reach on earth with a particle accelerator. These events are become common points of interest between astrophysicists and particle physicists and have promoted a deeper cooperation between astrophysics and elementary particle physics. (A.C.)

  11. Particle Physics Education Sites

    Science.gov (United States)

    back to home page Particle Physics Education Sites quick reference Education and Information - National Laboratory Education Programs - Women and Minorities in Physics - Other Physics Sites - Physics Alliance - Accelerators at National Laboratories icon Particle Physics Education and Information sites: top

  12. Review of particle properties

    Energy Technology Data Exchange (ETDEWEB)

    Yost, G P; Barnett, R M; Hinchliffe, I; Lynch, G R; Rittenberg, A; Ross, R R; Suzuki, M; Trippe, T G; Wohl, C G; Armstrong, B

    1988-04-14

    This review of the properties of gauge bosons, leptons, mesons, and baryons is an updating of the Review of Particle Properties, Particle Data Group (Phys. Lett. 170B (1986)). Data are evaluated, listed, averaged, and summarized in tables. We continue the more orderly set of particle names implemented in the 1986 edition. Numerous tables, figures, and formulae of interest to particle physicists are also included. A data booklet is available.

  13. Beyond the God particle

    CERN Document Server

    Lederman, Leon M

    2013-01-01

    On July 4, 2012, the long-sought Higgs Boson--aka "the God Particle"--was discovered at the world's largest particle accelerator, the LHC, in Geneva, Switzerland. On March 14, 2013, physicists at CERN confirmed it. This elusive subatomic particle forms a field that permeates the entire universe, creating the masses of the elementary particles that are the basic building blocks of everything in the known world--from viruses to elephants, from atoms to quasars.

  14. Particle physics and cosmology

    International Nuclear Information System (INIS)

    Schramm, D.N.; Turner, M.S.

    1982-06-01

    work is described in these areas: cosmological baryon production; cosmological production of free quarks and other exotic particle species; the quark-hadron transition in the early universe; astrophysical and cosmological constraints on particle properties; massive neutrinos; phase transitions in the early universe; and astrophysical implications of an axion-like particle

  15. Particle-nuclear intersections

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    With the traditional distinctions between particle and nuclear physics becoming increasing blurred, the Fifth Conference on the Intersections of Particle and Nuclear Physics, held from May 31 to June 6 in St. Petersburg, Florida, brought together particle and nuclear physicists to discuss common research efforts and to define and plan a united approach

  16. Review of particle properties

    International Nuclear Information System (INIS)

    Trippe, T.G.; Barbaro-Galtieri, A.; Kelly, R.L.; Rittenberg, A.; Rosenfeld, A.H.; Yost, G.P.; Barash-Schmidt, N.; Bricman, C.; Hemingway, R.J.; Losty, M.J.; Roos, M.; Chaloupka, V.; Armstrong, B.

    1976-01-01

    This review of the properties of leptons, mesons, and baryons is an updating of Review of Particle Properties, Particle Data Group [Phys. Letters 50B, No.1 (1974), and Supplement, Rev. Mod. Phys. 47 (1975) 535]. Data are evaluated, listed, averaged, and summarized in tables. Numerous tables, figures, and formulae of interest to particle physicists are also included. A data booklet is available

  17. Atomic Particle Detection

    Energy Technology Data Exchange (ETDEWEB)

    Hellman, Hal

    1970-01-01

    This booklet tells how scientists observe the particles and electromagnetic radiation that emerges from an atomic nucleus. The equipment used falls into two general categories: counters which count each particle as it passes by, and track detectors, which make a photographic record of the particle's track.

  18. Study of particle swarm optimization particle trajectories

    CSIR Research Space (South Africa)

    Van den Bergh, F

    2006-01-01

    Full Text Available . These theoretical studies concentrate mainly on simplified PSO systems. This paper overviews current theoretical studies, and extend these studies to investigate particle trajectories for general swarms to include the influence of the inertia term. The paper also...

  19. Light scattering by cosmic particles

    NARCIS (Netherlands)

    Hovenier, J.W.; Min, M.

    2008-01-01

    We define cosmic particles as particles outside the Earth. Two types of cosmic particles can be distinguished, namely liquid and solid particles. The solid particles are often called grains or cosmic dust particles. Cosmic particles occur in a great variety of astronomical objects and environments.

  20. Slowing of charged particles by particle methods

    International Nuclear Information System (INIS)

    Mercier, B.

    1985-03-01

    We review some facts about particle methods for solving linear hyperbolic equations. We show how one gets an evaluation of integral quantities like: ∫ u(x,t) zeta(x,t) dxdt where u denotes the solution and zeta an arbitrary weight function. Then, we apply the method to the equation describing charged particle transport in a plasma with emphasis on the evaluation of energy deposition on ions and electrons [fr

  1. Elementary particles. 2

    International Nuclear Information System (INIS)

    Ranft, G.; Ranft, J.

    1977-01-01

    In this part the subject is covered under the following headings, methods for producing high-energy particles; interaction of high-energy particles with matter; methods for the detection of high-energy particles; symmetry properties and conservation laws; quantum number and selection rules; theorem of scattering behaviour at asymptotically high energies; statistical methods in elementary particle physics; interaction of high-energy particles with nuclei; relations of high-energy physics to other branches of science and its response to engineering. Intended as information on high-energy physics for graduate students and research workers familiar with the fundamentals of classical and quantum physics

  2. Review of particle properties

    International Nuclear Information System (INIS)

    Montanet, L.; Gieselmann, K. Technical Associate; Barnett, R.M.; Groom, D.E.; Trippe, T.G.; Wohl, C.G.; Armstrong, B. Technical Associate; Wagman, G.S. Technical Associate; Murayama, H.; Stone, J.; Hernandez, J.J.; Porter, F.C.; Morrison, R.J.; Manohar, A.; Aguilar-Benitez, M.; Caso, C.; Lantero, P. Technical Associate; Crawford, R.L.; Roos, M.; Toernqvist, N.A.; Hayes, K.G.; Hoehler, G.

    1994-01-01

    This biennial review summarizes much of Particle Physics. Using data from previous editions, plus 2300 new measurements from 700 papers, we list evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, monopoles, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review

  3. Fluidization of spherocylindrical particles

    Science.gov (United States)

    Mahajan, Vinay V.; Nijssen, Tim M. J.; Fitzgerald, Barry W.; Hofman, Jeroen; Kuipers, Hans; Padding, Johan T.

    2017-06-01

    Multiphase (gas-solid) flows are encountered in numerous industrial applications such as pharmaceutical, food, agricultural processing and energy generation. A coupled computational fluid dynamics (CFD) and discrete element method (DEM) approach is a popular way to study such flows at a particle scale. However, most of these studies deal with spherical particles while in reality, the particles are rarely spherical. The particle shape can have significant effect on hydrodynamics in a fluidized bed. Moreover, most studies in literature use inaccurate drag laws because accurate laws are not readily available. The drag force acting on a non-spherical particle can vary considerably with particle shape, orientation with the flow, Reynolds number and packing fraction. In this work, the CFD-DEM approach is extended to model a laboratory scale fluidized bed of spherocylinder (rod-like) particles. These rod-like particles can be classified as Geldart D particles and have an aspect ratio of 4. Experiments are performed to study the particle flow behavior in a quasi-2D fluidized bed. Numerically obtained results for pressure drop and bed height are compared with experiments. The capability of CFD-DEM approach to efficiently describe the global bed dynamics for fluidized bed of rod-like particles is demonstrated.

  4. Monosodium titanate particle characterization

    International Nuclear Information System (INIS)

    Chandler, G.T.; Hobbs, D.T.

    1993-01-01

    A characterization study was performed on monosodium titanate (MST) particles to determine the effect of high shear forces expected from the In-Tank Precipitation (ITP) process pumps on the particle size distribution. The particles were characterized using particle size analysis and scanning electron microscopy (SEM). No significant changes in particle size distributions were observed between as-received MST and after 2--4 hours of shearing. Both as-received and sheared MST particles contained a large percentage of porosity with pore sizes on the order of 500 to 2,000 Angstroms. Because of the large percentage of porosity, the overall surface area of the MST is dominated by the internal surfaces. The uranium and plutonium species present in the waste solution will have access to both interior and exterior surfaces. Therefore, uranium and plutonium loading should not be a strong function of MST particle size

  5. Plant-derived chimeric virus particles for the diagnosis of primary Sjögren syndrome

    Directory of Open Access Journals (Sweden)

    Elisa eTinazzi

    2015-12-01

    Full Text Available Plants are ideal for the production of protein-based nanomaterials because they synthesize and assemble complex multimeric proteins that cannot be expressed efficiently using other platforms. Plant viruses can be thought of as self-replicating proteinaceous nanomaterials generally stable and easily produced in high titers. We used Potato virus X (PVX chimeric virus particles (CVPs and Cowpea mosaic virus (CPMV empty virus-like particles (eVLPs to display a linear peptide (lipo derived from human lipocalin , which is immunodominant in Sjögren’s syndrome (SjS and is thus recognized by autoantibodies in SjS patient serum. These virus-derived nanoparticles (VNPs were thus used to develop a diagnostic assay for SjS based on a direct enzyme linked immunosorbent assay (ELISA format. We found that PVX-lipo formulations were more sensitive than the chemically synthesized immunodominant peptide and equally specific when used to distinguish between healthy individuals and SjS patients. Our novel assay therefore allows the diagnosis of SjS using a simple, low-invasive serum test, contrasting with the invasive labial biopsy required for current tests. Our results demonstrate that nanomaterials based on plant viruses can be used as diagnostic reagents for SjS, and could also be developed for the diagnosis of other diseases.

  6. Intranasal P particle vaccine provided partial cross-variant protection against human GII.4 norovirus diarrhea in gnotobiotic pigs.

    Science.gov (United States)

    Kocher, Jacob; Bui, Tammy; Giri-Rachman, Ernawati; Wen, Ke; Li, Guohua; Yang, Xingdong; Liu, Fangning; Tan, Ming; Xia, Ming; Zhong, Weiming; Jiang, Xi; Yuan, Lijuan

    2014-09-01

    Noroviruses (NoVs) are the leading cause of nonbacterial acute gastroenteritis worldwide in people of all ages. The P particle is a novel vaccine candidate derived from the protruding (P) domain of the NoV VP1 capsid protein. This study utilized the neonatal gnotobiotic pig model to evaluate the protective efficacies of primary infection, P particles, and virus-like particles (VLPs) against NoV infection and disease and the T cell responses to these treatments. Pigs either were vaccinated intranasally with GII.4/1997 NoV (VA387)-derived P particles or VLPs or were inoculated orally with a GII.4/2006b NoV variant. At postinoculation day (PID) 28, pigs either were euthanized or were challenged with the GII.4/2006b variant and monitored for diarrhea and virus shedding for 7 days. The T cell responses in intestinal and systemic lymphoid tissues were examined. Primary NoV infection provided 83% homologous protection against diarrhea and 49% homologous protection against virus shedding, while the P particle and VLP vaccines provided cross-variant protection (47% and 60%, respectively) against diarrhea. The protection rates against diarrhea are significantly inversely correlated with T cell expansion in the duodenum and are positively correlated with T cell expansion in the ileum and spleen. The P particle vaccine primed for stronger immune responses than VLPs, including significantly higher numbers of activated CD4+ T cells in all tissues, gamma interferon-producing (IFN-γ+) CD8+ T cells in the duodenum, regulatory T cells (Tregs) in the blood, and transforming growth factor β (TGF-β)-producing CD4+ CD25- FoxP3+ Tregs in the spleen postchallenge, indicating that P particles are more immunogenic than VLPs at the same dose. In conclusion, the P particle vaccine is a promising vaccine candidate worthy of further development. The norovirus (NoV) P particle is a vaccine candidate derived from the protruding (P) domain of the NoV VP1 capsid protein. P particles can be

  7. Lecture II. Charmed particle spectroscopy

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    The discussion of charmed particle spectroscopy covers the particle properties and interrelations from a charmed quark composition point of view including SU(4)-symmetry generalities, mesons, baryons, charmed particle masses, and decays of charmed particles. 6 references

  8. Methods for forming particles

    Science.gov (United States)

    Fox, Robert V.; Zhang, Fengyan; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin

    2016-06-21

    Single source precursors or pre-copolymers of single source precursors are subjected to microwave radiation to form particles of a I-III-VI.sub.2 material. Such particles may be formed in a wurtzite phase and may be converted to a chalcopyrite phase by, for example, exposure to heat. The particles in the wurtzite phase may have a substantially hexagonal shape that enables stacking into ordered layers. The particles in the wurtzite phase may be mixed with particles in the chalcopyrite phase (i.e., chalcopyrite nanoparticles) that may fill voids within the ordered layers of the particles in the wurtzite phase thus produce films with good coverage. In some embodiments, the methods are used to form layers of semiconductor materials comprising a I-III-VI.sub.2 material. Devices such as, for example, thin-film solar cells may be fabricated using such methods.

  9. LHCb unveils new particles

    CERN Multimedia

    Stefania Pandolfi

    2016-01-01

    The LHCb collaboration announces the observation of four “exotic” particles from its analysis of the LHC data.   The LHCb experimental cavern. On 28 June, the LHCb collaboration reported the observation of three new "exotic" particles and confirmation of the existence of a fourth one in data from the LHC. These particles each appear to be formed by four quarks (the fundamental constituents of the matter inside all the atoms of the universe): two quarks and two antiquarks (that is, a tetraquark). Due to their non-standard quark content, the newly observed particles have been included in the broad category of so-called exotic particles, although their exact theoretical interpretation is still under study.            The quark model, proposed by Murray Gell-Mann and George Zweig in 1964, is considered to be the most valid scheme for the classification of hadrons (all the composite particles) that has been fou...

  10. Particle Swarm Optimization

    Science.gov (United States)

    Venter, Gerhard; Sobieszczanski-Sobieski Jaroslaw

    2002-01-01

    The purpose of this paper is to show how the search algorithm known as particle swarm optimization performs. Here, particle swarm optimization is applied to structural design problems, but the method has a much wider range of possible applications. The paper's new contributions are improvements to the particle swarm optimization algorithm and conclusions and recommendations as to the utility of the algorithm, Results of numerical experiments for both continuous and discrete applications are presented in the paper. The results indicate that the particle swarm optimization algorithm does locate the constrained minimum design in continuous applications with very good precision, albeit at a much higher computational cost than that of a typical gradient based optimizer. However, the true potential of particle swarm optimization is primarily in applications with discrete and/or discontinuous functions and variables. Additionally, particle swarm optimization has the potential of efficient computation with very large numbers of concurrently operating processors.

  11. Music of elementary particles

    International Nuclear Information System (INIS)

    Sternheimer, J.

    1983-01-01

    This Note offers a new point of view on particle masses. It is shown that they are distributed following a musical scale, the chromatic tempered scale -for stable particles- subdivided into microintervals including unstable particles. A theoretical explanation, based on causality, allows one also to calculate their global distribution along the mass scale, in agreement with experiment, and indicating the existence of ''musical'' laws in the vibratory organisation of matter [fr

  12. Low energy particle composition

    International Nuclear Information System (INIS)

    Gloeckler, G.

    1975-01-01

    More than 50 papers presented at this Conference dealt with the composition of low energy particles. The topics can be divided roughly into two broad categories. The first is the study of the energy spectra and composition of the steady or 'quiet-time' particle flux, whose origin is at this time unknown. The second category includes the study of particles and photons which are associated with solar flares or active regions on the sun. (orig.) [de

  13. Music of elementary particles

    Energy Technology Data Exchange (ETDEWEB)

    Sternheimer, J.

    1983-12-12

    This note offers a new point of view on particle masses. It is shown that they are distributed following a musical scale, the chromatic tempered scale -for stable particles- subdivided into microintervals including unstable particles. A theoretical explanation, based on causality, allows one also to calculate their global distribution along the mass scale, in agreement with experiment, and indicating the existence of ''musical'' laws in the vibratory organisation of matter.

  14. Review of particle properties

    International Nuclear Information System (INIS)

    Bricman, C.; Dionisi, C.; Hemingway, R.J.; Mazzucato, M.; Montanet, L.; Barash-Schmidt, N.; Crawford, R.C.; Roos, M.; Barbaro-Galtieri, A.; Horne, C.P.; Kelly, R.L.; Losty, M.J.; Rittenberg, A.; Trippe, T.G.; Yost, G.P.; Armstrong, B.

    1978-01-01

    This review of the properties of leptons, mesons, and baryons is an updating of Review of Particle Properties, Particle Data Group [Rev. Mod. Phys. 48 (1976) No. 2, Part II; and Supplement, Phys. Lett. 68B (1977) 1]. Data are evaluated, listed, averaged, and summarized in tables. Numerous tables, figures, and formulae of interest to particle physicists are also included. A data booklet is available. (Auth.)

  15. Condensed elementary particle matter

    International Nuclear Information System (INIS)

    Kajantie, K.

    1996-01-01

    Quark matter is a special case of condensed elementary particle matter, matter governed by the laws of particle physics. The talk discusses how far one can get in the study of particle matter by reducing the problem to computations based on the action. As an example the computation of the phase diagram of electroweak matter is presented. It is quite possible that ultimately an antireductionist attitude will prevail: experiments will reveal unpredicted phenomena not obviously reducible to the study of the action. (orig.)

  16. Particle correlations at ALICE

    Energy Technology Data Exchange (ETDEWEB)

    Erazmus, B.; Lednicky, R.; Lyuboshitz, V.; Martin, L.; Mikhailov, K.; Pluta, J.; Sinyukov, Yu.; Stavinsky, A.; Werner, K

    1998-12-31

    The ability of the ALICE detector for determination of the space-time characteristics of particle production in heavy-ion collisions at LHC from measurements of the correlation functions of identical and non-identical particles at small relative velocities is discussed. The possibility to use the correlations of non-identical particles for a direct determination of the delays in emission of various particle species at time scales as small as 10{sup -23} s is demonstrated. The influence of the multi-boson effects on pion multiplicities, single-pion spectra and two-pion correlation functions is discussed. (author) 63 refs.

  17. Particle Correlations at LEP

    CERN Document Server

    Kress, Thomas

    2002-01-01

    Particle correlations are extensively studied to obtain information about the dynamics of hadron production. From 1989 to 2000 the four LEP collaborations recorded more than 16 million hadronic Z0 decays and several thousand W+W- events. In Z0 decays, two-particle correlations were analysed in detail to study Bose-Einstein and Fermi-Dirac correlations for various particle species. In fully-hadronic W+W- decays, particle correlations were used to study whether the two W bosons decay independently. A review of selected results is presented.

  18. Particle Image Velocimetry

    DEFF Research Database (Denmark)

    Zhang, Chen; Vasilevskis, Sandijs; Kozlowski, Bartosz

    Particle image velocimetry (PIV) is a non-intrusive, whole filed optical method providing instantaneous velocity information in fluids. The flow is seeded with tracer particles. The particles are illuminated in the target area with a light sheet at least twice within a short time interval....... The camera images the target area and captures each light pulse in separate image frames. The displacement of the particle between the light pulses can be used to determine the velocity vectors. This guideline introduces the principle of the PIV system and the system configuration. The measurement procedure...

  19. Review of particle properties

    International Nuclear Information System (INIS)

    Hikasa, K.; Hagiwara, K.; Kawabata, S.; Barnett, R.M.; Groom, D.E.; Trippe, T.G.; Wohl, C.G.; Yost, G.P.; Armstrong, B. Technical Associate; Wagman, G.S. Technical Associate; Stone, J.; Porter, F.C.; Morrison, R.J.; Cutkosky, R.E.; Montanet, L.; Gieselmann, K. Technical Associate; Aguilar-Benitez, M.; Caso, C.; Crawford, R.L.; Roos, M.; Toernqvist, N.A.; Hayes, K.G.; Hoehler, G.; Manley, D.M.

    1992-01-01

    In this Review, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, the top quark, heavy neutrinos, monopoles, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. A booklet is available containing the Summary Tables and abbreviated versions of some other sections of this full Review

  20. Elementary particle theory

    International Nuclear Information System (INIS)

    Marciano, W.J.

    1984-12-01

    The present state of the art in elementary particle theory is reviewed. Topics include quantum electrodynamics, weak interactions, electroweak unification, quantum chromodynamics, and grand unified theories. 113 references

  1. Particle physics experiments 1983

    International Nuclear Information System (INIS)

    Stuart, G.W.

    1983-01-01

    The report describes work carried out in 1983 on experiments approved by the Particle Physics Experiments Selection Panel. The contents consist of unedited contributions from each experiment. (author)

  2. Particle Physics & Astrophysics (PPA)

    Data.gov (United States)

    Federal Laboratory Consortium — Scientists at SLAC's Particle Physics and Astrophysics develop and utilize unique instruments from underground to outer space to explore the ultimate laws of nature...

  3. Particle Swarm Optimisation with Spatial Particle Extension

    DEFF Research Database (Denmark)

    Krink, Thiemo; Vesterstrøm, Jakob Svaneborg; Riget, Jacques

    2002-01-01

    In this paper, we introduce spatial extension to particles in the PSO model in order to overcome premature convergence in iterative optimisation. The standard PSO and the new model (SEPSO) are compared w.r.t. performance on well-studied benchmark problems. We show that the SEPSO indeed managed...

  4. Violation of Particle Anti-particle Symmetry

    CERN Multimedia

    CERN. Geneva

    2001-01-01

    Symmetry is a fundamental concept which can be found in the whole range of human activities e. g. from arts to science. The beauty of a statues is often related to its symmetric form. In physics, all the laws are related to some sort of symmetry. Equally important is a small breakdown ofsymmetry. Even for the case of a statue, its beauty might be enhanced by introducing small distortions. In this course, we investigate the role symmetry in the world of elementary particles. Some symmetries found there are very similar to those which can be seen in our daily life, while others are more exotic and related to the quantum nature of the elementary particles. Our particular focus ismade on symmetry and its violation between the matter and anti-matter, known as CP violation. It is experimentally well established that particleand anti-particle behave a tiny bit differently in the world of elementary particles. We discuss how this would be explained and how we can extendour knowledge. Evolution of our universe is stro...

  5. Depth Filters Containing Diatomite Achieve More Efficient Particle Retention than Filters Solely Containing Cellulose Fibers.

    Science.gov (United States)

    Buyel, Johannes F; Gruchow, Hannah M; Fischer, Rainer

    2015-01-01

    The clarification of biological feed stocks during the production of biopharmaceutical proteins is challenging when large quantities of particles must be removed, e.g., when processing crude plant extracts. Single-use depth filters are often preferred for clarification because they are simple to integrate and have a good safety profile. However, the combination of filter layers must be optimized in terms of nominal retention ratings to account for the unique particle size distribution in each feed stock. We have recently shown that predictive models can facilitate filter screening and the selection of appropriate filter layers. Here we expand our previous study by testing several filters with different retention ratings. The filters typically contain diatomite to facilitate the removal of fine particles. However, diatomite can interfere with the recovery of large biopharmaceutical molecules such as virus-like particles and aggregated proteins. Therefore, we also tested filtration devices composed solely of cellulose fibers and cohesive resin. The capacities of both filter types varied from 10 to 50 L m(-2) when challenged with tobacco leaf extracts, but the filtrate turbidity was ~500-fold lower (~3.5 NTU) when diatomite filters were used. We also tested pre-coat filtration with dispersed diatomite, which achieved capacities of up to 120 L m(-2) with turbidities of ~100 NTU using bulk plant extracts, and in contrast to the other depth filters did not require an upstream bag filter. Single pre-coat filtration devices can thus replace combinations of bag and depth filters to simplify the processing of plant extracts, potentially saving on time, labor and consumables. The protein concentrations of TSP, DsRed and antibody 2G12 were not affected by pre-coat filtration, indicating its general applicability during the manufacture of plant-derived biopharmaceutical proteins.

  6. Depth filters containing diatomite achieve more efficient particle retention than filters solely containing cellulose fibers

    Directory of Open Access Journals (Sweden)

    Johannes Felix Buyel

    2015-12-01

    Full Text Available The clarification of biological feed stocks during the production of biopharmaceutical proteins is challenging when large quantities of particles must be removed, e.g. when processing crude plant extracts. Single-use depth filters are often preferred for clarification because they are simple to integrate and have a good safety profile. However, the combination of filter layers must be optimized in terms of nominal retention ratings to account for the unique particle size distribution in each feed stock. We have recently shown that predictive models can facilitate filter screening and the selection of appropriate filter layers. Here we expand our previous study by testing several filters with different retention ratings. The filters typically contain diatomite to facilitate the removal of fine particles. However, diatomite can interfere with the recovery of large biopharmaceutical molecules such as virus-like particles and aggregated proteins. Therefore, we also tested filtration devices composed solely of cellulose fibers and cohesive resin. The capacities of both filter types varied from 10 to 50 L m-2 when challenged with tobacco leaf extracts, but the filtrate turbidity was ~500-fold lower (~3.5 NTU when diatomite filters were used. We also tested pre coat filtration with dispersed diatomite, which achieved capacities of up to 120 L m-2 with turbidities of ~100 NTU using bulk plant extracts, and in contrast to the other depth filters did not require an upstream bag filter. Single pre-coat filtration devices can thus replace combinations of bag and depth filters to simplify the processing of plant extracts, potentially saving on time, labor and consumables. The protein concentrations of TSP, DsRed and antibody 2G12 were not affected by pre-coat filtration, indicating its general applicability during the manufacture of plant-derived biopharmaceutical proteins.

  7. Particle size determination

    International Nuclear Information System (INIS)

    Burr, K.J.

    1979-01-01

    A specification is given for an apparatus to provide a completely automatic testing cycle to determine the proportion of particles of less than a predetermined size in one of a number of fluid suspensions. Monitoring of the particle concentration during part of the process can be carried out by an x-ray source and detector. (U.K.)

  8. Elementary particle theory

    CERN Document Server

    Stefanovich, Eugene

    2018-01-01

    This book introduces notation, terminology, and basic ideas of relativistic quantum theories. The discussion proceeds systematically from the principle of relativity and postulates of quantum logics to the construction of Poincaré invariant few-particle models of interaction and scattering. It is the first of three volumes formulating a consistent relativistic quantum theory of interacting charged particles.

  9. History of Particle Physics

    Science.gov (United States)

    back to history page Back Particle Physics Timeline For over two thousand years people have thought the Standard Model. We invite you to explore this history of particle physics with a focus on the : Quantum Theory 1964 - Present: The Modern View (the Standard Model) back to history page Back Sections of

  10. Light particles in turbulence

    NARCIS (Netherlands)

    Nagendra Prakash, Vivek

    2013-01-01

    This thesis deals with the broad topic of particles in turbulence, which has applications in a diverse number of fields. A vast majority of fluid flows found in nature and in the industry are turbulent and contain dispersed elements. In this thesis, I have focused on light particles (air bubbles in

  11. Particle physics instrumentation

    International Nuclear Information System (INIS)

    Riegler, W.

    2011-01-01

    This report summarizes a series of three lectures aimed at giving an overview of basic particle detection principles, the interaction of particles with matter, the application of these principles in modern detector systems, as well techniques to read out detector signals in high-rate experiments. (author)

  12. Particles, contacts, bulk behavior

    NARCIS (Netherlands)

    Luding, Stefan; Tomas, J.

    2014-01-01

    Granular matter consists of discrete “particles”. These can be separate sand-grains, agglomerates (made of many primary particles), or solid materials like rock, composites, or metal-alloys—all with particulate inhomogeneous, possibly anisotropic micro-structure. Particles can be as small as

  13. Particle Astrophysics of Neutrinos

    Indian Academy of Sciences (India)

    Amol Dighe

    Energy spectra of neutrino sources. ASPERA. Page 4. Some unique features of neutrinos. The second most abundant particles in the universe. Cosmic microwave background photons: 400 / cm3. Cosmic background neutrinos: 330 / cm3. The lightest massive particles. A million times lighter than the electron. No direct mass ...

  14. Astro-particle-physics

    International Nuclear Information System (INIS)

    Salam, A.

    1985-09-01

    Opening remarks at the Fourth Marcel Grossman Meeting, 17-21 June 1985, in Rome, Italy, are reported. The meeting was concerned with the symbiosis of cosmology and particle physics. Numerous connections between work in particle physics and cosmology, in both experimental and theoretical areas, are pointed out

  15. When is a particle

    International Nuclear Information System (INIS)

    Drell, S.D.

    1978-01-01

    The concept of elementary constituents or ultimate building blocks of nature in recent years is reviewed. The quark hypothesis, neutrinos, color, hard collisions, psi and other recent resonances, flavor, quantum chromodynamics, the tau particle, and particle structure are among the ideas considered. 22 references

  16. Concepts of particle physics

    International Nuclear Information System (INIS)

    Gottfried, K.; Weisskopf, V.F.

    1984-01-01

    This volume elucidates basic and well-established concepts of particle physics for the autodidact who is curious about recent developments in fundamental physics. Elementary quantum mechanics is a background must. Contents, abridged: The evolution of the particle concept before the advent of quantum mechanics. Nonrelativistic quantum mechanics and atomic physics. Relativistic quantum theory. Nuclear phenomena. Subnuclear phenomena. Index

  17. RESEARCH IN PARTICLE PHYSICS

    Energy Technology Data Exchange (ETDEWEB)

    Kearns, Edward [Boston Universiy

    2013-07-12

    This is the final report for the Department of Energy Grant to Principal Investigators in Experimental and Theoretical Particle Physics at Boston University. The research performed was in the Energy Frontier at the LHC, the Intensity Frontier at Super-Kamiokande and T2K, the Cosmic Frontier and detector R&D in dark matter detector development, and in particle theory.

  18. Optics of charged particles

    International Nuclear Information System (INIS)

    Wollnik, H.

    1987-01-01

    Suitable for both the specialist and non-specialist, this book develops all statements from first principles. Key chapters of the book focus upon how to design particle-optical systems, the systematics of image abberations, the effects of fringing fields, systematics of beams, and solutions for particle-optical systems. An undergraduate background in physics and mathematics is required for this work

  19. Introduction to particle physics

    International Nuclear Information System (INIS)

    Zitoun, R.

    2000-01-01

    This book proposes an introduction to particle physics that requires only a high-school level mathematical knowledge. Elementary particles (leptons, quarks, bosons) are presented according to a modern view taking into account of their symmetries and interactions. The author shows how physicists have elaborated the standard model and what are its implications in cosmology. (J.S.)

  20. Microchip Coulter particle counter

    DEFF Research Database (Denmark)

    Larsen, Ulrik Darling; Blankenstein, Gert; Branebjerg, J.

    1997-01-01

    This paper presents a micro device employing the Coulter principle for counting and sizing of living cells and particles in liquid suspension. The microchip Coulter particle counter (μCPC) has been employed in a planar silicon structure covered with glass, which enables detailed observation during...

  1. Interactive Terascale Particle Visualization

    Science.gov (United States)

    Ellsworth, David; Green, Bryan; Moran, Patrick

    2004-01-01

    This paper describes the methods used to produce an interactive visualization of a 2 TB computational fluid dynamics (CFD) data set using particle tracing (streaklines). We use the method introduced by Bruckschen et al. [2001] that pre-computes a large number of particles, stores them on disk using a space-filling curve ordering that minimizes seeks, and then retrieves and displays the particles according to the user's command. We describe how the particle computation can be performed using a PC cluster, how the algorithm can be adapted to work with a multi-block curvilinear mesh, and how the out-of-core visualization can be scaled to 296 billion particles while still achieving interactive performance on PG hardware. Compared to the earlier work, our data set size and total number of particles are an order of magnitude larger. We also describe a new compression technique that allows the lossless compression of the particles by 41% and speeds the particle retrieval by about 30%.

  2. Teaching particle physics

    CERN Document Server

    Hanley, P

    2000-01-01

    Particle physics attracts many students who hear of news from CERN or elsewhere in the media. This article examines which current A-level syllabuses include which bits of particle physics and surveys the many different types of resource available to teachers and students. (0 refs).

  3. Particles, imaging and nuclei

    International Nuclear Information System (INIS)

    Harris, J.

    1986-01-01

    The book on particles, imaging and nuclei is one of the Background Readers for the Revised Nuffield Advanced Physics course. The contents contain five educational articles, which extend concepts covered in the course and examine recent developments in physics. Four of the articles on:- particles and the forces of nature, radioisotopes, lasers probe the atomic nucleus, and nuclear history, are indexed separately. (UK)

  4. Compact particle accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Elizondo-Decanini, Juan M.

    2017-08-29

    A compact particle accelerator having an input portion configured to receive power to produce particles for acceleration, where the input portion includes a switch, is provided. In a general embodiment, a vacuum tube receives particles produced from the input portion at a first end, and a plurality of wafer stacks are positioned serially along the vacuum tube. Each of the plurality of wafer stacks include a dielectric and metal-oxide pair, wherein each of the plurality of wafer stacks further accelerate the particles in the vacuum tube. A beam shaper coupled to a second end of the vacuum tube shapes the particles accelerated by the plurality of wafer stacks into a beam and an output portion outputs the beam.

  5. DEM Particle Fracture Model

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Boning [Univ. of Colorado, Boulder, CO (United States); Herbold, Eric B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Homel, Michael A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Regueiro, Richard A. [Univ. of Colorado, Boulder, CO (United States)

    2015-12-01

    An adaptive particle fracture model in poly-ellipsoidal Discrete Element Method is developed. The poly-ellipsoidal particle will break into several sub-poly-ellipsoids by Hoek-Brown fracture criterion based on continuum stress and the maximum tensile stress in contacts. Also Weibull theory is introduced to consider the statistics and size effects on particle strength. Finally, high strain-rate split Hopkinson pressure bar experiment of silica sand is simulated using this newly developed model. Comparisons with experiments show that our particle fracture model can capture the mechanical behavior of this experiment very well, both in stress-strain response and particle size redistribution. The effects of density and packings o the samples are also studied in numerical examples.

  6. Particle-assisted wetting

    International Nuclear Information System (INIS)

    Xu Hui; Yan Feng; Tierno, Pietro; Marczewski, Dawid; Goedel, Werner A

    2005-01-01

    Wetting of a solid surface by a liquid is dramatically impeded if either the solid or the liquid is decorated by particles. Here it is shown that in the case of contact between two liquids the opposite effect may occur; mixtures of a hydrophobic liquid and suitable particles form wetting layers on a water surface though the liquid alone is non-wetting. In these wetting layers, the particles adsorb to, and partially penetrate through, the liquid/air and/or the liquid/water interface. This formation of wetting layers can be explained by the reduction in total interfacial energy due to the replacement of part of the fluid/fluid interfaces by the particles. It is most prominent if the contact angles at the fluid/fluid/particle contact lines are close to 90 0

  7. Fermilab | Science | Particle Physics | Benefits of Particle Physics

    Science.gov (United States)

    Photos and videos Latest news For the media Particle Physics Neutrinos Fermilab and the LHC Dark matter initiatives Research and development Key discoveries Benefits of particle physics Particle Accelerators society Particle Physics 101 Science of matter, energy, space and time How particle physics discovery

  8. Linear particle accelerator

    International Nuclear Information System (INIS)

    Richards, J.A.

    1977-01-01

    A linear particle accelerator which provides a pulsed beam of charged particles of uniform energy is described. The accelerator is in the form of an evacuated dielectric tube, inside of which a particle source is located at one end of the tube, with a target or window located at the other end of the dielectric tube. Along the length of the tube are externally located pairs of metal plates, each insulated from each other in an insulated housing. Each of the plates of a pair are connected to an electrical source of voltage of opposed polarity, with the polarity of the voltage of the plates oriented so that the plate of a pair, nearer to the particle source, is of the opposed polarity to the charge of the particle emitted by the source. Thus, a first plate about the tube located nearest the particle source, attracts a particle which as it passes through the tube past the first plate is then repelled by the reverse polarity of the second plate of the pair to continue moving towards the target

  9. Charged particle detector

    International Nuclear Information System (INIS)

    Hagen, R.D.

    1975-01-01

    A device for detecting the emission of charged particles from a specimen is described. The specimen is placed within an accumulator means which statically accumulates any charged particles emitted from the specimen. The accumulator means is pivotally positioned between a first capacitor plate having a positive electrical charge and a second capacitor plate having a negative electrical charge. The accumulator means is attracted to one capacitor plate and repelled from the other capacitor plate by an amount proportional to the amount and intensity of charged particles emitted by the specimen. (auth)

  10. Cosmology and particle physics

    International Nuclear Information System (INIS)

    Barrow, J.D.

    1982-01-01

    A brief overview is given of recent work that integrates cosmology and particle physics. The observational data regarding the abundance of matter and radiation in the Universe is described. The manner in which the cosmological survival density of stable massive particles can be calculated is discussed along with the process of cosmological nucleosynthesis. Several applications of these general arguments are given with reference to the survival density of nucleons, neutrinos and unconfined fractionally charge particles. The use of nucleosynthesis to limit the number of lepton generations is described together with the implications of a small neutrino mass for the origin of galaxies and clusters. (Auth.)

  11. Particles near threshold

    International Nuclear Information System (INIS)

    Bhattacharya, T.; Willenbrock, S.

    1993-01-01

    We propose returning to the definition of the width of a particle in terms of the pole in the particle's propagator. Away from thresholds, this definition of width is equivalent to the standard perturbative definition, up to next-to-leading order; however, near a threshold, the two definitions differ significantly. The width as defined by the pole position provides more information in the threshold region than the standard perturbative definition and, in contrast with the perturbative definition, does not vanish when a two-particle s-wave threshold is approached from below

  12. Sources for charged particles

    International Nuclear Information System (INIS)

    Arianer, J.

    1997-01-01

    This document is a basic course on charged particle sources for post-graduate students and thematic schools on large facilities and accelerator physics. A simple but precise description of the creation and the emission of charged particles is presented. This course relies on every year upgraded reference documents. Following relevant topics are considered: electronic emission processes, technological and practical considerations on electron guns, positron sources, production of neutral atoms, ionization, plasma and discharge, different types of positive and negative ion sources, polarized particle sources, materials for the construction of ion sources, low energy beam production and transport. (N.T.)

  13. Cosmology and particle physics

    Energy Technology Data Exchange (ETDEWEB)

    Steigman, G [California Univ., Santa Barbara (USA). Inst. for Theoretical Physics; Bartol Research Foundation, Newark, Delaware (USA))

    1982-01-29

    The cosmic connections between physics on the very largest and very smallest scales are reviewed with an emphasis on the symbiotic relation between elementary particle physics and cosmology. After a review of the early Universe as a cosmic accelerator, various cosmological and astrophysical constraints on models of particle physics are outlined. To illustrate this approach to particle physics via cosmology, reference is made to several areas of current research: baryon non-conservation and baryon asymmetry; free quarks, heavy hadrons and other exotic relics; primordial nucleosynthesis and neutrino masses.

  14. Particle physics and cosmology

    International Nuclear Information System (INIS)

    Srednicki, M.

    1990-01-01

    At least eighty percent of the mass of the universe consists of some material which, unlike ordinary matter, neither emits nor absorbs light. This book collects key papers related to the discovery of this astonishing fact and its profound implications for astrophysics, cosmology, and the physics of elementary particles. The book focusses on the likely possibility that the dark matter is composed of an as yet undiscovered elementary particle, and examines the boundaries of our present knowledge of the properties such a particle must possess. (author). refs.; figs.; tabs

  15. Elementary particle interactions

    International Nuclear Information System (INIS)

    Bugg, W.M.; Condo, G.T.; Handler, T.; Hart, E.L.; Read, K.; Ward, B.F.L.

    1992-10-01

    Work continues on strange particle production in weak interactions using data from a high-energy neutrino exposure in a freon bubble chamber. Meson photoproduction has also consumed considerable effort. Detector research and development activities have been carried out

  16. Particle physics experiments 1989

    International Nuclear Information System (INIS)

    Bairstow, R.

    1990-01-01

    This report describes work carried out in 1989 on experiments approved by the Particle Physics Experiments Selection Panel of Rutherford Appleton Laboratory. The contents consist of unedited contributions from each experiment. (author)

  17. The Acquisition of Particles

    African Journals Online (AJOL)

    process of language acquisition on the basis of linguistic evidence the child is exposed to. ..... particle verbs are recognized in language processing differs from the way morphologically ..... In Natural Language and Linguistic Theory 11.

  18. Particle physics experiments 1987

    International Nuclear Information System (INIS)

    Stuart, G.W.

    1988-01-01

    This report describes work carried out in 1987 on experiments approved by the Particle Physics Experiments Selection Panel (United Kingdom). The contents consist of unedited contributions from each experiment. (author)

  19. Particle physics experiments

    International Nuclear Information System (INIS)

    Stuart, G.W.

    1986-01-01

    The report of the Rutherford Appleton Laboratory describes the work carried out in 1985 on experiments approved by the Particle Physics Experiments Selection Panel. The contents consist of unedited contributions from each experiment. (author)

  20. Particle physics experiments 1984

    International Nuclear Information System (INIS)

    Stuart, G.

    1985-01-01

    The Rutherford Appleton laboratory report describes work carried out in 1984 on experiments approved by the Particle Physics selection panel. The contents consist of unedited contributions from each experiment. (author)

  1. Modern particle physics

    CERN Document Server

    AUTHOR|(CDS)2079874

    2013-01-01

    Unique in its coverage of all aspects of modern particle physics, this textbook provides a clear connection between the theory and recent experimental results, including the discovery of the Higgs boson at CERN. It provides a comprehensive and self-contained description of the Standard Model of particle physics suitable for upper-level undergraduate students and graduate students studying experimental particle physics. Physical theory is introduced in a straightforward manner with full mathematical derivations throughout. Fully-worked examples enable students to link the mathematical theory to results from modern particle physics experiments. End-of-chapter exercises, graded by difficulty, provide students with a deeper understanding of the subject. Online resources available at www.cambridge.org/MPP feature password-protected fully-worked solutions to problems for instructors, numerical solutions and hints to the problems for students and PowerPoint slides and JPEGs of figures from the book

  2. Search for Hidden Particles

    CERN Multimedia

    Solovev, V

    The SHiP Experiment is a new general-purpose fixed target facility at the SPS to search for hidden particles as predicted by a very large number of recently elaborated models of Hidden Sectors which are capable of accommodating dark matter, neutrino oscillations, and the origin of the full baryon asymmetry in the Universe. Specifically, the experiment is aimed at searching for very weakly interacting long lived particles including Heavy Neutral Leptons - right-handed partners of the active neutrinos; light supersymmetric particles - sgoldstinos, etc.; scalar, axion and vector portals to the hidden sector. The high intensity of the SPS and in particular the large production of charm mesons with the 400 GeV beam allow accessing a wide variety of light long-lived exotic particles of such models and of SUSY. Moreover, the facility is ideally suited to study the interactions of tau neutrinos.

  3. Blog: the God particle

    CERN Multimedia

    2007-01-01

    "Dateline video journalist Aaron Lewis this week reprots on the search to find the elusive "God particle", which, if found, could explain to scientists how everything in the world got its mass."(1/2 page)

  4. Research in particle theory

    International Nuclear Information System (INIS)

    Mansouri, F.; Suranyi, P; Wijewardhana, L.C.R.

    1991-10-01

    In the test particle approximation, the scattering amplitude for two-particle scattering in (2+1)-dimensional Chern-Simons-Witten gravity and supergravity was computed and compared to the corresponding metric solutions. The formalism was then extended to the exact gauge theoretic treatment of the two-particle scattering problem and compared to 't Hooft's results from the metric approach. We have studied dynamical symmetry breaking in 2+1 dimensional field theories. We have analyzed strong Extended Technicolor (ETC) models where the ETC coupling is close to a critical value. There are effective scalar fields in each of the theories. We have worked our how such scalar particles can be produced and how they decay. The φ 4 field theory was investigated in the Schrodinger representation. The critical behavior was extracted in an arbitrary number of dimensions in second order of a systematic truncation approximation. The correlation exponent agrees with known values within a few percent

  5. Particle Engulfment and Pushing

    Science.gov (United States)

    2001-01-01

    As a liquefied metal solidifies, particles dispersed in the liquid are either pushed ahead of or engulfed by the moving solidification front. Similar effects can be seen when the ground freezes and pushes large particles out of the soil. The Particle Engulfment and Pushing (PEP) experiment, conducted aboard the fourth U.S. Microgravity Payload (USMP-4) mission in 1997, used a glass and plastic beads suspended in a transparent liquid. The liquid was then frozen, trapping or pushing the particles as the solidifying front moved. This simulated the formation of advanced alloys and composite materials. Such studies help scientists to understand how to improve the processes for making advanced materials on Earth. The principal investigator is Dr. Doru Stefanescu of the University of Alabama. This image is from a video downlink.

  6. Big Bang Day: 5 Particles - 5. The Next Particle

    CERN Multimedia

    Franck Close

    2008-01-01

    Simon Singh looks at the stories behind the discovery of 5 of the universe's most significant subatomic particles: the Electron, the Quark, the Anti-particle, the Neutrino and the "next particle". 5. The Next Particle The "sparticle" - a super symmetric partner to all the known particles could be the answer to uniting all the known particles and their interactions under one grand theoretical pattern of activity. But how do researchers know where to look for such phenomena and how do they know if they find them? Simon Singh reviews the next particle that physicists would like to find if the current particle theories are to ring true.

  7. Safe biodegradable fluorescent particles

    Science.gov (United States)

    Martin, Sue I [Berkeley, CA; Fergenson, David P [Alamo, CA; Srivastava, Abneesh [Santa Clara, CA; Bogan, Michael J [Dublin, CA; Riot, Vincent J [Oakland, CA; Frank, Matthias [Oakland, CA

    2010-08-24

    A human-safe fluorescence particle that can be used for fluorescence detection instruments or act as a safe simulant for mimicking the fluorescence properties of microorganisms. The particle comprises a non-biological carrier and natural fluorophores encapsulated in the non-biological carrier. By doping biodegradable-polymer drug delivery microspheres with natural or synthetic fluorophores, the desired fluorescence can be attained or biological organisms can be simulated without the associated risks and logistical difficulties of live microorganisms.

  8. PARTICLE BEAMS: Frontier course

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    Driven by the quest for higher energies and optimal physics conditions, the behaviour of particle beams in accelerators and storage rings is the subject of increasing attention. Thus the second course organized jointly by the US and CERN Accelerator Schools looked towards the frontiers of particle beam knowledge. The programme held at South Padre Island, Texas, from 23-29 October attracted 125 participants including some 35 from Europe

  9. Particle physics and cosmology

    International Nuclear Information System (INIS)

    Turner, M.S.; Schramm, D.N.

    1985-01-01

    During the past year, the research of the members of our group has spanned virtually all the topics at the interface of cosmology and particle physics: inflationary Universe scenarios, astrophysical and cosmological constraints on particle properties, ultra-high energy cosmic ray physics, quantum field theory in curved space-time, cosmology with extra dimensions, superstring cosmology, neutrino astronomy with large, underground detectors, and the formation of structure in the Universe

  10. Ionization particle detector

    International Nuclear Information System (INIS)

    Ried, L.

    1982-01-01

    A new device is claimed for detecting particles in a gas. The invention comprises a low cost, easy to assemble, and highly accurate particle detector using a single ionization chamber to contain a reference region and a sensing region. The chamber is designed with the radioactive source near one electrode and the second electrode located at a distance less than the distance of maximum ionization from the radioactive source

  11. PARTICLE BEAMS: Frontier course

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1987-01-15

    Driven by the quest for higher energies and optimal physics conditions, the behaviour of particle beams in accelerators and storage rings is the subject of increasing attention. Thus the second course organized jointly by the US and CERN Accelerator Schools looked towards the frontiers of particle beam knowledge. The programme held at South Padre Island, Texas, from 23-29 October attracted 125 participants including some 35 from Europe.

  12. The Least Particle Theory

    Science.gov (United States)

    Hartsock, Robert

    2011-10-01

    The Least Particle Theory states that the universe was cast as a great sea of energy. MaX Planck declared a quantum of energy to be the least value in the universe. We declare the quantum of energy to be the least particle in the universe. Stephen Hawking declared quantum mechanics to be of no value in todays gross mechanics. That's like saying the number 1 has no place in mathematics.

  13. Single particle dynamics

    International Nuclear Information System (INIS)

    Siemens, P.J.; Jensen, A.S.

    1985-01-01

    It is shown that the opening of the 3-quasiparticle continuum at 3Δ sets the energy scale for the enhancement of the effective mass near the Fermi surface of nuclei. The authors argue that the spreading width of single-particle states due to coupling with low-lying collective modes is qualitatively different from the two-body collision mechanism, and contributes little to the single-particle lifetime in the sense of the optical model. (orig.)

  14. Particle physics experiments 1986

    International Nuclear Information System (INIS)

    Stuart, G.W.

    1987-01-01

    The paper presents research work carried out in 1986 on 52 elementary particle experiments approved by the Particle Physics Experiments Selection Panel. Most of the experiments were collaborative and involved research groups from different countries. About half of the experiments were conducted at CERN, the remaining experiments employed the accelerators: LAMPT, LEP, PETRA, SLAC, and HERA. The contents consist of unedited contributions from each experiment. (U.K.)

  15. Gravity, particles and astrophysics

    International Nuclear Information System (INIS)

    Wesson, P.S.

    1980-01-01

    The author deals with the relationship between gravitation and elementary particle physics, and the implications of these subjects for astrophysics. The text is split up into two parts. The first part represents a relatively non-technical overview of the subject, while the second part represents a technical examination of the most important aspects of non-Einsteinian gravitational theory and its relation to astrophysics. Relevant references from the fields of gravitation, elementary particle theory and astrophysics are included. (Auth.)

  16. Particle electric dipole moments

    CERN Document Server

    Pendlebury, J M

    2000-01-01

    Measurements of particle electric dipole moments (EDMs) continue to put powerful constraints on theories of T-symmetry and CP-symmetry violation, which form currently one of the most prominent fields in particle physics. EDM measurements have been concentrated on neutral systems such as the neutron and atoms and molecules. These measurements allow one to deduce, in turn, the electric dipole moments of the fundamental fermions, that is, the lighter leptons and quarks and also those of some heavy nuclei.

  17. Applications of particle accelerators

    International Nuclear Information System (INIS)

    Barbalat, O.

    1994-01-01

    Particle accelerators are now widely used in a variety of applications for scientific research, applied physics, medicine, industrial processing, while possible utilisation in power engineering is envisaged. Earlier presentations of this subject, given at previous CERN Accelerator School sessions have been updated with papers contributed to the first European Conference on Accelerators in Applied Research and Technology (ECAART) held in September 1989 in Frankfurt and to the Second European Particle Accelerator Conference in Nice in June 1990. (orig.)

  18. Dispersal of sticky particles

    Science.gov (United States)

    Reddy, Ramana; Kumar, Sanjeev

    2007-12-01

    In this paper, we show through simulations that when sticky particles are broken continually, particles are dispersed into fine dust only if they are present in a narrow range of volume fractions. The upper limit of this range is 0.20 in the 2D and 0.10 in the 3D space. An increase in the dimensionality of space reduces the upper limit nearly by a factor of two. This scaling holds for dispersal of particles in hyperdimensional space of dimensions up to ten, the maximum dimension studied in this work. The maximum values of volume fractions obtained are significantly lower than those required for close packing and random packing of discs in 2D and spheres in 3D space. These values are also smaller than those required for critical phenomena of cluster percolation. The results obtained are attributed to merger cascades of sticky particles, triggered by breakup events. A simple theory that incorporates this cascade is developed to quantitatively explain the observed scaling of the upper limit with the dimensionality of space. The theory also captures the dynamics of the dispersal process in the corresponding range of particle volume fractions. The theory suggests that cascades of order one and two predominantly decide the upper limit for complete dispersal of particles.

  19. spinning self-dual particles

    International Nuclear Information System (INIS)

    Gamboa, J.; Rivelles, V.O.

    1989-01-01

    Self-dual particles in two-dimensions are presented. They were obtained from chiral boson particle by square root technique. The propagator of spinning self-dual particle is calculated using the BFV formalism. (M.C.K.)

  20. Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: current advances.

    Science.gov (United States)

    Vicente, Tiago; Mota, José P B; Peixoto, Cristina; Alves, Paula M; Carrondo, Manuel J T

    2011-01-01

    The advent of advanced therapies in the pharmaceutical industry has moved the spotlight into virus-like particles and viral vectors produced in cell culture holding great promise in a myriad of clinical targets, including cancer prophylaxis and treatment. Even though a couple of cases have reached the clinic, these products have yet to overcome a number of biological and technological challenges before broad utilization. Concerning the manufacturing processes, there is significant research focusing on the optimization of current cell culture systems and, more recently, on developing scalable downstream processes to generate material for pre-clinical and clinical trials. We review the current options for downstream processing of these complex biopharmaceuticals and underline current advances on knowledge-based toolboxes proposed for rational optimization of their processing. Rational tools developed to increase the yet scarce knowledge on the purification processes of complex biologicals are discussed as alternative to empirical, "black-boxed" based strategies classically used for process development. Innovative methodologies based on surface plasmon resonance, dynamic light scattering, scale-down high-throughput screening and mathematical modeling for supporting ion-exchange chromatography show great potential for a more efficient and cost-effective process design, optimization and equipment prototyping. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Alphavirus replicon particles containing the gene for HER2/neu inhibit breast cancer growth and tumorigenesis

    International Nuclear Information System (INIS)

    Wang, Xiaoyan; Wang, Jian-Ping; Maughan, Maureen F; Lachman, Lawrence B

    2005-01-01

    Overexpression of the HER2/neu gene in breast cancer is associated with an increased incidence of metastatic disease and with a poor prognosis. Although passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) has shown some effect, a vaccine capable of inducing T-cell and humoral immunity could be more effective. Virus-like replicon particles (VRP) of Venezuelan equine encephalitis virus containing the gene for HER2/neu (VRP-neu) were tested by an active immunotherapeutic approach in tumor prevention models and in a metastasis prevention model. VRP-neu prevented or significantly inhibited the growth of HER2/neu-expressing murine breast cancer cells injected either into mammary tissue or intravenously. Vaccination with VRP-neu completely prevented tumor formation in and death of MMTV-c-neu transgenic mice, and resulted in high levels of neu-specific CD8 + T lymphocytes and serum IgG. On the basis of these findings, clinical testing of this vaccine in patients with HER2/neu + breast cancer is warranted

  2. Functional analysis of HPV-like particle-activated Langerhans cells in vitro.

    Science.gov (United States)

    Yan, Lisa; Woodham, Andrew W; Da Silva, Diane M; Kast, W Martin

    2015-01-01

    Langerhans cells (LCs) are antigen-presenting cells responsible for initiating an immune response against human papillomaviruses (HPVs) entering the epithelial layer in vivo as they are the first immune cell that HPV comes into contact with. LCs become activated in response to foreign antigens, which causes internal signaling resulting in the increased expression of co-stimulatory molecules and the secretion of inflammatory cytokines. Functionally activated LCs are then capable of migrating to the lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response in vivo. However, HPV has evolved in a manner that suppresses LC function, and thus the induction of antigen-specific T cells is hindered. While many methods exist to monitor the activity of LCs in vitro, the migration and induction of cytotoxic T cells is ultimately indicative of a functional immune response. Here, methods in analyzing functional migration and induction of antigen-specific T cells after stimulation of LCs with HPV virus-like particles in vitro are described.

  3. Proton: the particle.

    Science.gov (United States)

    Suit, Herman

    2013-11-01

    The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10(80). Protons were created at 10(-6) -1 second after the Big Bang at ≈1.37 × 10(10) years beforethe present. Proton life span has been experimentally determined to be ≥10(34) years; that is, the age of the universe is 10(-24)th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W(+), W(-), Z(0), and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter. Copyright © 2013 Elsevier Inc. All

  4. Proton: The Particle

    Energy Technology Data Exchange (ETDEWEB)

    Suit, Herman

    2013-11-01

    The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10{sup 80}. Protons were created at 10{sup −6} –1 second after the Big Bang at ≈1.37 × 10{sup 10} years beforethe present. Proton life span has been experimentally determined to be ≥10{sup 34} years; that is, the age of the universe is 10{sup −24}th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W{sup +}, W{sup −}, Z{sup 0}, and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter.

  5. Entanglement between particle partitions in itinerant many-particle states

    NARCIS (Netherlands)

    Haque, M.; Zozulya, O.S.; Schoutens, K.

    2009-01-01

    We review 'particle-partitioning entanglement' for itinerant many-particle systems. This is defined as the entanglement between two subsets of particles making up the system. We identify generic features and mechanisms of particle entanglement that are valid over whole classes of itinerant quantum

  6. Preparation by alkaline treatment and detailed characterisation of empty hepatitis B virus core particles for vaccine and gene therapy applications

    Science.gov (United States)

    Strods, Arnis; Ose, Velta; Bogans, Janis; Cielens, Indulis; Kalnins, Gints; Radovica, Ilze; Kazaks, Andris; Pumpens, Paul; Renhofa, Regina

    2015-06-01

    Hepatitis B virus (HBV) core (HBc) virus-like particles (VLPs) are one of the most powerful protein engineering tools utilised to expose immunological epitopes and/or cell-targeting signals and for the packaging of genetic material and immune stimulatory sequences. Although HBc VLPs and their numerous derivatives are produced in highly efficient bacterial and yeast expression systems, the existing purification and packaging protocols are not sufficiently optimised and standardised. Here, a simple alkaline treatment method was employed for the complete removal of internal RNA from bacteria- and yeast-produced HBc VLPs and for the conversion of these VLPs into empty particles, without any damage to the VLP structure. The empty HBc VLPs were able to effectively package the added DNA and RNA sequences. Furthermore, the alkaline hydrolysis technology appeared efficient for the purification and packaging of four different HBc variants carrying lysine residues on the HBc VLP spikes. Utilising the introduced lysine residues and the intrinsic aspartic and glutamic acid residues exposed on the tips of the HBc spikes for chemical coupling of the chosen peptide and/or nucleic acid sequences ensured a standard and easy protocol for the further development of versatile HBc VLP-based vaccine and gene therapy applications.

  7. Particle physics and cosmology

    International Nuclear Information System (INIS)

    Kolb, E.W.

    1986-10-01

    This series of lectures is about the role of particle physics in physical processes that occurred in the very early stages of the bug gang. Of particular interest is the role of particle physics in determining the evolution of the early Universe, and the effect of particle physics on the present structure of the Universe. The use of the big bang as a laboratory for placing limits on new particle physics theories will also be discussed. Section 1 reviews the standard cosmology, including primordial nucleosynthesis. Section 2 reviews the decoupling of weakly interacting particles in the early Universe, and discusses neutrino cosmology and the resulting limits that may be placed on the mass and lifetime of massive neutrinos. Section 3 discusses the evolution of the vacuum through phase transitions in the early Universe and the formation of topological defects in the transitions. Section 4 covers recent work on the generation of the baryon asymmetry by baryon-number violating reactions in Grand Unified Theories, and mentions some recent work on baryon number violation effects at the electroweak transition. Section 5 is devoted to theories of cosmic inflation. Finally, Section 6 is a discussion of the role of extra spatial dimensions in the evolution of the early Universe. 78 refs., 32 figs., 6 tabs

  8. Neutron particle injection device

    International Nuclear Information System (INIS)

    Hashimoto, Kiyoshi.

    1997-01-01

    Plasma particles are used as target particles for converting ions to neutral particles by a charge exchange reaction in a neutralization cell, and a neutralization cell is disposed in adjacent with drawing electrodes. In addition, a magnetic field generation means is disposed additionally for generating magnetic rays substantially in parallel with the drawing electrode at the downmost stream in the progressing direction of the ions. The intensity of electric fields between the drawing electrode at the downmost stream and the nearest electrode, among electrodes present at the upstream, is made smaller than the intensity of electric fields between other electrodes. Since magnetic rays substantially in parallel with the drawing electrode at the downmost stream in the progressing direction of the ions are generated, the ions are prevented from being accelerated in the direction reverse to the progressing direction thereby further enhancing the neutralization efficiency of the neutralizing cell. Then, there can be provided effects that the constitution of the electrode of NBI (Neutral particle Beam Injector) can be simplified and the power source for preventing acceleration of neutral particles can be saved. (N.H.)

  9. Cosmology and particle physics

    International Nuclear Information System (INIS)

    Salati, P.

    1986-01-01

    If the hot Big Bang model is correct, the very early universe provides us with a good laboratory to test our ideas on particle physics. The temperature and the density at that time are so high that each known particle must exist in chemical and in thermal equilibrium with the others. When the universe cools, the particles freeze out, leaving us today with a cosmic background. Such a kind of relic is of great interest because we can probe the Big Bang Model by studying the fossilized gas of a known particle. Conversely we can use that model to derive information about a hypothetical particle. Basically the freezing of a gas occurs a temperature T o and may be thermal or chemical. Studying the decoupling of a stable neutrino brings information on its mass: if the mass M ν lies in the forbidden range, the neutrino has to be unstable and its lifetime is constrained by cosmology. As for the G.U.T. Monopole, cosmology tells us that its present mass density is either to big or to small (1 monopole/observable universe) owing to a predicted flux far from the Parker Limit. Finally, the super red-giant star life time constrains the axion or the Higgs to be more massive than .2 MeV [fr

  10. New particle searches

    International Nuclear Information System (INIS)

    Derrick, M.

    1985-01-01

    The Standard Model is a remarkable result of decades of work in particle physics, but it is clearly an incomplete representation of the world. Exploring possibilities beyond the Standard Model is a major preoccupation of both theorists and experimentalists. Despite the many suggestions that are extant about the missing links within the Standard Model as well as extensions beyond it, no hard experimental evidence exists. In particular, in more than five years of experimentation both at PETRA and PEP no new particles have been found that would indicate new physics. Several reasons are possible for these negative results: the particles may be too heavy; the experiments may not be looking in the proper way; the cross sections may be too small or finally the particles may not exist. A continuing PEP program, at high luminosity will ensure that the second and third reason continue to be addressed. The higher energy e + e - storage rings such as TRISTAN and LEP will extend the mass limits. High mass particles can also be produced at the CERN collider and soon with the Tevatron collider. A concise summary of the mass limits from the PETRA experiments has been given in a recent Mark J publication. The results shown provide a convenient yardstick against which to measure future search experiments

  11. Big Bang Day: 5 Particles - 3. The Anti-particle

    CERN Multimedia

    Franck Close

    2008-01-01

    Simon Singh looks at the stories behind the discovery of 5 of the universe's most significant subatomic particles: the Electron, the Quark, the Anti-particle, the Neutrino and the "next particle". 3. The Anti-particle. It appears to be the stuff of science fiction. Associated with every elementary particle is an antiparticle which has the same mass and opposite charge. Should the two meet and combine, the result is annihilation - and a flash of light. Thanks to mysterious processes that occurred after the Big Bang there are a vastly greater number of particles than anti-particles. So how could their elusive existence be proved? At CERN particle physicists are crashing together subatomic particles at incredibly high speeds to create antimatter, which they hope will finally reveal what happened at the precise moment of the Big Bang to create the repertoire of elementary particles and antiparticles in existence today.

  12. Particles in flows

    CERN Document Server

    Galdi, Giovanni; Nečasová, Šárka

    2017-01-01

    This book aims to face particles in flows from many different, but essentially interconnected sides and points of view. Thus the selection of authors and topics represented in the chapters, ranges from deep mathematical analysis of the associated models, through the techniques of their numerical solution, towards real applications and physical implications. The scope and structure of the book as well as the selection of authors was motivated by the very successful summer course and workshop "Particles in Flows'' that was held in Prague in the August of 2014. This meeting revealed the need for a book dealing with this specific and challenging multidisciplinary subject, i.e. particles in industrial, environmental and biomedical flows and the combination of fluid mechanics, solid body mechanics with various aspects of specific applications.

  13. Charged particle accelerator

    International Nuclear Information System (INIS)

    Ress, T.I.; Nolde, G.V.

    1974-01-01

    A charged particle accelerator is described. It is made of an enclosure arranged for channeling a stream of charged particles along a predetermined path, and propelling means juxtaposed to said enclosure for generating therein a magnetic field moving in a predetermined direction with respect to each point of said path, the magnetic flux vector of that field being transverse to that path at every point, which gives the particles, along said path, a velocity connected to that of the mobile field by a predetermined relation. This can be applied to the fast production of chemical compounds, to the emission of neutrons and of thermal energy, and to the production of mechanical energy for propelling space ships [fr

  14. Detectors for Particle Radiation

    Science.gov (United States)

    Kleinknecht, Konrad

    1999-01-01

    This textbook provides a clear, concise and comprehensive review of the physical principles behind the devices used to detect charged particles and gamma rays, and the construction and performance of these many different types of detectors. Detectors for high-energy particles and radiation are used in many areas of science, especially particle physics and nuclear physics experiments, nuclear medicine, cosmic ray measurements, space sciences and geological exploration. This second edition includes all the latest developments in detector technology, including several new chapters covering micro-strip gas chambers, silicion strip detectors and CCDs, scintillating fibers, shower detectors using noble liquid gases, and compensating calorimeters for hadronic showers. This well-illustrated textbook contains examples from the many areas in science in which these detectors are used. It provides both a coursebook for students in physics, and a useful introduction for researchers in other fields.

  15. Charged particle accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Ress, T I; Nolde, G V

    1974-11-25

    A charged particle accelerator is described. It is made of an enclosure arranged for channeling a stream of charged particles along a predetermined path, and propelling means juxtaposed to the enclosure for generating a magnetic field moving in a predetermined direction with respect to each point of the path, the magnetic flux vector of that field being transverse to that path at every point, which gives the particles, along said path, a velocity connected to that of the mobile field by a predetermined relation. This can be applied to the fast production of chemical compounds, to the emission of neutrons and of thermal energy, and to the production of mechanical energy for propelling space ships.

  16. Radiance and particle fluence

    International Nuclear Information System (INIS)

    Papiez, L.; Battista, J.J.

    1994-01-01

    The International Commission on Radiological Units and Measurements (ICRU) has defined fluence in terms of the number of the radiation particles crossing a small sampling sphere. A second definition has been proposed in which the length of track segments contained within any sampling volume are used to calculate the incident fluence. This approach is often used in Monte Carlo simulations of individual particle tracks, allowing the fluence to be scored in small volumes of any shape. In this paper we stress that the second definition generalizes the classical (ICRU) concept of fluence. We also identify the assumptions inherent in the two definitions of fluence and prove their equivalence for the case of straight-line particle trajectories. (author)

  17. New particle data

    CERN Multimedia

    2002-01-01

    The 2002 edition of the Review of Particle Physics has been published. It appears in the July 1st edition of Physical Review D with the reference: K. Hagiwara et al., Physical Review D66, 010001 (2002). The printing of the Particle Physics Booklets is planned to be finished at the end of August, so copies are expected to arrive at CERN for distribution by mid-September. The full data are available at the Berkeley site, as well as at various other mirrors around the world. As for copies of the full Review, for which CERN is responsible for the distribution outside the Americas, the Far East and Australasia, the quantity has been reduced by 60% compared to the 2000 edition. It will thus no longer be possible for all individuals to have their personal copy. Priority will be given to ensure that copies are sent to all groups and institutes engaged in particle physics research.

  18. Particle accelerator physics

    CERN Document Server

    Wiedemann, Helmut

    2015-01-01

    This book by Helmut Wiedemann is a well-established, classic text, providing an in-depth and comprehensive introduction to the field of high-energy particle acceleration and beam dynamics. The present 4th edition has been significantly revised, updated and expanded. The newly conceived Part I is an elementary introduction to the subject matter for undergraduate students. Part II gathers the basic tools in preparation of a more advanced treatment, summarizing the essentials of electrostatics and electrodynamics as well as of particle dynamics in electromagnetic fields. Part III is an extensive primer in beam dynamics, followed, in Part IV, by an introduction and description of the main beam parameters and including a new chapter on beam emittance and lattice design. Part V is devoted to the treatment of perturbations in beam dynamics. Part VI then discusses the details of charged particle acceleration. Parts VII and VIII introduce the more advanced topics of coupled beam dynamics and describe very intense bea...

  19. The particle zoo

    CERN Document Server

    AUTHOR|(CDS)2079223

    2016-01-01

    What is everything really made of? If we split matter down into smaller and infinitesimally smaller pieces, where do we arrive? At the Particle Zoo - the extraordinary subatomic world of antimatter, neutrinos, strange-flavoured quarks and yetis, gravitons, ghosts and glueballs, mindboggling eleven-dimensional strings and the elusive Higgs boson itself. Be guided around this strangest of zoos by Gavin Hesketh, experimental particle physicist at humanity's greatest experiment, the Large Hadron Collider. Concisely and with a rare clarity, he demystifies how we are uncovering the inner workings of the universe and heading towards the next scientific revolution. Why are atoms so small? How did the Higgs boson save the universe? And is there a theory of everything? The Particle Zoo answers these and many other profound questions, and explains the big ideas of Quantum Physics, String Theory, The Big Bang and Dark Matter...and, ultimately, what we know about the true, fundamental nature of reality.

  20. Precision wood particle feedstocks

    Science.gov (United States)

    Dooley, James H; Lanning, David N

    2013-07-30

    Wood particles having fibers aligned in a grain, wherein: the wood particles are characterized by a length dimension (L) aligned substantially parallel to the grain, a width dimension (W) normal to L and aligned cross grain, and a height dimension (H) normal to W and L; the L.times.H dimensions define two side surfaces characterized by substantially intact longitudinally arrayed fibers; the W.times.H dimensions define two cross-grain end surfaces characterized individually as aligned either normal to the grain or oblique to the grain; the L.times.W dimensions define two substantially parallel top and bottom surfaces; and, a majority of the W.times.H surfaces in the mixture of wood particles have end checking.

  1. Magnetic particle inspection

    Science.gov (United States)

    Sastri, Sankar

    1990-01-01

    The purpose of this experiment is to familiarize the student with magnetic particle inspection and relate it to classification of various defects. Magnetic particle inspection is a method of detecting the presence of cracks, laps, tears, inclusions, and similar discontinuities in ferromagnetic materials such as iron and steel. This method will most clearly show defects that are perpendicular to the magnetic field. The Magnaglo method uses a liquid which is sprayed on the workpiece to be inspected, and the part is magnetized at the same time. The workpiece is then viewed under a black light, and the presence of discontinuity is shown by the formation of a bright indication formed by the magnetic particles over the discontinuity. The equipment and experimental procedures are described.

  2. Particle fuel bed tests

    International Nuclear Information System (INIS)

    Horn, F.L.; Powell, J.R.; Savino, J.M.

    1985-01-01

    Gas-cooled reactors, using packed beds of small diameter coated fuel particles have been proposed for compact, high-power systems. The particulate fuel used in the tests was 800 microns in diameter, consisting of a thoria kernel coated with 200 microns of pyrocarbon. Typically, the bed of fuel particles was contained in a ceramic cylinder with porous metallic frits at each end. A dc voltage was applied to the metallic frits and the resulting electric current heated the bed. Heat was removed by passing coolant (helium or hydrogen) through the bed. Candidate frit materials, rhenium, nickel, zirconium carbide, and zirconium oxide were unaffected, while tungsten and tungsten-rhenium lost weight and strength. Zirconium-carbide particles were tested at 2000 K in H 2 for 12 hours with no visible reaction or weight loss

  3. WORKSHOP: Stable particle motion

    International Nuclear Information System (INIS)

    Ruggiero, Alessandro G.

    1993-01-01

    Full text: Particle beam stability is crucial to any accelerator or collider, particularly big ones, such as Brookhaven's RHIC heavy ion collider and the larger SSC and LHC proton collider schemes. A workshop on the Stability of Particle Motion in Storage Rings held at Brookhaven in October dealt with the important issue of determining the short- and long-term stability of single particle motion in hadron storage rings and colliders, and explored new methods for ensuring it. In the quest for realistic environments, the imperfections of superconducting magnets and the effects of field modulation and noise were taken into account. The workshop was divided into three study groups: Short-Term Stability in storage rings, including chromatic and geometric effects and correction strategies; Long-Term Stability, including modulation and random noise effects and slow varying effects; and Methods for determining the stability of particle motion. The first two were run in parallel, but the third was attended by everyone. Each group considered analytical, computational and experimental methods, reviewing work done so far, comparing results and approaches and underlining outstanding issues. By resolving conflicts, it was possible to identify problems of common interest. The workshop reaffirmed the validity of methods proposed several years ago. Major breakthroughs have been in the rapid improvement of computer capacity and speed, in the development of more sophisticated mathematical packages, and in the introduction of more powerful analytic approaches. In a typical storage ring, a particle may be required to circulate for about a billion revolutions. While ten years ago it was only possible to predict accurately stability over about a thousand revolutions, it is now possible to predict over as many as one million turns. If this trend continues, in ten years it could become feasible to predict particle stability over the entire storage period. About ninety participants

  4. Plasma particle accelerators

    International Nuclear Information System (INIS)

    Dawson, J.M.

    1988-01-01

    The Superconducting Supercollider (SSC) will require an 87-kilometer accelerator ring to boost particles to 40 TeV. The SSC's size is due in part to the fact that its operating principle is the same one that has dominated accelerator design for 50 years: it guides particles by means of magnetic fields and propels them by strong electric fields. If one were to build an equally powerful but smaller accelerator, one would need to increase the strength of the guiding and propelling fields. Actually, however, conventional technology may not be able to provide significant increases in field strength. There are two reasons. First, the forces from magnetic fields are becoming greater than the structural forces that hold a magnetic material together; the magnets that produce these fields would themselves be torn apart. Second, the energy from electric fields is reaching the energies that bind electrons to atoms; it would tear electrons from nuclei in the accelerator's support structures. It is the electric field problem that plasma accelerators can overcome. Plasma particle accelerators are based on the principle that particles can be accelerated by the electric fields generated within a plasma. Because the plasma has already been ionized, plasma particle accelerators are not susceptible to electron dissociation. They can in theory sustain accelerating fields thousands of times stronger that conventional technologies. So far two methods for creating plasma waves for accelerators have been proposed and tested: the wakefield and the beat wave. Although promising electric fields have been produced, more research is necessary to determine whether plasma particle accelerators can compete with the existing accelerators. 7 figs

  5. Composite magnetic particles

    International Nuclear Information System (INIS)

    Davies, G.E.; Janata, J.

    1981-01-01

    This patent claim on behalf of I.C.I. Ltd., relates to the preparation and use of composite magnetic particles, comprising a low density core, and having a magnetic coating over at least a proportion of the surface. The density of such particles can be chosen to suit a range of applications, e.g. in affinity chromatography, in radioimmunoassay, in the transport of the associated component, such as a drug or enzyme, to a specific site in a living organism. (U.K.)

  6. Overview of particle physics

    International Nuclear Information System (INIS)

    Salam, A.

    1993-01-01

    This article presents an overview of the situation in particle physics and a prognosis of its future: ideas which have been tested or will soon be tested (standard model and the light Higgs particle), ideas whose time has not yet come (supersymmetry, supersymmetry and N=1 supergravity, right-left symmetry and preons, unification of gravity with other forces, anomaly-free supergravities, supersymmetry strings, string theory as the ''Theory of Everything'' (T.O.E.); passive and non accelerator experiments. 6 figs., 2 tabs

  7. Collection of particles

    International Nuclear Information System (INIS)

    Frew, J.D.

    1979-01-01

    Apparatus and a method for collecting particles formed by vaporisation during a high temperature treatment of steel (eg cutting or welding) are described in which gas is drawn from the area in which the treatment is taking place through a collector in which the particles are separated magnetically. The air may be drawn by an air ejector from a hood around the treatment area. The invention has particular application where the high temperature treatment is the laser cutting of the stainless steel wrapper around a nuclear fuel sub-assembly. (author)

  8. The paradox particle

    Energy Technology Data Exchange (ETDEWEB)

    Sutton, Christine

    1993-11-15

    As well as being a leading physics writer, Christine Sutton of Oxford is also a particle physicist, currently working on the Zeus experiment at DESY's HERA electron-proton collider. Her latest book ''Spaceship Neutrino'' Cambridge University Press ISBN 0 521 36404 3 [hardback] or 0 521 36703 4 [paperback]) is a fascinating account of the emergence of the neutrino on the stage of science. In sixty years, the neutrino has been transformed from an apologetic idea its originator dared not publish to one of the main experimental tools of modern high energy research, while cosmologists have realized that this bizarre particle could play a major role in the Universe.

  9. Beta particle measurement fundamentals

    International Nuclear Information System (INIS)

    Alvarez, J.L.

    1986-01-01

    The necessary concepts for understanding beta particle behavior are stopping power, range, and scattering. Dose as a consequence of beta particle interaction with tissue can be derived and explained by these concepts. Any calculations of dose, however, assume or require detailed knowledge of the beta spectrum at the tissue depth of calculation. A rudimentary knowledge of the incident spectrum can be of use in estimating dose, interpretating dose measuring devices and designing protection. The stopping power and range based on the csda will give a conservative estimate in cases of protection design, as scattering will reduce the range. Estimates of dose may be low because scattering effects were neglected

  10. Particles and forces

    International Nuclear Information System (INIS)

    Peierls, R.

    1981-01-01

    The particles and forces of matter, found in the Universe, are discussed with especial reference to some of the laws which govern behaviour in the sub-atomic world and which determine the way forces work to give matter its various characteristics. The recent history of the search for elementary constituents of matter in this century is outlined and the replacement of the simplicity anticipated in the 1930s by the proliferation of particle states uncovered in the 1950s and 1960s which led to the quark model is examined. (U.K.)

  11. Single particle detecting telescope system

    International Nuclear Information System (INIS)

    Yamamoto, I.; Tomiyama, T.; Iga, Y.; Komatsubara, T.; Kanada, M.; Yamashita, Y.; Wada, T.; Furukawa, S.

    1981-01-01

    We constructed the single particle detecting telescope system for detecting a fractionally charged particle. The telescope consists of position detecting counters, wall-less multi-cell chambers, single detecting circuits and microcomputer system as data I/0 processor. Especially, a frequency of double particle is compared the case of the single particle detecting with the case of an ordinary measurement

  12. Amorphous silicon ionizing particle detectors

    Science.gov (United States)

    Street, Robert A.; Mendez, Victor P.; Kaplan, Selig N.

    1988-01-01

    Amorphous silicon ionizing particle detectors having a hydrogenated amorphous silicon (a--Si:H) thin film deposited via plasma assisted chemical vapor deposition techniques are utilized to detect the presence, position and counting of high energy ionizing particles, such as electrons, x-rays, alpha particles, beta particles and gamma radiation.

  13. New particle searches and discoveries

    International Nuclear Information System (INIS)

    Trippe, T.G.; Barbaro-Galtieri, A.; Horne, C.P.; Kelly, R.L.; Rittenberg, A.; Rosenfeld, A.H.; Yost, G.P.; Armstrong, B.; Bricman, C.; Hemingway, R.J.; Losty, M.J.; Roos, M.

    1977-01-01

    This supplement to the 1976 edition of 'Review of particle properties', Particle Data Group [Rev. Mod. Phys. 48, No. 2, Part II (1976)], contains tabulations of experimental data bearing on the 'new particles' and related topics; categories covered include charmed particles, psi's and their decay products, and heavy leptons. Errata to the previous edition are also given. (Auth.)

  14. Matter: the fundamental particles

    CERN Multimedia

    Landua, Rolf

    2007-01-01

    "The largest particle physics centre in the world is located in Europe. It straddles the Franco-Swiss border, near Geneva. At CERN - the European Organisation for Nuclear Research , which is focused on the science of nuclear matter rather than on the exploitation of atomic energy - there are over 6 500 scientists." (1 page)

  15. Our Particle Universe

    Indian Academy of Sciences (India)

    and “why is the universe the way it is?” Not long before ... to each other. The interactions of particles in the universe ... theory by Jean Perrin in 1908 convinced people that atoms and ..... ing the origin and evolution of our universe13. This is an ...

  16. Elementary particle interactions

    International Nuclear Information System (INIS)

    Bugg, W.M.; Condo, G.T.; Handler, T.; Hart, E.L.; Ward, B.F.L.; Close, F.E.; Christophorou, L.G.

    1990-10-01

    This report discusses freon bubble chamber experiments exposed to μ + and neutrinos, photon-proton interactions; shower counter simulations; SLD detectors at the Stanford Linear Collider, and the detectors at the Superconducting Super Collider; elementary particle interactions; physical properties of dielectric materials used in High Energy Physics detectors; and Nuclear Physics

  17. Particle physics and cosmology

    International Nuclear Information System (INIS)

    Ellis, J.; Nanopoulos, D.

    1983-01-01

    The authors describe the connection between cosmology and particle physics in an introductory way. In this connection the big bang theory and unified gauge models of strong, electromagnetic, and weak interactions are considered. Furthermore cosmological nucleosynthesis is discussed in this framework, and the problem of cosmic neutrinos is considered with special regards to its rest mass. (HSI).

  18. Charged particle beams

    CERN Document Server

    Humphries, Stanley

    2013-01-01

    Detailed enough for a text and sufficiently comprehensive for a reference, this volume addresses topics vital to understanding high-power accelerators and high-brightness-charged particle beams. Subjects include stochastic cooling, high-brightness injectors, and the free electron laser. Humphries provides students with the critical skills necessary for the problem-solving insights unique to collective physics problems. 1990 edition.

  19. Lord of the particles

    CERN Multimedia

    Loll, Anna-Cathrin

    2009-01-01

    "Rolf-Dieter Heuer is the new director general of the world's largest particle physics research center. Though the German physicist never expected to gain this influential position in Switzerland, it seems a natural step in his career trajectory" (1.5 pages)

  20. Particle physics experiments 1982

    International Nuclear Information System (INIS)

    Rousseau, M.D.; Stuart, G.

    1983-01-01

    Work carried out in 1982 on 52 experiments approved by the Particle Physics Experiments Selection Panel is described. Each experiment is listed under title, collaboration, technique, accelerator, year of running, status and spokesman. Unedited contributions are given from each experiment. (U.K.)

  1. Energetic solar particles

    International Nuclear Information System (INIS)

    Biswas, M.

    1975-01-01

    In this review, some of the important aspects of energetic solar particles and their relation to solar physics are discussed. The major aspects of solar cosmic ray studies currently under investigation are identified and attention is focussed on the problems of the physical processes in the sun which may be responsible for these phenomena. The studies of the composition and energy spectra of solar cosmic ray nuclei are related to the basic problem of particle acceleration process in sun and to the composition of elements in solar atmosphere. The composition of higher energy (>20 MeV/amu) multiply charged nuclei of He, C, N, O, Ne, Mg, Si and Fe give information on the abundance of elements in the solar atmosphere. At lower energies (approximately 1-10 MeV/amu), the abundances of these elements show enhancements relative to solar abundances and these enhancements are believed to be due to particle acceleration mechanisms operative in the sun which are not fully understood at present. Studies of the relative abundances of H 2 , H 3 and He 3 isotopes and Li, Be, B nuclei in the solar cosmic rays can also be studied. The question of the relationship of the accelerated particles in the sun to the optical flare phenomena is discussed. Further studies of different aspects of these phenomena may give important clues to a wide ranging phenomena in the active sun. The observational methods employed for these studies are mentioned. (A.K.)

  2. Exotic Long - Lived Particles

    CERN Document Server

    Jørgensen, Morten Dam

    A search for hadronising long-lived massive particles at the Large Hadron Collider is conducted with the ATLAS detector. No excess events are found. Based on statistical analysis, upper limits on the production cross section are observed to be between $0.01$ pb and $0.006$ pb for colour octet particles (gluinos) with masses ranging from $300 \\ \\mathrm{GeV/c}^2$ to $1400 \\ \\mathrm{GeV/c}^2$, and $0.01$ pb to $0.004$ pb for colour triplet particles (stops and sbottoms) with masses ranging from $200 \\ \\mathrm{GeV/c}^2$ to $900 \\ \\mathrm{GeV/c}^2$. In the context of Supersymmetry with decoupled sfermion and sboson sectors (Split-SUSY), this gives a lower limit on the gluino mass of $989 \\ \\mathrm{GeV/c}^2$, and $683 \\ \\mathrm{GeV/c}^2$ for the stop mass and $618 \\ \\mathrm{GeV/c}^2$ for the sbottom mass. In addition, a new method is presented that improves the speed ($\\beta$) estimation for long-lived particles in the ATLAS tile calorimeter with a factor of $7$ improvement in resolution at low-$\\beta$ and ...

  3. Particle physics experiments 1988

    International Nuclear Information System (INIS)

    Bairstow, R.

    1989-01-01

    This report describes work carried out in 1988 on experiments approved by the Particle Physics Experiments Selection Panel. The contents consist of unedited contributions from each experiment. More than forty projects at different accelerators (SPS, ISIS, PETRA, LAMPF, LEP, HERA, BNL, ILL, LEAR) are listed. Different organisations collaborate on different projects. A brief progress report is given. References to published articles are given. (author)

  4. Lévy particles

    DEFF Research Database (Denmark)

    Hansen, Linda Vadgård; Thorarinsdottir, Thordis Linda; Gneiting, Tilmann

    to a von Mises–Fisher density, or uniform on a spherical cap, the correlation function of the associated random field admits a closed form expression. Using a Gaussian basis, the fractal or Hausdorff dimension of the surface of the Lévy particle reflects the decay of the correlation function at the origin...

  5. Two beautiful new particles

    CERN Multimedia

    Antonella Del Rosso

    2012-01-01

    In beautiful agreement with the Standard Model, two new excited states (see below) of the Λb beauty particle have just been observed by the LHCb Collaboration. Similarly to protons and neutrons, Λb is composed of three quarks. In the Λb’s case, these are up, down and… beauty.   Although discovering new particles is increasingly looking like a routine exercise for the LHC experiments (see previous features), it is far from being an obvious performance, particularly when the mass of the particles is high. Created in the high-energy proton-proton collisions produced by the LHC, these new excited states of the Λb particle have been found to have a mass of, respectively, 5912 MeV/c2 and 5920 MeV/c2. In other words, they are over five times heavier than the proton or the neutron. Physicists only declare a discovery when data significantly show the relevant signal. In order to do that, they often have to analyse large samples of data. To ...

  6. Prospects of particle physics

    International Nuclear Information System (INIS)

    Meyer-Berkhout, U.

    1986-01-01

    Remarkable progress has been achieved in the last two decades in the field of particle physics. From the insight gained by the many experimental data, physicists derive a framework picture of matter on the sub-nuclear level, consisting of fundamental components which interact with each other in a defined and quantitatively detectable manner. The data now available allowed a quantum field theory of strong interactions to be set up for the first time, and a unified theory of electromagnetic and weak interaction. Particle physicists today take particular interest in the problem of whether the strong interaction might fit into an extended unified theory. Such a grand unified theory would have a far-reaching impact on the conceptual models both of the cosmic and sub-nuclear dimensions, and possibly lead to observable effects in domains of energy and mass which will be opened up for experiments by the new accelerator generation underway. Current activities throughout the world for constructing or projecting the new high-energy particle accelerators are outlined in the article, together with the prospects expected by particle physicists, and a look back on the history and achievements of this field of science. (orig.) [de

  7. Particle physics experiments 1992

    International Nuclear Information System (INIS)

    Roberts, B.A.

    1993-03-01

    The research programs described here were carried out in 1992 at Rutherford Appleton Laboratory and funded by the United Kingdom Science and Engineering Research Council. The area covered in these experiments is particle physics. Unedited contributions from over forty experimental programs are included. Experiments are listed according to their current status, the accelerator used and its years of operation. (UK)

  8. Fuel particle coating data

    International Nuclear Information System (INIS)

    Hollabaugh, C.M.; Wagner, P.; Wahman, L.A.; White, R.W.

    1977-01-01

    Development of coating on nuclear fuel particles for the High-Temperature Fuels Technology program at the Los Alamos Scientific Laboratory included process studies for low-density porous and high-density isotropic carbon coats, and for ZrC and ''alloy'' C/ZrC coats. This report documents the data generated by these studies

  9. Elementary particles physics

    International Nuclear Information System (INIS)

    1990-01-01

    It is discussed the physics in Brazil in the next decade with regard to elementary particles and field theories. The situation of brazilian research institutes as well as its personnel is also presented. Some recommendations and financing of new projects are also considered. (A.C.A.S.)

  10. Elementary particle physics: Experimental

    International Nuclear Information System (INIS)

    Lord, J.J.; Burnett, T.H.; Wilkes, R.J.

    1989-01-01

    We are carrying out a research program in high energy experimental particle physics. Studies of high energy hadronic interactions and leptoproduction processes continue using several experimental techniques. Progress has been made on the study of multiparticle production processes in nuclei. Ultra-high energy cosmic ray nucleus-nucleus interactions have been investigated by the Japanese American Cosmic Emulsion Experiment (JACEE) using balloon-borne emulsion chamber detectors. In the area of particle astrophysics, our studies of cosmic ray nuclear interactions have enabled use to make the world's most accurate determination of the comparison of the cosmic rays above 10 13 eV. We have only the detector that can observe interaction vertices and identify particles at energies up to 10**15 eV. Our observations are getting close to placing limits on the acceleration mechanisms postulated for pulsars in which the spin and magnetic moment axes are at different angles. In June, 1989 approval was given by NASA for our participation in the Space Station program. The SCINATT experiment will make use of emulsion chamber detectors, similar to the planned JACEE hybrid balloon flight detectors. These detector will permit precise determination of secondary particle charges, momenta and rapidities, and the accumulation of data will be at least a factor of 10 to 100 greater than in balloon experiments. Emulsion chamber techniques ate also employed in an experiment using accelerator heavy ion beams at CERN and Brookhaven National Laboratory to investigate particle production processes in central collisions of nuclei in the energy range 15 -- 200A GeV. Our study of hadroproduction in lepton interactions is continuing with approval of another 8 months run for deep inelastic muon scattering experiment E665 at Fermilab

  11. Particle Swarm Optimization Toolbox

    Science.gov (United States)

    Grant, Michael J.

    2010-01-01

    The Particle Swarm Optimization Toolbox is a library of evolutionary optimization tools developed in the MATLAB environment. The algorithms contained in the library include a genetic algorithm (GA), a single-objective particle swarm optimizer (SOPSO), and a multi-objective particle swarm optimizer (MOPSO). Development focused on both the SOPSO and MOPSO. A GA was included mainly for comparison purposes, and the particle swarm optimizers appeared to perform better for a wide variety of optimization problems. All algorithms are capable of performing unconstrained and constrained optimization. The particle swarm optimizers are capable of performing single and multi-objective optimization. The SOPSO and MOPSO algorithms are based on swarming theory and bird-flocking patterns to search the trade space for the optimal solution or optimal trade in competing objectives. The MOPSO generates Pareto fronts for objectives that are in competition. A GA, based on Darwin evolutionary theory, is also included in the library. The GA consists of individuals that form a population in the design space. The population mates to form offspring at new locations in the design space. These offspring contain traits from both of the parents. The algorithm is based on this combination of traits from parents to hopefully provide an improved solution than either of the original parents. As the algorithm progresses, individuals that hold these optimal traits will emerge as the optimal solutions. Due to the generic design of all optimization algorithms, each algorithm interfaces with a user-supplied objective function. This function serves as a "black-box" to the optimizers in which the only purpose of this function is to evaluate solutions provided by the optimizers. Hence, the user-supplied function can be numerical simulations, analytical functions, etc., since the specific detail of this function is of no concern to the optimizer. These algorithms were originally developed to support entry

  12. Thermo-resistance Acquisition of A Mesophilic Bacterium with The Aid of Vector Particles Originating from Thermophiles

    Science.gov (United States)

    Sugitate, T.; Inaba, N.; Kurusu, Y.; Hoaki, T.; Chiura, H. X.

    2004-12-01

    The present study was aimed to examine whether virus-like particles (VLPs) would be able to transfer and express the thermo-resistance gene of thermophilic microbes in the mesophilic auxotrophic Escherichia coli AB1157 mutant. A hyper-thermophilic archaea, Thermococcus kodakaraensis B41, that was isolated from the Suiyo Seamount APSK06 boring core, released particles (KD-VLPs) during culture. Transduction towards recipient E. coli AB1157 was carried out using KD-VLP as the gene transfer mediator, in order to examine the lethal effect and thermo-resistant gene transfer capability of the particle. The colony forming ability of the cells was examined in 7 % of gelrite supplemented-LB plates (LB-gelrite plates) at 50, 56, and 70 ° C. Regardless of UV irradiation, KD-VLP showed a reduced efficiency of plating (EOP) of recipient viable cell population to ca 65 %. Four colonies were formed in LB-gelrite plates at 50 ° C, which were named as KD-E-Trans, and the gene transfer frequency was estimated to be 5.12 × 10-8 cfu/particle. Obtained KD-E-Trans was cultured in LB liquid medium employing the same high temperature conditions. The cells grew 1.6 ˜ 6 fold of the inocula in 13 days at all the examined temperatures, and the generation time of the transductants were as follows: ca 28 hours at 50 ° C, ca 73 hours at 56 ° C, ca 266 hours at 70 ° C. Thus, the gene transfer of thermo-resistance to mesophilic E. coli from another Domain with the aid of KD-VLPs was demonstrated.

  13. Particle physics in your pocket!

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    CERN physicists, take out your smartphones! Two new particle physics applications for Android phones have been developed by a physicist from the University of Bern: “Particle Properties” and “Particle Physics Booklet 2010”.   “When I'm on shift, I enjoy looking at the online event displays,” says Igor Kreslo from the Laboratory for High Energy Physics at the University of Bern, the physicist who has developed the two particle physics applications for Android. “Sometimes very beautiful events appear, with many different particles. I like to discuss these displays with my students, just to develop their ability to identify particles. We try to find out which particle is which and how it might decay… I think that's the best way to teach students the phenomenology of particle physics.” When scientists study particle physics, they require some vital information, such as the decay branching ...

  14. Quantum Dots Encapsulated with Canine Parvovirus-Like Particles Improving the Cellular Targeted Labeling.

    Directory of Open Access Journals (Sweden)

    Dan Yan

    Full Text Available Quantum dots (QDs have a promising prospect in live-cell imaging and sensing because of unique fluorescence features. QDs aroused significant interest in the bio-imaging field through integrating the fluorescence properties of QDs and the delivery function of biomaterial. The natural tropism of Canine Parvovirus (CPV to the transferrin receptor can target specific cells to increase the targeting ability of QDs in cell imaging. CPV virus-like particles (VLPs from the expression of the CPV-VP2 capsid protein in a prokaryotic expression system were examined to encapsulate the QDs and deliver to cells with an expressed transferrin receptor. CPV-VLPs were used to encapsulate QDs that were modified using 3-mercaptopropionic acid. Gel electrophoresis, fluorescence spectrum, particle size, and transmission electron microscopy verified the conformation of a complex, in which QDs were encapsulated in CPV-VLPs (CPV-VLPs-QDs. When incubated with different cell lines, CPV-VLPs-QDs significantly reduced the cytotoxicity of QDs and selectively labeled the cells with high-level transferrin receptors. Cell-targeted labeling was achieved by utilizing the specific binding between the CPV capsid protein VP2 of VLPs and cellular receptors. CPV-VLPs-QDs, which can mimic the native CPV infection, can recognize and attach to the transferrin receptors on cellular membrane. Therefore, CPV-VLPs can be used as carriers to facilitate the targeted delivery of encapsulated nanomaterials into cells via receptor-mediated pathways. This study confirmed that CPV-VLPs can significantly promote the biocompatibility of nanomaterials and could expand the application of CPV-VLPs in biological medicine.

  15. Canine parvovirus-like particles, a novel nanomaterial for tumor targeting

    Directory of Open Access Journals (Sweden)

    Destito Giuseppe

    2006-02-01

    Full Text Available Abstract Specific targeting of tumor cells is an important goal for the design of nanotherapeutics for the treatment of cancer. Recently, viruses have been explored as nano-containers for specific targeting applications, however these systems typically require modification of the virus surface using chemical or genetic means to achieve tumor-specific delivery. Interestingly, there exists a subset of viruses with natural affinity for receptors on tumor cells that could be exploited for nanotechnology applications. For example, the canine parvovirus (CPV utilizes transferrin receptors (TfRs for binding and cell entry into canine as well as human cells. TfRs are over-expressed by a variety of tumor cells and are widely being investigated for tumor-targeted drug delivery. We explored whether the natural tropism of CPV to TfRs could be harnessed for targeting tumor cells. Towards this goal, CPV virus-like particles (VLPs produced by expression of the CPV-VP2 capsid protein in a baculovirus expression system were examined for attachment of small molecules and delivery to tumor cells. Structural modeling suggested that six lysines per VP2 subunit are presumably addressable for bioconjugation on the CPV capsid exterior. Between 45 and 100 of the possible 360 lysines/particle could be routinely derivatized with dye molecules depending on the conjugation conditions. Dye conjugation also demonstrated that the CPV-VLPs could withstand conditions for chemical modification on lysines. Attachment of fluorescent dyes neither impaired binding to the TfRs nor affected internalization of the 26 nm-sized VLPs into several human tumor cell lines. CPV-VLPs therefore exhibit highly favorable characteristics for development as a novel nanomaterial for tumor targeting.

  16. Experimental Particle Physics

    Energy Technology Data Exchange (ETDEWEB)

    Rosenfeld, Carl [Univ of South Carolina; Mishra, Sanjib R. [Univ of South Carolina; Petti, Roberto [Univ of South Carolina; Purohit, Milind V. [Univ of South Carolina

    2014-08-31

    The high energy physics group at the University of South Carolina, under the leadership of Profs. S.R. Mishra, R. Petti, M.V. Purohit, J.R. Wilson (co-PI's), and C. Rosenfeld (PI), engaged in studies in "Experimental Particle Physics." The group collaborated with similar groups at other universities and at national laboratories to conduct experimental studies of elementary particle properties. We utilized the particle accelerators at the Fermi National Accelerator Laboratory (Fermilab) in Illinois, the Stanford Linear Accelerator Center (SLAC) in California, and the European Center for Nuclear Research (CERN) in Switzerland. Mishra, Rosenfeld, and Petti worked predominantly on neutrino experiments. Experiments conducted in the last fifteen years that used cosmic rays and the core of the sun as a source of neutrinos showed conclusively that, contrary to the former conventional wisdom, the "flavor" of a neutrino is not immutable. A neutrino of flavor "e," "mu," or "tau," as determined from its provenance, may swap its identity with one of the other flavors -- in our jargon, they "oscillate." The oscillation phenomenon is extraordinarily difficult to study because neutrino interactions with our instruments are exceedingly rare -- they travel through the earth mostly unimpeded -- and because they must travel great distances before a substantial proportion have made the identity swap. Three of the experiments that we worked on, MINOS, NOvA, and LBNE utilize a beam of neutrinos from an accelerator at Fermilab to determine the parameters governing the oscillation. Two other experiments that we worked on, NOMAD and MIPP, provide measurements supportive of the oscillation experiments. Good measurements of the neutrino oscillation parameters may constitute a "low energy window" on related phenomena that are otherwise unobservable because they would occur only at energies way above the reach of conceivable accelerators. Purohit and Wilson participated in the Ba

  17. Fundamentals of gas particle flow

    CERN Document Server

    Rudinger, G

    1980-01-01

    Fundamentals of Gas-Particle Flow is an edited, updated, and expanded version of a number of lectures presented on the "Gas-Solid Suspensions” course organized by the von Karman Institute for Fluid Dynamics. Materials presented in this book are mostly analytical in nature, but some experimental techniques are included. The book focuses on relaxation processes, including the viscous drag of single particles, drag in gas-particles flow, gas-particle heat transfer, equilibrium, and frozen flow. It also discusses the dynamics of single particles, such as particles in an arbitrary flow, in a r

  18. Particle measurement systems and methods

    Science.gov (United States)

    Steele, Paul T [Livermore, CA

    2011-10-04

    A system according to one embodiment includes a light source for generating light fringes; a sampling mechanism for directing a particle through the light fringes; and at least one light detector for detecting light scattered by the particle as the particle passes through the light fringes. A method according to one embodiment includes generating light fringes using a light source; directing a particle through the light fringes; and detecting light scattered by the particle as the particle passes through the light fringes using at least one light detector.

  19. Effective particle magnetic moment of multi-core particles

    International Nuclear Information System (INIS)

    Ahrentorp, Fredrik; Astalan, Andrea; Blomgren, Jakob; Jonasson, Christian; Wetterskog, Erik; Svedlindh, Peter; Lak, Aidin; Ludwig, Frank; IJzendoorn, Leo J. van; Westphal, Fritz; Grüttner, Cordula; Gehrke, Nicole; Gustafsson, Stefan; Olsson, Eva; Johansson, Christer

    2015-01-01

    In this study we investigate the magnetic behavior of magnetic multi-core particles and the differences in the magnetic properties of multi-core and single-core nanoparticles and correlate the results with the nanostructure of the different particles as determined from transmission electron microscopy (TEM). We also investigate how the effective particle magnetic moment is coupled to the individual moments of the single-domain nanocrystals by using different measurement techniques: DC magnetometry, AC susceptometry, dynamic light scattering and TEM. We have studied two magnetic multi-core particle systems – BNF Starch from Micromod with a median particle diameter of 100 nm and FeraSpin R from nanoPET with a median particle diameter of 70 nm – and one single-core particle system – SHP25 from Ocean NanoTech with a median particle core diameter of 25 nm

  20. Effective particle magnetic moment of multi-core particles

    Science.gov (United States)

    Ahrentorp, Fredrik; Astalan, Andrea; Blomgren, Jakob; Jonasson, Christian; Wetterskog, Erik; Svedlindh, Peter; Lak, Aidin; Ludwig, Frank; van IJzendoorn, Leo J.; Westphal, Fritz; Grüttner, Cordula; Gehrke, Nicole; Gustafsson, Stefan; Olsson, Eva; Johansson, Christer

    2015-04-01

    In this study we investigate the magnetic behavior of magnetic multi-core particles and the differences in the magnetic properties of multi-core and single-core nanoparticles and correlate the results with the nanostructure of the different particles as determined from transmission electron microscopy (TEM). We also investigate how the effective particle magnetic moment is coupled to the individual moments of the single-domain nanocrystals by using different measurement techniques: DC magnetometry, AC susceptometry, dynamic light scattering and TEM. We have studied two magnetic multi-core particle systems - BNF Starch from Micromod with a median particle diameter of 100 nm and FeraSpin R from nanoPET with a median particle diameter of 70 nm - and one single-core particle system - SHP25 from Ocean NanoTech with a median particle core diameter of 25 nm.

  1. Effective particle magnetic moment of multi-core particles

    Energy Technology Data Exchange (ETDEWEB)

    Ahrentorp, Fredrik; Astalan, Andrea; Blomgren, Jakob; Jonasson, Christian [Acreo Swedish ICT AB, Arvid Hedvalls backe 4, SE-411 33 Göteborg (Sweden); Wetterskog, Erik; Svedlindh, Peter [Department of Engineering Sciences, Uppsala University, Box 534, SE-751 21 Uppsala (Sweden); Lak, Aidin; Ludwig, Frank [Institute of Electrical Measurement and Fundamental Electrical Engineering, TU Braunschweig, D‐38106 Braunschweig Germany (Germany); IJzendoorn, Leo J. van [Department of Applied Physics, Eindhoven University of Technology, 5600 MB Eindhoven (Netherlands); Westphal, Fritz; Grüttner, Cordula [Micromod Partikeltechnologie GmbH, D ‐18119 Rostock (Germany); Gehrke, Nicole [nanoPET Pharma GmbH, D ‐10115 Berlin Germany (Germany); Gustafsson, Stefan; Olsson, Eva [Department of Applied Physics, Chalmers University of Technology, SE-412 96 Göteborg (Sweden); Johansson, Christer, E-mail: christer.johansson@acreo.se [Acreo Swedish ICT AB, Arvid Hedvalls backe 4, SE-411 33 Göteborg (Sweden)

    2015-04-15

    In this study we investigate the magnetic behavior of magnetic multi-core particles and the differences in the magnetic properties of multi-core and single-core nanoparticles and correlate the results with the nanostructure of the different particles as determined from transmission electron microscopy (TEM). We also investigate how the effective particle magnetic moment is coupled to the individual moments of the single-domain nanocrystals by using different measurement techniques: DC magnetometry, AC susceptometry, dynamic light scattering and TEM. We have studied two magnetic multi-core particle systems – BNF Starch from Micromod with a median particle diameter of 100 nm and FeraSpin R from nanoPET with a median particle diameter of 70 nm – and one single-core particle system – SHP25 from Ocean NanoTech with a median particle core diameter of 25 nm.

  2. Charmed particle lifetimes

    International Nuclear Information System (INIS)

    Rosner, J.L.

    1979-01-01

    Conventional estimates are reviewed for charmed particle lifetimes. Free-quark models give values of (a few) x 10 -13 sec to (a few) x 10 -12 sec. The shorter of these values also follows from an extrapolation based on D → Ke/sup nu/. Possible differences among the lifetimes and production rates of D 0 , D + , F + , C 0 + , the heavy lepton tau, and the fifth quark b are discussed. Extreme values of mixing angles in a six-quark model could extend charmed particle lifetimes by a factor of at most three from the above estimates, while shorter lifetimes than those predicted could occur for some species like D 0 or F + if their nonleptonic decays were enhanced. The predictions are discussed in the light of some current experimental results, and it is estimated that sigma(pp → charm) approx. = 10 μb at 400 GeV/c. 95 references

  3. Research in particle physics

    International Nuclear Information System (INIS)

    1993-08-01

    This proposal presents the research accomplishments and ongoing activities of Boston University researchers in high energy physics. Some changes have been made in the structure of the program from the previous arrangement of tasks. Task B, Accelerator Design Physics, is being submitted as a separate proposal for an independent grant; this will be consistent with the nature of the research and the source of funding. We are active in seven principal areas which will be discussed in this report: Colliding Beams - physics of e + e - and bar pp collisions; MACRO Experiment - search for magnetic monopoles and study of cosmic rays; Proton Decay - search for nucleon instability and study of neutrino interactions; Particle Theory - theoretical high energy particle physics, including two Outstanding Junior Investigator awards; Muon G-2 - measurement of the anomalous magnetic moment of the muon; SSCintcal - calorimetry for the GEM Experiment; and Muon detectors for the GEM Experiment

  4. Particle therapy planning

    International Nuclear Information System (INIS)

    Zink, S.

    1987-01-01

    The Radiation Research Program (RRP) supports a variety of research through grants and contracts. During the last few years, considerable effort has been devoted to treatment planning evaluation in particle, photon and electron radiotherapy. In 1981, RRP issued a request for proposals (RFP) for the evaluation of treatment planning with particle beam radiotherapy - to include protons, heavy ions and neutrons. Contracts were subsequently awarded to four institutions: Massachusetts General Hospital (MGH), University of Texas and M.D. Anderson Hospital (MDAH), the heavy ion project at Lawrence Berkeley Laboratory (LBL) and University of Pennsylvania (UPa). These contracts reached completion December 31, 1986. The work for the contracts was carried out at the individual institutions and guided through a Working Group made up of the Project Officer and Principal Investigators and primary physicians and physicists at each of the participating institutions. This report summarizes the findings of the Working Group and makes recommendations for further research

  5. Ultralight particle dark matter

    International Nuclear Information System (INIS)

    Ringwald, A.

    2013-10-01

    We review the physics case for very weakly coupled ultralight particles beyond the Standard Model, in particular for axions and axion-like particles (ALPs): (i) the axionic solution of the strong CP problem and its embedding in well motivated extensions of the Standard Model; (ii) the possibility that the cold dark matter in the Universe is comprised of axions and ALPs; (iii) the ALP explanation of the anomalous transparency of the Universe for TeV photons; and (iv) the axion or ALP explanation of the anomalous energy loss of white dwarfs. Moreover, we present an overview of ongoing and near-future laboratory experiments searching for axions and ALPs: haloscopes, helioscopes, and light-shining-through-a-wall experiments.

  6. A palette of particles

    CERN Document Server

    Bernstein, Jeremy

    2013-01-01

    From molecules to stars, much of the cosmic canvas can be painted in brushstrokes of primary color: the protons, neutrons, and electrons we know so well. But for meticulous detail, we have to dip into exotic hues - leptons, mesons, hadrons, quarks. Bringing particle physics to life as few authors can, Jeremy Bernstein here unveils nature in all its subatomic splendor. In this graceful account, Bernstein guides us through high-energy physics from the early twentieth century to the present, including such highlights as the newly discovered Higgs boson. Beginning with Ernest Rutherford's 1911 explanation of the nucleus, a model of atomic structure emerged that sufficed until the 1930s, when new particles began to be theorized and experimentally confirmed. In the postwar period, the subatomic world exploded in a blaze of unexpected findings leading to the theory of the quark, in all its strange and charmed variations. An eyewitness to developments at Harvard University and the Institute for Advanced Study in Prin...

  7. SYMPOSIUM: Particle identification

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1989-07-15

    Typical elementary particle experiments consist of a source of interactions (an external beam and a fixed target or two colliding beams) and a detector system including most of the following components: a tracking system and analysis magnet, calorimetry (measurement of energy deposition), hadron and electron identification, muon detection, trigger counters and processors, and data acquisition electronics. Experiments aimed at future high luminosity hadron collider (proton-proton or proton-antiproton) projects such as an upgraded Tevatron at Fermilab, the Large Hadron Collider (LHC) idea at CERN, and the proposed US Superconducting Supercollider (SSC), must ideally cover the entire solid angle and be capable of not only surviving the collisions, but also providing high resolution event information at incredible interaction rates. The Symposium on Particle Identification at High Luminosity Hadron Colliders held at Fermilab from 5-7 April (sponsored by Fermilab, the US Department of Energy, and the SSC Central Design Group) focused on this single facet of detector technology.

  8. Ultralight particle dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Ringwald, A.

    2013-10-15

    We review the physics case for very weakly coupled ultralight particles beyond the Standard Model, in particular for axions and axion-like particles (ALPs): (i) the axionic solution of the strong CP problem and its embedding in well motivated extensions of the Standard Model; (ii) the possibility that the cold dark matter in the Universe is comprised of axions and ALPs; (iii) the ALP explanation of the anomalous transparency of the Universe for TeV photons; and (iv) the axion or ALP explanation of the anomalous energy loss of white dwarfs. Moreover, we present an overview of ongoing and near-future laboratory experiments searching for axions and ALPs: haloscopes, helioscopes, and light-shining-through-a-wall experiments.

  9. Particles and nuclei, letters

    International Nuclear Information System (INIS)

    2000-01-01

    The present collection of letters from JINR, Dubna, contains seven separate records on the integral representation for structure functions and target mass effects, multiscale properties of DNA primary structure including cross-scale correlations, dissipative evolution of the elementary act, the fine structure of the M T =1 Gamow-Teller resonance in 147g Tb→ 147 Gd β + /EC decay, the behaviour of the TVO temperature sensors in the magnetic fields, a fast method for searching for tracks in multilayer drift chambers of HADES spectrometer, a novel approach to particle track etching including surfactant enhanced control of pore morphology, azimuthal correlations of secondary particles in 32 S induced interactions with Ag(Br) nuclei at 4.5 GeV/ c/ nucleon

  10. Particle detector spatial resolution

    International Nuclear Information System (INIS)

    Perez-Mendez, V.

    1992-01-01

    Method and apparatus for producing separated columns of scintillation layer material, for use in detection of X-rays and high energy charged particles with improved spatial resolution is disclosed. A pattern of ridges or projections is formed on one surface of a substrate layer or in a thin polyimide layer, and the scintillation layer is grown at controlled temperature and growth rate on the ridge-containing material. The scintillation material preferentially forms cylinders or columns, separated by gaps conforming to the pattern of ridges, and these columns direct most of the light produced in the scintillation layer along individual columns for subsequent detection in a photodiode layer. The gaps may be filled with a light-absorbing material to further enhance the spatial resolution of the particle detector. 12 figs

  11. The paradox particle

    International Nuclear Information System (INIS)

    Sutton, Christine

    1993-01-01

    As well as being a leading physics writer, Christine Sutton of Oxford is also a particle physicist, currently working on the Zeus experiment at DESY's HERA electron-proton collider. Her latest book ''Spaceship Neutrino'' Cambridge University Press ISBN 0 521 36404 3 [hardback] or 0 521 36703 4 [paperback]) is a fascinating account of the emergence of the neutrino on the stage of science. In sixty years, the neutrino has been transformed from an apologetic idea its originator dared not publish to one of the main experimental tools of modern high energy research, while cosmologists have realized that this bizarre particle could play a major role in the Universe

  12. Supersymmetric particles at LEP

    International Nuclear Information System (INIS)

    Barbiellini, G.; Coignet, G.; Gaillard, M.K.; Bonneaud, G.; Ellis, J.; Matteuzzi, C.; Wiik, H.

    1979-10-01

    The authors examine whether the supersymmetrization of nature at a mass scale up to 100 GeV can be confirmed or excluded by experiments with LEP. They review the qualitative features of the spectroscopy suggested by supersymmetric theories. Then they discuss possible production rates and means of detection of these particles at LEP. In this framework they make some remarks about other projects for future high energy physics machines which can be used for the study of supersymmetric phenomena. (HSI)

  13. Relaxation from particle production

    Energy Technology Data Exchange (ETDEWEB)

    Hook, Anson; Marques-Tavares, Gustavo [Stanford Institute for Theoretical Physics, Stanford University, Stanford, CA 94305 (United States)

    2016-12-20

    We consider using particle production as a friction force by which to implement a “Relaxion” solution to the electroweak hierarchy problem. Using this approach, we are able to avoid superplanckian field excursions and avoid any conflict with the strong CP problem. The relaxation mechanism can work before, during or after inflation allowing for inflationary dynamics to play an important role or to be completely decoupled.

  14. Making elementary particles visible

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Eyal [ArSciMed (art, science, media), 100, rue du Faubourg Saint Antoine, 75012 Paris (France)

    1994-07-15

    Ever since the days of the ancient Greek atomists, the notion that matter is made up of tiny fundamental elements has dominated the history of scientific theories. Elementary particles (and now strings...) are the latest in this chronological list of fundamental objects. Our notions of what a physical theory should be like, and what precisely ''matter is made up of...'' really means, have evolved with the years, undergoing a profound revolution with quantum mechanics.

  15. Forecasting report. Particle physics

    International Nuclear Information System (INIS)

    The present status of particle and antiparticle physics is examined. As for electromagnetic interactions, the quantum electrodynamics theory is briefly reviewed and the various types of hadronic electromagnetic interactions classified. The theoretical approaches of strong interactions are outlined with hadron spectroscopy. Dynamical models and high energy phenomena are presented. The theoretical problems of weak interaction physics are examined with some experimental aspects. Experimental investigations of the hadron internal structure are briefly surveyed [fr

  16. Making elementary particles visible

    International Nuclear Information System (INIS)

    Cohen, Eyal

    1994-01-01

    Ever since the days of the ancient Greek atomists, the notion that matter is made up of tiny fundamental elements has dominated the history of scientific theories. Elementary particles (and now strings...) are the latest in this chronological list of fundamental objects. Our notions of what a physical theory should be like, and what precisely ''matter is made up of...'' really means, have evolved with the years, undergoing a profound revolution with quantum mechanics

  17. An active particle accelerator

    International Nuclear Information System (INIS)

    Goldman, T.

    1991-01-01

    Although a static charge is difficult to maintain on macroscopic particles, it is straightforward to construct a small object with a regularly oscillating electric dipole moment. For objects of a given size, one may then construct an accelerator by appropriately matching the frequency and separations of an external array of electrodes to this size. Physically feasible size ranges, an accelerator design, and possible applications of such systems are discussed. 8 refs., 9 figs

  18. Introduction to elementary particles

    CERN Document Server

    Griffiths, David J

    2008-01-01

    This is the first quantitative treatment of elementary particle theory that is accessible to undergraduates. Using a lively, informal writing style, the author strikes a balance between quantitative rigor and intuitive understanding. The first chapter provides a detailed historical introduction to the subject. Subsequent chapters offer a consistent and modern presentation, covering the quark model, Feynman diagrams, quantum electrodynamics, and gauge theories. A clear introduction to the Feynman rules, using a simple model, helps readers learn the calculational techniques without the complicat

  19. Particle beam accelerator

    International Nuclear Information System (INIS)

    Turner, N.L.

    1982-01-01

    A particle beam accelerator is described which has several electrodes that are selectively short circuited together synchronously with changes in the magnitude of a DC voltage applied to the accelerator. By this method a substantially constant voltage gradient is maintained along the length of the unshortened electrodes despite variations in the energy applied to the beam by the accelerator. The invention has particular application to accelerating ion beams that are implanted into semiconductor wafers. (U.K.)

  20. Multiscale Simulations Using Particles

    DEFF Research Database (Denmark)

    Walther, Jens Honore

    vortex methods for problems in continuum fluid dynamics, dissipative particle dynamics for flow at the meso scale, and atomistic molecular dynamics simulations of nanofluidic systems. We employ multiscale techniques to breach the atomistic and continuum scales to study fundamental problems in fluid...... dynamics. Recent work on the thermophoretic motion of water nanodroplets confined inside carbon nanotubes, and multiscale techniques for polar liquids will be discussed in detail at the symposium....

  1. Radiation in Particle Simulations

    International Nuclear Information System (INIS)

    More, R.; Graziani, F.; Glosli, J.; Surh, M.

    2010-01-01

    Hot dense radiative (HDR) plasmas common to Inertial Confinement Fusion (ICF) and stellar interiors have high temperature (a few hundred eV to tens of keV), high density (tens to hundreds of g/cc) and high pressure (hundreds of megabars to thousands of gigabars). Typically, such plasmas undergo collisional, radiative, atomic and possibly thermonuclear processes. In order to describe HDR plasmas, computational physicists in ICF and astrophysics use atomic-scale microphysical models implemented in various simulation codes. Experimental validation of the models used to describe HDR plasmas are difficult to perform. Direct Numerical Simulation (DNS) of the many-body interactions of plasmas is a promising approach to model validation but, previous work either relies on the collisionless approximation or ignores radiation. We present four methods that attempt a new numerical simulation technique to address a currently unsolved problem: the extension of molecular dynamics to collisional plasmas including emission and absorption of radiation. The first method applies the Lienard-Weichert solution of Maxwell's equations for a classical particle whose motion is assumed to be known. The second method expands the electromagnetic field in normal modes (planewaves in a box with periodic boundary-conditions) and solves the equation for wave amplitudes coupled to the particle motion. The third method is a hybrid molecular dynamics/Monte Carlo (MD/MC) method which calculates radiation emitted or absorbed by electron-ion pairs during close collisions. The fourth method is a generalization of the third method to include small clusters of particles emitting radiation during close encounters: one electron simultaneously hitting two ions, two electrons simultaneously hitting one ion, etc. This approach is inspired by the virial expansion method of equilibrium statistical mechanics. Using a combination of these methods we believe it is possible to do atomic-scale particle simulations of

  2. 'Hot particle' intercomparison dosimetry

    International Nuclear Information System (INIS)

    Kaurin, D.G.L.; Baum, J.W.; Charles, M.W.; Darley, D.P.J.; Durham, J.S.; Scannell, M.J.; Soares, C.G.

    1996-01-01

    Dosimetry measurements of four 'hot particles' were made at different density thickness values using five different methods. The hot particles had maximum dimensions of 650 μm and maximum beta energies of 0.97, 046, 0.36, and 0.32 MeV. Absorbers were used to obtain the dose at different depths for each dosimeter. Measurements were made using exoelectron dosimeters, an extrapolation chamber, NE Extremity Tape Dosimeters (tm), Eberline RO-2 and RO-2A survey meters, and two sets of GafChromic (tm) dye film with each set read out at a different institution. From these results the dose was calculated averaged over 1 cm 2 of tissue at 18, 70, 125, and 400 μm depth. Comparisons of tissue-dose averaged over 1 cm 2 for 18, 70, and 125 μm depth based on interpolated measured values, were within 30% for the GafChromic (tm) dye film, extrapolation chamber, NE Extremity Tape Dosimeters (tm), and Eberline RO-2 and 2A (tm) survey meters except for the hot particle with 0.46 MeV maximum beta energy. The results for this source showed differences of up to 60%. The extrapolation chamber and NE Extremity Tape dosimeters under-responded for measurements at 400 μm by about a factor of 2 compared with the GafChromic dye films for two hot particles with maximum beta energy of 0.32 and 0.36 MeV which each emitted two 100% 1 MeV photons per disintegration. Tissue doses determined using exoelectron dosimeters were a factor of 2 to 5 less than those determined using other dosimeters, possibly due to failures of the equipment. (author)

  3. Theory of particle interactions

    International Nuclear Information System (INIS)

    Belokurov, V.V.; Shirkov, D.V.

    1986-01-01

    Development and modern state of the theory of elementary particle interactions is described. The main aim of the paper is to give a picture of quantum field theory development in the form easily available for physicists not occupied in this field of science. Besides the outline of chronological development of main representations, the description of renormalization and renorm-groups, gauge theories, models of electro-weak interactions and quantum chromodynamics, the latest investigations related to joining all interactions and supersymmetries is given

  4. Particles, fields, Universe

    International Nuclear Information System (INIS)

    Zeldovich, Ya. B.

    1984-01-01

    A general review is given on the historical development and on the present status of main physical ideas and theories. The concepts of particles, fields and interactions are discussed in detail including most recent developments. The present basic theories of physics: general relativity, gauge theory of electroweak interaction and quantum chromodynamics, their new results and their possible unification are analyzed. The author emphasizes the importance of knowledge as an inherent need of mankind. (D.Gy)

  5. Particles beams and applications

    International Nuclear Information System (INIS)

    Uzureau, J.L.

    1996-01-01

    This issue of the ''Chocs'' journal is devoted to particles beams used by the D.A.M. (Direction of Military Applications) and to their applications. The concerned beams are limited to those in an energy range from hundred of Kev to several Gev. Light ions (protons, deuterons, alpha) where it is easy to produce neutrons sources and heavy ions (from carbon to gold). (N.C.). 8 refs., 2 figs

  6. Particle ID in LHCb

    International Nuclear Information System (INIS)

    Powell, Andrew

    2010-01-01

    Particle identification (PID) is a fundamental requirement for LHCb and is provided by CALO, MUON and RICH sub-detectors. The Calorimeters provide identification of electrons, photons and hadrons in addition to the measurement of their energies and positions. As well as being part of the LHCb trigger, the MUON system provides identification of muons to a very high level of purity, essential for many CP-sensitive measurements that have J/ψ's in their final states. Hadron identification, in particular the ability to distinguish kaons and pions, is crucial to many LHCB analyses, particularly where the final states of interest are purely hadronic. The LHCb RICH system provides this, covering a momentum range between 1 and 100 GeV/c. To maintain the integrity of the LHCb physics performance, it is essential to measure and monitor the particle identification efficiency and mis-identification fraction over time. This can be done by using specific decays, such as K-shorts, φ's, Λ's, J/ψ's and D*'s, for which pure samples can be isolated using only kinematic quantities, due to their unique decay topologies. This allows for clean samples of known particle types to be selected, which can then be used to calibrate and monitor the PID performance from data. The procedures for performing this will be presented, together with preliminary results from the 2009 and 2010 LHC runs. (author)

  7. From particles to plasmas

    International Nuclear Information System (INIS)

    Van Dam, J.W.

    1989-01-01

    The title of this book, From Particles to Plasmas, has more than one meaning. First, it reflects how the scientific career of Marshall Rosenbluth has evolved, beginning in the field of elementary particle physics and extending into his major area of plasma physics. Secondly, it is meant to suggest the wide spectrum of subject matters addressed in the individual lectures, ranging from numerical simulation and space physics and accelerators to various subfields in the physics of plasmas. In the third place, the title is a reference to the way in which the theoretical description of plasmas is often constructed, namely starting from the motion of single particles and then incorporating collective effects. Most of the contributions in this book do concern various aspects of fusion plasma physics, which is the field in which most of Marshall Rosenbluth's scientific contributions have been and are being made. In this field his eminence and authority are indicated by the sobriquet pope of plasma physics that is often applied to him

  8. The particle suppliers

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    Particles are supplied to the LHC by six accelerators inter-connected by several kilometres of transfer lines. This represents yet another complex chain of processes whereby particles are produced, bunched, synchronised and injected into the LHC at the precise moment it's ready to receive them. In other words, for collisions to be produced at the end of the chain, all the injectors must be in perfect working order.   Among all the questions asked by the many visitors to CERN, one in particular comes up time and time again: "Why don't you just connect the LHC directly to the proton source?" In other words, why do you need this whole chain of accelerators acting as an "injector" for the LHC? Before colliding inside the LHC, particles first have to pass through no fewer than six different accelerators: the 90 keV duoplasmatron source, the 750 keV RFQ, the 50 MeV Linac 2, the 1.4 GeV synchrotron injector ("PS Booster" or PSB), the 25 GeV Proton Sy...

  9. Rainbow Particle Imaging Velocimetry

    KAUST Repository

    Xiong, Jinhui

    2017-04-27

    Despite significant recent progress, dense, time-resolved imaging of complex, non-stationary 3D flow velocities remains an elusive goal. This work tackles this problem by extending an established 2D method, Particle Imaging Velocimetry, to three dimensions by encoding depth into color. The encoding is achieved by illuminating the flow volume with a continuum of light planes (a “rainbow”), such that each depth corresponds to a specific wavelength of light. A diffractive component in the camera optics ensures that all planes are in focus simultaneously. With this setup, a single color camera is sufficient to track 3D trajectories of particles by combining 2D spatial and 1D color information. For reconstruction, this thesis derives an image formation model for recovering stationary 3D particle positions. 3D velocity estimation is achieved with a variant of 3D optical flow that accounts for both physical constraints as well as the rainbow image formation model. The proposed method is evaluated by both simulations and an experimental prototype setup.

  10. Superconductivity of small particles

    International Nuclear Information System (INIS)

    Leavens, C.R.; Fenton, E.W.

    1981-01-01

    The Eliashberg gap equations are used to investigate the contribution of surface-phonon softening to the size dependence of the superconducting transition temperature (T/sub c/) of small metallic particles. Because of our limited quantitative knowledge of phonon spectra and electron-phonon coupling in the surface region, the effect cannot be calculated with certainty. Previous calculations which agree with experiment depend on a fortuitous choice of input parameters which cannot be justified at present. For this reason the absence of any observable size effect for T/sub c/ in Pb is especially important. This null effect is obtained in Pb if the electron-phonon coupling strength is the same in the surface region as in the bulk. This assumption can be tested experimentally because it means that the energy gap of Pb should not be independent of particle size but rather should increase significantly with decreasing radius. Hence, measurement of the size dependence of the energy gap for well-characterized small particles of Pb could provide information regarding the importance of the phonon-softening mechanism, at least for Pb

  11. Turbulence and particle acceleration

    International Nuclear Information System (INIS)

    Scott, J.S.

    1975-01-01

    A model for the production of high energy particles in the supernova remnant Cas A is considered. The ordered expansion of the fast moving knots produce turbulent cells in the ambient interstellar medium. The turbulent cells act as magnetic scattering centers and charged particles are accelerated to large energies by the second order Fermi mechanism. Model predictions are shown to be consistent with the observed shape and time dependence of the radio spectrum, and with the scale size of magnetic field irregularities. Assuming a galactic supernova rate at 1/50 yr -1 , this mechanism is capable of producing the observed galactic cosmic ray flux and spectrum below 10 16 eV/nucleon. Several observed features of galactic cosmic rays are shown to be consistent with model predictions. A model for the objects known as radio tall galaxies is also presented. Independent blobs of magnetized plasma emerging from an active radio galaxy into an intracluster medium become turbulent due to Rayleigh--Taylor and Kelvin--Helmholz instabilities. The turbulence produces both in situ betatron and 2nd order Fermi accelerations. Predictions of the dependence of spectral index and flux on distance along the tail match observations well. Fitting provides values of physical parameters in the blobs. The relevance of this method of particle acceleration for the problem of the origin of x-ray emission in clusters of galaxies is discussed

  12. Quantum principles and particles

    CERN Document Server

    Wilcox, Walter

    2012-01-01

    QUANTUM PRINCIPLESPerspective and PrinciplesPrelude to Quantum MechanicsStern-Gerlach Experiment Idealized Stern-Gerlach ResultsClassical Model AttemptsWave Functions for Two Physical-Outcome CaseProcess Diagrams, Operators, and Completeness Further Properties of Operators/ModulationOperator ReformulationOperator RotationBra-Ket Notation/Basis StatesTransition AmplitudesThree-Magnet Setup Example-CoherenceHermitian ConjugationUnitary OperatorsA Very Special OperatorMatrix RepresentationsMatrix Wave Function RecoveryExpectation ValuesWrap Up ProblemsFree Particles in One DimensionPhotoelectric EffectCompton EffectUncertainty Relation for PhotonsStability of Ground StatesBohr ModelFourier Transform and Uncertainty RelationsSchrödinger EquationSchrödinger Equation ExampleDirac Delta FunctionsWave Functions and ProbabilityProbability CurrentTime Separable SolutionsCompleteness for Particle StatesParticle Operator PropertiesOperator RulesTime Evolution and Expectation ValuesWrap-UpProblemsSome One-Dimensional So...

  13. Duality and 'particle' democracy

    Science.gov (United States)

    Castellani, Elena

    2017-08-01

    Weak/strong duality is usually accompanied by what seems a puzzling ontological feature: the fact that under this kind of duality what is viewed as 'elementary' in one description gets mapped to what is viewed as 'composite' in the dual description. This paper investigates the meaning of this apparent 'particle democracy', as it has been called, by adopting an historical approach. The aim is to clarify the nature of the correspondence between 'dual particles' in the light of a historical analysis of the developments of the idea of weak/strong duality, starting with Dirac's electric-magnetic duality and its successive generalizations in the context of (Abelian and non-Abelian) field theory, to arrive at its first extension to string theory. This analysis is then used as evidential basis for discussing the 'elementary/composite' divide and, after taking another historical detour by analyzing an instructive analogy case (DHS duality and related nuclear democracy), drawing some conclusions on the particle-democracy issue.

  14. New particles and interactions

    International Nuclear Information System (INIS)

    Gilman, F.J.; Grannis, P.D.

    1984-04-01

    The Working Group on New Particles and Interactions met as a whole at the beginning and at the end of the Workshop. However, much of what was accomplished was done in five subgroups. These were devoted to: (1) new quarks and leptons; (2) technicolor; (3) supersymmetry; (4) rare decays and CP; and (5) substructure of quarks and leptons. Other aspects of new particles, e.g., Higgs, W', Z', fell to the Electroweak Working Group to consider. The central question of this Workshop of comparing anti pp (with L = 10 32 /cm 2 -sec) with pp (with L = 10 33 /cm 2 -sec) colliders carried through to all these subgroups. In addition there were several other aspects of hadron colliders which were considered: what does an increase in √s gain in cross section and resultant sensitivity to new physics versus an increase in luminosity; will polarized beams or the use of asymmetries be essential in finding new interactions; where and at what level do rate limitations due to triggering or detection systems play a role; and how and where will the detection of particles with short, but detectable, lifetimes be important. 25 references

  15. Particle production by neutrinos

    International Nuclear Information System (INIS)

    Schreiner, P.

    1979-01-01

    A review is given of particle production by neutrinos in charged-current inclusive and exclusive channels. The production rates for various particles in neutrino-nucleon interactions at a beam energy of 25 GeV are compared. The mesons are, of course, dominated by pion production. The p 0 (760) rate is an order of magnitude smaller. Strange and charm pseudoscalar mesons are a further factor of two down in rate. The strange vector mesons are suppressed by more than an order of magnitude relative to K 0 production; however, the charmed D* + (2010) is only a factor of two smaller in rate than the D 0 (1860). With regards to the baryons, most of them are, of course, nucleons. The Λ 0 and Y*(1385) rates are down by one and two orders of magnitudes, respectively. The lower limit on the charmed Σ/sub c/ ++ baryon rate is similar to the Y*(1385) rate. Finally, the quasielastic and one-pion production exclusive channels have about the same cross section as that of the D* + ; associated production of strange particles in the νn → μ - K + Λ channel and the ΔS = +ΔΩ process νp → μ - pK + are down by factors of five and twenty, respectively, compared to the quasielastic cross section

  16. Charged Particle Radiography

    International Nuclear Information System (INIS)

    Morris, Chris

    2004-01-01

    The Coulomb multiple scattering of charged particles as they pass through material allows them to be used as a radiographic probe. This forms the basis for a new kind of radiography that is finding application where conventional x-ray radiography is limited by flux or backgrounds. Charged-particle radiography is providing a versatile new probe that has advantages over conventional x-ray radiography for some unique application. Proton radiography has been used to make quantitative motion pictures of high explosive driven experiments and proves to be of great value for radiographing experiments that mock up nuclear weapon primaries for stockpile certification. By taking advantage of magnetic lens to magnify images and by using the very bright beams that can be made with electrons, charged-particle radiography may be useful for studying the fine spatial detail and very fast motion in laser driven implosion experiments at the National Ignition Facility. Finally, radiographs can be made using cosmic-ray muons for searching vehicles and cargo containers for surreptitious cargo of high z materials such as uranium or plutonium.

  17. Cosmology with decaying particles

    International Nuclear Information System (INIS)

    Turner, M.S.

    1984-09-01

    We consider a cosmological model in which an unstable massive relic particle species (denoted by X) has an initial mass density relative to baryons β -1 identically equal rho/sub X//rho/sub B/ >> 1, and then decays recently (redshift z less than or equal to 1000) into particles which are still relativistic today (denoted by R). We write down and solve the coupled equations for the cosmic scale factor a(t), the energy density in the various components (rho/sub X/, rho/sub R/, rho/sub B/), and the growth of linear density perturbations (delta rho/rho). The solutions form a one parameter (β) family of solutions; physically β -1 approx. = (Ω/sub R//Ω/sub NR/) x (1 + z/sub D/) = (ratio today of energy density of relativistic to nonrelativistic particles) x (1 + redshift of (decay)). We discuss the observational implications of such a cosmological model and compare our results to earlier results computed in the simultaneous decay approximation. In an appendix we briefly consider the case where one of the decay products of the X is massive and becomes nonrelativistic by the present epoch. 21 references

  18. Cosmology with decaying particles

    Energy Technology Data Exchange (ETDEWEB)

    Turner, M.S.

    1984-09-01

    We consider a cosmological model in which an unstable massive relic particle species (denoted by X) has an initial mass density relative to baryons ..beta../sup -1/ identically equal rho/sub X//rho/sub B/ >> 1, and then decays recently (redshift z less than or equal to 1000) into particles which are still relativistic today (denoted by R). We write down and solve the coupled equations for the cosmic scale factor a(t), the energy density in the various components (rho/sub X/, rho/sub R/, rho/sub B/), and the growth of linear density perturbations (delta rho/rho). The solutions form a one parameter (..beta..) family of solutions; physically ..beta../sup -1/ approx. = (..cap omega../sub R//..cap omega../sub NR/) x (1 + z/sub D/) = (ratio today of energy density of relativistic to nonrelativistic particles) x (1 + redshift of (decay)). We discuss the observational implications of such a cosmological model and compare our results to earlier results computed in the simultaneous decay approximation. In an appendix we briefly consider the case where one of the decay products of the X is massive and becomes nonrelativistic by the present epoch. 21 references.

  19. Is an elementary particle really: (i) a particle? (ii) elementary?

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Is an elementary particle really: (i) a particle? (ii) elementary? Over centuries, naïve notions about this have turned out incorrect. Particles are not really pointlike. The word elementary is not necessarily well-defined. Notes:

  20. Alumina particle degradation during solid particle impact on glass

    NARCIS (Netherlands)

    Slikkerveer, P.J.; Veld, in 't H.; Verspui, M.A.; With, de G.; Reefman, D.

    2000-01-01

    Particle degradation limits the reuse of powders in industrial powder-blast processes. In this paper the degradation behavior of Al2O3 powder is studied during erosion of glass substrates. Three techniques were used on original and multiply used powders: particle size measurements, single particle

  1. Particles and cosmology

    International Nuclear Information System (INIS)

    Tkachev, Igor

    1993-01-01

    When the common ground between particle physics, astrophysics and cosmology started to become a developing area, the Institute for Nuclear Research (INR) of the Russian Academy of Sciences had the foresight in 1981 to institute the Baksan Schools on Particles and Cosmology. This now traditional event, held biannually in the Baksan Valley, has gone on to attract international participation. The site is close to the INR Baksan Neutrino Observatory with its underground and surface installations, including the SAGE gallium solar neutrino detector, the Underground Scintillation Telescope, and the 'Carpet' extensive air shower array. Participation is mainly from experimentalists working in non accelerator particle physics and particle astrophysics. The most recent School, held from April 21 to 28, began with an opening address by INR Director V. A. Matveev. J.Frieman reviewed standard big bang cosmology, emphasizing how the recent COBE results and the observations of large scale galaxy clustering fit into a standard cosmology framework. For inflationary cosmology, he showed how different models may be tested through their predictions for large-scale galactic structure and for cosmic microwave background anisotropy. A.Stebbins presented details of the large scale distribution of galaxies which, combined with velocity information and microwave background anisotropy data, provide strong constraints on theories of the origin of primordial inhomogeneities. Inflation requires, and theories of the large scale structure strongly favour the critical value for the cosmic mass density, while, as D.Seckel explained in his lecture on nucleosynthesis and abundances of the light elements, the baryon contribution to this density has to be tens of times smaller. A general review on the observational evidence for dark matter, dark matter particle candidates and the strategy of dark matter searches was given by I. Tkachev, who stressed the gravitational microlensing MACHO

  2. Particle accelerator; the Universe machine

    CERN Multimedia

    Yurkewicz, Katie

    2008-01-01

    "In summer 2008, scientists will switch on one of the largest machines in the world to search for the smallest of particle. CERN's Large Hadron Collider particle accelerator has the potential to chagne our understanding of the Universe."

  3. Steering particles by breaking symmetries

    Science.gov (United States)

    Bet, Bram; Samin, Sela; Georgiev, Rumen; Burak Eral, Huseyin; van Roij, René

    2018-06-01

    We derive general equations of motions for highly-confined particles that perform quasi-two-dimensional motion in Hele-Shaw channels, which we solve analytically, aiming to derive design principles for self-steering particles. Based on symmetry properties of a particle, its equations of motion can be simplified, where we retrieve an earlier-known equation of motion for the orientation of dimer particles consisting of disks (Uspal et al 2013 Nat. Commun. 4), but now in full generality. Subsequently, these solutions are compared with particle trajectories that are obtained numerically. For mirror-symmetric particles, excellent agreement between the analytical and numerical solutions is found. For particles lacking mirror symmetry, the analytic solutions provide means to classify the motion based on particle geometry, while we find that taking the side-wall interactions into account is important to accurately describe the trajectories.

  4. Particle acceleration by plasma waves

    International Nuclear Information System (INIS)

    Joshi, C.

    2006-01-01

    In an advanced particle accelerator particles are driven near by light velocity through ionized gas. Such plasma devices are compact, cost efficient and usable in many fields. Examples are given in detail. (GL)

  5. Relating particles and texture perception

    NARCIS (Netherlands)

    Engelen, L.; Wijk, de R.A.; Bilt, van der A.; Prinz, J.F.; Janssen, A.M.; Bosman, F.

    2005-01-01

    Practically all foods contain particles. It has been suggested that the presence of particles in food may affect the perception of sensory attributes. In the present study we investigated the effect of size and type (hardness and shape) of particles added to a CMC based vanilla custard dessert. The

  6. Particle levitation and laboratory scattering

    International Nuclear Information System (INIS)

    Reid, Jonathan P.

    2009-01-01

    Measurements of light scattering from aerosol particles can provide a non-intrusive in situ method for characterising particle size distributions, composition, refractive index, phase and morphology. When coupled with techniques for isolating single particles, considerable information on the evolution of the properties of a single particle can be gained during changes in environmental conditions or chemical processing. Electrostatic, acoustic and optical techniques have been developed over many decades for capturing and levitating single particles. In this review, we will focus on studies of particles in the Mie size regime and consider the complimentarity of electrostatic and optical techniques for levitating particles and elastic and inelastic light scattering methods for characterising particles. In particular, we will review the specific advantages of establishing a single-beam gradient force optical trap (optical tweezers) for manipulating single particles or arrays of particles. Recent developments in characterising the nature of the optical trap, in applying elastic and inelastic light scattering measurements for characterising trapped particles, and in manipulating particles will be considered.

  7. Particle acceleration by electromagnetic pulses

    International Nuclear Information System (INIS)

    Lai, H.M.

    1982-01-01

    Particle interaction with plane electromagnetic pulses is studied. It is shown that particle acceleration by a wavy pulse, depending on the shape of the pulse, may not be small. Further, a diffusive-type particle acceleration by multiple weak pulses is described and discussed. (author)

  8. Quantum entanglement of identical particles

    International Nuclear Information System (INIS)

    Shi Yu

    2003-01-01

    We consider entanglement in a system with a fixed number of identical particles. Since any operation should be symmetrized over all the identical particles and there is the precondition that the spatial wave functions overlap, the meaning of identical-particle entanglement is fundamentally different from that of distinguishable particles. The identical-particle counterpart of the Schmidt basis is shown to be the single-particle basis in which the one-particle reduced density matrix is diagonal. But it does not play a special role in the issue of entanglement, which depends on the single-particle basis chosen. The nonfactorization due to (anti)symmetrization is naturally excluded by using the (anti)symmetrized basis or, equivalently, the particle number representation. The natural degrees of freedom in quantifying the identical-particle entanglement in a chosen single-particle basis are occupation numbers of different single-particle basis states. The entanglement between effectively distinguishable spins is shown to be a special case of the occupation-number entanglement

  9. Random packing of digitized particles

    NARCIS (Netherlands)

    Korte, de A.C.J.; Brouwers, H.J.H.

    2013-01-01

    The random packing of regularly and irregularly shaped particles has been studied extensively. Within this paper, packing is studied from the perspective of digitized particles. These digitized particles are developed for and used in cellular automata systems, which are employed for the simple

  10. Single particle distributions, ch.2

    International Nuclear Information System (INIS)

    Blokzijl, R.

    1977-01-01

    A survey of inclusive single particle distributions is given for various particles. A comparison of particle cross-sections measured in K - p experiments at different center of mass energies shows that some of these cross-sections remain almost constant over a wide range of incoming K - momenta

  11. Random packing of digitized particles

    NARCIS (Netherlands)

    de Korte, A.C.J.; Brouwers, Jos

    2012-01-01

    The random packing of regularly and irregularly shaped particles has been studied extensively. Within this paper, packing is studied from the perspective of digitized particles. These digitized particles are developed for and used in cellular automata systems, which are employed for the simple

  12. Particle-two particle interaction in configuration space

    International Nuclear Information System (INIS)

    Kuzmichev, V.E.

    1982-07-01

    The problem if three indentical particles with zero-range two-particle interaction is considered. An explicit expression for the effective potential between one particle and the remaining two-particle system is obtained in the coordinate representation. It is shown that for arbitrary energies, at small and, for zero energy, at large distances rho between the one particle and centre of mass of the other two particles the diagonal matrix element of the effective potential is attractive and proportional to 1/rho 2 . This property of the effective potenial explains both the Thomas singularity and the Efimov effect. In the case of zero total energy of the system the general form of the solution of the three-particle integral equation is found in configuration space. (orig.)

  13. Particle size distribution control of Pt particles used for particle gun

    Science.gov (United States)

    Ichiji, M.; Akiba, H.; Nagao, H.; Hirasawa, I.

    2017-07-01

    The purpose of this study is particle size distribution (PSD) control of submicron sized Pt particles used for particle gun. In this report, simple reaction crystallization is conducted by mixing H2PtCl6 and ascorbic acid. Without the additive, obtained Pt particles have broad PSD and reproducibility of experiment is low. With seeding, Pt particles have narrow PSD and reproducibility improved. Additionally, mean particle diameter of 100-700 nm is controlled by changing seeding amount. Obtained particles are successfully characterized as Pt by XRD results. Moreover, XRD spectra indicate that obtained particles are polycrystals. These experimental results suggest that seeding consumed nucleation, as most nuclei attached on the seed surface. This mechanism virtually restricted nucleation to have narrow PSD can be obtained.

  14. Particle acceleration in binaries

    Directory of Open Access Journals (Sweden)

    Sinitsyna V.G.

    2017-01-01

    Full Text Available Cygnus X-3 massive binary system is one of the powerful sources of radio and X-ray emission consisting of an accreting compact object, probably a black hole, with a Wolf-Rayet star companion. Based on the detections of ultra high energy gamma-rays by Kiel and Havera Park, Cygnus X-3 has been proposed to be one of the most powerful sources of charged cosmic ray particles in the Galaxy. The results of long-term observations of the Cyg X-3 binary at energies 800 GeV–85 TeV detected by SHALON in 1995 are presented with images, integral spectra and spectral energy distribution. The identification of source with Cygnus X-3 detected by SHALON was secured by the detection of its 4.8 hour orbital period in TeV gamma-rays. During the whole observation period of Cyg X-3 with SHALON significant flux increases were detected at energies above 0.8 TeV. These TeV flux increases are correlated with flaring activity at a lower energy range of X-ray and/or at observations of Fermi LAT as well as with radio emission from the relativistic jets of Cygnus X-3. The variability of very high-energy gamma-radiation and correlation of radiation activity in the wide energy range can provide essential information on particle mechanism production up to very high energies. Whereas, modulation of very high energy emission connected to the orbital motion of the binary system, provides an understanding of the emission processes, nature and location of particle acceleration.

  15. Hadron particle theory

    International Nuclear Information System (INIS)

    Alonso, J.R.

    1995-05-01

    Radiation therapy with ''hadrons'' (protons, neutrons, pions, ions) has accrued a 55-year track record, with by now over 30,000 patients having received treatments with one of these particles. Very good, and in some cases spectacular results are leading to growth in the field in specific well-defined directions. The most noted contributor to success has been the ability to better define and control the radiation field produced with these particles, to increase the dose delivered to the treatment volume while achieving a high degree of sparing of normal tissue. An additional benefit is the highly-ionizing, character of certain beams, leading to creater cell-killing potential for tumor lines that have historically been very resistant to radiation treatments. Until recently these treatments have been delivered in laboratories and research centers whose primary, or original mission was physics research. With maturity in the field has come both the desire to provide beam facilities more accessible to the clinical setting, of a hospital, as well as achieving, highly-efficient, reliable and economical accelerator and beam-delivery systems that can make maximum advantage of the physical characteristics of these particle beams. Considerable work in technology development is now leading, to the implementation of many of these ideas, and a new generation of clinically-oriented facilities is beginning to appear. We will discuss both the physical, clinical and technological considerations that are driving these designs, as well as highlighting, specific examples of new facilities that are either now treating, patients or that will be doing so in the near future

  16. Particle and nuclear physics

    International Nuclear Information System (INIS)

    Ning, H.; Chong-shi, W.

    1986-01-01

    This book contains the proceedings of the September symposium. There are two parts to this book divided according to particle physics and nuclear physics. Some of the titles of the papers are as follows: Bifurcation and Dynamical Symmetry Breaking, Negative Binomial Distribution for the Multiplicity Distributions in e/sup +/e/sup -/ Annihilation, Variational Study of Lattice QCD, Rescaling for Kaon Structure Function, SDG Boson Model and its Application, The Pair-Aligned Intrinsic Wave Function in Single-j Configuration, and The Short Range Effective Interaction and the Spectra of Calcium Isotopes in (f-p) Space

  17. Online Particle Physics Information

    International Nuclear Information System (INIS)

    Kreitz, Patricia A

    2003-01-01

    This list describes a broad set of online resources that are of value to the particle physics community. It is prescreened and highly selective. It describes the scope, size, and organization of the resources so that efficient choices can be made amongst many sites which may appear similar. A resource is excluded if it provides information primarily of interest to only one institution. Because this list must be fixed in print, it is important to consult the updated version of this compilation which includes newly added resources and hypertext links to more complete information at: http://www.slac.stanford.edu/library/pdg/

  18. Acceleration of polarized particles

    International Nuclear Information System (INIS)

    Buon, J.

    1992-05-01

    The spin kinetics of polarized beams in circular accelerators is reviewed in the case of spin-1/2 particles (electrons and protons) with emphasis on the depolarization phenomena. The acceleration of polarized proton beams in synchrotrons is described together with the cures applied to reduce depolarization, including the use of 'Siberian Snakes'. The in-situ polarization of electrons in storage rings due to synchrotron radiation is studied as well as depolarization in presence of ring imperfections. The applications of electron polarization to accurately calibrate the rings in energy and to use polarized beams in colliding-beam experiments are reviewed. (author) 76 refs., 19 figs., 1 tab

  19. Particles and nuclei, letters

    International Nuclear Information System (INIS)

    2002-01-01

    The present collection of letters from JINR, Dubna, contains eight separate records on the role of the complanar emission of particles in nuclear interaction for E 0 >10 16 eV detected in the stratosphere, 10 B nucleus fragment yields, nuclear teleportation (proposal for an experiment), invisible 'glue' bosons in model field theory, calculation of the ionization differential effective cross sections in fast ion-atom collisions, interactions of ultracold neutrons near surface of solids, g factors as a probe for high-spin structure of neutron-rich Dy isotopes, search for periodicities in experimental data by the autoregressive model methods

  20. Quantum principles and particles

    CERN Document Server

    Wilcox, Walter

    2018-01-01

    This textbook offers a unique introduction to quantum mechanics progressing gradually from elementary quantum mechanics to aspects of particle physics. It presents the microscopic world by analysis of the simplest possible quantum mechanical system (spin 1/2). A special feature is the author’s use of visual aids known as process diagrams, which show how amplitudes for quantum mechanical processes are computed. The second edition include a new chapter on time-dependent processes, in addition to many new problems and improved illustrations.