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Sample records for papilloma virus-like particles

  1. 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

  2. 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...

  3. 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)

  4. Characterization of chikungunya virus-like particles.

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

  6. Vaccine potential of Nipah virus-like particles.

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    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.

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

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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

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

    Science.gov (United States)

    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.

  13. 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...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  1. 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

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

    Science.gov (United States)

    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.

  3. 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

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

    Science.gov (United States)

    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.

  5. 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 ...

  6. 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...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  9. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Andrea Jegerlehner

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. 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

  15. [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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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

  4. 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...

  5. 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.

  6. 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.

  7. 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

  8. 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...

  9. 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 ...

  10. 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.

  11. 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.

  12. 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

  13. 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...

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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...

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  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.

    Directory of Open Access Journals (Sweden)

    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

    Directory of Open Access Journals (Sweden)

    Shaoheng Chen

    2015-01-01

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

  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

    Directory of Open Access Journals (Sweden)

    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.

    Science.gov (United States)

    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

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    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. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  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.

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    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.

    Science.gov (United States)

    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. Human papilloma virus in oral cancer.

    Science.gov (United States)

    Kim, Soung Min

    2016-12-01

    Cervical cancer is the second most prevalent cancer among women, and it arises from cells that originate in the cervix uteri. Among several causes of cervical malignancies, infection with some types of human papilloma virus (HPV) is well known to be the greatest cervical cancer risk factor. Over 150 subtypes of HPV have been identified; more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region and oral cavity. The recently introduced vaccine for HPV infection is effective against certain subtypes of HPV that are associated with cervical cancer, genital warts, and some less common cancers, including oropharyngeal cancer. Two HPV vaccines, quadrivalent and bivalent types that use virus-like particles (VLPs), are currently used in the medical commercial market. While the value of HPV vaccination for oral cancer prevention is still controversial, some evidence supports the possibility that HPV vaccination may be effective in reducing the incidence of oral cancer. This paper reviews HPV-related pathogenesis in cancer, covering HPV structure and classification, trends in worldwide applications of HPV vaccines, effectiveness and complications of HPV vaccination, and the relationship of HPV with oral cancer prevalence.

  14. 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

  15. 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.

  16. 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.

  17. Systemic Immunization with Papillomavirus L1 Protein Completely Prevents the Development of Viral Mucosal Papillomas

    Science.gov (United States)

    Suzich, Joann A.; Ghim, Shin-Je; Palmer-Hill, Frances J.; White, Wendy I.; Tamura, James K.; Bell, Judith A.; Newsome, Joseph A.; Bennett Jenson, A.; Schlegel, Richard

    1995-12-01

    Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

  18. 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

  19. BREAST INTRADUCTAL PAPILLOMA

    OpenAIRE

    Shantanu Kumar Sahu; Prashant Kumar Singh; Birinder Pal Singh; Smriti Bhushan; Kush Aeron; Mohanish Sinha; Praveendra Kumar Sachan

    2012-01-01

    Introduction Intraductal papilloma of the breast is characterized by a proliferation of epithelial and myoepithelial cells overlying fibrovascular stalks creating an arborescent structure within the lumen of duct. Case report We present a 36 years female patient with history of bleeding from the nipple of right breast since last 3months. Examination of right nipple revealed bleeding and mammography show a right ductal papilloma. We performed microdochectomy of the involved duct with excision ...

  20. 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.

  1. 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.

  2. Construction and characterisation of a recombinant fowlpox virus that expresses the human papilloma virus L1 protein

    Directory of Open Access Journals (Sweden)

    Zanotto Carlo

    2011-11-01

    Full Text Available Abstract Background Human papilloma virus (HPV-16 is the most prevalent high-risk mucosal genotype. Virus-like-particle (VLP-based immunogens developed recently have proven to be successful as prophylactic HPV vaccines, but are still too expensive for developing countries. Although vaccinia viruses expressing the HPV-16 L1 protein (HPV-L1 have been studied, fowlpox-based recombinants represent efficient and safer vectors for immunocompromised hosts due to their ability to elicit a complete immune response and their natural host-range restriction to avian species. Methods A new fowlpox virus recombinant encoding HPV-L1 (FPL1 was engineered and evaluated for the correct expression of HPV-L1 in vitro, using RT-PCR, immunoprecipitation, Western blotting, electron microscopy, immunofluorescence, and real-time PCR assays. Results The FPL1 recombinant correctly expresses HPV-L1 in mammalian cells, which are non-permissive for the replication of this vector. Conclusion This FPL1 recombinant represents an appropriate immunogen for expression of HPV-L1 in human cells. The final aim is to develop a safe, immunogenic, and less expensive prophylactic vaccine against HPV.

  3. Congenital papillomas and papillomatoses associated with the Human Papilloma Virus (HPV: report on 5 cases

    Directory of Open Access Journals (Sweden)

    Eliane Pedra Dias

    Full Text Available The authors present a study of five cases of vulvar congenital papillomas and papillomatoses in stillborns and neonates dead upon birth. The studied material was collected from five necropsies. The histopathological evaluation showed hyperkeratosis, acanthosis, papillomatosis, perinuclear haloes, and nuclear abnormalities. In three of the cases, the electron microscopy identified nuclear and cytoplasmatic viral particles ranging from 40 to 60 nm in size, compatible with HPV. The immunohistochemical study of those lesions showed nuclear and cytoplasmatic positivity. The authors concluded that the presence of viral particles suggestive of HPV added to the immunopositivity indicated the possibility of viral infection.

  4. HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7

    Directory of Open Access Journals (Sweden)

    I. S. Malakhov

    2016-01-01

    Full Text Available The cervical cancer is one of the most common diseases in world. This malignancy is the seventh highest prevalence oncological disease worldwide and the second highest prevalence oncological disease of women in the world. Meanwhile women need to be infected by human papilloma virus (HPV is absolutely necessary for it further evolution, HPV DNA was found in 99.97% cases of disease. Except cervical cancer, HPV cause 85% of rectal cancer, 50% of the vulva, vagina and penis cancers, 20% of oropharyngeal cancer and 10% of larynx and esophagus cancers. In 2009, 14 000 women were diagnosed with cervical cancer in Russia. The growth in morbidity was 19% (in comparison with 1999. The most effective recognised measure for almost each infection prophylaxis is a vaccination. Two human papilloma virus vaccines are available in Russia nowadays — Gardasil and Cervarix, produced in Belgium and the Netherlands respectively. Cervarix is a bivalent vaccine based on virus-like particles (VLP of two types. Recombinant major capsid proteins L1 HPV 16 and HPV 18 express in baculovirus expression system and self-assembled into virus-like particles (about 70 percent of cervical cancers are caused by HPV 16 and HPV 18. VLP of each strain produced in different baculovirus vectors and then combined in single drug. Gardasil is like Cervarix with few exceptions. Producing organisms are fungi S. cerevisiae in this case, and this vaccine contains low-risk HPV 6 and HPV 11 VLP. Thus, Gardasil is quadrivalent HPV-6/11/16/18 vaccine. These vaccines are very effective in averting infection of disease and don’t have significant side-effects, however they have some disadvantages. Firstly, they have a high price because of necessity of their expression in eukaryotic cells. Secondly, they are strain-specific, so vaccines are completely effective only for virus’s strains which are represented in the vaccine. Thirdly, it`s the absence of therapeutic (treatment of established

  5. [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.

  6. Molecular cloning and characterization of human papilloma virus DNA derived from a laryngeal papilloma.

    OpenAIRE

    Gissmann, L; Diehl, V; Schultz-Coulon, H J; zur Hausen, H

    1982-01-01

    Papilloma virus DNA from a laryngeal papilloma was cloned in phage lambda L 47 and characterized after cleavage with different restriction enzymes. Hybridization with the DNAs of human papilloma virus types 1, 2, 3, 4, 5, and 8 showed no homology under stringent hybridization conditions. Human papilloma virus type 6 DNA, however, was partially identical to laryngeal papilloma virus DNA; different restriction enzyme fragments hybridizing with the other DNA were identified on each genome. The d...

  7. RECCURENT LARYNGEAL PAPILLOMA

    Directory of Open Access Journals (Sweden)

    Nyilo Purnami

    2012-01-01

    Full Text Available A case of respiratory papillomatosis was reported. The patient suffered from the disease since eight months old with chief complaint progressive hoarseness and dyspnea. It was diagnosed with respiratory papillomatosis and scheduled for performing tracheotomy and continued with the first microlaryngeal surgery (MLS. Decanulation was taken after 2nd surgery of removing papillomas. Finally was reported she got serial of surgery for 22 times during 18 years of age. It was costly and deteriorating quality of life. The problem remains persisted because of frequent recurrences and need for repetitive surgeries. Specimen biopsy for histologic examination was shown the signs of HPV infection, papilomatic coated squamous epithel with mild dysplasia and coilocytosis. The threatening of upper airway obstruction is the main important reason for patient's coming. The patency of airway assessed by Direct Laryngoscopy then the next treatment was decided with schedule of Micro Laryngeal Surgery (MLS. Finally the MLS treatment is just only for temporarily recovery. A further research to define the proper treatment in the future is required, especially for prevention of the diseases related to the viral causes of infection.

  8. Ultrasonographic Diagnosis of Intraductal Papilloma

    International Nuclear Information System (INIS)

    Seong, Ki Ho; Cho, Dae Hyoun; Hwang, Mi Soo

    1996-01-01

    To demonstrate the ultrasonographic findings in the diagnosis of intraductal papilloma by comparing it with mammography and ductography. The findings of mammography (n = 22), ultrasonography (n= 15), and ductography (n = 5) were analyzed in 25 women with intraductal papilloma. The mammographic findings were asymmetric focal increase in density (n = 4 : 18%), mass without calcification (n = 6 : 27%), mass with calcification (n = 2 : 9%), and calcification only (n = 1 : 5%). Nine studies (41%) showed no abnormal findings. The ultrasonographic findings were ductal dilatation with a mass (n = 7 : 47%), mass only (n = 5 : 33%),and intra cystic mass (n = 3 : 20%). There is no case of normal findings on ultrasonography. Three ductograms (60%)showed a filling defect within duct : the other two studies were normal. Ultrasonography offers very useful findings in early detecting the intraductal papilloma in conjunction with mammography and ductography

  9. Association between septal deviation and sinonasal papilloma.

    Science.gov (United States)

    Nomura, Kazuhiro; Ogawa, Takenori; Sugawara, Mitsuru; Honkura, Yohei; Oshima, Hidetoshi; Arakawa, Kazuya; Oshima, Takeshi; Katori, Yukio

    2013-12-01

    Sinonasal papilloma is a common benign epithelial tumor of the sinonasal tract and accounts for 0.5% to 4% of all nasal tumors. The etiology of sinonasal papilloma remains unclear, although human papilloma virus has been proposed as a major risk factor. Other etiological factors, such as anatomical variations of the nasal cavity, may be related to the pathogenesis of sinonasal papilloma, because deviated nasal septum is seen in patients with chronic rhinosinusitis. We, therefore, investigated the involvement of deviated nasal septum in the development of sinonasal papilloma. Preoperative computed tomography or magnetic resonance imaging findings of 83 patients with sinonasal papilloma were evaluated retrospectively. The side of papilloma and the direction of septal deviation showed a significant correlation. Septum deviated to the intact side in 51 of 83 patients (61.4%) and to the affected side in 18 of 83 patients (21.7%). Straight or S-shaped septum was observed in 14 of 83 patients (16.9%). Even after excluding 27 patients who underwent revision surgery and 15 patients in whom the papilloma touched the concave portion of the nasal septum, the concave side of septal deviation was associated with the development of sinonasal papilloma (p = 0.040). The high incidence of sinonasal papilloma in the concave side may reflect the consequences of the traumatic effects caused by wall shear stress of the high-velocity airflow and the increased chance of inhaling viruses and pollutants. The present study supports the causative role of human papilloma virus and toxic chemicals in the occurrence of sinonasal papilloma.

  10. 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.

  11. Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

    Science.gov (United States)

    Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

    2010-06-01

    This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

  12. Papilloma of lip associated with human papilloma viruses-32 infection in a child.

    Science.gov (United States)

    Sabeena, Sasidharanpillai; Pallade, Sadashiva Rao; Kamath, Nutan; Mathew, Mary; Arunkumar, Govindakarnavar

    2016-01-01

    Squamous papilloma is the most common benign oral epithelial lesion, and it is well known to be associated with human papilloma virus 6 and 11. Here, we report a case of squamous papilloma associated with human papilloma viruses (HPV)-32 in a 4-year-old boy who presented with a verrucous lesion on the lower lip. HPV-32 is often associated with a rare benign condition focal epithelial hyperplasia (FEH). A limited number of lesions and the absence of characteristic histology ruled out FEH in our patient. To the best of our knowledge, the association of oral squamous papilloma with HPV-32 is hitherto unreported.

  13. Schneiderian papilloma of the temporal bone

    NARCIS (Netherlands)

    van der Putten, L.; Bloemena, E.; Merkus, P.; Hensen, E.F.

    2013-01-01

    Temporal bone Schneiderian papilloma may present as a primary tumour originating from the middle ear and mastoid process, or an extension from sinonasal disease. Both forms are rare, this being only the 18th case of primary temporal bone Schneiderian papilloma described to date. Although the current

  14. NASAL INVERTED PAPILLOMA OF UNUSUAL ORIGIN

    OpenAIRE

    kasim s. kasim; Universiti Tunku Abdul Rahman; BALWANT SINGH GENDEH

    2013-01-01

    Two cases of Schneiderian papilloma of the nasal septum are presented. The condition is rare, as indicated by a review of previously published cases. The clinical course of the lesion suggests that it behaves like Schneiderian papillomas elsewhere in the nasal cavity and paranasal sinuses. The need for aggressive surgical management and careful follow-up is emphasized.

  15. 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...

  16. Pharyngeal squamous cell papilloma in adult Japanese: comparison with laryngeal papilloma in clinical manifestations and HPV infection.

    Science.gov (United States)

    Hirai, Ryoji; Makiyama, Kiyoshi; Higuti, Yusho; Ikeda, Atsuo; Miura, Masatoshi; Hasegawa, Hisashi; Kinukawa, Noriko; Ikeda, Minoru

    2012-10-01

    A number of reports have investigated the relationship between laryngeal papilloma and human papilloma virus (HPV) infection. On the other hand, it is unclear whether the HPV infection is involved in the occurrence of pharyngeal papilloma. We hypothesized that HPV infection was involved in the occurrence of pharyngeal papilloma similarly to laryngeal papilloma. To verify this hypothesis, we investigated the presence of HPV infection. Furthermore, clinical manifestations of pharyngeal papilloma, which had rarely been reported, were discussed. A male-to-female ratio, solitary or multiple occurrences, and koilocytosis were examined in cases with pharyngeal papilloma. HPV DNA was examined with unfixed surgically resected specimens of pharyngeal papilloma. A screening test by the liquid-phase hybridization method was carried out for the HPV high-risk group (16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59, and 68) and HPV low-risk group (6, 11, 42, 43, 44). As a control, 15 cases with laryngeal papilloma for which the same screening test was carried out were employed. Pharyngeal papilloma occurred as a solitary lesion more often, whereas laryngeal papilloma occurred as multiple tumors more frequently. The HPV infection rate was 0% in pharyngeal papilloma cases, which was in stark contrast with 66.7% in the HPV low-risk group in laryngeal papilloma cases. Pharyngeal papilloma occurred as a solitary lesion in females more frequently. Contrary to our hypothesis, the involvement of HPV infection was unlikely in the occurrence of pharyngeal papilloma.

  17. Prevalence of Human Papilloma Virus in Sinonasal Papilloma in Southern Iranian Population

    OpenAIRE

    Valibeigi, Behnaz; Ashraf, Mohamad Javad; Kerdegari, Narges; Safai, Akbar; Abedi, Elham; Khademi, Bijan; Azarpira, Negar

    2017-01-01

    Statement of the Problem: Sinonasal papilloma (SNP) is a rare benign lesion characterized by high recurrence rate and malignant transformation. Purpose: This study aimed to investigate the prevalence of human papilloma virus (HPV) infection in these lesions in South of Iran. Materials and Method: In this cross sectional retrospective study, a total of 41 patients, 38 SNP and 3 SNP/Squamous cell carcinoma cases, from 2007 to 2014 were studied. Human papilloma virus (HPV) DNA detection w...

  18. 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...

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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...

  6. [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.

  7. VIRUS OF HUMAN PAPILLOMA. EPIDEMIOLOGY, LABORATORY DIAGNOSTICS AND PREVENTION OF PAPILLOMA VIRAL INFECTION

    Directory of Open Access Journals (Sweden)

    O. V. Narvskaya

    2011-01-01

    Full Text Available Abstract. The information reflected modern knowledge about virus of human papilloma (VHP and pathogenesis of papilloma viral infection is presented in the lecture. The actual problems of epidemiology, laboratory diagnostics and prevention of VHP associated damage of cervical epithelium have been described.

  8. Conjunctival papilloma: Clinical features, outcome, and factors related to recurrence

    Directory of Open Access Journals (Sweden)

    Yi-Ming Huang

    2018-01-01

    CONCLUSION: The recurrence of conjunctival papilloma is not uncommon, especially for those patients underwent surgical excision alone. Surgical excision with adjunctive therapy and long-term follow-up is rational for the treatment of conjunctival papilloma.

  9. Effect of human papilloma virus expression on clinical course of laryngeal papilloma.

    Science.gov (United States)

    Kim, Kwang Moon; Cho, Nam Hoon; Choi, Hong Shik; Kim, Young Ho; Byeon, Hyung Kwon; Min, Hyun Jin; Kim, Se-Heon

    2008-10-01

    Our observations suggest that human papilloma virus (HPV) 6/11 is the main causative agent of laryngeal papilloma and that detection of active HPV DNA expression may be helpful in identifying patients with aggressive recurrent laryngeal papilloma. HPV is assumed to be the main causative agent of this disease. We investigated the expression of the entire genotype of HPV in cases of laryngeal papilloma and correlated their expression with the clinical course of the disease. Seventy cases of laryngeal papilloma were evaluated for the presence of the HPV genome by in situ hybridization (ISH) using wide-spectrum HPV DNA probe. Specific types of HPV infection were determined by DNA ISH using type-specific HPV DNA probes (HPV 6, 11, 16, 18, 31, 33). Separate analyses were conducted comparing viral types, frequency of recurrences and duration of disease-free periods. We detected HPV DNA in 40 of the 70 laryngeal papilloma cases (57%). In particular, HPV DNA was detected in 75% of the juvenile types. There were significant associations between HPV and laryngeal papilloma (p<0.01). Among the HPV-positive cases, major specific types were HPV 6/11 (97%). Significant associations were also noted between viral expression and clinical course.

  10. Does human papilloma virus play a role in sinonasal inverted papilloma?

    Science.gov (United States)

    Govindaraj, Satish; Wang, Hailun

    2014-02-01

    Inverted papillomas are a benign sinonasal tumor with a propensity for recurrence and malignant transformation. Although many investigations have been made into the nature of this disease, its etiology and causes for malignant transformation have yet to be fully elucidated. It is the authors' objective to present a review on management of the disease and evaluate the present relationship between human papilloma virus (HPV) and inverted papilloma. A causal relationship between HPV and the pathogenesis and progression of inverted papilloma has been posited since the 1980s. Although widely varied HPV detection rates have been reported, recent studies have noted a substantial increase in both recurrence and malignant transformation in HPV-infected inverted papillomas. However, exact cellular mechanisms by which infection leads to subsequent recurrence and development of carcinoma have yet to be elucidated. Evidence exists suggesting that HPV infection plays a role in the progression of inverted papilloma and confers an increased risk for recurrence and malignant transformation. PCR is the preferred detection method, and fresh or frozen specimens are the ideal source of tissue for evaluation. Although multiple studies have detected an association between HPV and inverted papilloma (both recurrent and malignant transformation), further studies are necessary to elucidate the underlying molecular pathways before an association can be changed to causation.

  11. Human papilloma virus vaccine associated uveitis.

    Science.gov (United States)

    Holt, Henry D; Hinkle, David M; Falk, Naomi S; Fraunfelder, Frederick T; Fraunfelder, Frederick W

    2014-03-01

    To report a possible association between human papilloma virus (HPV) vaccination and uveitis. Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization and Food and Drug Administration were collected on uveitis associated with human papilloma virus vaccination. A MEDLINE search was performed using keywords "uveitis," "iritis," "iridocyclitis," "human papilloma virus," "Cervarix", and "Gardasil." Data garnered from spontaneous reports included the age, gender, adverse drug reaction (ADR), date of administration, concomitant administration of other vaccinations, time until onset of ADR, other systemic reactions, and dechallenge and rechallenge data. A total of 24 case reports of uveitis associated with human papilloma virus vaccination were identified, all cases were female, and the median age was 17. Median time from HPV vaccination to reported ADR was 30 days (range 0-476 days). According to World Health Organization criteria, the relationship between human papilloma virus vaccination and uveitis is "possible." Causality assessments are based on the time relationship of drug administration, uveitis development and re-challenge data. Clinicians should be aware of a possible bilateral uveitis and papillitis following HPV vaccination.

  12. [Vaccine against human papilloma virus].

    Science.gov (United States)

    Juárez-Albarrán, Alfredo César; Juárez-Gámez, Carlos Alberto

    2008-01-01

    Genital human papilloma virus infection (HPV) is the most common sexually transmitted infection worldwide, it is the cause of genital warts, and it is related with cervical cancer, the second most common cause of death from cancer in women in America, and the first in underdeveloped countries, and it is related with penis and prostate cancer in males also, and with anal cancer in both genders. This review examines the most important actual facts about HPV infection, and the new prophylactic vaccines. Two versions of the vaccine had been developed, both target HPV 16 and HPV 18, which involve approximately 70% of cervical cancer. One of them also targets HPV 6 and HPV 11, which account for approximately 90% of external genital warts. Both vaccines have an excellent safety profile, are highly immunogenic, and have atributed complete type specific protection against persistent infection and associated lesions in fully vaccinated girls and young women. The role of men as carriers of HPV as well as vectors for transmission is well documented. Several clinical trials are currently under way to determine the efficacy of vaccinating men. Reducing the cost of vaccination would be a priority for the developing world in order to get a broad target in poor countries.

  13. Human Papilloma Virus and Autophagy

    Directory of Open Access Journals (Sweden)

    Domenico Mattoscio

    2018-06-01

    Full Text Available Human papilloma viruses (HPVs are a group of double-stranded DNA viruses known to be the primary cause of cervical cancer. In addition, evidence has now established their role in non-melanoma skin cancers, head and neck cancer (HNC, and the development of other anogenital malignancies. The prevalence of HPV-related HNC, in particular oropharyngeal cancers, is rapidly increasing, foreseeing that HPV-positive oropharyngeal cancers will outnumber uterine cervical cancers in the next 15–20 years. Therefore, despite the successful advent of vaccines originally licensed for cervical cancer prevention, HPV burden is still very high, and a better understanding of HPV biology is urgently needed. Autophagy is the physiological cellular route that accounts for removal, degradation, and recycling of damaged organelles, proteins, and lipids in lysosomal vacuoles. In addition to this scavenger function, autophagy plays a fundamental role during viral infections and cancers and is, therefore, frequently exploited by viruses to their own benefit. Recently, a link between HPV and autophagy has clearly emerged, leading to the conceivable development of novel anti-viral strategies aimed at restraining HPV infectivity. Here, recent findings on how oncogenic HPV16 usurp autophagy are described, highlighting similarities and differences with mechanisms adopted by other oncoviruses.

  14. Isolated corneal papilloma-like lesion associated with human papilloma virus type 6.

    Science.gov (United States)

    Park, Choul Yong; Kim, Eo-Jin; Choi, Jong Sun; Chuck, Roy S

    2011-05-01

    To report a case of a corneal papilloma-like lesion associated with human papilloma virus type 6. A 48-year-old woman presented with a 2-year history of ocular discomfort and gradual visual deterioration in her right eye. Ophthalmic examination revealed an elevated, semitranslucent, well-defined vascularized mass approximately 4 × 2.5 mm in size localized to the right cornea. The surface of the mass appeared smooth and many small, shallow, and irregular elevations were noted. An excisional biopsy was performed. The underlying cornea was markedly thinned, and fine ramifying vasculature was also noted on the exposed corneal stroma. Typical koilocytic change was observed on the histopathologic examination. Polymerase chain reaction revealed the existence of human papilloma virus type 6 DNA. Here we describe a case of an isolated corneal papilloma-like lesion. Although the corneal extension of the limbal or the conjunctival papillomas has been commonly observed, an isolated corneal papilloma-like lesion with underlying stromal destruction has only rarely been reported.

  15. Bibliographic review on sinonasal inverted papilloma

    International Nuclear Information System (INIS)

    Benavides Vilchez, Juan Vicente

    2014-01-01

    Surgical management recommendations, the index of recurrence and malignancy of the sinonasal inverted papilloma were identified through a bibliographic review of publications from 2002 to 2012. In the literature reviewed several aspects were determined: the risk of recurrences and the possibility of malignization of the inverted papilloma is diminished by complete surgical resection. The actual extent of the injury must be determined in an appropriate manner. The open approaches are recommended for a better visualization of the tumor, allowing the complete resection of the lesion. Endoscopic resection is considered a posterior surgical option, to evaluate the extension of the lesion without requiring incisions in the skin, it is recommended for the treatment of lesions in early stages and as a therapeutic option for some lesions in advanced stages. The recurrence rate is lower through endoscopy in relation to traditional approaches. The unilateral nasal obstruction and the presence of a mass in the nasal cavity are clinical manifestations of the inverted papilloma, whose highest incidence occurs in men and women, between 50 and 70 years of age. By means of clinical, radiological and biopsy suspicion this pathology is confirmed. The recurrence rate is 22% in a period of time from eight to 48 months after the initial surgery. The rate of malignization is 10%, which usually occurs between six and 60 months from the diagnosis of papilloma until the appearance of carcinoma [es

  16. Human papilloma virus prevalence in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E

    2007-08-01

    To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

  17. Prevalence of human papilloma virus in marginal periodontium and its association with periodontitis: A cross sectional study.

    Science.gov (United States)

    Jacob, Anila; Janam, Presanthila; Babu Vijayamma, Janki Mohan

    2014-07-01

    Bacterial pathogens in dental plaque are necessary for the development of periodontitis but this etiology alone does not explain all its clinicopathologic features. Researchers have proven the role of certain viruses like herpes virus in periodontal disease which implies that other viral agents like human papilloma virus may also be involved. This cross-sectional study was conducted to determine the proportion of patients with human papilloma virus (HPV-16) in marginal periodontium by analyzing DNA from the gingival tissue sample and to understand its association with periodontitis. 102 systemically healthy patients between the age group of 15 and 70 years reporting to the Department of Periodontology who required surgical intervention (flap surgery for patients with periodontitis and crown lengthening for healthy patients) with internal bevel gingivectomy were selected. After scaling and root planning, gingival tissue was collected during the respective surgical procedure. DNA was isolated and amplified using specific primers for HPV-16 by polymerase chain reaction (PCR). The amplified products were checked by agarose gel electrophoresis. No HPV DNA was detected in the 102 samples analyzed. Marginal periodontium does not contain HPV in this study population and hence there was no association between HPV and periodontitis.

  18. Prevalence of human papilloma virus in marginal periodontium and its association with periodontitis: A cross sectional study

    Directory of Open Access Journals (Sweden)

    Anila Jacob

    2014-01-01

    Full Text Available Context: Bacterial pathogens in dental plaque are necessary for the development of periodontitis but this etiology alone does not explain all its clinicopathologic features. Researchers have proven the role of certain viruses like herpes virus in periodontal disease which implies that other viral agents like human papilloma virus may also be involved. Aims: This cross-sectional study was conducted to determine the proportion of patients with human papilloma virus (HPV-16 in marginal periodontium by analyzing DNA from the gingival tissue sample and to understand its association with periodontitis. Settings and Design: 102 systemically healthy patients between the age group of 15 and 70 years reporting to the Department of Periodontology who required surgical intervention (flap surgery for patients with periodontitis and crown lengthening for healthy patients with internal bevel gingivectomy were selected. Materials and Methods: After scaling and root planning, gingival tissue was collected during the respective surgical procedure. DNA was isolated and amplified using specific primers for HPV-16 by polymerase chain reaction (PCR. The amplified products were checked by agarose gel electrophoresis. Results: No HPV DNA was detected in the 102 samples analyzed. Conclusion: Marginal periodontium does not contain HPV in this study population and hence there was no association between HPV and periodontitis.

  19. Human papilloma virus in oral cancer

    OpenAIRE

    Kim, Soung Min

    2016-01-01

    Cervical cancer is the second most prevalent cancer among women, and it arises from cells that originate in the cervix uteri. Among several causes of cervical malignancies, infection with some types of human papilloma virus (HPV) is well known to be the greatest cervical cancer risk factor. Over 150 subtypes of HPV have been identified; more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region and oral cavity. The recently introduced vaccine ...

  20. Evidence that human papillomavirus causes inverted papilloma is sparse.

    Science.gov (United States)

    Justice, Jeb M; Davis, Kern M; Saenz, Daniel A; Lanza, Donald C

    2014-12-01

    Controversy exists regarding the pathogenesis of inverted papilloma as it relates to the involvement of human papillomavirus (HPV). The purpose of this report is to describe the prevalence of HPV in nondysplastic, "early inverted papilloma" and to summarize HPV detection rates in the general population and in other HPV related neoplasia. This case series report characterizes consecutive inverted papilloma patients from January 2005 to August 2012 with regard to smoking history, dysplasia, and HPV detection rates. Presence or absence of low/high risk HPV was determined by standardized in situ hybridization DNA probes. Medline literature review was performed to determine the prevalence of HPV in inverted papilloma without moderate or severe dysplasia. Thirty-six consecutive patients were identified with an average age of 63.6 (range, 40-84) years; gender: 23 men, 13 women. More than half (55%) were active or former smokers (14% active and 41% former). High/low risk HPV was present in 1 in 36 (2.7%) patients and 1 in 36 (2.7%) had mild dysplasia. In the literature review: (1) HPV was detected in 16.4% of inverted papilloma without dysplasia; (2) oral cavity HPV detection was 4.2% to 11.4% in the normal population; and (3) HPV was normally detected in 85% to 95% of HPV-related neoplasia. Given histological features of inverted papilloma and comparatively low detection rates of HPV in inverted papilloma without dysplasia (2.7%), as well as the summary of the world literature, HPV is not related to the initial pathogenesis of inverted papilloma or inverted papilloma's tendency to persist or recur. It is postulated that since inverted papilloma is more an inflammatory polyp, it is susceptible to secondary HPV infection because of its metaplasia. Tobacco and other causes of respiratory epithelium remodeling are more plausible explanations for the initial tissue transformation to inverted papilloma. © 2014 ARS-AAOA, LLC.

  1. Psittacid herpesviruses associated with mucosal papillomas in neotropical parrots

    International Nuclear Information System (INIS)

    Styles, Darrel K.; Tomaszewski, Elizabeth K.; Jaeger, Laurie A.; Phalen, David N.

    2004-01-01

    Mucosal papillomas are relatively common lesions in several species of captive neotropical parrots. They cause considerable morbidity and in some cases, result in mortality. Previous efforts to identify papillomavirus DNA and proteins in these lesions have been largely unsuccessful. In contrast, increasing evidence suggests that mucosal papillomas may contain psittacid herpesviruses (PsHVs). In this study, 41 papillomas from 30 neotropical parrots were examined by PCR with PsHV-specific primers. All 41 papillomas were found to contain PsHV DNA. This 100% prevalence of PsHV infection in the papilloma population was found to be significantly higher than PsHV infection prevalence observed in other surveys of captive parrots. PsHV genotypes 1, 2, and 3, but not 4 were found in these lesions. Psittacus erithacus papillomavirus DNA and finch papillomavirus DNA were not found in the papillomas. A papilloma from a hyacinth macaw (Anodorhynchus hyacinthinus) was found to contain cells that had immunoreactivity to antiserum made to the common antigenic region of human papillomavirus (HPV) L1 major capsid protein. However, four other mucosal papillomas were negative for this immunoreactivity, and negative control tissues from a parrot embryo showed a similar staining pattern to that seen in the cloaca papilloma of the hyacinth macaw, strongly suggesting that the staining seen in hyacinth macaw papilloma was nonspecific. Based on these findings, it was concluded that specific genotypes of PsHV play a direct role in the development of mucosal papillomas of neotropical parrots and there is no evidence to suggest the concurrent presence of a papillomavirus in these lesions

  2. 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 ...

  3. Prevalence of Human Papilloma Virus in Sinonasal Papilloma in Southern Iranian Population.

    Science.gov (United States)

    Valibeigi, Behnaz; Ashraf, Mohamad Javad; Kerdegari, Narges; Safai, Akbar; Abedi, Elham; Khademi, Bijan; Azarpira, Negar

    2017-06-01

    Sinonasal papilloma (SNP) is a rare benign lesion characterized by high recurrence rate and malignant transformation. This study aimed to investigate the prevalence of human papilloma virus (HPV) infection in these lesions in South of Iran. In this cross sectional retrospective study, a total of 41 patients, 38 SNP and 3 SNP/Squamous cell carcinoma cases, from 2007 to 2014 were studied. Human papilloma virus (HPV) DNA detection was performed by nested PCR method and positive cases were analyzed for high risk HPV-16 and HPV-18. HPV was detected in 31.7%; HPV- 16 in 4.9% and HPV 18 was not detected at all. Dysplastic epithelium was detected in 53% that was not associated with HPV. Three cases were accompanied with malignant transformation that HPV genome was detected in only one case and none of them were positive for HPV16 /18 genomic DNA. Current research suggests that HPV may be involved in the development of SNP. But the high risk HPV is not important in malignant transformation. More studies are needed to elucidate the possible etiologic mechanism between HPV, inverted papilloma, and squamous cell carcinoma.

  4. 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)

  5. Assessment of human papilloma virus infection in adult laryngeal papilloma using a screening test.

    Science.gov (United States)

    Makiyama, Kiyoshi; Hirai, Ryoji; Matsuzaki, Hiroumi; Ikeda, Minoru

    2013-03-01

    Human papilloma virus (HPV) infection is involved in both juvenile and adult laryngeal papilloma. We wished to determine which types of adult laryngeal papilloma were clinically related to HPV infection. We hypothesized that multiple-site and recurrent papillomas would have a strong relationship to HPV and conducted the present study to test this hypothesis. Thirteen male patients with adult laryngeal papilloma who underwent resection of papilloma between August 2006 and September 2009 were studied. We examined the relationships between whether the tumor was solitary or multiple, presence or absence of recurrence after surgery, and HPV infection. High-risk HPV types (HPV-DNA types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk HPV types (6, 11, 42, 43, and 44) were tested by a liquid-phase hybridization method. In addition, HPV typing was performed for patients positive for low-risk HPV types. Twenty patients with laryngeal carcinoma or laryngeal leukoplakia were enrolled as the control group. In the laryngeal papilloma group, all patients tested were negative for high-risk HPV and 69.2% were positive for low-risk HPV. Typing performed for seven of the patients who tested positive for low-risk HPV showed that one patient was positive for HPV-11, whereas the remaining six patients were positive for HPV-6. All patients with recurrent laryngeal papillomatosis (RLP) were positive for low-risk HPV. All patients who were positive for low-risk HPV had RLP. Tumor samples from repeat operations were positive for low-risk HPV in all patients tested. HPV was not detected in the control group. The relationship between RLP and low-risk HPV was strong, with all cases that were positive for low-risk HPV showing recurrence. Tumor tissue resected at the time of repeat surgery was positive for low-risk HPV in all cases tested. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  6. Analyzing esophageal squamous cell papillomas for the presence of human papilloma virüs.

    Science.gov (United States)

    Tiftikçi, Arzu; Kutsal, Eser; Altıok, Ender; İnce, Ümit; Çicek, Bahattin; Saruç, Murat; Türkel, Nurten; Ersoy, Özdal; Yenmiş, Güven; Tözün, Nurdan

    2017-05-01

    Human Papilloma Virus (HPV) infection can be a predisposing condition for the development of squamous cell papilloma (SCP) of the esophagus, which can progress to dysplasia and to carcinoma as a result of chronic infection. The aim of the present study was to search for the presence of HPV in the esophageal SCP, and to genotype the detected HPV. Data from patients with definite diagnosis of SCP of the esophagus were identified from pathology records for two years period at different Hospitals. Slides from each patient were reviewed and samples with satisfactory papilloma tissues were submitted to molecular analysis. DNA has been isolated. DNA sequencing has been performed for genotyping HPV for all types. Our study group consisted of 21 women and 17 men (a total of 38 patients), mean age was 41 years (range 17-67 years). Most of the papillomas were located at mid-esophagus (68%). Eight out of 38 patients (21%) had associated erosive esophagitis, and fourteen patients (36.8%) had Helicobacter Pylori (H. pylori). Of the 38 SCP analyzed, seven (19%) were positive for HPV DNA. Three of them were of genotype 6, whereas four were of genotype 16, 18, 31, 81 that are known as highly oncogenic. There were no correlations between the presence of HPV and the patient's age, the presence of reflux esophagitis or H. pylori, smoking habit and the location of the papillomas. The presence of high-risk type HPV in esophageal SCP may implicate a role of the virus in the pathogenesis of the esophageal tumor.

  7. Immunohistochemical study on the expression of matrix metalloproteinase 2 and high-risk human papilloma virus in the malignant progression of papillomas

    Science.gov (United States)

    Lee, Ho-Jin

    2013-01-01

    Objectives Papilloma frequently develops as a benign tumor of the head and neck area, but its potential for malignant transformation has yet to be studied. This study aims to provide basic information for papillomas using the immunohistochemical staining of matrix metalloproteinase 2 (MMP-2) and human papilloma virus (HPV) 16 and 18. Materials and Methods To evaluate the malignant transformation of papillomas, the selected tissue samples were serially diagnosed with pre-cancerous papilloma (with epithelial dysplasia, pseudo-epitheliomatous hyperplasia) or malignant lesion (squamous cell carcinoma, SCC) after the first diagnosis (squamous papilloma, inverted papilloma). The selected tissues were stained with an antibody to MMP-2 and HPV 16-E7, HPV 18-L1. A statistical analysis was performed according to each transformation step. Results The epithelial layer of papilloma and pre-cancerous papilloma lesions had a similar MMP-2 expression, but that of the malignant lesion had a significantly increased MMP-2 expression. HPV 16 and 18 infection rates were 28.6%, 33.3% and 63.6% in papillomas, pre-cancerous papilloma lesions, and SCC. Conclusions A relatively high MMP-2 expression and HPV 16 or 18 infection of papillomas may be associated with early events in the multistep processes of malignant transformation of papillomas. PMID:24471049

  8. Histopathological development of equine cutaneous papillomas.

    Science.gov (United States)

    Hamada, M; Oyamada, T; Yoshikawa, H; Yoshikawa, T; Itakura, C

    1990-05-01

    The histopathological development of equine cutaneous papillomas was studied in 78 warts naturally occurring in 50 one to 3-year-old Thoroughbred or Arab horses and in 54 warts experimentally induced in three 2-year-old Thoroughbreds. Lesions in the natural cases were categorized into three phases, growth, development and regression. Main lesions of the growing phase were marked hyperplasia of the basal cells and mild to moderate acanthosis, hyper- and parakeratosis with a few intranuclear inclusion bodies (IIB) which were positive with anti-bovine papillomavirus serum. In the developing phase, there was prominent acanthosis with cellular swelling and fusion, and marked hyper- and parakeratosis. Many IIB were also present in swollen or degenerative prickle cells and granular cells, with a high degree of parakeratosis in keratinocytes. In the regressing phase, epidermal layers were almost normal with only slight hyperplastic change. However, there was rete peg proliferation downward into the dermis with moderate proliferation of fibroblasts and collagen fibres. In addition, in 10 spontaneous and one experimental wart, the lesions were fibropapillomas and this has never been described in horses previously. It was concluded that papillomas were initiated by basal cell hyperplasia without viral antigen production, with formation of acanthosis and hyper- and parakeratosis with IIB production. These findings were confirmed by examination of the experimental cases on the basis of the gross diameter of the warts.

  9. Acute proptosis: Unusual initial presentation of sinonasal inverted papilloma

    Institute of Scientific and Technical Information of China (English)

    Norihan Ibrahim; Baharuddin Abdullah; Regunath Kandasamy; Nor Hayati Othman; Mohtar Ibrahim; Adil Hussein

    2017-01-01

    Inverted papilloma is an uncommon histopathological finding of maxillary sinus tumor. We reported here a rare case of inverted papilloma of maxillary sinus presented initially with ipsilateral proptosis. A middle-aged lady with history of having allergic rhinitis presented with progressive left eye proptosis. Assessment revealed presence of orbital mass arising from paranasal sinus, in which the histopathological examination was initially inconclusive, and later it turned up to be inverted papilloma, partly with malignant transformation. High index of suspicion is necessary especially in those patients with recurrent non-specific sinonasal symptoms, which may need repeated biopsy and histopathological examination. Ocular manifestation signifies a more advance disease.

  10. 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

  11. 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...

  12. 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.

  13. 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...

  14. Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?

    Science.gov (United States)

    Jain, Sonia P; Gulhane, Sachin; Pandey, Neha; Bisne, Esha

    2015-01-01

    Psoriasis is an autoimmune chronic inflammatory skin disease known to be triggered by streptococcal and HIV infections. However, human papilloma virus infection (HPV) as a triggering factor for the development of psoriasis has not been reported yet. We, hereby report a case of plaque type with inverse psoriasis which probably could have been triggered by genital warts (HPV infection) and discuss the possible pathomechanisms for their coexistence and its management.

  15. Acceptability of human papilloma virus vaccine and cervical cancer ...

    African Journals Online (AJOL)

    2012-07-14

    Jul 14, 2012 ... names in a prepared sampling frame of each group of workers, and thereafter ... Following individual counseling of eligible participants, .... Stanley M. Human Papilloma Virus Vaccines versus cervical cancer screening.

  16. Awareness and Uptake of Human Papilloma Virus Vaccination and ...

    African Journals Online (AJOL)

    Awareness and Uptake of Human Papilloma Virus Vaccination and Cervical ... Multistage sampling was used to select 400 female undergraduate students that ... None of the respondents knew that sexual exposure to HPV could result in ...

  17. Human Papilloma Virus Vaccination for Control of Cervical Cancer ...

    African Journals Online (AJOL)

    Human Papilloma Virus Vaccination for Control of Cervical Cancer: A ... Primary HPV prevention may be the key to reducing incidence and burden of cervical cancer ... Other resources included locally-published articles and additional internet ...

  18. Knowledge of the Human Papilloma Virus vaccines, and opinions

    African Journals Online (AJOL)

    AJRH Managing Editor

    Keywords: Human papilloma Virus Vaccine, HPV, Knowledge, Perception, Nigeria .... of the opinion that HPV vaccine should be paid for ... relationships between gender, marital status, grade ... various stages suggest that there is a critical gap.

  19. Local Risk Factors in Genital Human Papilloma Virus Infection in ...

    African Journals Online (AJOL)

    Keywords: Genital human papilloma virus, Pap smear, Risk factors. Access this article online .... their Pap smears taken and questionnaires on sexual attitudes, .... the high‑risk types, which mediate the response of the enhancer to steroid ...

  20. Bug breakfast in the bulletin: human papilloma virus.

    Science.gov (United States)

    Wallace, Cate; Weisberg, Edith; McCaffery, Kirsten

    2007-01-01

    The Bug Breakfast topic for October was Human Papilloma Virus (HPV). The presenters covered the epidemiology of HPV, the newly introduced HPV vaccine and social and psychological issues relating to HPV vaccination.

  1. A case report of inverted papilloma of the posterior urethra

    OpenAIRE

    徳光, 正行; 井内, 裕満; 森川, 満; 八竹, 直

    1992-01-01

    A case of inverted papilloma of the posterior urethra is reported. A 59-year-old male was admitted with the chief complaint of hematuria. Urethrogram revealed a small defect in the neck of the bladder. Endoscopic examination revealed a polypoid tumor on the stalk arising from prostatic urethra, and transurethral resection was performed. The patient has been subsequently followed up and there has been no evidence of recurrence. Although 141 cases of inverted papilloma have been reported in man...

  2. A case report of inverted papilloma of the posterior urethra

    OpenAIRE

    長谷川, 総一郎; 絹川, 常郎; 松浦, 治; 竹内, 宜久; 服部, 良平; 小野, 佳成; 大島, 伸一; 村上, 榮

    1987-01-01

    Sixty-seven cases of inverted papilloma have been reported in many anatomical sites of urinary tract but only 9 cases involving the posterior urethra have been described in Japan. We report the 10th case of inverted papilloma of the posterior urethra in a 27-year-old male who complained of macroscopic hematuria. The lesion was diagnosed cystoscopically and treated by transurethral resection.

  3. Multiple cutaneous inverted papillomas in a dog : clinical communication

    Directory of Open Access Journals (Sweden)

    E.P. Lane

    2007-06-01

    Full Text Available Cutaneous inverted papillomas are described in an 8-month-old mixed breed domestic dog from Windhoek, Namibia. Multiple firm, rapidly growing, doughnut-shaped masses formed on the ventral abdomen, which histologically consisted of a cup-shaped rim of marked epithelial hyperplasia, giant keratohyaline granules and prominent koilocytes and marked hyperkeratosis filling the centre of the mass. Current literature on canine papillomas is briefly reviewed.

  4. Human papilloma virus vaccination: perceptions of young Korean women.

    Science.gov (United States)

    Kang, Hee Sun; Shin, Hyunsook; Hyun, Myung-Sun; Kim, Mi Ja

    2010-09-01

    This paper is a report of a descriptive study of young Korean women's perceptions of use of the human papilloma virus vaccine. In Korea, cervical cancer is one of the leading cancers in women, and the rate of human papilloma virus infection is increasing. A national media campaign has recently begun to promote human papilloma virus vaccination. However, research addressing the acceptability of this vaccine to women in Korea has been limited. Twenty-five Korean women, 21-30 years of age, participated in seven focus groups. The data were collected in 2007. Participants were concerned about the potential harmful effects of the human papilloma virus vaccine, a possible increase in unsafe sexual behaviours, and the high cost of the vaccine, which is not covered by health insurance. They suggested group vaccination at-cost or free of charge. They discussed ambivalence about the vaccination, the need for more information about the vaccine, and questions about its effectiveness. Most preferred to wait until more people have been vaccinated. There is a need for more aggressive dissemination of information about the safety and efficacy of the human papilloma virus vaccine. More reasonable cost, insurance coverage, or free vaccination using a group approach might increase young Korean women's acceptance and use of the human papilloma virus vaccine.

  5. Immunotherapy of Human Papilloma Virus Induced Disease

    Science.gov (United States)

    van der Burg, Sjoerd H

    2012-01-01

    Immunotherapy is the generic name for treatment modalities aiming to reinforce the immune system against diseases in which the immune system plays a role. The design of an optimal immunotherapeutic treatment against chronic viruses and associated diseases requires a detailed understanding of the interactions between the target virus and its host, in order to define the specific strategies that may have the best chance to deliver success at each stage of disease. Recently, a first series of successes was reported for the immunotherapy of Human Papilloma Virus (HPV)-induced premalignant diseases but there is definitely room for improvement. Here I discuss a number of topics that in my opinion require more study as the answers to these questions allows us to better understand the underlying mechanisms of disease and as such to tailor treatment. PMID:23341861

  6. [Study on the correlation between EGFR-STAT3 signal pathway and laryngeal papilloma].

    Science.gov (United States)

    Wang, Xinhua; Sun, Jingwu

    2009-09-01

    To explore the relationship between the expression of EGFR and STAT3 in human laryngeal papilloma and its biological behavior. Reverse transcription polymerase chain reaction(RT-PCR), immunohistochemical staining and Western blot were used to evaluate the mRNA and protein expression of EGFR and STAT3 (p-STAT3) in 42 laryngeal papilloma tissues and 15 samples of normal laryngeal tissue, and the relationship between the protein expression of them and clinic pathological parameters was also analyzed. The mRNA expression levels of EGFR and STAT3 in laryngeal papilloma tissue were significantly higher than that in normal laryngeal tissue (P papilloma than normal laryngeal tissue by immunohistochemistry and western blot (P papilloma (P papilloma (P papilloma,, and the persistent activation of STAT3 gene plays an important role in the recurrence and canceration of laryngeal papilloma.

  7. CT and MR findings of the inverted papilloma

    International Nuclear Information System (INIS)

    Lim, Seong Youb; Kim, Hak Jin; Lee, Jun Woo; Park, Jae Yeong; Lee, Sung Gap; Kim, Byung Soo; Roh, Hwan Jung; Baik, Seung Kook

    1997-01-01

    The purpose of this study is to describe the CT and MR findings of inverted papilloma and to determine the specific differential finding between inverted papilloma with and without coexisting malignancy. Twenty-two histopathologically proven inverted papillomas were included in this study ; in six patients there was coexisting malignancy. Twenty-two CT images and eight MR images were retrospectively reviewed. On CT images, the inverted papillomas were seen as unilateral sinonasal masses with bone remodeling (n=15) rather than bone destruction (n=1) and showed iso- or slightly high attenuation. Three of the six malignant cases showed aggressive bone destruction and widespread extension into the orbit, intracranial and buccal spaces, and pterygopalatine fossa. On MR images, the inverted papillomas (n=3) were iso- (n=2) or slightly high (n=1) in signal intensity in relation to muscle on T1-weighted images, and high (n=3) on T2-weighted images. Gadolinium enhanced images showed heterogenous moderate enhancement. In the cases of coexisting malignancy (n=5), the masses were iso- (n=5) on T1-weighted images, high (n=5) on T2-weighted images and also showed heterogenous moderate enhancement. Inverted papilloma should be considered in the differential diagnosis of a bulky unilateral nasal mass extending into the adjacent paranasal sinuses, especially in an elderly patient with chronic nasal obstruction. Although there were no specific differential findings in signal intensity and enhancement pattern on CT and MR images between benign and malignant inverted papilloma, aggressive bone destruction and widespread extension beyond the sinonasal cavity are findings which are highly suggestive of coexisting malignancy

  8. Solitary Tracheobronchial Papilloma: Cytomorphology and ancillary studies with histologic correlation

    Directory of Open Access Journals (Sweden)

    Tee U Lang

    2011-01-01

    Full Text Available Solitary tracheobronchial papilloma (STBP is a rare benign tumor that primarily involves the tracheobronchial tree. Human papilloma virus (HPV infection is associated with dysplasia and a high risk of carcinoma in these lesions. The cytomorphology of STBP is not well established in the literature. Our aim is to characterize the cytomorphologic features of STBP, with histologic correlation in a series of 6 patients - 4 males and 2 females - with a mean age of 67 years (range, 53-88 years. There were 5 biopsy-proven squamous papillomas and 1 glandular papilloma. On surgical biopsy, squamous papillomas exhibited cytological atypia (4 graded mild and 1 graded moderate with focal severe dysplasia, surface erosion, and inflammation. Cytology specimens available for review included a combination of 4 fine-needle aspirations (FNAs, 2 bronchoalveolar lavages and 2 (of 3 bronchial brushings. Cytologic findings associated with squamous papillomas included atypical squamous cells and rare squamous cell resembling koilocyte in 1 bronchial brushing. Sheets of squamous cells were identified in another specimen. Several cases had a prominent background of acute inflammation, and candida was present in 1 specimen. HPV in-situ hybridization was positive in 1 case and negative in 2 cases. A p16 immunocytochemical stain performed on 1 cell block was negative. In conclusion, although STBP is a rare neoplasm, these cases may be encountered in respiratory cytology samples. FNA of papillomas yields fewer lesional cells compared to exfoliative samples. These lesions may be mistaken in cytology specimens for squamous cell carcinoma, squamous-lined cavitary lesions, an infectious (fungal process, reactive squamous metaplasia, or oral contamination.

  9. Solitary Tracheobronchial Papilloma: Cytomorphology and ancillary studies with histologic correlation.

    Science.gov (United States)

    Lang, Tee U; Khalbuss, Walid E; Monaco, Sara E; Pantanowitz, Liron

    2011-03-03

    Solitary tracheobronchial papilloma (STBP) is a rare benign tumor that primarily involves the tracheobronchial tree. Human papilloma virus (HPV) infection is associated with dysplasia and a high risk of carcinoma in these lesions. The cytomorphology of STBP is not well established in the literature. Our aim is to characterize the cytomorphologic features of STBP, with histologic correlation in a series of 6 patients - 4 males and 2 females - with a mean age of 67 years (range, 53-88 years). There were 5 biopsy-proven squamous papillomas and 1 glandular papilloma. On surgical biopsy, squamous papillomas exhibited cytological atypia (4 graded mild and 1 graded moderate with focal severe dysplasia), surface erosion, and inflammation. Cytology specimens available for review included a combination of 4 fine-needle aspirations (FNAs), 2 bronchoalveolar lavages and 2 (of 3) bronchial brushings. Cytologic findings associated with squamous papillomas included atypical squamous cells and rare squamous cell resembling koilocyte in 1 bronchial brushing. Sheets of squamous cells were identified in another specimen. Several cases had a prominent background of acute inflammation, and candida was present in 1 specimen. HPV in-situ hybridization was positive in 1 case and negative in 2 cases. A p16 immunocytochemical stain performed on 1 cell block was negative. In conclusion, although STBP is a rare neoplasm, these cases may be encountered in respiratory cytology samples. FNA of papillomas yields fewer lesional cells compared to exfoliative samples. These lesions may be mistaken in cytology specimens for squamous cell carcinoma, squamous-lined cavitary lesions, an infectious (fungal) process, reactive squamous metaplasia, or oral contamination.

  10. [Genotyping of oncogenic human papilloma viruses in women with HG SIL diagnosis].

    Science.gov (United States)

    Kedzia, Witold; Pruski, Dominik; Józefiak, Agata; Rokita, Wojciech; Spaczyński, Marek

    2010-10-01

    Development of primary prevention of cervical cancer in other words a vaccination against selected, oncogenic HPV types, entails an increasing importance of epidemiological studies and prevalence of various types of human papilloma virus. The incidence of HPV varies depending on the geographic location of the population. The effectiveness of primary prevention against HPV 16, 18, in the context of reducing the incidence of cervical cancer will depend, among others, on the prevalence of these types in the population and virus-like antigens, which are partially cross-resistant. Identification of the most frequent, oncogenic HPV types in women with HG SIL diagnosis from Central and Western Poland to assess the merits of the development of primary prevention. For the purpose of molecular tests identifying the presence of 13 DNA oncogenic virus types, swabs were taken with the cyto-brush from 76 women diagnosed with CIN 2 or CIN 3 (HG SIL). Patients eligible for the study were diagnosed at the Laboratory of Pathophysiology of Uterine Cervix, Gynecology and Obstetrics Clinical Hospital of Karol Marcinkowski University of Medical Sciences. Patients came from Central and Western parts of Poland. Cell material in which the method of Amplicor HPV (Roche Diagnostics) identified the presence of DNA of oncogenic HPV types was in each case subsequently subjected to genotyping using the molecular test - Linear Array HPV Genotyping (Roche Diagnostics). Five most common oncogenic HPV types in order of detection included: 16, 33, 18, 31, 56. Together these five types of virus comprised 75.86% (88/116) of all detected HPV types. 1. In women from Central and Western Poland, diagnosed with HG SIL, the most common HPV genotypes were HPV 16, HPV33, HPV 18, HPV31, HPV56. 2. Two HPV types 16 and 18, against which vaccinations are directed, belong to the group of three genotypes of HPV most commonly identified in the evolution of CIN 2, CIN 3 diagnosed in women from Central and Western

  11. Transnasal endoscopic medial maxillectomy in recurrent maxillary sinus inverted papilloma.

    Science.gov (United States)

    Kamel, Reda H; Abdel Fattah, Ahmed F; Awad, Ayman G

    2014-12-01

    Maxillary sinus inverted papilloma entails medial maxillectomy and is associated with high incidence of recurrence. To study the impact of prior surgery on recurrence rate after transnasal endoscopic medial maxillectomy. Eighteen patients with primary and 33 with recurrent maxillary sinus inverted papilloma underwent transnasal endoscopic medial maxillectomy. Caldwell-Luc operation was the primary surgery in 12 patients, transnasal endoscopic resection in 20, and midfacial degloving technique in one. The follow-up period ranged between 2 to 19.5 years with an average of 8.8 years. Recurrence was detected in 8/51 maxillary sinus inverted papilloma patients (15.7 %), 1/18 of primary cases (5.5 %), 7/33 of recurrent cases (21.2 %); 3/20 of the transnasal endoscopic resection group (15%) and 4/12 of the Caldwell-Luc group (33.3%). Redo transnasal endoscopic medial maxillectomy was followed by a single recurrence in the Caldwell-Luc group (25%), and no recurrence in the other groups. Recurrence is more common in recurrent maxillary sinus inverted papilloma than primary lesions. Recurrent maxillary sinus inverted papilloma after Caldwell-Luc operation has higher incidence of recurrence than after transnasal endoscopic resection.

  12. Multiple intraductal papillomas of breast clinically masquerading as malignancy

    Directory of Open Access Journals (Sweden)

    Singh Pallavi

    2010-01-01

    Full Text Available Background: Intraductal papilloma is characterized by proliferation of epithelial and myoepithelial cells overlying fibro-vascular stalks creating an arborescent structure within the lumen of duct. Some times multiple papillomas with florid proliferation of epithelium may be confused with malignancy. A case of multiple intraductal papillomas of breast with ulceration of overlying skin and large lump leading to clinical diagnosis of malignancy is documented here. Case Report: A 45-year-old female presented with ulcerated mass of six months duration in the left breast. On examination, a firm, immobile lump of 8× 10 cm in size involving nipple with excoriation of surrounding skin and serosanguinous discharge from nipple was present. There was no axillary lymphadenopathy. No family history of carcinoma breast was present. Fine needle aspiration smears showed benign cellular changes with apocrine metaplasia. Biopsy from an area adjacent to nipple showed intraductal papilloma. Simple mastectomy showed lobulated dirty white mass with well circumscribed nodules below the nipple and areola. On histology with immunohistochemistry a diagnosis of multiple intraductal papillomas was made. Patient is on regular follow-up and doing well. Conclusion: The case highlights the problem in differentiating marked papillomatosis from a malignant lesion of breast and importance of biopsy with immunohistochemistry in such cases for proper management.

  13. Human papilloma virus infection and cervical dysplasia.

    Science.gov (United States)

    Melinte-Popescu, Alina; Costăchescu, Gh

    2012-01-01

    Pap testing is considered to be the best screening tool for cervical cancer but there is currently great interest in the possible application of human papilloma virus (HPV) testing to supplement Pap screening for cervical cancer. To determine the prevalence of high-risk HPV types in the studied population and to explore the association between high-risk HPV types and cervical dysplasia. Cross-sectional study conducted at the Iasi Cuza Voda Obstetrics-Gynecology Hospital and Suceava County Hospital. 332 women who underwent colposcopy for cervical lesions between 2006 and 2011 were included in this study. The overall prevalence of HPV was 57.23%. HPV prevalence differs significantly in the three age groups up to 50 years. It was highest in patients below the age of 40 and progressively lower with advancing age. The overall prevalence of cervical dysplasia was 56.62%. The prevalence of cervical dysplasia was highest in the age groups up to 40 years. The most important determinant of HPV infection is age. Persistence of HPV appears to be associated with progression to squamous intraepithelial lesion. Dysplasia is often missed in a cervical sample either because of human error in screening and interpretation, or because of suboptimal quality of Pap smear. Incorporation of HPV testing into the present Pap screening program has the potential of making screening for cervical cancer more effective, and a necessary prelude to assessing this is by determining the prevalence of the high-risk types.

  14. Laryngeal squamous cell papilloma is highly associated with human papillomavirus.

    Science.gov (United States)

    Orita, Yorihisa; Gion, Yuka; Tachibana, Tomoyasu; Ikegami, Kana; Marunaka, Hidenori; Makihara, Seiichiro; Yamashita, Yasuhiko; Miki, Kentaro; Makino, Takuma; Akisada, Naoki; Akagi, Yusuke; Kimura, Miyuki; Yoshino, Tadashi; Nishizaki, Kazunori; Sato, Yasuharu

    2018-04-01

    To delineate the association between characteristics of adult-onset laryngeal squamous cell papilloma and human papillomavirus (HPV) infection. Clinical records and paraffin-embedded specimens of 77 papilloma patients who had been treated between 1998 and 2014 were collected. Of the 77 cases, 34 were identified in the larynx, 28 in the oral cavity and 15 in the oropharynx. Specimens were investigated by polymerase chain reaction (PCR) to detect HPV 6, 11, 16, 18, 31, 33, 35, 52b and 58, and immunohistochemical (IHC) staining for anti-p16INK4a antibody. In 21 cases (61.8%) with laryngeal squamous cell papilloma, various types of HPV were detected: 14 cases (41.2%) were positive of high-risk HPV, 18 (52.9%) were positive of low-risk HPV and 11 (32.4%) were positive of both high-risk HPV and low-risk HPV. Younger patients (papilloma, no malignant transformation was observed during the study period. With IHC staining, positive expression of p16 was observed in 20 cases (58.8%). HPV infection and p16-expression were associated with the pathological finding of koilocytosis. Only four cases (14.3%) showed HPV-positivity in the oral cavity, and none of the 15 oropharyngeal cases were positive for HPV, and none of the oral cavity and oropharyngeal cases showed koilocytosis. Results of HPV-PCR and p16-IHC staining were significantly correlated each other. HPV infection is frequently associated with laryngeal squamous cell papilloma, and koilocytosis is a characteristic pathological finding. To the best of our knowledge, this is the first report which have described infections with multiple HPV types in laryngeal papilloma.

  15. Benign papilloma of the male breast following chronic phenothiazine therapy.

    Science.gov (United States)

    Sara, A S; Gottfried, M R

    1987-05-01

    Benign intraductal papilloma is a rare lesion in the male breast. The authors report the occurrence of an intraductal papilloma in a male with more than a ten-year history of phenothiazine therapy (Mellaril and Prolixin). Phenothiazines have been demonstrated to cause elevated serum prolactin levels. The literature regarding the relationship between prolactin and mammary tumors in rodents and in humans remains controversial. The occurrence of this rare male breast tumor in the setting of chronic phenothiazine therapy raises further questions as to the role of prolactin in the development of mammary tumors.

  16. [A case of laryngeal papilloma with sudden dyspnea].

    Science.gov (United States)

    Pabiszczak, Maciej; Wierzbicka, Małgorzata; Borucki, Lukasz; Iwanik, Katarzyna

    2005-01-01

    Laryngeal papilloma is one of the most common non-malignant tumors of the larynx. In adult they are included to pre-cancerous diseases. In morphological examination, it is a solid tumor. Often it is possible to cure them during one surgical procedure. The disease is mostly localized on the anterior commissurae region, vocal fold, ventricules, and on the laryngeal surface of the epiglottis. If the malignant transformation is suspected, a large excision with margin has to be performed, completed by a histological evaluation. A case of a huge laryngeal papilloma with dyspnea is presented.

  17. Smoking, not human papilloma virus infection, is a risk factor for recurrence of sinonasal inverted papilloma.

    Science.gov (United States)

    Roh, Hwan-Jung; Mun, Sue Jean; Cho, Kyu-Sup; Hong, Sung-Lyong

    2016-01-01

    The recurrence rate of sinonasal inverted papillomas (SNIP) is 15-20%. However, few studies have investigated patient-dependent factors related to recurrence of SNIPs. To analyze risk factors, including human papilloma virus (HPV) infection and smoking, as well as other factors, for recurrence of SNIPs. Fifty-four patients who were diagnosed with SNIP and underwent surgery were enrolled: 39 men and 15 women, with the mean age of 54.0 years. Their mean follow-up was 40.6 months. Demographics and information about the history of smoking, previous surgery, tumor extent, follow-up, and recurrence were reviewed retrospectively. Those patients whose tumors were associated with malignant transformation were excluded in this study. HPV detection and genotyping in the tumor specimens were performed with the HPV DNA chip, a polymerase chain reaction-based DNA microarray system. Seven patients (13.0%) had recurrence, with a mean time to recurrence of 39.8 months. Recurrence rates in T1, T2, T3, and T4 of the Krouse staging system were 0% (0/4), 8.3% (2/24), 17.4% (4/23), and 33.3% (1/3), respectively (p > 0.5). Eight patients (14.8%) were positive for HPV DNA. All of these patients belonged to the group without recurrence (p > 0.5). However, recurrence rates according to HPV DNA positivity were not statistically different (0% versus 15.2%). Three (42.9%) in the group with recurrence and four (8.5%) in the group without recurrence were smokers (p < 0.5). Smoking was associated with recurrence of SNIP. However, HPV infection is not a recurrence of SNIP risk factor.

  18. inverted papilloma of the nasal cavity and paranasal sinuses

    African Journals Online (AJOL)

    1971-05-08

    May 8, 1971 ... Although the inverted papilloma of the nasal cavity has been studied for over 100 years, the clinical approach to this lesion remains ill-defined and wide recognition of the problems involved is still not evident. This may be attributed to the infrequency of the condition, the ease with which it may be mistaken ...

  19. Knowledge of the Human Papilloma Virus vaccines, and opinions of ...

    African Journals Online (AJOL)

    The objective of this study was to determine the knowledge and perception of Nigerian Obstetricians and Gynaecologists towards human papilloma virus vaccine use in Nigeria. A cross sectional study was conducted amongst participants that attended the 42nd Society of Gynaecology and Obstetrics of Nigeria. The findings ...

  20. The influence of marital factors on genital human papilloma virus ...

    African Journals Online (AJOL)

    Aim: To study the association between marital factors and human papilloma virus (HPV) infection of the cervix. Method: The subjects were 450 randomly selected sexually active women attending the antenatal, postnatal, gynaecology and family planning clinics in the Department of Obstetrics and Gynaecology of the ...

  1. Human Papilloma Virus Vaccine: Determinants of Acceptability by ...

    African Journals Online (AJOL)

    Vaccination of adolescent females against Human Papilloma Virus (HPV), the causative agent for cervical cancer has recently become available. As minors, parental acceptance of the vaccines for adolescent daughters requires exploration. This was a cross-sectional survey of 201 mothers attending the gynaecology clinic ...

  2. Suspected side effects to the quadrivalent human papilloma vaccine

    DEFF Research Database (Denmark)

    Brinth, Louise; Theibel, Ann Cathrine; Pors, Kirsten

    2015-01-01

    INTRODUCTION: The quadrivalent vaccine that protects against human papilloma virus types 6, 11, 16 and 18 (Q-HPV vaccine, Gardasil) was included into the Danish childhood vaccination programme in 2009. During the past years, a collection of symptoms primarily consistent with sympathetic nervous...

  3. Health Disparity in Human Papilloma Virus Related Infections | Poku ...

    African Journals Online (AJOL)

    In spite of the volume of information of Human Papilloma Virus (HPV) and the HPV vaccines, there are racial and gender differences in the knowledge and awareness of HPV among Guyanese. The study aimed to assess the knowledge and attitude towards HPV infection, cervical cancer and HPV vaccines. The study was ...

  4. Human Papilloma Virus vaccination: knowledge, attitude and uptake ...

    African Journals Online (AJOL)

    Human Papilloma Virus vaccination: knowledge, attitude and uptake among female medical and dental students in a tertiary institution in Benin-City, Nigeria. ... Age (p = 0.001), faculty (p = 0.014) and level of study (p = 0.014) was observed to be significant determinants of knowledge. A higher proportion of respondents ...

  5. Human papilloma virus: a new risk factor in a subset of head and neck cancers.

    Science.gov (United States)

    Bisht, Manisha; Bist, Sampan Singh

    2011-01-01

    Head and neck cancer is the sixth most common malignancy worldwide. Tobacco smoking and alcohol consumption are two well known behavioral risk factors associated with head and neck cancer. Recently, evidence is mounting that infection with human papilloma virus, most commonly human papilloma virus-16 is responsible for a subset of head and neck squamous cell carcinoma especially tumors of tonsillar origin. The molecular pathway used by human papilloma virus to trigger malignant transformation of tissue is different from that of other well known risk factors, i.e. smoking and alcohol, associated with squamous cell carcinoma. Apparently, these subsets of patients with human papilloma virus positive tumor are more likely to have a better prognosis than human papilloma virus negative tumor. Considering this fact, the human papilloma virus infection should be determined in all oropharyngeal cancers since it can have a major impact on the decision making process of the treatment.

  6. 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)

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Women's awareness of the human papilloma virus and related health problems.

    Science.gov (United States)

    Akyuz, Aygul; Yılmaz, Cevriye; Yenen, Müfit Cemal; Yavan, Tülay; Kılıç, Ayşe

    2011-12-01

    This paper is a report of a study of women's awareness of the human papilloma virus and related health problems. Cervical cancer is an important cause of mortality, making up approximately 12% of all cancers in women. Awareness on the part of carriers of human papilloma virus is crucial in preventing transmission of the infection and protecting against cervical cancer. The study was performed as a cross-sectional descriptive study. The study consists of 79 human papilloma virus-positive women who had not been diagnosed with cervical cancer and 150 women who had not been diagnosed with human papilloma virus. Data were collected via questionnaires between November 2007 and April 2008. Percentages and chi-square test were used. A significantly higher percentage of women with positive human papilloma virus knew the definition of human papilloma virus, the fact that it is transmitted via sexual contact and that it can lead to cervical cancer than did women with negative human papilloma virus. It was established that approximately half the women with positive human papilloma virus presented at the hospital with a genital wart. None of the women knew that a Pap smear test was a necessary tool in the prevention of cervical cancer. Women with positive human papilloma virus have insufficient knowledge of human papilloma virus, sexually transmitted diseases, the health risks associated with human papilloma virus and the means of preventing these risks. It is therefore necessary to evaluate the education of health workers, and especially of nurses, on human papilloma virus and its prevention. © 2011 Blackwell Publishing Ltd.

  12. Modulation of TIP60 by Human Papilloma Virus in Breast Cancer

    Science.gov (United States)

    2013-04-01

    1 AG________ Award Number: W81XWH-11-1-0687 Title Modulation of TIP60 by Human Papilloma Virus in Breast Cancer... Human Papilloma Virus in Breast Cancer 5b. GRANT NUMBER 1 H 11 1 06 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT...virus (EBV), Hepatitis B Virus (HBV), Hepatitis C virus (HCV), Human Papilloma virus (HPV), Human T-cell lymphotropic virus (HTLV-1) and Kaposi’s

  13. 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

  14. Radiomic analysis in prediction of Human Papilloma Virus status.

    Science.gov (United States)

    Yu, Kaixian; Zhang, Youyi; Yu, Yang; Huang, Chao; Liu, Rongjie; Li, Tengfei; Yang, Liuqing; Morris, Jeffrey S; Baladandayuthapani, Veerabhadran; Zhu, Hongtu

    2017-12-01

    Human Papilloma Virus (HPV) has been associated with oropharyngeal cancer prognosis. Traditionally the HPV status is tested through invasive lab test. Recently, the rapid development of statistical image analysis techniques has enabled precise quantitative analysis of medical images. The quantitative analysis of Computed Tomography (CT) provides a non-invasive way to assess HPV status for oropharynx cancer patients. We designed a statistical radiomics approach analyzing CT images to predict HPV status. Various radiomics features were extracted from CT scans, and analyzed using statistical feature selection and prediction methods. Our approach ranked the highest in the 2016 Medical Image Computing and Computer Assisted Intervention (MICCAI) grand challenge: Oropharynx Cancer (OPC) Radiomics Challenge, Human Papilloma Virus (HPV) Status Prediction. Further analysis on the most relevant radiomic features distinguishing HPV positive and negative subjects suggested that HPV positive patients usually have smaller and simpler tumors.

  15. The management of sinonasal inverted papilloma: our experience.

    Science.gov (United States)

    Terzakis, Georgios; Vlachou, Stamatia; Kyrmizakis, Dionysios; Helidonis, Emmanuel

    2002-03-01

    The inverted papilloma of the nose and paranasal sinuses is a controversial disease. It invades surrounded structures, shows a high recurrence rate after surgical excision and may coexist with squamous cell carcinoma. The use of the optimal surgical approach and technique is of the utmost importance, as it is related to the possibility of recurrence. In cases of tumors of limited size a conservative local excision is sufficient, while, in larger tumors filling the nasal cavity and the paranasal sinuses a more aggressive strategy is needed, such as a medial maxillectomy after lateral rhinotomy. In this paper we present our experience from treating 42 sinonasal inverted papillomas, using a surgical technique which is based on the conservation of as much part of the healthy lateral nasal wall as possible. This modified medial maxillectomy allows us to create a limited in size and normally functioning nasal cavity, thus minimizing the disadvantages of the classical medial maxillectomy without jeopardizing the safety of the operation.

  16. A theory of the genesis of breast duct papilloma.

    Science.gov (United States)

    WHANG, J

    1960-03-01

    While it is not the intent to argue that papilloma never develops in the conventionally accepted manner (proliferative growth from the wall of a pre-existing cavity) a new, perhaps alternative, genesis is suggested. The concept is that, beginning with the usual lobular structure of the breast, first by hyperplasia and then by coalescence of alveoli, seen earliest at the periphery of the lobule, spaces appear between the content of the lobule and the wall. By confluence of these spaces a larger cystic cavity is formed. Coalescence of alveoli through the body of the central mass, in the same way as at the periphery, develops the familiar pattern of "papilloma." Following the earlier hyperplasia, regressive changes appear and may go on to complete disintegration of the papillary mass, leaving a smooth-walled cavity.

  17. Multiple papillomas in a diamond python, Morelia spilota spilota.

    Science.gov (United States)

    Gull, Jessica M; Lange, Christian E; Favrot, Claude; Dorrestein, Gerry M; Hatt, Jean-Michel

    2012-12-01

    A 4-yr-old male diamond python (Morelia spilota spilota) was evaluated for multiple black papillated exophytic skin proliferations and signs of pneumonia. The histopathologic structure of the skin biopsy specimens led to the diagnosis of a benign papilloma-like neoplasia. In this case, papillomavirus DNA could be amplified from a biopsy sample with a broad range polymerase chain reaction. Nested pan-herpes polymerase chain reaction was negative, and herpesvirus inclusion bodies were not found. Because of the histologically benign nature of the papilloma, the skin proliferations were left untreated. Ten mo after the first presentation, the skin lesions had regressed almost completely; 34 mo later, only scars from the biopsies were left.

  18. Multimodal Counseling Interventions: Effect on Human Papilloma Virus Vaccination Acceptance

    OpenAIRE

    Oroma Nwanodi; Helen Salisbury; Curtis Bay

    2017-01-01

    Human papilloma virus (HPV) vaccine was developed to reduce HPV-attributable cancers, external genital warts (EGW), and recurrent respiratory papillomatosis. Adolescent HPV vaccination series completion rates are less than 40% in the United States of America, but up to 80% in Australia and the United Kingdom. Population-based herd immunity requires 80% or greater vaccination series completion rates. Pro-vaccination counseling facilitates increased vaccination rates. Multimodal counseling inte...

  19. Denture hyperplasia with areas simulating oral inverted ductal papilloma.

    Science.gov (United States)

    Vargas, Pablo Agustin; Perez, Danyel Elias da Cruz; Jorge, Jacks; Rangel, Ana Lúcia Carrinho Ayrosa; León, Jorge Esquiche; Almeida, Oslei Paes de

    2005-07-01

    Denture hyperplasia is a reactive lesion of the oral mucosa, usually associated to an ill-fitting denture. This lesion is easily diagnosed and in some cases distinct microscopic variations such as osseous, oncocytic and squamous metaplasia may be found. These metaplastic alterations probably are associated with the lymphocytic infiltrate usually present in denture hyperplasia. We present a case of denture hyperplasia containing salivary gland tissue with ductal alterations mimicking an oral inverted ductal papilloma.

  20. "Multiple Papillomas - a case report and review of literature"

    Directory of Open Access Journals (Sweden)

    Gaurav Sharma

    2007-01-01

    Full Text Available We report a unique case of extensive papilIomatosis of the left buccal mucosa in an 80 year old female patient. We document and discuss the probable multifactorial etiology of the lesions and the possible involvement of a syndromic association. This report illustrates the need for careful clinical investigation and follow-up of individuals presenting with multifocal involvement of papillomas.

  1. Assessment of the incidence of squamous cell papilloma of the esophagus and the presence of high-risk human papilloma virus.

    Science.gov (United States)

    Pantham, Ganesh; Ganesan, Santhi; Einstadter, Douglas; Jin, Ge; Weinberg, Aaron; Fass, Ronnie

    2017-01-01

    There has been a recent increase in the incidence of oropharyngeal cancer (OPC) associated with high-risk human papilloma virus (HPV) infection. We investigated the incidence of esophageal papilloma and the presence of high-risk HPV infection. This is a cross-sectional study conducted at a County teaching hospital. Patients with esophageal papilloma between January 2000 and December 2013 were identified. Patients with sufficient specimens were tested for the HPV virus. Sixty patients with esophageal papilloma lesions were identified from 2000 to 2013. (31 males, age 51 ± 13 years). The incidence was 0.13% in 2000 and increased to 0.57% in 2013 (P papilloma that was more than 5 mm in size, and 20% had multiple lesions. The papilloma was located in the distal esophagus in 35 (58.3%) patients, mid esophagus in 17 (28.3%) patients, and proximal in 8 (13.3%) patients. Three (5%) patients had associated OPC, and 9 (47.4%) of the 19 patients tested were positive for high-risk HPV serotype 16. The incidence of esophageal papilloma has increased by fourfolds over the past 14 years. About half of the tested patients demonstrated high risk HPV. This may suggest a potential growing risk for esophageal squamous cell cancer in the future. © 2016 International Society for Diseases of the Esophagus.

  2. DYSPHONIA AS AN UNCOMMON PRESENTATION OF PONTOCEREBELLAR CHOROID PLEXUS PAPILLOMA.

    Science.gov (United States)

    Rotim, Krešimir; Sajko, Tomislav; Zmajević, Marina; Šumonja, Ilijana; Grgić, Marko

    2015-06-01

    A case is presented of a patient with dysphonia, hearing loss and ataxia due to vestibulocochlear and vagal nerve compression by choroid plexus papilloma in the cerebellopontine angle. Choroid plexus papillomas are rare tumors usually arising in the lateral and fourth ventricle, and rarely found in the cerebellopontine angle, making the neuroimaging characteristics usually not sufficient for diagnosis. Patients usually present with headache and hydrocephalus but tumors in the cerebellopontine angle can cause vestibulocochlear dysfunction and cerebellar symptoms. Dysphonia along with hearing loss was a dominant symptom in the case presented. After complete surgical removal of the tumor, deterioration of dysphonia was noticed; it could be explained as peripheral vagal nerve neuropathy due to tumor compression and intraoperative manipulation. In this case report, we describe dysphonia as an uncommon presentation of a rare posterior fossa tumor. To our knowledge, a case of choroid plexus papilloma presenting with dysphonia has not been described before. Our case extends the differential diagnosis of dysphonia from the otorhinolaryngological to the neurosurgical field.

  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. Etiological role of human papillomavirus infection for inverted papilloma of the bladder.

    Science.gov (United States)

    Shigehara, Kazuyoshi; Sasagawa, Toshiyuki; Doorbar, John; Kawaguchi, Shohei; Kobori, Yoshitomo; Nakashima, Takao; Shimamura, Masayoshi; Maeda, Yuji; Miyagi, Tohru; Kitagawa, Yasuhide; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Koh, Eitetsu; Namiki, Mikio

    2011-02-01

    The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin-fixed and paraffin-embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri-Max HPV genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV-18 was detected in two cases, including one inverted papilloma with atypia, and HPV-16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16-INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected in all HPV-positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High-risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential. 2010 Wiley-Liss, Inc.

  5. Bilateral Endoscopic Medial Maxillectomy for Bilateral Inverted Papilloma

    Science.gov (United States)

    Kodama, Satoru; Kawano, Toshiaki; Suzuki, Masashi

    2012-01-01

    Inverted papilloma (IP) is a benign tumor of the nasal cavity and paranasal sinuses that is unilateral in most cases. Bilateral IP, involving both sides of the nasal cavity and sinuses, is extremely rare. This paper describes a large IP that filled in both sides of the nasal cavity and sinuses, mimicking association with malignancy. The tumor was successfully treated by bilateral endoscopic medial maxillectomy (EMM). The patient is without evidence of the disease 24 months after surgery. If preoperative diagnosis does not confirm the association with malignancy in IP, endoscopic sinus surgery (ESS) should be selected, and ESS, including EMM, is a good first choice of the treatment for IP. PMID:22953103

  6. Bowen's Disease Associated With Two Human Papilloma Virus Types.

    Science.gov (United States)

    Eftekhari, Hojat; Gharaei Nejad, Kaveh; Azimi, Seyyede Zeinab; Rafiei, Rana; Mesbah, Alireza

    2017-09-01

    Bowen's disease (BD) is an epidermal in-situ squamous cell carcinoma (SCC). Most Human Papilloma Viruses (HPV)-positive lesions in Bowen's disease are localized to the genital region or distal extremities (periungual sites) in which HPV type-16 is frequently detected. Patient was a 64-year-old construction worker for whom we detected 2 erythematous psoriasiform reticular scaly plaques on peri-umbilical and medial knee. Biopsy established the diagnosis of Bowen's disease and polymerase chain reaction assay showed HPV-6, -18 co-infection. Patient was referred for surgical excision.

  7. Human Papilloma Virus in Retinoblastoma Tissues from Korean Patients

    Science.gov (United States)

    Ryoo, Na-Kyung; Kim, Ji-Eun; Kim, Namju; Lee, Min-Jeong; Khwarg, Sang-In

    2013-01-01

    Purpose Recent reports suggest the association of human papilloma virus (HPV) with retinoblastoma. This study was performed to elucidate whether HPV infection is related to retinoblastoma among Koreans. Methods A total of 54 cases diagnosed with retinoblastoma were enrolled from Seoul National University Children's Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. Presence of human papilloma viral DNA was detected by in situ hybridization in formalin-fixed paraffin-embedded retinoblastoma tissues using both probes against high- and low risk HPV types. Results The mean age at diagnosis was 22.0 months (range, 1.1 to 98.0 months), and the mean age at enucleation was 27.8 months (range, 1.5 to 112.7 months) among the 54 patients with retinoblastoma. HPV was not detected in any of the retinoblastoma samples using either high risk or low risk HPV probes. Conclusions Our study, being the first study in the Korean population, proposes that HPV infection may have no causal relationship with retinoblastoma in Koreans. PMID:24082775

  8. Can mumps vaccine induce remission in recurrent respiratory papilloma?

    Science.gov (United States)

    Pashley, Nigel R T

    2002-07-01

    To describe our experience using laser excision and locally injected mumps vaccine to induce remission in patients with recurrent respiratory papilloma (RRP). Tertiary care regional medical center. Initially, 11 children with RRP treated in a pilot study with laser excision at regular intervals for at least a year without adjuvant therapy; later, a series of 18 children and 20 adults with RRP, some of whom had used various adjuvant therapy with interval laser excision. Both patient groups continued their same interval laser excision with the same or similar laser, same clinical setting, and same surgeon. Locally injected mumps vaccine was then administered into the excision site after each laser removal of papilloma. Larynx and trachea were microphotographed with each treatment. Two consecutive disease-free intervals and a follow-up of at least 1 year were required criteria for remission. In the pilot study, remission was induced in 9 (82%) of 11 patients by 1 to 10 injections, with follow-up of 5 to 19 years. In the subsequent series, remission was induced in 29 (76%) of 38 patients by 4 to 26 injections, and follow-up was 2 to 5 years. Combined with serial laser excision, mumps vaccine positively influences induction of remission in children with RRP. The mechanisms of this effect are unclear, but the treatment is readily available, inexpensive, and has a low risk of adverse effects.

  9. Inverted papillomas and benign nonneoplastic lesions of the nasal cavity

    Science.gov (United States)

    Casiano, Roy R.

    2012-01-01

    Background: Benign lesions of the nasal cavity represent a diverse group of pathologies. Furthermore, each of these disorders may present differently in any given patient as pain and discomfort, epistaxis, headaches, vision changes, or nasal obstruction. Although these nasal masses are benign, many of them have a significant capacity for local tissue destruction and symptomatology secondary to this destruction. Advances in office-based endoscopic nasendoscopy have equipped the otolaryngologist with a safe, inexpensive, and rapid means of directly visualizing lesions within the nasal cavity and the initiation of appropriate treatment. Methods: The purpose of this study is to review the diagnosis, management, and controversies of many of the most common benign lesions of the nasal cavity encountered by the primary care physician or otolaryngologist. Results: This includes discussion of inverted papilloma (IP), juvenile angiofibroma, squamous papilloma, pyogenic granuloma, hereditary hemorrhagic telangiectasia, schwannoma, benign fibro-osseous lesions, and other benign lesions of the nasal cavity, with particular emphasis on IP and juvenile angiofibroma. Conclusion: A diverse array of benign lesions occur within the nasal cavity and paranasal cavities. Despite their inability to metastasize, many of these lesions have significant capability for local tissue destruction and recurrence. PMID:22487294

  10. [Human papilloma virus and its association with oral cancer].

    Science.gov (United States)

    Bologna-Molina, Ronell E; Castañeda-Castaneira, Raúl E; Molina-Frechero, Nelly; Pérez-Rodríguez, Eréndira

    2006-01-01

    Oral cancer it a pathology of multifactorial etiology, where some factors such as age, sex, race, genetic predisposition, nutrition, and the use of tobacco and alcohol have a bearing on. In the last years, some authors showed the implication of the human papilloma virus (HPV) in the development of precarcinogenic lesions and of oral squamous cell carcinoma. The infection by HPV has been associated to hyperplastic epithelial lesions, papilloma and warty carcinoma in skin and in different types of mucosa, including the anus-genital, cervical, urethral, tracheobronchial, nasal, laryngeal and oral mucosa tracts. The viral high-risk geno-types (oncogenic) such as 16, 18, 31, 33 and 35 are frequently associated to leukoplakia and squamous carcinoma. An association of HPV with oral squamous carcinoma in patients that consume tobacco and alcohol has been fundamentally established. It is important to study and to frequently review the role that viral infections and cancer have, and maybe in the future, it would be possible to create a vaccine that diminishes the frequency of oncological problems.

  11. Incidental intraductal papillomas (breast diagnosed on needle core biopsy do not need to be excised.

    Science.gov (United States)

    Jaffer, Shabnam; Bleiweiss, Ira J; Nagi, Chandandeep

    2013-01-01

    Most authors recommend excision of intraductal papillomas diagnosed on core needle biopsy. This leads to the question of whether or not excision is necessary for incidental intraductal papillomas on core needle biopsy as opposed to those corresponding to imaging findings. Using the pathology computerized data base we retrospectively identified 46 incidental intraductal papillomas diagnosed on core needle biopsy from 1/2000 to 12/2008. Clinical, radiologic, and pathologic information was gathered and correlated. All core needle biopsies were reviewed to confirm the diagnosis of incidental intraductal papillomas, and excision specimens reviewed when available. Of the 46 patients, follow-up information was available in only 38. The age of the patients ranged from 39 to 82 years (mean = 48 years). Most incidental intraductal papillomas were diagnosed by mammotome core needle biopsy (36 cases). A total of 33 cases were performed for calcifications with the following indications: clustered = 21, new = 4, pleomorphic = 3, increasing = 3, indeterminant = 2. The correlating diagnoses included the following: fibrocystic changes with calcium phosphate = 18 or calcium oxalate = 10, fibroadenoma with calcifications = 5. The three masses were: two cases of cystic papillary apocrine metaplasia (I Ultrasound and 1 MRI) and 1 fibroadenoma (Ultrasound). In all cases, the intraductal papillomas were ≤0.2 cm, were not associated with calcifications, and were incidental to them or the underlying mass. A total of 14 patients underwent excision, whereas the remaining 24 have remained radiologically stable for over 12 months. The excision specimen findings were: fibrocystic changes = 8 and intraductal papilloma = 6. With the exception of one case, all the intraductal papilloma remained incidental to imaging findings. In this solitary case, the calcifications were described as pleomorphic and corresponded to fibrocystic changes calcifications on core needle

  12. A case report of an inverted papilloma infiltrating into maxillary sinus

    International Nuclear Information System (INIS)

    Ji, Yong Hwa; Choi, Bo Ram; Huh, Kyung Hoe; Lee, Sam Sun; An, Chang Hyeon

    2009-01-01

    The present study reports a case of inverted papilloma of the nasal cavity and infiltrating into the maxillary sinus. Inverted papilloma is an uncommon and locally aggressive benign tumor of the sinonasal region. The patient, 51-year-old male, presented with unilateral nasal obstruction and periodic swelling on the palate without pain. Enhanced CT scan revealed a heterogeneously enhancing solid mass in the nasal cavity and infiltrating into the right maxillary sinus, as well as an incidental, secondarily infected residual cyst in the periapical area of the right maxillary canine. The sinonasal mass was revealed as an inverted papilloma on histopathologic examination.

  13. A case report of an inverted papilloma infiltrating into maxillary sinus

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Yong Hwa; Choi, Bo Ram; Huh, Kyung Hoe; Lee, Sam Sun [School of Dentistry, Seoul National University, Seoul (Korea, Republic of); An, Chang Hyeon [Department of Oral and Maxillofacial Radiology, School of Dentistry, Kyungpook National University, Daegu (Korea, Republic of)

    2009-06-15

    The present study reports a case of inverted papilloma of the nasal cavity and infiltrating into the maxillary sinus. Inverted papilloma is an uncommon and locally aggressive benign tumor of the sinonasal region. The patient, 51-year-old male, presented with unilateral nasal obstruction and periodic swelling on the palate without pain. Enhanced CT scan revealed a heterogeneously enhancing solid mass in the nasal cavity and infiltrating into the right maxillary sinus, as well as an incidental, secondarily infected residual cyst in the periapical area of the right maxillary canine. The sinonasal mass was revealed as an inverted papilloma on histopathologic examination.

  14. 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.

  15. 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.

  16. 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

  17. 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...

  18. 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

  19. 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...

  20. 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

  1. 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

  2. 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.

  3. 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...

  4. 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.

  5. Oncogenic impact of human papilloma virus in head and neck cancer.

    LENUS (Irish Health Repository)

    Heffernan, C B

    2012-02-01

    There is considerable debate within the literature about the significance of human papilloma virus in head and neck squamous cell carcinoma, and its potential influence on the prevention, diagnosis, grading, treatment and prognosis of these cancers. Cigarette smoking and alcohol consumption have traditionally been cited as the main risk factors for head and neck cancers. However, human papilloma virus, normally associated with cervical and other genital carcinomas, has emerged as a possible key aetiological factor in head and neck squamous cell carcinoma, especially oropharyngeal cancers. These cancers pose a significant financial burden on health resources and are increasing in incidence. The recent introduction of vaccines targeted against human papilloma virus types 16 and 18, to prevent cervical cancer, has highlighted the need for ongoing research into the importance of human papilloma virus in head and neck squamous cell carcinoma.

  6. Association of human papilloma virus infection and oral squamous cell carcinoma in Bangladesh.

    Science.gov (United States)

    Akhter, Mahmuda; Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-03-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18.

  7. Surgical Excision of Benign Papillomas Diagnosed with Core Biopsy: A Community Hospital Approach

    International Nuclear Information System (INIS)

    Rozentsvayg, Eka; Carver, Kristen; Borkar, Sunita; Mathew, Melvy; Enis, Sean; Friedman, Paul

    2011-01-01

    Our goal was to assess the value of surgical excision of benign papillomas of the breast diagnosed on percutaneous core biopsy by determining the frequency of upgrade to malignancies and high risk lesions on a final surgical pathology. We reviewed 67 patients who had biopsies yielding benign papilloma and underwent subsequent surgical excision. Surgical pathology of the excised lesions was compared with initial core biopsy pathology results. 54 patients had concordant benign core and excisional pathology. Cancer (ductal carcinoma in situ and invasive ductal carcinoma) was diagnosed in five (7%) patients. Surgery revealed high-risk lesions in 8 (12%) patients, including atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ. Cancer and high risk lesions accounted for 13 (19%) upstaging events from benign papilloma diagnosis. Our data suggests that surgical excision is warranted with core pathology of benign papilloma

  8. Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh

    Science.gov (United States)

    Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-01-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18. PMID:23617206

  9. Laser treatment of an oral squamous papilloma in a pediatric patient: A case report

    Directory of Open Access Journals (Sweden)

    Ahmet Ferhat Misir

    2013-01-01

    Full Text Available Oral squamous papilloma is a benign proliferation of the stratified squamous epithelium, which results in a papillary or verrucous exophytic mass induced by human papilloma virus (HPV. These oral mucosa lesions are most often asymptomatic and have small progression. Laser assisted surgery is common nowadays with several advantages including successful hemostasis, devoid of sutures, wound sterilization and minimal post-operative pain and edema. The aim of this report is to present the oral squamous papilloma in a pediatric patient and its treatment with soft tissue laser. The lesion was excised with diode laser and the healing was uneventful in follow-up visit after one year. Oral squamous papillomas can be found in child′s oral cavity and laser dentistry can be used by dental clinicians to treat these kinds of oral lesions and should be considered as an alternative to conventional surgery.

  10. Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases.

    Science.gov (United States)

    McKenney, Jesse K; Amin, Mahul B; Young, Robert H

    2003-07-01

    The existence of a papillary lesion of the urinary bladder with a benign clinical course and recognizable morphologic features that merit the benign categorization "papilloma" has been controversial. The clinical aspects and histologic features of these lesions remain to be fully elucidated. We have studied the clinicopathologic features of 26 patients with urothelial papillomas and correlated them with outcome. Papillomas occurred in two distinct clinical settings: (1) de novo neoplasms (23/26) or (2) those occurring in patients with a known clinical history of bladder cancer ("secondary" papillomas; 3/26). Follow-up information was available in 14/23 of the de novo cases (mean = 39 mo) and in 3/3 secondary cases (mean = 24 mo). Patients with de novo papillomas had a mean age of 46 years; 16 were male and 7 were female. Twelve of 14 had a benign clinical course with no recurrences; 1 developed a recurrent papilloma at 3 years, and 1 developed a pT3a high-grade papillary urothelial carcinoma at 4 years. Patients with secondary papillomas had a mean age of 66 years; two were male and one was a female. One of these patients developed two additional recurrences, and two patients had no new recurrences. Morphologically, the papillary architecture ranged from a common simple, nonhierarchical arrangement to, infrequently, more complex anastomosing papillae with budding. The individual papillae ranged from small (most common), with scant stroma and slender fibrovascular cores, to large, with marked stromal edema and/or cystitis cystica-like urothelial invaginations. Common to all was a lining of normal-appearing urothelium without hyperplasia, maintenance of normal polarity, and frequent prominence of the umbrella cell layer. Overall, no patient with a diagnosis of papilloma died of disease; only one patient with a de novo lesion (7.0%) had a recurrent papilloma, and 1/14 (7.0%) progressed to a higher grade and stage of disease, although this patient was on

  11. IS SYSTEMATIC VACCINATION OF GIRLS-ADOLESCENTS AGAINST HUMAN PAPILLOMA VIRUS NECESSARY?

    Directory of Open Access Journals (Sweden)

    G. N. Minkina

    2011-01-01

    Full Text Available World Health Organization and European Center of Prophylaxis and Control over Morbidity recommend inclusion of systematic vaccination against human papilloma virus in girls-adolescents in national immunization programs. The article makes a review of vaccination reasonability as in countries with developed programs of neck of uterus cancer, as in societies with absence of adequate screening. Author discusses the age of vaccination and presents a foreign experience of vaccine against human papilloma virus inclusion into National Immunization Programs.

  12. MRI features of intraductal papilloma of the breast: sheep in wolf's clothing?

    International Nuclear Information System (INIS)

    Kurz, Kathinka D; Roy, Sumit; Saleh, Andreas; Diallo-Danebrock, Raihana; Skaane, Per

    2011-01-01

    Background: Intraductal papillomas often present as small, smooth masses, dilated ducts or microcalcifications at mammography and as smooth, hypoechoic masses at sonography. At magnetic resonance imaging (MRI), intraductal papillomas often present as small smooth masses, however, often with strong enhancement with type 2 or 3 time intensity curves. The result of the MR analysis is therefore not infrequently inconclusive in order to characterize the mass as benign or malignant. Purpose: To characterize the appearance of intraductal papillomas of the breast at MRI, and determine whether the application of diagnostic rules described in literature could contribute to correctly classifying the lesions as benign. Material and Methods: Twenty patients with histologically proven intraductal papillomas were included. Two radiologists independently reviewed the MR images of the breast. The BI-RADS nomenclature was used to describe morphology and contrast-enhancement kinetics. Interobserver agreement in the interpretation of the MR images by the two investigators was performed. Kappa coefficient was calculated as index for the level of agreement. Subsequently, three sets of diagnostic rules, including the Goettinger score described by Fischer and the interpretation flowcharts according to Kinkel and to Tozaki were applied to characterize whether a biopsy should be recommended or not. Results: All papillomas presented as masses on dynamic contrast-enhanced MRI. Only five papillomas showed a round, oval, or lobulated shape combined with smooth margins and continuous rise of the time intensity curve. Using the Goettinger score, biopsy would be recommended in 16 patients. Based on the interpretation flowcharts of Kinkel and of Tozaki, an additional 13 and 10 papillomas, respectively, were correctly classified as benign. Dilated ducts were visible in 10 patients. The interobserver agreement was good or excellent for all included variables. Conclusion: Including systematic analysis

  13. MRI features of intraductal papilloma of the breast: sheep in wolf's clothing?

    Energy Technology Data Exchange (ETDEWEB)

    Kurz, Kathinka D; Roy, Sumit (Dept. of Radiology, Stavanger Univ. Hospital, Stavanger (Norway)), e-mail: kurk@sus.no; Saleh, Andreas (Inst. of Diagnostic Radiology, Duesseldorf Univ. Hospital, Duesseldorf (Germany)); Diallo-Danebrock, Raihana (Inst. of Pathology, Duesseldorf Univ. Hospital, Duesseldorf (Germany)); Skaane, Per (Dept. of Radiology, Ullevaal Univ. Hospital, Univ. of Oslo, Oslo (Norway))

    2011-04-15

    Background: Intraductal papillomas often present as small, smooth masses, dilated ducts or microcalcifications at mammography and as smooth, hypoechoic masses at sonography. At magnetic resonance imaging (MRI), intraductal papillomas often present as small smooth masses, however, often with strong enhancement with type 2 or 3 time intensity curves. The result of the MR analysis is therefore not infrequently inconclusive in order to characterize the mass as benign or malignant. Purpose: To characterize the appearance of intraductal papillomas of the breast at MRI, and determine whether the application of diagnostic rules described in literature could contribute to correctly classifying the lesions as benign. Material and Methods: Twenty patients with histologically proven intraductal papillomas were included. Two radiologists independently reviewed the MR images of the breast. The BI-RADS nomenclature was used to describe morphology and contrast-enhancement kinetics. Interobserver agreement in the interpretation of the MR images by the two investigators was performed. Kappa coefficient was calculated as index for the level of agreement. Subsequently, three sets of diagnostic rules, including the Goettinger score described by Fischer and the interpretation flowcharts according to Kinkel and to Tozaki were applied to characterize whether a biopsy should be recommended or not. Results: All papillomas presented as masses on dynamic contrast-enhanced MRI. Only five papillomas showed a round, oval, or lobulated shape combined with smooth margins and continuous rise of the time intensity curve. Using the Goettinger score, biopsy would be recommended in 16 patients. Based on the interpretation flowcharts of Kinkel and of Tozaki, an additional 13 and 10 papillomas, respectively, were correctly classified as benign. Dilated ducts were visible in 10 patients. The interobserver agreement was good or excellent for all included variables. Conclusion: Including systematic analysis

  14. Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh

    OpenAIRE

    Akhter, Mahmuda; Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-01-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell car...

  15. A solitary bronchial papilloma with unusual endoscopic presentation: case study and literature review

    Directory of Open Access Journals (Sweden)

    Frejeville Marie

    2009-08-01

    Full Text Available Abstract Background Solitary endobronchial papillomas (SEP are rare tumors and most of them are described by case report. A misdiagnosis is common with viral related papillomas. A histopathological classification has recently permitted a major advancement in the understanding of the disease. Case Presentation We report a case of a mixed bronchial papilloma with an unusual endoscopic presentation. The literature was extensively reviewed to ascertain the unusual characteristics of the current case. A 39-year of age male was referred to our institution for the investigation of a slight hemoptysis. Routine examination was normal. A fibroscopy revealed an unusual feature of the right main bronchus. The lesion was a plane, non-bleeding, non-glistering sub-mucosal proliferation. No enhanced coloration was noticed. Biopsies revealed a mixed solitary bronchial papilloma. In situ HPV hybridization was negative. Endoscopic treatment (electrocautery was effective with no relapse. Conclusion This lesion contrasts with the data of the literature where papilloma were described as wart-like lesions or cauliflower tumors, with symptoms generally related to bronchial obstruction. We advise chest physicians to be cautious with unusually small swollen lesions of the bronchi that may reveal a solitary bronchial papilloma. Endoscopic imaging can significantly contribute to the difficult diagnosis of SEP by pulmonary physicians and endoscopists.

  16. Bilateral Endoscopic Medial Maxillectomy for Bilateral Inverted Papilloma

    Directory of Open Access Journals (Sweden)

    Satoru Kodama

    2012-01-01

    Full Text Available Inverted papilloma (IP is a benign tumor of the nasal cavity and paranasal sinuses that is unilateral in most cases. Bilateral IP, involving both sides of the nasal cavity and sinuses, is extremely rare. This paper describes a large IP that filled in both sides of the nasal cavity and sinuses, mimicking association with malignancy. The tumor was successfully treated by bilateral endoscopic medial maxillectomy (EMM. The patient is without evidence of the disease 24 months after surgery. If preoperative diagnosis does not confirm the association with malignancy in IP, endoscopic sinus surgery (ESS should be selected, and ESS, including EMM, is a good first choice of the treatment for IP.

  17. Vaccines against human papilloma virus and cervical cancer: An overview

    Directory of Open Access Journals (Sweden)

    Sharma Savita

    2008-01-01

    Full Text Available The paradigm of preventing human papilloma virus (HPV infection through currently approved vaccines, namely, Gardasil, manufactured by Merck and Co., Inc. (Whitehouse Station, NJ and Cervarix, manufactured by GlaxoSmithKline (GSK, Philadelphia holds tremendous promise for the developing countries in decreasing the burden of HPV infection and its sequelae, such as cervical cancer, genital warts and anogenital cancers. Effective screening programs that have reduced the burden of this killer disease in the developed countries are still lacking in India, despite the high incidence of cervical cancer and the implementation of the National Cancer Control Programme since 1975. The recent breakthrough in the global war against cervical cancer will provide new insight for meeting the future challenge of the prevention of cervical cancer in India.

  18. Human Papilloma Virus and Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Hayedeh Haeri

    2013-04-01

    Full Text Available Human papilloma virus (HPV has been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in substantial number of esophageal SCCs in our region is unlikely.

  19. HUMAN PAPILLOMA VIRUS. PREVENTION OF HPV-ASSOCIATED DISEASES

    Directory of Open Access Journals (Sweden)

    F. C. Shakhtakhtinskaya

    2015-01-01

    Full Text Available High prevalence of sexually transmitted diseases among the population attracts attention of specialists in all countries due to frequent development of complications resulting in reproductive dysfunction. The article presents one of the urgent issues of modern medicine — papillomavirus infection, which is the most common sexually transmitted disease. 70–80% of the sexually active persons contract human papilloma virus at one point. HPV induces a broad range of oncological reproductive diseases, including cervical, vulvar, vaginal and anal cancer and anogenital condylomae, which are observed both in men and women. The only reliable method of preventing papillomavirus infection is vaccination. The authors present new data on the use of the quadrivalent vaccine, including a new immunization pattern for 9–14-years-old girls.

  20. Distribution of Human papilloma virus genotypes in cervical cancer tissues

    Directory of Open Access Journals (Sweden)

    Stamenković M.

    2014-01-01

    Full Text Available Cervical cancer incidence and mortality rates in Serbia are among the highest in Europe and data on Human papilloma virus (HPV type distribution are scarce. The aim of this study was to determine the prevalence of HPV types in archival specimens of cervical cancer tissues of women in the Serbian population. A total of 45 paraffin-embedded tissue samples of cervical carcinoma were used in this study. The procedure included deparaffinization of tissue samples, DNA extraction, PCR, gel electrophoresis and HPV genotyping by direct sequencing. HPV was detected in 32 samples (71%. Genotyping revealed the presence of 6 high-risk HPV types 16, 18, 33, 45, 53 and 58, where HPV type 16 was the most prevalent type (73.7%. The results of this study and further studies will provide more detailed information about HPV genotype distribution and may contribute to the formulation of national guidelines for the prevention of cervical cancer. [175073

  1. [Prophylactic and therapeutic vaccines against human papilloma virus].

    Science.gov (United States)

    Albers, A E; Hoffmann, T K; Klussmann, J P; Kaufmann, A M

    2010-08-01

    Infection with human papilloma virus (HPV) has been identified as the cause of recurrent papillomatosis and of a subgroup of squamous cell carcinomas of the head and neck. A change in prevalence of these lesions, especially for oropharyngeal carcinoma, can be expected as a consequence of the introduction of prophylactic HPV vaccines for young women, targeting the most frequent high- and low-risk HPV subtypes. Vaccination for the major low-risk HPV types has proven to be highly effective against genital warts and activity against papillomatosis can be expected. The possibilities of prophylactic HPV vaccination as well as new developments and the rationale for therapeutic vaccines are discussed on the basis of the current literature.

  2. Conjunctival papilloma caused by human papillomavirus type 11 treated with systemic interferon in a five-year-old boy.

    Science.gov (United States)

    Okan, Gökhan; Ayan, Inci; Karslioğlu, Safak; Altiok, Ender; Yenmiş, Güven; Vural, Gürcan

    2010-01-01

    Conjunctival papilloma is a benign tumor of the conjunctival mucosa. In childhood, papilloma represents 7-10% of conjunctival tumors. Human papillomavirus (HPV)-6 and HPV-11 are the major HPV types responsible for conjunctival lesions. A five-year-old boy with a two-year history of conjunctival papilloma caused by HPV type 11 treated with systemic interferon alpha is reported and the literature is reviewed.

  3. CARCINOMA OF THE LARYNX AND HUMAN PAPILLOMA VIRUS INFECTION

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    Georgi N. Nikolov

    2016-03-01

    Full Text Available Background: Laryngeal carcinoma is one of the most common form of head and neck cancer. During the last two decades, it has been recognized that this cancer is causally related to human papillomavirus (HPV. Objective: We presented a study on prevalence of human papilloma viruses (HPV in patients with laryngeal carcinoma. Methods: This study consists of 43 patients with laryngeal carcinoma who were diagnosed and treated with surgical techniques in Department of Otorhinolaryngology, University Hospital, Pleven, Bulgaria. Immunohistochemistry of p16INK4a and Ki-67 were used to prove the relationship between high-risk-HPV (HR-HPV and carcinogenesis. Results: Papilloma virus infection with high-risk oncogenic types of HPV was determined in more than 39.5% of surgically treated patients with histologically proven laryngeal cancer. HPV-induced carcinogenesis was assumed in 17 (13.9% of all patients whose spouses were operated from cervical cancer. The patients with HPV-positive laryngeal carcinoma were younger than the others in the group (8 years on average. Risk factors for development of HPV-associated laryngeal carcinoma were related to higher number of sexual partners and the practice of oral sex. Frequently, in patients with HPV-associated laryngeal carcinoma we find data for so-called “family’s carcinogenesis”. The possibility of appearance (either preceding or following the treatment of a second carcinoma and/or tumour recurrence is higher in HPV-positive laryngeal carcinomas. Conclusion: It is recommended to extend the diagnostic methods for laryngeal and hypo pharyngeal cancer with a routine search for high-risk oncogenic HPV strains.

  4. [THE COMPARATIVE ANALYSIS OF RESULTS OF DETECTION OF CARCINOGENIC TYPES OF HUMAN PAPILLOMA VIRUS BY QUALITATIVE AND QUANTITATIVE TESTS].

    Science.gov (United States)

    Kuzmenko, E T; Labigina, A V; Leshenko, O Ya; Rusanov, D N; Kuzmenko, V V; Fedko, L P; Pak, I P

    2015-05-01

    The analysis of results of screening (n = 3208; sexually active citizen aged from 18 to 59 years) was carried out to detect oncogene types of human papilloma virus in using qualitative (1150 females and 720 males) and quantitative (polymerase chain reaction in real-time (843 females and 115 males) techniques. The human papilloma virus of high oncogene type was detected in 65% and 68.4% of females and in 48.6% and 53% of males correspondingly. Among 12 types of human papilloma virus the most frequently diagnosed was human papilloma virus 16 independently of gender of examined and technique of analysis. In females, under application of qualitative tests rate of human papilloma virus 16 made up to 18.3% (n = 280) and under application of quantitative tests Rte of human papilloma virus made up to 14.9% (n = 126; p ≤ 0.05). Under examination of males using qualitative tests rate of human papilloma virus 16 made up to 8.3% (n = 60) and under application of qualitative tests made up to 12.2% (n = 14; p ≥ 0.05). Under application of qualitative tests rate of detection on the rest ofoncogene types of human papilloma virus varied in females from 3.4% to 8.4% and in males from 1.8% to 5.9%. Under application of qualitative tests to females rate of human papilloma virus with high viral load made up to 68.4%, with medium viral load - 2.85% (n = 24) and with low viral load -0.24% (n = 2). Under application of quantitative tests in males rate of detection of types of human papilloma virus made up to 53% and at that in all high viral load was established. In females, the most of oncogene types of human papilloma virus (except for 31, 39, 59) are detected significantly more often than in males.

  5. Predictors associated with the willingness to take human papilloma virus vaccination.

    Science.gov (United States)

    Naing, Cho; Pereira, Joanne; Abe, Tatsuki; Eh Zhen Wei, Daniel; Rahman Bajera, Ibrizah Binti Abdul; Kavinda Perera, Undugodage Heshan

    2012-04-01

    Human papilloma virus vaccine is considered to be the primary form of cervical cancer prevention. The objectives were (1) to determine knowledge about, and perception of human papilloma virus infection in relation to cervical cancer, (2) to explore the intention of the community to be vaccinated with human papilloma virus vaccine, and (3) to identify variables that could predict the likelihood of uptake of the vaccine. A cross-sectional survey was carried out in a semi-urban Town of Malaysia, using a pre-tested structured questionnaire. Summary statistics, Pearson chi-square test and a binary logistic regression were used for data analysis. A total of 232 respondents were interviewed. Overall, only a few had good knowledge related to human papilloma virus (14%) or vaccination (8%). Many had misconceptions that it could be transmitted through blood transfusion (57%). Sixty percent had intention to take vaccination. In the binary logistic model, willingness to take vaccination was significant with 'trusts that vaccination would be effective for prevention of cervical cancer' (P = 0.001), 'worries for themselves' (P human papilloma virus infection and cervical cancer would be helpful to increase the acceptability of vaccination program.

  6. Detection of human papillomavirus in pterygium and conjunctival papilloma by hybrid capture II and PCR assays.

    Science.gov (United States)

    Takamura, Y; Kubo, E; Tsuzuki, S; Akagi, Y

    2008-11-01

    To elucidate the putative role of human papillomavirus (HPV) infection in pterygium and conjunctival papilloma. Hybrid capture II (HC-II) and polymerase chain reaction (PCR) assays were performed to detect HPV in pterygium (42 samples obtained from 40 patients) and conjunctival papilloma (8 samples from 6 patients). The amount of HPV DNA was evaluated by measurement of relative light units (RLUs) on a luminometer. All papilloma samples were positive for HPV DNA by PCR and HC-II. The RLU values for specimens of recurrent and re-recurrent papilloma were markedly higher than those for specimens of primary lesions. HPV was detected by PCR in 2 of 42 (4.8%) beta-globin-positive pterygium specimens, whereas HC-II showed that HPV was negative in all pterygium samples. Our results support the hypothesis that HPV DNA is associated with the pathogenesis of conjunctival papilloma, but not pterygium. RLU measurement by HC-II may serve as a marker for evaluating the activity of HPV in conjunctival tumours.

  7. MODERN APPROACHES TO THE THERAPY OF VIRAL PAPILLOMA SKIN INFECTION IN INFANCY

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    L.K. Aslamazian

    2006-01-01

    Full Text Available To improve the methods of prevention and treatment of viral papilloma infection, the researchers examined 80 children, suffering from skin forms of a disease. They examined peculiarities of a disease and interferon status of all the children. The data of clinic and laboratory research allowed them to assume that viral papilloma infection grows along with the reduction of immune mechanisms and it grows among the children, suffering from the genetic burden to viral diseases. All the patients, suffering from the disorder of interferon status, have undergone the complex therapy, which included medications of recombinant interferon (Viferon in suppositories and extrinsic. For the first time, the researchers removed the skin papillomas by a combination method: cryofreezing and photovaporization. The analysis of treatment and observation within a year and a half showed that in a group of children, who received a combination treatment, including Viferon therapy and removal of verrucas by 2 surgical methods. No backset of a disease detected. In general, the findings of the research pointed out the high efficiency of topical and systemic Viferon medications, as well as combination method of verruca removal in complex treatment of viral papilloma skin infection among the children.Key words: interferon status of children, interferon al'fa 2b, verrucas, viral papilloma infection.

  8. Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

    Science.gov (United States)

    Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia; Norrild, Bodil; Prause, Jan Ulrik; Vinding, Troels; Heegaard, Steffen

    2007-08-01

    To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

  9. Epidemiology of lymphocystis, epidermal papilloma and skin ulcers in common dab Limanda limanda along the west coast of Denmark

    DEFF Research Database (Denmark)

    Mellergaard, Stig; Nielsen, Else

    1997-01-01

    and the disease prevalence in the present case, the disease pattern showed evident similarities with formerly described oxygen deficiency-induced outbreaks of lymphocystis and epidermal papilloma in dab in the Kattegat. In 1988, the prevalence of lymphocystis and epidermal papilloma increased significantly...

  10. Multimodal Counseling Interventions: Effect on Human Papilloma Virus Vaccination Acceptance

    Directory of Open Access Journals (Sweden)

    Oroma Nwanodi

    2017-11-01

    Full Text Available Human papilloma virus (HPV vaccine was developed to reduce HPV-attributable cancers, external genital warts (EGW, and recurrent respiratory papillomatosis. Adolescent HPV vaccination series completion rates are less than 40% in the United States of America, but up to 80% in Australia and the United Kingdom. Population-based herd immunity requires 80% or greater vaccination series completion rates. Pro-vaccination counseling facilitates increased vaccination rates. Multimodal counseling interventions may increase HPV vaccination series non-completers’ HPV-attributable disease knowledge and HPV-attributable disease prophylaxis (vaccination acceptance over a brief 14-sentence counseling intervention. An online, 4-group, randomized controlled trial, with 260 or more participants per group, found that parents were more likely to accept HPV vaccination offers for their children than were childless young adults for themselves (68.2% and 52.9%. A combined audiovisual and patient health education handout (PHEH intervention raised knowledge of HPV vaccination purpose, p = 0.02, and HPV vaccination acceptance for seven items, p < 0.001 to p = 0.023. The audiovisual intervention increased HPV vaccination acceptance for five items, p < 0.001 to p = 0.006. That HPV causes EGW, and that HPV vaccination prevents HPV-attributable diseases were better conveyed by the combined audiovisual and PHEH than the control 14-sentence counseling intervention alone.

  11. Multimodal Counseling Interventions: Effect on Human Papilloma Virus Vaccination Acceptance.

    Science.gov (United States)

    Nwanodi, Oroma; Salisbury, Helen; Bay, Curtis

    2017-11-06

    Human papilloma virus (HPV) vaccine was developed to reduce HPV-attributable cancers, external genital warts (EGW), and recurrent respiratory papillomatosis. Adolescent HPV vaccination series completion rates are less than 40% in the United States of America, but up to 80% in Australia and the United Kingdom. Population-based herd immunity requires 80% or greater vaccination series completion rates. Pro-vaccination counseling facilitates increased vaccination rates. Multimodal counseling interventions may increase HPV vaccination series non-completers' HPV-attributable disease knowledge and HPV-attributable disease prophylaxis (vaccination) acceptance over a brief 14-sentence counseling intervention. An online, 4-group, randomized controlled trial, with 260 or more participants per group, found that parents were more likely to accept HPV vaccination offers for their children than were childless young adults for themselves (68.2% and 52.9%). A combined audiovisual and patient health education handout (PHEH) intervention raised knowledge of HPV vaccination purpose, p = 0.02, and HPV vaccination acceptance for seven items, p HPV vaccination acceptance for five items, p HPV causes EGW, and that HPV vaccination prevents HPV-attributable diseases were better conveyed by the combined audiovisual and PHEH than the control 14-sentence counseling intervention alone.

  12. Public knowledge and attitudes towards Human Papilloma Virus (HPV) vaccination

    Science.gov (United States)

    Walsh, Charlotte Devereaux; Gera, Aradhana; Shah, Meeraj; Sharma, Amit; Powell, Judy E; Wilson, Sue

    2008-01-01

    Background Human Papilloma Virus (HPV) vaccine has undergone successful trials and has recently been approved for use for the primary prevention of cervical cancer. The aim of this study was to determine knowledge and attitudes towards HPV vaccination. Methods Semi-structured interview and questionnaire delivered in a street survey. Standardised HPV-related statements used to measure HPV knowledge and attitudes to vaccination. The setting was three different areas of Birmingham, to target a mix of social class and ethnicity. The sample population was composed of 16–54 year olds. Results A total of 420 participants were recruited. Poor knowledge of HPV and its links with cervical cancer were observed. 81% had a knowledge score of zero. Knowledge about HPV was associated with different ethnic group and socio-economic group. The majority (88%) of participants were in favour of vaccination, with 83.6% indicating that they would allow a child under their care to be vaccinated. Conclusion Initial responses to the proposed HPV vaccination within the UK public are favourable. However, knowledge levels are poor and media and health professional promotion are required to raise awareness. PMID:18947430

  13. [HPV (Human Papilloma Virus) implication in other cancers than gynaecological].

    Science.gov (United States)

    Badoual, C; Tartour, E; Roussel, H; Bats, A S; Pavie, J; Pernot, S; Weiss, L; Mohamed, A Si; Thariat, J; Hoffmann, C; Péré, H

    2015-08-01

    Worldwide, approximately 5 to 10% of the population is infected by a Human Papilloma Virus (HPV). Some of these viruses, with a high oncogenic risk (HPV HR), are responsible for about 5% of cancer. It is now accepted that almost all carcinomas of the cervix and the vulva are due to an HPV HR (HPV16 and 18) infection. However, these viruses are known to be involved in the carcinogenesis of many other cancers (head and neck [SCCHN], penis, anus). For head and neck cancer, HPV infection is considered as a good prognostic factor. The role of HPV HR in anal cancer is also extensively studied in high-risk patient's population. The role of HPV infection in the carcinogenesis of esophageal, bladder, lung, breast or skin cancers is still debated. Given the multiple possible locations of HPV HR infection, the question of optimizing the management of patients with a HPV+ cancer arises in the implementation of a comprehensive clinical and biological monitoring. It is the same in therapeutics with the existence of a preventive vaccination, for example. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  14. Human Papilloma Virus in Head and Neck Squamous Cell Cancer

    Science.gov (United States)

    Asvadi Kermani, I; Seifi, SH; Dolatkhah, R; Sakhinia, E; Dastgiri, S; Ebrahimi, A; Lotfy, A; Esmaeili, HA; G, Mohammadi; M, Naderpour; SH, Hajalipour; Haggi A, Asghari; M, Nadri

    2012-01-01

    Background Epidemiologic and molecular evidences have established a strong link between high risk types of Human Papilloma Virus and a subgroup of Head and Neck Squamous Cell Carcinomas (HNSCC). We evaluated the frequency of HPV positivity in HNSCC and its relationship to demographic and some risk factor variables in an open case- control study. Methods Fourteen recently diagnosed patients with squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin-embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94 control cancer-free subjects were collected for DNA analysis. Multivariable logistic regression method was used to calculate odds ratio for case-control comparisons. Results High risk HPV was detected in 6(42.8%) patients, and 6(5.3%) control subjects which was statistically significant (p<0.0001). HPV-18 was the most frequent type both in the cases and controls. HPV-16 DNA was detected in two patients of the case group, but it was not detected in any of the controls. The relation between demographic and risk factor variables was not statistically significant. Conclusion HPV infection has a significant impact on HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant degeneration in such cancers amongst some communities. It is vital to introduce and conduct immunization schedules in health care systems to protect communities to some extent. PMID:25780535

  15. Human papilloma virus infection in head and neck cancer.

    Science.gov (United States)

    Tribius, Silke; Hoffmann, Markus

    2013-03-01

    The causal link between cervical cancer and human papilloma virus (HPV) is well known. It is now becoming clear that some types of squamous-cell carcinoma of the head and neck, particularly oropharyngeal carcinoma (OPC), are also linked to HPV infection. The development of vaccines against certain HPV genotypes has changed the management strategy for HPV-associated diseases of the uterine cervix. An analogous approach is now being considered for the prevention of HPV-associated diseases of the head and neck. We review pertinent articles retrieved by a selective search of the literature for phase II and III trials providing evidence about a possible effect of HPV status on the survival rates of patients with OPC. Seven trials fulfilled our search criteria: four phase III trials with retrospective HPV analysis and three phase II trials with retrospective and prospective HPV analysis. Patients with HPV-positive OPC survive significantly longer than those with HPV-negative OPC. Tobacco smoking has been identified as a negative prognostic factor in patients with either HPV-negative or HPV-positive disease. The established treatment strategy for OPC in patients with and without the traditional risk factors (tobacco and alcohol consumption) is now being reconsidered in the light of what we have learned about the role of HPV infection. Ongoing and projected clinical trials with risk-factor stratification may soon lead to changes in treatment. Further study is needed to answer the question whether HPV infection in the head and neck region is carcinogenic.

  16. Mullerian papilloma-like proliferation arising in cystic pelvic endosalpingiosis.

    Science.gov (United States)

    McCluggage, W Glenn; O'Rourke, Declan; McElhenney, Clodagh; Crooks, Michael

    2002-09-01

    This report describes an unusual epithelial proliferation occurring in pelvic cystic endosalpingiosis. A cyst mass lined by a layer of ciliated epithelial cells involved the posterior surface of the cervix and vagina. The epithelial proliferation within the wall resembled a mullerian papilloma with fibrous and fibrovascular cores lined by bland cuboidal epithelial cells. Other areas had a microglandular growth pattern resembling cervical microglandular hyperplasia, and focally there was a solid growth pattern. Foci of typical endosalpingiosis involved the surface of both ovaries and pelvic soft tissues. The cystic lesion recurred after partial cystectomy and drainage and was followed up radiologically and with periodic fine-needle aspiration. Part of the wall of the cyst removed 11 years after the original surgery showed an identical epithelial proliferation. MIB1 staining showed a proliferation index of less than 5%, contrasting with the higher proliferation index of a typical serous borderline tumor. The differential diagnosis is discussed. As far as we are aware, this is the first report of such a benign epithelial proliferation involving cystic endosalpingiosis. Copyright 2002, Elsevier Science (USA). All rights reserved.

  17. INFECTION WITH HUMAN PAPILLOMA VIRUS IN CERVICAL NEOPLASIA

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    Eduard Crauciuc

    2010-09-01

    Full Text Available The purpose of this study was to establish if the infection with human papilloma virus (HPV presents a potential irreversible evolution towards malignancy. Materials and methods. The study was made on a number of 1885 patients that were suspected to have cervical neoplasia, which were monitored between 2001-2010 in „Elena-Doamna” Clinical Hospital of Obstetrics and Gynecology in Ia�i, the Military Hospital Gala�i, the County Hospital Gala�i and the Emergency Hospital Buzau. Results and discussions. The study proved that the risk of contacting a genital infection with HPV and cervical cancer is influenced by the sexual activity, the risk of getting infected with HPV during a person’ s lifetime is at least 50% for those sexually active. Conclusions. The patients benefited from colposcopy and biopsy only if the repeated cytology suggested more severe changes. The conservative conduct is represented by a repeated cytology when the patients are admitted into the lot (the initial cytology is performed before this moment

  18. Sinonasal inverted papilloma associated with squamous cell carcinoma

    International Nuclear Information System (INIS)

    But-Hadzic, Jasna; Jenko, Klemen; Poljak, Mario; Kocjan, Bostjan J; Gale, Nina; Strojan, Primoz

    2011-01-01

    The aims of the study were to review single-institution experiences with sinonasal inverted papilloma associated with squamous cell carcinoma (IP/SCC), to analyze the presence of human papillomavirus (HPV) and to evaluate the role of radiotherapy. Five patients with IP/SCC were identified in the prospective institutional databases (1995–2005) and HPV status was determined in all five tumors. Four out of five patients had T3-4 tumors; no nodal involvement was seen in any of them. Four patients had curative surgery, supplemented in three of them with radiotherapy. Debulking surgery was performed in the patient with a non-resectable tumor followed by radical radiotherapy. Tumor was controlled locally in three patients at 8, 46 and 58 months post-surgery. Local failure occurred in two patients: after endoscopic resection of a T1 tumor (the recurrent tumor was successfully salvaged with additional surgery) and in a patient with an inoperable tumor. No regional or distant metastases occurred. HPV status was determined in all five tumors and three of them were found positive for HPV type 11. In operable sinonasal IP/SCC, upfront surgery and postoperative radiotherapy to the tumor bed with dose levels comparable to those used for invasive SCC are recommended. For non-resectable disease, radical radiotherapy to a dose of 66–70 Gy could be of benefit

  19. Microwave therapy for cutaneous human papilloma virus infection.

    Science.gov (United States)

    Bristow, Ivan; Lim, Wen Chean; Lee, Alvin; Holbrook, Daniel; Savelyeva, Natalia; Thomson, Peter; Webb, Christopher; Polak, Marta; Ardern-Jones, Michael R

    2017-10-01

    Human papilloma virus (HPV) infects keratinocytes of the skin and mucous membranes, and is associated with the induction of cutaneous warts and malignancy. Warts can induce significant morbidity and disability but most therapies, including cryotherapy, laser, and radiofrequency devices show low efficacy and induce discomfort through tissue destruction. Microwaves are readily capable of passing through highly keratinised skin to deliver energy and induce heating of the tissue in a highly controllable, uniform manner. To determine the effects of microwave on cutaneous HPV infection. We undertook a pilot study of microwave therapy to the skin in 32 consecutive individuals with 52 recalcitrant long-lived viral cutaneous warts. Additionally, we undertook a molecular characterisation of the effects of microwaves on the skin. Tissue inflammation was minimal, but 75.9% of lesions cleared which compares favourably with previous studies showing a clearance rate of 23-33% for cryotherapy or salicylic acid. We show that microwaves specifically induce dendritic cell cross-presentation of HPV antigen to CD8+ T cells and suggest that IL-6 may be important for DC IRF1 and IRF4 modulation to enhance this process. Keratinocyte-skin dendritic cell cross-talk is integral to host defence against HPV infections, and this pilot study supports the concept of microwave induction of anti-HPV immunity which offers a promising approach for treatment of HPV-induced viral warts and potentially HPV-related cancers.

  20. Nasal rhinosporidiosis: differential diagnosis of fungal sinusitis and inverted papilloma

    Directory of Open Access Journals (Sweden)

    Crosara, Paulo Fernando Tormin Borges

    2009-03-01

    Full Text Available Introduction: Clinical case report of rhinosporidiosis, a rare and chronic granulomatous disease, caused by Rhinosporidium seeberi. Objective: To include this disease in the differential diagnoses of polypoid lesions of the nasal mass. Report: A male patient from the North of Brazil evolved a three-year papilomatous polypoid lesion of the left nasal cavity. He was submitted to sinusectomy with resection of the entire lesion, located in ethmoid bulla and uncinated process. Inverted papilloma or fungal sinusitis were differential diagnoses. The histopathological examination revealed a strong infestation by numerous fungal structures with sporangia shape full of sporangiospores. The microorganisms were positive for colorations of Grocott, PAS and Mayer's Mucicarmin; opposite from Coccidioides immitis, which presents no contrast by the mucicarmin. We didn't choose complimentary treatment and after one year of follow-up he presents with no sign of recurrence. Final Comments: Rhinosporidiosis must be considered to be a nasal polypoid lesion differential diagnosis. In the intranasal lesions diagnosis we should keep in mind the patient's origin. The anatomopathological study is mandatory to set the diagnosis. In the rhinosporidiosis, the surgical exeresis can be a curative treatment.

  1. Human Papilloma Viruses and Breast Cancer – Assessment of Causality

    Science.gov (United States)

    Lawson, James Sutherland; Glenn, Wendy K.; Whitaker, Noel James

    2016-01-01

    High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case–control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is “specificity.” HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers. PMID:27747193

  2. Human Papilloma Viruses and Breast Cancer - Assessment of Causality.

    Science.gov (United States)

    Lawson, James Sutherland; Glenn, Wendy K; Whitaker, Noel James

    2016-01-01

    High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case-control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is "specificity." HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers.

  3. Surgical management of inverted papilloma: approaching a new standard for surgery.

    Science.gov (United States)

    Carta, Filippo; Blancal, Jean-Philippe; Verillaud, Benjamin; Tran, Hugo; Sauvaget, Elisabeth; Kania, Romain; Herman, Philippe

    2013-10-01

    Inverted papilloma surgery is currently performed primarily with an endoscopic approach, a technique that has a recurrence rate of 12%. However, a recent study reported a recurrence rate of 5% with a strategy based on subperiosteal dissection of the tumor, with limited indications for using an external approach. The aim of this work was to evaluate whether different teams using the same surgical concepts could reproduce the excellent results that were recently reported. This study is a retrospective chart review of 71 consecutive patients with inverted papilloma who were treated during the last 10 years. In all, 80% of the patients were treated using a purely endoscopic approach. The mean follow-up period was 31.6 months. The recurrence rate was 3.3% for cases with at least a 12-month follow-up. This work confirms the results described in recent literature and further supports transnasal endoscopic surgery to manage inverted papilloma. Copyright © 2013 Wiley Periodicals, Inc.

  4. Detection of Human Papillomavirus Type 2 Related Sequence in Oral Papilloma

    Science.gov (United States)

    Yamaguchi, Taihei; Shindoh, Masanobu; Amemiya, Akira; Inoue, Nobuo; Kawamura, Masaaki; Sakaoka, Hiroshi; Inoue, Masakazu; Fujinaga, Kei

    1998-01-01

    Oral papilloma is a benign tumourous lesion. Part of this lesion is associated with human papillomavirus (HPV) infection. We analysed the genetical and histopathological evidence for HPV type 2 infection in three oral papillomas. Southern blot hybridization showed HPV 2a sequence in one lesion. Cells of the positive specimen appeared to contain high copy numbers of the viral DNA in an episomal state. In situ staining demonstrated virus capsid antigen in koilocytotic cells and surrounding cells in the hyperplastic epithelial layer. Two other specimens contained no HPV sequences by labeled probe of full length linear HPVs 2a, 6b, 11, 16, 18, 31 and 33 DNA under low stringency hybridization conditions. These results showed the possibility that HPV 2 plays a role in oral papilloma. PMID:9699941

  5. Case of choroid plexus papilloma of the lateral ventricle presenting as a primary intracranial hemorrhage

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    Kurokawa, Hiroyuki; Kikuchi, Kenji; Gito, Yoji; Goto, Tsuneo; Ito, Yasunobu; Fujii, Satoshi

    1988-04-01

    A case of a choroid plexus papilloma of the lateral ventricle that was revealed by a massive intracranial hemorrhage in a 61-year-old man is presented. This patient had an intracranial hemorrhage at the onset. The presence of brain tumor was suspected after a radiologic evaluation using computerized tomography (CT) and angiography; the correctness of this histological diagnosis was confirmed by surgical specimens. Choroid plexus papillomas, rare tumors of neuroectodermal origin, account for 0.5 to 0.6 % of all intracranial tumors. They most frequently appear during the first 2 years of life. A case manifesting intracranial hemorrhage associated with choroid plexus papilloma in an adult is described, with a review of the literature. The importance of adequate radiological investigation is emphasized.

  6. A case of choroid plexus papilloma of the lateral ventricle presenting as a primary intracranial hemorrhage

    International Nuclear Information System (INIS)

    Kurokawa, Hiroyuki; Kikuchi, Kenji; Gito, Yoji; Goto, Tsuneo; Ito, Yasunobu; Fujii, Satoshi

    1988-01-01

    A case of a choroid plexus papilloma of the lateral ventricle that was revealed by a massive intracranial hemorrhage in a 61-year-old man is presented. This patient had an intracranial hemorrhage at the onset. The presence of brain tumor was suspected after a radiologic evaluation using computerized tomography (CT) and angiography; the correctness of this histological diagnosis was confirmed by surgical specimens. Choroid plexus papillomas, rare tumors of neuroectodermal origin, account for 0.5 to 0.6 % of all intracranial tumors. They most frequently appear during the first 2 years of life. A case manifesting intracranial hemorrhage associated with choroid plexus papilloma in an adult is described, with a review of the literature. The importance of adequate radiological investigation is emphasized. (author)

  7. A rare case of anal carcinosarcoma with human papilloma virus infection in both biphasic tumor elements: An immunohistochemical, molecular and ultrastructural study

    Directory of Open Access Journals (Sweden)

    Richard A. Hickman

    2016-12-01

    Full Text Available Carcinosarcoma of the anus is rare and has yet to be reportedly associated with the keratinocyte-specific Human Papilloma Virus (HPV. We describe a case of anal carcinosarcoma with HPV infection in both the epithelial and mesenchymal components of the tumor by immunohistochemistry, chromogenic in-situ hybridization (CISH and further supported by electron microscopy (EM. Microscopic examination of the tumor showed nests of poorly-differentiated invasive squamous cell carcinoma with basaloid features intermixed with a hypercellular, atypical spindle cell proliferation. Immunohistochemistry demonstrated that the epithelial component was positive for AE1/AE3, p63, CK5/6 and p16, whilst the mesenchymal component was positive for smooth muscle actin, vimentin, and focally positive for desmin and p16, consistent with carcinosarcoma. The tumor was negative for GATA-3, CK7 and CK20. CISH demonstrated that the tumor was positive for high risk HPV (subtype 16/18 in both tumor components. EM further supported the presence of intracellular virus particles (~50 nm that is compatible with HPV infection. Infection of both epithelial and mesenchymal tumor components by HPV has not been previously observed in the gastrointestinal tract. This finding may represent initial epithelial HPV infection with subsequent divergent tumoral differentiation and suggests the presence of viral replication in both biphasic tumor components. Keywords: Carcinosarcoma, Human Papilloma Virus, Gastrointestinal

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

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    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.

  9. Human papilloma virus infection in female kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Shirin Ghazizadeh

    2011-01-01

    Full Text Available The objective of this study was to evaluate the incidence of genital human papilloma virus (HPV infection and cervical intra-epithelial lesions in transplanted patients. Cervical Papanicolaou (Pap smear/HPV test and colposcopic examinations were performed in 58 patients who were candidates for renal transplant surgery; these tests were repeated one year later. Their age range was 26-53 years (mean, 37.2 years. Hypertension was the most common cause of renal insufficiency (34.4%, while in 41.4% of the patients, the causative pathology was unknown. In 24.1% of the patients, there was no history of dialysis, i.e. they had pre-emptive transplantation. The mean duration of marriage (years since first intercourse was 16.2 years (range, 1-35. Coitus interruptus was the most common contraceptive method used (37.9%, followed by tubal ligation and condom (10.3% and 6.9%, respectively. All patients had negative Pap tests and normal gynecologic exam before undergoing transplantation. The Pap test remained normal after transplant surgery, although the HPV test became positive in four patients (6.9%. There were five cases of white epithelium on colposcopy, but biopsy showed normal metaplasia. Two cases of extensive anogenital warts were treated by CO 2 laser, and one patient had recurrent warts, which responded well to second laser surgery. None of the study patients had squamous intra-epithelial lesions (SIL or vulvar intra-epithelial neoplasia. Our study suggests that screening with HPV and Pap test should be performed before transplant surgery and should be repeated at regular intervals in order to avoid irreversible situations such as high-grade SILs, which are difficult to treat. Avoiding high-risk sexual relations in this group of patients is highly recommended.

  10. BENIGN EPITHELIAL NEOPLASIA ASSOCIATED WITH BETA-HUMAN PAPILLOMA VIRUS

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    V. A. Molochkov

    2014-01-01

    Full Text Available Aim: To study an association between acrochordon and human papilloma virus (HPV using quantitative analysis of viral desoxyribonucleic acid (DNA; to detect different phenotypes of beta-HPV. Materials and methods: We examined 52  patients (22 immuno-suppressed patients and 30 immunocompetent subjects in the Dermatovenereology and Dermato-Oncology Department and Chronic Dialysis and Kidney Transplantation Department of the Moscow Regional Research and Clinical Institute (MONIKI. Control group included 49 healthy donors. Burr biopsy samples (micro-samples of acrochordon and intact skin (apper arm were collected in sterile conditions. After sample procession and DNA isolation using DNK-sorb-C kit (Central Research Institute for Epidemiology – CRIE, polymerase chain reaction for HPV was performed with real-time fluorescent hybridization detection. For DNA amplification and detection we used RotorGene 3000 analyzer (Corbett Research, Australia. In the beta-HPV assay, recombinant plasmids were used as positive controls and control human beta-globin gene fragments (CRIE. 4 oligo-nucleotide systems (group-specific primers and probes were used for the detection of beta-HPV DNA. Results: Preliminary data indicated that acrochordons of open and covered skin regions were common in renal transplant recipients. Beta-HPV DNA was more frequent in acrochordons and intact skin (64% and 54% of renal transplant recipients compared to healthy donors (47%. 57% of renal transplant recipients demonstrated mixed infection in acrochordons. Conclusion: HPV DNA was frequently detected in acrochordons and intact skin of renal transplant recipients. In immunocompetent patients prevalence of HPV DNA in acrochordons was significantly higher compared to intact skin.

  11. Human papilloma virus prevalence in a multiethnic screening population.

    Science.gov (United States)

    Chen, Kang Mei; Stephen, Josena K; Ghanem, Tamer; Stachler, Robert; Gardner, Glendon; Jones, Lamont; Schweitzer, Vanessa P; Hall, Francis; Divine, George; Worsham, Maria J

    2013-03-01

    The goal was to determine the prevalence of high-risk HPV16 using saliva in a screening population in Detroit, Michigan. Real-time quantitative polymerase chain reaction was applied to detect HPV16 in saliva DNA from 349 screening subjects without head and neck cancer (HNC), 156 with HNC, and 19 controls. Cut points for human papilloma virus (HPV) positivity were >0 and >0.001 copy/cell. Proportions were compared between groups using exact χ(2) or Fisher exact tests (P 0, each group had an overall HPV prevalence of more than 5%, with a higher prevalence of 30.8% in the HNC patient group. At a cut point >0.001, the prevalence was lower: 0% in the control, 1.2% in the screening, and 16.7% in the HNC group. In the latter, for both cut points, HPV prevalence was different across sites (0, women in the screening group had a higher prevalence of HPV than did men (P = .010), and at >0.001, the prevalence was higher for men in the HNC group than for women (P = .035). In the screening group, at >0, only African Americans had a higher prevalence than Caucasian Americans (P = .025). In the screening group, a 6.9% and 1.2% screening rate was noted at cut points >0 and >0.001, respectively. The results provide data to inform public health considerations of the feasibility of saliva as a screening tool in at-risk populations with the long-term goal of prophylactic vaccination against oral HPV.

  12. The use of film imaging techniques in the diagnosis of mammary intraductal papilloma (report of 23 cases)

    International Nuclear Information System (INIS)

    Wei Shaohua; Liu Genshou

    2001-01-01

    Objective: To summarize the value of the film imaging techniques in the diagnosis of mammary intraductal papilloma. Methods: Retrospectively analysis 23 in patients with mammary intraductal papilloma which was confirmed by diagnosis with multiple function ultrasound instrument, mammography and breast duct imaging techniques. Results: The diagnosis sensitivities of multiple function ultrasound instrument and breast duct imaging techniques were 66.7% and 70.6% respectively (P > 0.05). Both of them had a definite value in diagnosis of mammary intraductal papilloma. Conclusion: Film imaging techniques are valuable to locate lesions, but is not useful for making pathological diagnosis

  13. Genital sanguineous discharge in prepuberty: a case of mullerian papilloma of vagina in a nine-year-old girl.

    Science.gov (United States)

    Tumini, Stefano; Carinci, Silvia; Anzellotti, Maria Teresa; Chiesa, Pier Luigi Lelli; Rossi, Carlo; Stuppia, Liborio; Bertelloni, Silvano; Chiarelli, Francesco

    2010-08-01

    Vaginal bleeding in prepuberty is an alarming symptom that must be carefully investigated. Among quite common causes of genital sanguineous discharge, there are rarer conditions responsible for bleeding at this age like Mullerian papilloma of the genital tract. In this report, we describe a case of Mullerian papilloma of the vagina in a 9-year-old girl. We believe in the importance of a correct clinical setting and histological definition to avoid wrong diagnosis and consequent inadequate treatments. Mullerian papilloma, a benign tumor, can in fact be treated only with local excision.

  14. "TuNa-saving" endoscopic medial maxillectomy: a surgical technique for maxillary inverted papilloma.

    Science.gov (United States)

    Pagella, Fabio; Pusateri, Alessandro; Matti, Elina; Avato, Irene; Zaccari, Dario; Emanuelli, Enzo; Volo, Tiziana; Cazzador, Diego; Citraro, Leonardo; Ricci, Giampiero; Tomacelli, Giovanni Leo

    2017-07-01

    The maxillary sinus is the most common site of sinonasal inverted papilloma. Endoscopic sinus surgery, in particular endoscopic medial maxillectomy, is currently the gold standard for treatment of maxillary sinus papilloma. Although a common technique, complications such as stenosis of the lacrimal pathway and consequent development of epiphora are still possible. To avoid these problems, we propose a modification of this surgical technique that preserves the head of the inferior turbinate and the nasolacrimal duct. A retrospective analysis was performed on patients treated for maxillary inverted papilloma in three tertiary medical centres between 2006 and 2014. Pedicle-oriented endoscopic surgery principles were applied and, in select cases where the tumour pedicle was located on the anterior wall, a modified endoscopic medial maxillectomy was carried out as described in this paper. From 2006 to 2014 a total of 84 patients were treated. A standard endoscopic medial maxillectomy was performed in 55 patients (65.4%), while the remaining 29 (34.6%) had a modified technique performed. Three recurrences (3/84; 3.6%) were observed after a minimum follow-up of 24 months. A new surgical approach for select cases of maxillary sinus inverted papilloma is proposed in this paper. In this technique, the endoscopic medial maxillectomy was performed while preserving the head of the inferior turbinate and the nasolacrimal duct ("TuNa-saving"). This technique allowed for good visualization of the maxillary sinus, good oncological control and a reduction in the rate of complications.

  15. Carbon dioxide (CO2) laser treatment of cutaneous papillomas in a common snapping turtle, Chelydra serpentina.

    Science.gov (United States)

    Raiti, Paul

    2008-06-01

    Carbon dioxide (CO2) laser was used to treat multiple cutaneous papillomas on an adult female common snapping turtle, Chelydra serpentina serpentina. A combination of excisional and ablative techniques provided excellent intraoperative visibility and postoperative results due to the laser's unique ability to incise and vaporize soft tissue.

  16. The role of miRNAs in human papilloma virus (HPV)-associated cancers

    DEFF Research Database (Denmark)

    Lajer, C B; Garnæs, E; Friis-Hansen, L

    2012-01-01

    Although the role of human papilloma virus (HPV) in cervical squamous cell carcinoma (CSCC) is well established, the role in head and neck SCC (HNSCC) is less clear. MicroRNAs (miRNAs) have a role in the cancer development, and HPV status may affect the miRNA expression pattern in HNSCC. To explore...

  17. Heterogeneity of uroplakin localization in human normal urothelium, papilloma and papillary carcinoma

    International Nuclear Information System (INIS)

    Zupancic, Dasa; Romih, Rok

    2013-01-01

    Uroplakins are differentiation-related membrane proteins of urothelium. We compared uroplakin expression and ultrastructural localization in human normal urothelium, papilloma and papillary carcinoma. Because of high recurrence rate of these tumours, treated by transurethral resection, we investigated urothelial tumour, resection border and uninvolved urothelium. Urinary bladder samples were obtained from tumour free control subjects and patients with papilloma and papillary carcinoma. Immunohistochemical and immunoelectron labelling of uroplakins were performed. In normal human urothelium with continuous uroplakin-positive superficial cell layer uroplakins were localized to flattened mature fusiform vesicles and apical plasma membrane of umbrella cells. Diverse uroplakin expression was found in papilloma and papillary carcinoma. Three aberrant differentiation stages of urothelial cells, not found in normal urothelium, were recognized in tumours. Diverse uroplakin expression and aberrant differentiation were occasionally found in resection border and in uninvolved urothelium. We demonstrated here that uroplakin expression and localization in urothelial tumours is altered when compared to normal urothelium. In patients with papilloma and papillary carcinoma immunolabelling of uroplakins at ultrastructural level shows aberrant urothelial differentiation. It is possible that aberrant differentiation stages of urothelial cells in resection border and in uninvolved urothelium contribute to high recurrence rate

  18. Problem-Solving Test: The Mechanism of Action of a Human Papilloma Virus Oncoprotein

    Science.gov (United States)

    Szeberenyi, Jozsef

    2009-01-01

    Terms to be familiar with before you start to solve the test: human papilloma virus; cervical cancer; oncoproteins; malignant transformation; retinoblastoma protein; cell cycle; quiescent and cycling cells; cyclin/cyclin-dependent kinase (Cdk) complexes; E2F; S-phase genes; enhancer element; proto-oncogenes; tumor suppressor genes; radioactive…

  19. Evaluation of Human Papilloma Virus Communicative Education Strategies: A Pilot Screening Study for Cervical Cancer

    Science.gov (United States)

    Barrera-Clavijo, Lizeth K.; Wiesner-Ceballos, Carolina; Rincón-Martínez, Lina M.

    2016-01-01

    Background: High-risk human papilloma virus (HR-HPV) is highly prevalent in sexually active men and women; HR-HPV has been classified as a sexually transmitted infection (STI) and as a necessary, but not sufficient, causal agent for cervical cancer. Women who test positive for HPV often experience serious psychosocial consequences such as fear,…

  20. A clinical and molecular review of inverted papilloma of the urinary tract

    DEFF Research Database (Denmark)

    Jørgensen, Peter Hjorth; Vainer, Ben; Hermann, Gregers Gautier

    2015-01-01

    Inverted papilloma (IP) of the urinary tract is classified by the World Health Organisation as a non-invasive urothelial tumour with normal to minimal cytological atypia of the neoplastic cells. During the 1980s, it came under suspicion of having a premalignant or malignant potential and of being...

  1. Prevalence of herpes simplex, Epstein Barr and human papilloma viruses in oral lichen planus.

    Science.gov (United States)

    Yildirim, Benay; Sengüven, Burcu; Demir, Cem

    2011-03-01

    The aim of the present study was to assess the prevalence of Herpes Simplex virus, Epstein Barr virus and Human Papilloma virus -16 in oral lichen planus cases and to evaluate whether any clinical variant, histopathological or demographic feature correlates with these viruses. The study was conducted on 65 cases. Viruses were detected immunohistochemically. We evaluated the histopathological and demographic features and statistically analysed correlation of these features with Herpes Simplex virus, Epstein Barr virus and Human Papilloma virus-16 positivity. Herpes Simplex virus was positive in six (9%) cases and this was not statistically significant. The number of Epstein Barr virus positive cases was 23 (35%) and it was statistically significant. Human Papilloma virus positivity in 14 cases (21%) was statistically significant. Except basal cell degeneration in Herpes Simplex virus positive cases, we did not observe any significant correlation between virus positivity and demographic or histopathological features. However an increased risk of Epstein Barr virus and Human Papilloma virus infection was noted in oral lichen planus cases. Taking into account the oncogenic potential of both viruses, oral lichen planus cases should be detected for the presence of these viruses.

  2. Immunohistochemical Differentiation between Urothelial Papillomas and Papillary Neoplasms of Low Malignant Potential of the Urinary Bladder.

    Science.gov (United States)

    Alrashidy, Mohammed; Atef, Aliaa; Baky, Tarek Abdel

    2016-01-01

    Urothelial papilloma and non-invasive papillary carcinoma are common neoplasms of the urinary bladder. Distinguishing papillomas and papillary carcinomas, especially the low grade type, is often debatable on the basis of histological features alone. We investigated immunohistochemical expression of cytokeratin 20 (CK20), p53, and Ki-67 in a group of 20 urothelial papilloma cases and 30 noninvasive papillary neoplasms of low malignant potential (PNLMP) of the urinary bladder. Whole tissue sections were examined. Among the 30 carcinoma cases, 12 (40%) showed strong reactivity for the whole panel, 16 (53%) reacted positively for two markers, and 2 (7%) reacted just to one of them. Ki-67 was considered positive in 27 cases (90%) and p53 in 24 (80%), CK20 showed positive reactivity in 21 cases (70%). Only small percentages of papillomas were positive, and then only weakly. We concluded that the intense positivity of suspicious cells for at least one of these markers would confirm the presence of malignant changes and favours the diagnosis of carcinoma.

  3. The use of mitomycin-C for respiratory papillomas: Clinical, histologic and biochemical correlation

    International Nuclear Information System (INIS)

    Hamza, Ashraf H.; Nasr, Manal M.; Deghady, Akram A.

    2005-01-01

    To assess the clinical effects of mitomycin-C (MMC) on human papilloma virus (HPV)-infected tissues of the airway. We included 10 patients with previous histologic diagnosis of recurrent respiratory papillomas (RRP) in this prospective study, conducted at the Department of Otolaryngology-Head and Neck Surgery, University of Alexandria, Egypt, between January 2000 and December 2002. Under general anesthesia, each patient underwent laser excision of all visible papillomas, followed by topical application of 1 cc of 0.5 mg/ml MMC. The procedure was repeated weekly until no visible papillomas could be microscopically detected. We histopathologically studied the obtained specimens and tested for the presence of HPV DNA using polymerase chain reaction (PCR) technique. We collected blood samples from all patients and from another 10 healthy volunteers for determination of serum interleukin-2 (IL-2) level using enzyme-linked immunosorbent assay technique. We achieved clinical remission in 8 of the patients (80%), a fact that was confirmed histopathologically and by PCR data. The mean serum IL-2 levels +/- SD was significantly lower in papilloma patients (83.6 +/- 28.83 pg/ml) than in control subjects (196.3 +/- 42.46 pg/ml) (p<0.01). Among patients with RRP, serum IL-2 levels +/-SD was lower in initial samples (83.6 +/- 28.83) than follow-up (95.7 +/- 27.98 and 112.3 +/- 33.8 and 129.4 +/- 34.04) and remission samples (154 +/- 37.84 pg/ml). Our result suggests that topical application of MMC may act adjunctively to laser surgery for RRP. (author)

  4. [The awareness and attitude of population of Kazakhstan to inoculation against human papilloma virus].

    Science.gov (United States)

    Nasritdinova, N Yu; Reznik, V L; Kuatbaieva, A M; Kairbaiev, M R

    2016-01-01

    The vaccines against human papilloma virus are a potential tool for prevention of cervix cancer and particular other types of cancer. The high inclusion of target group in applied vaccination program is economically effective and successful activity depending in many instances on reliable knowledge and positive attitude of population to inoculation. The cross-sectional study was carried out using previously developed anonymous questionnaires for various groups of population in four pilot regions of Kazakhstan where national ministry of health proposes for inoculation of girls aged 9-13 years two vaccines against human papilloma virus (four- and two-valence) The data base was organized using software Microsoft Access. The materials were integrated and processed using variation statistics techniques in software IBM SPSS Statistics 19 and applying Student criterion and calculating correlation dependences. Out of all respondents, 66% were aware about existence of human papilloma virus/ the main portion of parents 'female adolescents learned about vaccination against human papilloma virus from Internet and medical workers. The most significant factor preventing implementation of vaccination and the proper perception by respondents was absence of confidence in safety of vaccine. About 54% of parents of female adolescents and 75% of teachers consider vaccine as unsafe. And only 72% of medical workers consider vaccine as safe. Despite known effectiveness of vaccination against human papilloma virus, number of problems exist related to implementation of program. The level of awareness and understanding of different groups of population concerning the role of vaccination in development of oncologic pathology and possibility of prevention of cancer at the expense of vaccination. The intersectoral relationships are to be developed between medicine and education system. The significance of information activities of medical control organs and organizations is to be enhanced.

  5. Enhancing the Sensitivity of DNA Microarray Using Dye-Doped Silica Nanoparticles: Detection of Human Papilloma Virus

    Science.gov (United States)

    Enrichi, F.; Riccò, R.; Meneghello, A.; Pierobon, R.; Canton, G.; Cretaio, E.

    2010-10-01

    DNA microarray is a high-throughput technology used for detection and quantification of nucleic acid molecules and others of biological interest. The analysis is based on the specific hybridization between probe sequences deposited in array and a target ss-DNA amplified by PCR and functionalized by a fluorescent dye. Organic labels have well known disadvantages like photobleaching and low signal intensities, which put a limitation to the lower amount of DNA material that can be detected. Therefore for trace analysis the development of more efficient biomarkers is required. With this aim we present in this paper the synthesis and application of alternative hybrid nanosystems obtained by incorporating standard fluorescent molecules into monodisperse silica nanoparticles. Efficient application to the detection of Human Papilloma Virus is demonstrated. This virus is associated to the formation of cervical cancer, a leading cause of death by cancer for women worldwide. It is shown that the use of the novel biomarkers increases the optical signal of about one order of magnitude with respect to the free dyes or quantum dots in conventional instruments. This is due to the high number of molecules that can be accommodated into each nanoparticle, to the reduced photobleaching and to the improved environmental protection of the dyes when encapsulated in the silica matrix. The cheap and easy synthesis of these luminescent particles, the stability in water, the surface functionalizability and bio-compatibility make them very promising for present and future bio-labeling and bio-imaging applications.

  6. Ultrastructural localization of human papilloma virus by nonradioactive in situ hybridization on tissue of human cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Multhaupt, H A; Rafferty, P A; Warhol, M J

    1992-01-01

    BACKGROUND: A nonradioactive in situ hybridization was developed to localize human papilloma virus (HPV) at the ultrastructural level. EXPERIMENTAL DESIGN: Cervical biopsies from human uterine cervices clinically suspicious of condyloma were embedded in Lowicryl K4M at low temperature...

  7. Long-term survival outcomes in patients with surgically treated oropharyngeal cancer and defined human papilloma virus status.

    Science.gov (United States)

    Dale, O T; Sood, S; Shah, K A; Han, C; Rapozo, D; Mehanna, H; Winter, S C

    2016-11-01

    This study investigated long-term survival outcomes in surgically treated oropharyngeal cancer patients with known human papilloma virus status. A case note review was performed of all patients undergoing primary surgery for oropharyngeal cancer in a single centre over a 10-year period. Human papilloma virus status was determined via dual modality testing. Associations between clinicopathological variables and survival were identified using a log-rank test. Of the 107 cases in the study, 40 per cent (n = 41) were human papilloma virus positive. The positive and negative predictive values of p16 immunohistochemistry for human papilloma virus status were 57 per cent and 100 per cent, respectively. At a mean follow up of 59.5 months, 5-year overall and disease-specific survival estimates were 78 per cent and 69 per cent, respectively. Human papilloma virus status (p = 0.014), smoking status (p = 0.021) and tumour stage (p = 0.03) were significant prognostic indicators. The long-term survival rates in surgically treated oropharyngeal cancer patients were comparable to other studies. Variables including human papilloma virus status and tumour stage were associated with survival in patients treated with primary surgery; however, nodal stage and presence of extracapsular spread were non-prognostic.

  8. Tubular forms of papova viruses in human laryngeal papilloma.

    Science.gov (United States)

    Arnold, W

    1979-01-01

    In two cases of recurrent laryngeal papillomatosis tubular forms of papova viruses could be observed. The same material revealed the close relation between nuclear chromatine and the release of particles, as well as a capsomere like substructure of the virions.

  9. Virus del Papiloma humano Human Papilloma virus (HPV

    Directory of Open Access Journals (Sweden)

    José G Sanabria Negrín

    2009-12-01

    browsed on line were published in: Cochrane, Dynamed, Evidence-based Medicine Update, New England Journal of Medicine, J Clinical Oncology, Medscape, PubMed, IARC and Human Papilloma Virus Today, in English, French, Portuguese or Spanish, from the last 5 years; taking also as reference important original articles from previous years. Terms used for the search were: definitions, epidemiology, etiology, HPV, risk factors, clinical features of the HPV infection, clinical implications, mass screening, treatment, primary/secondary prevention and social repercussion. HPV is a sexually-transmitted infection; thus it is preventable and curable. HPV is a DNA virus needing for an epithelium for its replication and to accomplish its vital cycle. The expression of the genes varies inside the epithelial tissue, and from one part of it to the other depending on the type of lesion. Infection is detected from the childhood, even without sexual intercourse, reaching a climax around 30 years old, and then decreasing. The current alternatives are: the primary prevention by means of the use of barrier methods of contraception and the prophylactic vaccines; mass screening and developing-therapeutic vaccines are used after the infection. In every step of the diagnosis and treatment of the disease social problems may arise from the anxiety burden, the infection and its consequences. A discussion about all these aspects was carried out.

  10. 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

  11. Association of Krouse Classification for Sinonasal Inverted Papilloma With Recurrence: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Lisan, Quentin; Moya-Plana, Antoine; Bonfils, Pierre

    2017-11-01

    The risk factors for the recurrence of sinonasal inverted papilloma are still unclear. To investigate the potential association between the Krouse classification and the recurrence rates of sinonasal inverted papilloma. The EMBASE and MEDLINE databases were searched for the period January 1, 1964, through September 30, 2016, using the following search strategy: (paranasal sinuses [Medical Subject Headings (MeSH) terms] OR sinonasal [all fields]) AND (inverted papilloma [MeSH terms] OR (inverted [all fields] AND papilloma [all fields]). The inclusion criteria were (1) studies including sinonasal inverted papilloma only and no other forms of papillomas, such as oncocytic papilloma; (2) minimum follow-up of 1 year after the surgery; and (3) clear report of cases (recurrence) and controls according to the Krouse classification system or deducible from the full-text article. Literature search was performed by 2 reviewers. Of the 625 articles retrieved in the literature, 97 full-text articles were reviewed. Observational cohort studies or randomized controlled trials were included, and the following variables were extracted from full-text articles: authors of the study, publication year, follow-up data, and number of cases (recurrence) and controls (no recurrence) in each of the 4 stages of the Krouse classification system. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Odds ratios (ORs) and 95% CIs were estimated, and data of included studies were pooled using a random-effects model. The main outcome was recurrence after surgical removal of sinonasal inverted papilloma according to each stage of the Krouse classification system. Thirteen studies comprising 1787 patients were analyzed. A significant increased risk of recurrence (51%) was highlighted for Krouse stage T3 disease when compared with stage T2 (pooled OR, 1.51; 95% CI, 1.09-2.09). No significant difference in risk of recurrence was found between Krouse stages T1

  12. Confronting human papilloma virus/oropharyngeal cancer: a model for interprofessional collaboration.

    Science.gov (United States)

    Fried, Jacquelyn L

    2014-06-01

    A collaborative practice model related to Human Papilloma Virus (HPV) associated oropharyngeal cancer highlights the role of the dental hygienist in addressing this condition. The incidence of HPV associated head and neck cancer is rising. Multiple professionals including the dental hygienist can work collaboratively to confront this growing public health concern. A critical review applies the growth and utilization of interprofessional education (IPE) and interprofessional collaboration (IPC) to multi-disciplinary models addressing the human papilloma virus and oropharyngeal cancers. A model related to HPV associated oropharyngeal cancer addresses an oral systemic condition that supports the inclusion of a dental hygienist on collaborative teams addressing prevention, detection, treatment and cure of OPC. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Urothelial papilloma of the bladder: a review of 34 de novo cases.

    Science.gov (United States)

    Magi-Galluzzi, Cristina; Epstein, Jonathan I

    2004-12-01

    Urothelial papilloma of the bladder is an uncommon entity when using restrictive diagnostic criteria. We retrospectively studied 34 patients who were diagnosed with urothelial papilloma of the bladder using the criteria of the 1998 WHO/ISUP classification system. Six cases were in-house and the remaining 28 were referred from other institutions as consults to one of the authors. In all cases, the diagnosis of papilloma was the first manifestation of urothelial neoplasia. The mean age of the patients at diagnosis was 57.8 years (range, 23-87 years). The male-to-female ratio was 2.4:1 (24 males and 10 females). The tumor size averaged 3.3 mm (range, 1-20 mm; median, 2 mm). Simple papillary fronds were seen in all cases; in 5 cases the additional finding of secondary budding off of small fronds from larger ones was also seen. In all cases, the fronds had a round morphology; yet in 4 cases elongated fronds were also noted. In 5 cases, dilated lymphatics within the fibrovascular fronds were apparent. One case had foamy histiocytes within the fibrovascular stalks. In all cases, the lining consisted of normal-appearing urothelium without hyperplasia, dysplasia, and/or mitotic figures. Some of the distinctive histologic features seen were changes in the umbrella cells: vacuolization (n = 4), prominence with cytologic atypia (n = 2), eosinophilic syncytial morphology (n = 1), apocrine-like morphology (n = 1), and mucinous metaplasia (n = 1). Follow-up was available in 26 cases with a mean follow-up for those without evidence of progression of 28.9 months (range, 3-127 months). Three patients (8.8%) developed recurrent papilloma 4, 15, and 18 months after the initial diagnosis of papilloma; 1 of these patients also showed progression to noninvasive low-grade urothelial carcinoma at the time of recurrence (15 months). Three patients (8.8%) progressed to higher-grade disease: 2 to noninvasive low grade urothelial carcinoma (11 and 15 months after the original diagnosis) and 1

  14. Use of a powered shaver to remove multiple oral cavity papillomas.

    Science.gov (United States)

    Miller, Robert Sean; Tami, Thomas A

    2005-05-01

    We report a previously undescribed method of removing multiple oral papillomas, which we performed on 5 men with human immunodeficiency virus (HIV) infection. Patients were brought to the operating room and placed under general anesthesia. In addition, 1% lidocaine with 1:100,000 epinephrine was injected under and around the lesions. We then removed the lesions with a Tricut laryngeal blade attached to a handheld powered shaver Postoperatively, patients were sent home on clindamycin, a pain medication, and Peridex. At the 1-week follow-up, patients reported only minimal pain, and their wounds were well healed. We observed no adverse events associated with the shaving procedure. Our method expedites the process of removing multiple oral cavity papillomas while reducing the morbidity generally associated with other procedures.

  15. Anal Papilloma: An Exceptional Presentation of Fibrocystic Disease in Anogenital Mammary-Like Glands

    Directory of Open Access Journals (Sweden)

    Priya Subashchandrabose

    2015-01-01

    Full Text Available Previously ectopic breast tissue was thought to be derived from the caudal remnants of the primitive embryonic milk ridges; anogenital mammary-like glands are presently considered as normal constituents of the anogenital region. We report a case of young female, who presented with an anal papilloma. Histopathological examination revealed extensive fibrocystic changes in anogenital mammary-like glands. To date, a lot of benign changes and a wide range of benign and malignant neoplasms have been reported in these glands. However, extensive fibrocystic change of these glands in anal region is very rare. In addition, fibrocystic disease of anal mammary glands, masquerading clinically as an anal papilloma, has not been reported in literature. Hence, it is essential for clinicians and the pathologists to be aware of such a rare presentation. The features of fibrocystic disease in perianal region are also discussed.

  16. Anal Papilloma: An Exceptional Presentation of Fibrocystic Disease in Anogenital Mammary-Like Glands.

    Science.gov (United States)

    Subashchandrabose, Priya; Esakkai, Muthuvel; Venugopal, Palani; Kannaiyan, Ilavarasan; Srinivasan, Chitra; Reddy, Punuru Tejashwini; Ebenezer, Evelyn Elizabeth

    2015-01-01

    Previously ectopic breast tissue was thought to be derived from the caudal remnants of the primitive embryonic milk ridges; anogenital mammary-like glands are presently considered as normal constituents of the anogenital region. We report a case of young female, who presented with an anal papilloma. Histopathological examination revealed extensive fibrocystic changes in anogenital mammary-like glands. To date, a lot of benign changes and a wide range of benign and malignant neoplasms have been reported in these glands. However, extensive fibrocystic change of these glands in anal region is very rare. In addition, fibrocystic disease of anal mammary glands, masquerading clinically as an anal papilloma, has not been reported in literature. Hence, it is essential for clinicians and the pathologists to be aware of such a rare presentation. The features of fibrocystic disease in perianal region are also discussed.

  17. MODERN DATA ON PAPILLOMA VIRUS INFECTION, AND OPPORTUNITIES OF ITS PROPHYLAXIS

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    I.S. Tarasov

    2009-01-01

    Full Text Available This article analyzes questions of quadrivalent vaccine Gardasil use for the protection of human papilloma virus (HPV type 6, 11, 16, and 18, responsible to 70% of carcinoma of uterine cervix cases, and 90% of anogenital condylomas. The results of wide ranging trials show that vaccine is effective in almost 100% of cases for the prevention of pre oncological intraepithelial dysplasia of uterine cervix, vulva, and vagina, anogenital condylomas, caused by vaccine types of HPV. Studies describe vaccine's high immunogenicity and safety. The vaccine was included in immunizations schedule in many countries. Obtained data give us hope that vaccination against uterine cervix cancer will be included in Russian National immunizations schedule in the immediate future.Key words: human papilloma virus, carcinoma of uterine cervix, quadrivalent vaccine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(3:35-41

  18. Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect

    Science.gov (United States)

    Nishat, Roquaiya; Ramachandra, Sujatha; Kumar, Harish; Bandyopadhyay, Alokenath

    2015-01-01

    Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID:26266234

  19. Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study

    Science.gov (United States)

    Sharma, Anjana; Panda, Anita

    2007-01-01

    Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians. PMID:17699945

  20. Cytomorphology of nipple discharge and fine needle aspiration of duct papilloma

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    H B Bannur

    2012-01-01

    Full Text Available The primary role of fine needle aspiration (FNA of the breast is the distinction between benign and malignant lesions; but in many cases, additional information may be obtained. The major breast lesions that yield papillary fragments on FNA are papillary carcinoma, papilloma, fibroadenoma, and invasive ductal carcinoma that have a papillary component. We present cytomorphological features of nipple discharge and FNA of breast lump in a 32-year female.

  1. Fluorouracil as a treatment for corneal papilloma in a Malayan tapir.

    Science.gov (United States)

    Karpinski, Lorraine G; Miller, Christine L

    2002-09-01

    A 26-year-old, wild caught, male Malayan tapir at the Miami Metrozoo with bilateral corneal papillomas was serially immobilized and given subconjunctival injections of fluorouracil. Over the course of 17 weeks five bilateral injections of 25 mg fluorouracil were given. This treatment caused regression of the corneal lesions as evidenced by decreased lesion diameter, decreased corneal vascularity, increased corneal clarity, and improved visual function. No adverse drug effects were observed.

  2. Human Papilloma Virus and oral cancer: Narrative review of the literature.

    OpenAIRE

    Alejandra Fernández; Maureen Marshall; Alfredo Esguep

    2014-01-01

    ABSTRACT The Human Papilloma Virus (HPV) infection is now more common sexually transmitted diseases, with an incidence of 5.5 million worldwide, with 85% of the carrier of this virus adult population. Their oncogenic potential and increased oral lesions associated with oral HPV infection have led us to make a narrative of the literature on the role of HPV in oral cancer, especially types 16 and 18. Here we refer to the possible routes of infection, oncogenic mechanisms, both benign and potent...

  3. Prevalence of herpes simplex, Epstein Barr and human papilloma viruses in oral lichen planus

    OpenAIRE

    Yildirim, Benay; Sengüven, Burcu; Demir, Cem

    2011-01-01

    Objectives: The aim of the present study was to assess the prevalence of Herpes Simplex virus, Epstein Barr virus and Human Papilloma virus -16 in oral lichen planus cases and to evaluate whether any clinical variant, histopathological or demographic feature correlates with these viruses. Study Design: The study was conducted on 65 cases. Viruses were detected immunohistochemically. We evaluated the histopathological and demographic features and statistically analysed correlation of these...

  4. Prevalence of Oral Human Papilloma Virus in Healthy Individuals in East Azerbaijan Province of Iran

    OpenAIRE

    SEIFI, Sharareh; ASVADI KERMANI, Iraj; DOLATKHAH, Roya; ASVADI KERMANI, Atabak; SAKHINIA, Ebrahim; ASGARZADEH, Mohammad; DASTGIRI, Saeed; EBRAHIMI, Ayoub; ASGHARI HAGGI, Arezou; NADRI, Mahsa; ASVADI KERMANI, Touraj

    2013-01-01

    Background: Human papilloma virus causes benign and malignant abnormalities in different part of the body. The link between high risk types of HPV and some anogenital and aerodigestive tract cancer is well established. Oral HPV infection plays a role in developing oropharyngeal squamous cell carcinoma. We studied the prevalence of oral HPV in healthy individuals and its relative risk factors. Methods: Saliva samples of 114 healthy subjects were collected for HPV DNA analysis. Volunteers compl...

  5. Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

    OpenAIRE

    Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

    2015-01-01

    Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and...

  6. Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy

    OpenAIRE

    Jastreboff, A; Cymet, T

    2002-01-01

    Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially d...

  7. Squamous Cell Carcinoma Arising from Inverted Schneiderian Papilloma: A Case Report with Oral Involvement

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    Alexandre Simões Garcia

    2014-01-01

    Full Text Available Inverted Schneiderian papilloma is an uncommon benign tumor that presents tendency to recur and propensity to be associated with malignancy in approximately 10% of the cases. Some of these lesions are isolated in the maxillary sinus, and predominantly affect white males with mean age of 50 years. We report a case of squamous cell carcinoma arising from inverted Schneiderian papilloma in the maxillary sinus extending to the mouth. The patient was submitted to extraction of a maxillary molar tooth four months before the exacerbation of the symptoms of nasal airway obstruction and facial enlargement. Computed tomography scan revealed a sinonasal mass causing opacification of the right maxillary sinus with destruction of the lateral nasal wall and maxillary sinus floor. The patient was referred to an oncology center for treatment and died from tumor progression one year after the cancer was diagnosed. The intention of this report is to alert dentists to include the inverted Schneiderian papilloma, either associated with squamous cell carcinoma, or not, in the differential diagnosis of maxillary sinus tumors with aggressive behavior, which may extend to the oral cavity or involve roots of teeth.

  8. Concept Analysis: Health-Promoting Behaviors Related to Human Papilloma Virus (HPV) Infection.

    Science.gov (United States)

    McCutcheon, Tonna; Schaar, Gina; Parker, Karen L

    2015-01-01

    The concept of health-promoting behaviors incorporates ideas presented in the Ottawa Charter of Public Health and the nursing-based Health Promotion Model. Despite the fact that the concept of health-promoting behaviors has a nursing influence, literature suggests nursing has inadequately developed and used this concept within nursing practice. A further review of literature regarding health promotion behaviors and the human papilloma virus suggest a distinct gap in nursing literature. This article presents a concept analysis of health-promoting behaviors related to the human papilloma virus in order to encourage the application of the concept into nursing practice, promote continued nursing research regarding this concept, and further expand the application of health-promoting behaviors to other situations and populations within the nursing discipline. Attributes of health-promoting behaviors are presented and include empowerment, participation, community, and a positive concept of health. Antecedents, consequences, and empirical referents are also presented, as are model, borderline, and contrary cases to help clarify the concept. Recommendations for human papilloma virus health-promoting behaviors within the nursing practice are also provided. © 2014 Wiley Periodicals, Inc.

  9. [Esophageal papilloma: case report, molecular identification of human papillomavirus and literature review].

    Science.gov (United States)

    Barbaglia, Yanina; Jiménez, Félix; Tedeschi, Fabián; Zalazar, Fabián

    2013-09-01

    sophageal squamous papilloma is an uncommon, usually asymptomatic, benign tumor of the squamous epithelium consisting of a raised, sessile, small and round (smooth or rough) lesion. The prevalence is between 0.01 and 0.45% of cases, with a male/female ratio of 3:1. The etiology and pathogenesis appear to be a mechanical or chemical irritation of the mucosa in addition to the presence of human papillomavirus (HPV), important agent in the evolution to a squamous carcinoma, especially HPV types 16 and 18. In this paper, we describe a case of esophageal papilloma whose diagnosis involved endoscopic images, pathological studies and detection of viral DNA by polymerase chain reaction. By using molecular techniques (PCR-RFLP) a profile consistent with HPV type 16 has been obtained. The patient underwent polypectomy and currently, after 3 years of diagnosis, he remains asymptomatic. This work is one of the first national reports of a patient with esophageal papilloma in which one of the most frequently HPV genotypes associated with esophageal carcinoma (HPV 16) has been detected.

  10. Detection and genotyping of human papilloma virus in cervical cancer specimens from Saudi patients.

    Science.gov (United States)

    Al-Badawi, Ismail A; Al-Suwaine, Abdulrahman; Al-Aker, Murad; Asaad, Lina; Alaidan, Alwaleed; Tulbah, Asma; Fe Bohol, Marie; Munkarah, Adnan R

    2011-07-01

    To determine the rates and types of human papilloma virus (HPV) infection in cervical cancer specimens from Saudi patients. One hundred specimens were randomly selected and retrieved from the achieved samples stored in the pathology department accessioned under the diagnosis of cervical cancer and carcinoma in situ between the years 1997 and 2007. Human papilloma virus in the clinical samples was detected using polymerase chain reaction amplification methods. Two primer systems are commonly used: the MY09-MY11 primers and the GP5+-GP6+ that amplify a wide range of HPV genotypes. Human papilloma virus isolates were genotyped using DNA sequencing and reverse line blot hybridization assay to identify the high-risk HPV genotypes. Ninety cases fulfilled the diagnostic criteria and were analyzed. The rate of HPV genotype detection among cervical cancer samples was 95.5%. The most common HPV genotype detected by both methods was HPV-16 (63.4%), followed by HPV-18 (11.1%), HPV-45 (4.5%), HPV-33 (3.3%), and HPV-31, HPV-52, HPV-53, HPV-58, HPV-59, and HPV-66 with 2.2% prevalence rate each. Prevalence of HPV genotypes among patients with cervical cancer in Saudi Arabia is comparable to the international rates. The use of the reverse line blot hybridization assay genotyping method could be useful for classifying oncogenic HPV-positive women. It is relatively inexpensive and reliable and can be performed in routine practice or epidemiological study compared with the available standard commercial kits.

  11. Programmed death-1 (PD-1)-dependent functional impairment of CD4(+) T cells in recurrent genital papilloma.

    Science.gov (United States)

    Chang, Dong-Yeop; Song, Sang Hoon; You, Sooseong; Lee, Jino; Kim, Jihye; Racanelli, Vito; Son, Hwancheol; Shin, Eui-Cheol

    2014-08-01

    Genital papilloma is caused by human papilloma virus (HPV) infection and recurs frequently. Although T cells are known to play a critical role in the control of HPV infection and papilloma development, the function and phenotype of these cells in the lesion remain to be elucidated. In the present study, we examined the function and phenotype of CD4(+) T cells isolated from the lesions of primary (n = 9) and recurrent (n = 11) genital papillomas. In recurrent papillomas, the frequency of proliferating (Ki-67(+)) CD4(+) T cells was significantly reduced compared with primary papillomas. Cytokine production was evaluated by intracellular cytokine staining in anti-CD3/anti-CD28-stimulated CD4(+) T cells. CD4(+) T cells from recurrent lesions showed impaired production of IL-2, IFN-γ, and TNF-α. Of interest, the frequency of cytokine-producing CD4(+) T cells significantly correlated with the frequency of Ki-67(+)CD4(+) T cells. We also studied expression of programmed death-1 (PD-1), a T-cell exhaustion marker. The frequency of PD-1(+)CD4(+) T cells was significantly increased in recurrent lesions and inversely correlated with the frequency of cytokine-producing CD4(+) T cells. The functional significance of PD-1 expression was determined in blocking assays with anti-PD-L1, which restored cytokine production of CD4(+) T cells from recurrent lesions. Taken together, in recurrent genital papilloma lesions, proliferation, and cytokine production by CD4(+) T cells are impaired and the PD-1/PD-L1 interaction is responsible for the functional impairment of CD4(+) T cells.

  12. Is radical surgery of an inverted papilloma of the maxillary sinus obsolete? a case report

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    Vedat Yildirim

    2016-12-01

    Full Text Available Abstract Background Sinonasal inverted papilloma is a locally aggressive tumor arising from the Schneiderian membrane which lines the nasal cavity and paranasal sinuses. Aggressive surgical approaches, such as lateral rhinotomy, were used until recently for complete removal of the inverted papilloma. Currently, endoscopic resection is the gold standard in the treatment of inverted papilloma. However, there are situations that justify an open approach. For example there are studies that report a higher postoperative recurrence rate after endonasal endoscopic resection, particularly in the treatment of recurrent diseases. While endoscopic resection performed by an experienced surgeon is definitely a minimally invasive therapy, an open approach is not necessarily associated with functional and aesthetic disadvantages. This case report describes the treatment of inverted papilloma by an open approach. This has been described before but the new gold standard of endoscopic resection has to be taken into account before any treatment decision is made nowadays. Case presentation Contrast-enhanced magnetic resonance imaging of the head and neck area was indicated in a 72-year-old white German man who presented with suspected squamous cell carcinoma of his lower lip. Magnetic resonance imaging additionally revealed a 3×2 cm2 polycyclic arranged mucosal thickening with cystic and solid contrast affine shares at the antral laterocaudal area of his right maxillary sinus, extending from his right lateral nasal wall to his maxillary sinus floor. He received antral polypectomy with medial maxillectomy via a unilateral LeFort I osteotomy approach. His pterygoid plate was preserved. A histological examination demonstrated a tumor composed of hyperplastic squamous epithelium protruding into the stroma (surface epithelial cells grew downward into the underlying supportive tissue, thus producing a grossly convoluted cerebriform appearance. Two weeks later, the

  13. Diagnosis of a Nonpalpable Intraductal Papilloma without Radiological Abnormality by Nipple Discharge Smear Examination: A Case Report

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    Anshul Singh

    2014-01-01

    Full Text Available Nipple discharge is the third most common breast complaint after breast pain and breast mass, most commonly associated with endocrine alterations and/or medications, pregnancy, lactation, post lactation, fibrocystic disease, intraductal papilloma, duct ectasia, nipple adenoma, infection, chronic mastitis, subareolar abscess, and least frequently, breast carcinoma. Cytological examination of nipple discharge (ND is a noninvasive method of diagnosing the underlying breast pathology. We report a 46 year old female, who presented with pain and blood-mixed ND from the right breast with an impalpable mass. Cytological examination of the discharge was done and diagnosis of papillary neoplasm with degeneration, metaplasia, and atypia was given, which was further confirmed on histology and positive IHC for HMWCK and p63. Final diagnosis was intraductal papilloma of the lactiferous duct with squamous metaplasia and infarction. Differentiating benign papilloma from a carcinoma is challenging to the cytopathologist and requires clinicopathological correlation and a good knowledge of cytology.

  14. Atypical choroid plexus papilloma: spontaneous resolution of diffuse leptomeningeal contrast enhancement after primary tumor removal in 2 pediatric cases.

    Science.gov (United States)

    Scala, Marcello; Morana, Giovanni; Milanaccio, Claudia; Pavanello, Marco; Nozza, Paolo; Garrè, Maria Luisa

    2017-09-01

    Atypical choroid plexus papillomas can metastasize in the form of leptomeningeal seeding. Postoperative chemotherapy is the recommended first-line treatment when gross-total removal is not achieved or in cases of disseminated disease. Here the authors report on 2 children with atypical choroid plexus papillomas and MRI findings of diffuse leptomeningeal enhancement at diagnosis, later presenting with spontaneous resolution of the leptomeningeal involvement after removal of the primary lesions. Observations in this report expand our knowledge about the natural history and biological behavior of these tumors and highlight the role of close neuroimaging surveillance in the management of atypical choroid plexus papillomas in cases with MRI evidence of diffuse leptomeningeal enhancement at presentation.

  15. Detection of human papillomavirus type 6/11 DNA in conjunctival papillomas by in situ hybridization with radioactive probes

    International Nuclear Information System (INIS)

    McDonnell, P.J.; McDonnell, J.M.; Kessis, T.; Green, W.R.; Shah, K.V.

    1987-01-01

    Twenty-three conjunctival papillomas and 28 conjunctival dysplasias were examined for human papillomavirus (HPV)-DNA sequences by in situ hybridization with nick-translated 35 S-labeled HPV probes. Adjacent paraffin sections were hybridized with HPV type 2, 6, 16, and 18 probes at Tm - 17 degrees C. Fifteen tissues, all papillomas, displayed positive hybridization with the HPV-6 probe. Infection with HPV-6 (or the closely related HPV-11) appeared to be responsible for most of the conjunctival papillomas of children and young adults. The presence of genital tract HPV-6 in these lesions suggests that some of the infections were acquired during passage through an infected birth canal. The lack of hybridization in adult conjunctival dysplasias indicates either that HPVs are not associated with this condition or that the probes and the technique utilized were not adequate for demonstration of this association

  16. Inverted papilloma of the cervix and vagina: report of 2 cases of a rare lesion associated with human papillomavirus 42.

    Science.gov (United States)

    Hennell, Claire; Jamison, Jackie; Wells, Michael; McCluggage, W Glenn

    2012-03-01

    We report 2 cases of a lesion that we term inverted papilloma of the lower female genital tract, occurring in the cervix and upper vagina of 60- and 50-year-old women, respectively. Microscopically, the features were similar to those of inverted transitional papilloma of the urinary bladder with interconnecting islands, trabeculae, and solid sheets of bland transitional epithelium with an inverted growth pattern. There were small foci of squamous and glandular differentiation in the cervical case. Linear array human papillomavirus genotyping revealed human papillomavirus type 42 in both cases. Inverted papilloma in the lower female genital tract is extremely rare with, as far as we are aware, only 3 previously reported similar cases in the cervix and none in the vagina. Our results suggest that these neoplasms when occurring in the lower female genital tract may be associated with low-risk human papillomavirus, perhaps specifically human papillomavirus 42. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. FIRST APPLICATION EXPERIENCE OF THE QUADRIVALENT VACCINE FOR PREVENTION OF THE PAPILLOMA VIRAL INFECTION AND CERVICAL CANCER

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    M.G. Galitskaya

    2008-01-01

    Full Text Available In this article, the authors demonstrate high spread of the human papilloma viral contamination and danger, which this virus poses for the health of population. Taking into account that this is the only virus, for which it is proved that there are properties for inducing the neoplastic process in the human body, the interest revealed by the scientists from all over the world towards the creation of a specific vaccine is beyond any doubt. The researchers showed the results of application of the primary vaccine prevention for papilloma viral infection abroad. They have also highlighted their own experience in vaccination, which is probably most valuable for the pediatricians, who understand the reality of a danger and attempt to avert it.Key words: human papilloma virus, prevalence, papillomatosis, oncogenous properties, prevention.

  18. 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...

  19. Papiloma invertido (Papiloma Schneideriano com envolvimento da cavidade oral: relato de caso incomum Inverted papilloma (Schneiderian papilloma with involvement of the oral cavity: report of an unusual case

    Directory of Open Access Journals (Sweden)

    Marta Rabello Piva

    2011-08-01

    Full Text Available O papiloma invertido schneideriano é uma neoplasia de origem no epitélio de revestimento que surge da mucosa respiratória revestindo a cavidade nasal e os seios paranasais. Frequentemente, surge como uma lesão unilateral no septo nasal e estende-se secundariamente para o nariz e os seios paranasais. Este trabalho relata um caso incomum desta patologia, com o envolvimento da cavidade oral em um homem branco, de 61 anos de idade, cuja avaliação clínica revelou uma massa vegetante no rebordo alveolar direito da maxila, com duração de aproximadamente 4 meses. Após avaliação radiográfica, constatouse o envolvimento do seio maxilar. A análise microscópica, hibridização in situ e análise imunoistoquímica da peça cirúrgica levaram a um diagnóstico de displasia moderada em PIS associado à infecção por HPVInverted Schneiderian papilloma (ISP is a neoplasm of epithelial lining origin which arises in the respiratory mucosa that lines the nasal cavity and paranasal sinuses. The inverted Schneiderian papilloma frequently appears as a unilateral lesion in the nasal septum and extends secondarily to the nasal and paranasal sinuses. This paper reports an unusual case of this pathology with involvement of the oral cavity in a 61-year-old white man. Clinical evaluation revealed a vegetating mass in the alveolar ridge of the right maxilla that had been present for approximately 4 months. After radiographic evaluation, involvement of the maxillary sinus was detected. Microscopic evaluation, in situ hybridization and immunohistochemical analysis of the specimen led to a diagnosis of ISP moderate dysplasia associated with HPV infection

  20. Human Papilloma Virus Infection Does Not Predict Response to Interferon Therapy in Ocular Surface Squamous Neoplasia.

    Science.gov (United States)

    Galor, Anat; Garg, Nisha; Nanji, Afshan; Joag, Madhura; Nuovo, Gerard; Palioura, Sotiria; Wang, Gaofeng; Karp, Carol L

    2015-11-01

    To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN) and to evaluate differences in clinical features and treatment response of tumors with positive versus negative HPV results. Retrospective case series. Twenty-seven patients with OSSN. Ocular surface squamous neoplasia specimens were analyzed for the presence of HPV. Clinical features and response to interferon were determined retrospectively and linked to the presence (versus absence) of HPV. Clinical characteristics of OSSN by HPV status. Twenty-one of 27 tumors (78%) demonstrated positive HPV results. The HPV genotypes identified included HPV-16 in 10 tumors (48%), HPV-31 in 5 tumors, HPV-33 in 1 tumor, HPV-35 in 2 tumors, HPV-51 in 2 tumors, and a novel HPV in 3 tumors (total of 23 tumors because 1 tumor had 3 identified genotypes). Tumors found in the superior limbus were more likely to show positive HPV results (48% vs. 0%; P=0.06, Fisher exact test). Tumors with positive HPV-16 results were larger (68 vs. 34 mm2; P=0.08, Mann-Whitney U test) and were more likely to have papillomatous morphologic features (50% vs. 12%; P=0.07, Fisher exact test) compared with tumors showing negative results for HPV-16. Human papilloma virus status was not found to be associated with response to interferon therapy (P=1.0, Fisher exact test). Metrics found to be associated with a nonfavorable response to interferon were male gender and tumors located in the superior conjunctivae. The presence of HPV in OSSN seems to be more common in lesions located in the nonexposed, superior limbus. Human papilloma virus presence does not seem to be required for a favorable response to interferon therapy. Copyright © 2015 American Academy of Ophthalmology. All rights reserved.

  1. Herpes viruses and human papilloma virus in nasal polyposis and controls

    Directory of Open Access Journals (Sweden)

    Dimitrios Ioannidis

    2015-12-01

    Full Text Available ABSTRACT INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6 and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4% versus controls (4/38; 10.5%, but the difference did not reach significance (p = 0.06. Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29% versus controls (10/38; 26.32%,p = 0.13. In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%, and another was cytomegalovirus-positive (1/91; 1.1%, versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and low-risk-human papilloma viruses (6, 11. CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

  2. Herpes viruses and human papilloma virus in nasal polyposis and controls.

    Science.gov (United States)

    Ioannidis, Dimitrios; Lachanas, Vasileios A; Florou, Zoe; Bizakis, John G; Petinaki, Efthymia; Skoulakis, Charalampos E

    2015-01-01

    Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  3. Two Cases of Acute Disseminated Encephalomyelitis Following Vaccination Against Human Papilloma Virus

    Science.gov (United States)

    Sekiguchi, Kenji; Yasui, Naoko; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

    2016-01-01

    We herein present two cases of acute disseminated encephalomyelitis (ADEM) following vaccination against human papilloma virus (HPV). Case 1 experienced diplopia and developed an unstable gait 14 days after a second vaccination of Cervarix. Brain magnetic resonance imaging (MRI) showed an isolated small, demyelinating lesion in the pontine tegmentum. Case 2 experienced a fever and limb dysesthesia 16 days after a second vaccination of Gardasil. Brain MRI revealed hyperintense lesion in the pons with slight edema on a T2-weighted image. Both cases resolved completely. It is important to accumulate further data on confirmed cases of ADEM temporally associated with HPV vaccination. PMID:27803416

  4. Lung Cancer and Human Papilloma Viruses (HPVs: Examining the Molecular Evidence

    Directory of Open Access Journals (Sweden)

    Priya R. Prabhu

    2012-01-01

    Full Text Available Human papilloma virus (HPV, known to be an etiological agent for genital cancers, has been suggested also to be a possible contributory agent for lung cancer. Alternatively, lung cancer, formerly considered to be solely a smoker's disease, may now be more appropriately categorised into never smoker's and smoker's lung cancer. Through this paper we attempt to bring forth the current knowledge regarding mechanisms of HPV gaining access into the lung tissue, various strategies involved in HPV-associated tumorigenesis in lung tissue.

  5. Development of procedures for the identification of human papilloma virus DNA fragments in laser plume

    Science.gov (United States)

    Woellmer, Wolfgang; Meder, Tom; Jappe, Uta; Gross, Gerd; Riethdorf, Sabine; Riethdorf, Lutz; Kuhler-Obbarius, Christina; Loening, Thomas

    1996-01-01

    For the investigation of laser plume for the existence of HPV DNA fragments, which possibly occur during laser treatment of virus infected tissue, human papillomas and condylomas were treated in vitro with the CO2-laser. For the sampling of the laser plume a new method for the trapping of the material was developed by use of water-soluble gelatine filters. These samples were analyzed with the polymerase chain reaction (PCR) technique, which was optimized in regard of the gelatine filters and the specific primers. Positive PCR results for HPV DNA fragments up to the size of a complete oncogene were obtained and are discussed regarding infectiousity.

  6. Human Papilloma Viral DNA Replicates as a Stable Episome in Cultured Epidermal Keratinocytes

    Science.gov (United States)

    Laporta, Robert F.; Taichman, Lorne B.

    1982-06-01

    Human papilloma virus (HPV) is poorly understood because systems for its growth in tissue culture have not been developed. We report here that cultured human epidermal keratinocytes could be infected with HPV from plantar warts and that the viral DNA persisted and replicated as a stable episome. There were 50-200 copies of viral DNA per cell and there was no evidence to indicate integration of viral DNA into the cellular genome. There was also no evidence to suggest that viral DNA underwent productive replication. We conclude that cultured human epidermal keratinocytes may be a model for the study of certain aspects of HPV biology.

  7. [Pulmonary cystic disease may be a rare complication to recurrent respiratory human papilloma virus infection].

    Science.gov (United States)

    Laurberg, Peter Thaysen; Weinreich, Ulla M Øller

    2014-12-08

    A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.

  8. Characterization of humoral and cellular immune responses in patients with human papilloma virus

    International Nuclear Information System (INIS)

    Clares Pochet, Maria del Carmen; Ferrer Cosme, Belkis Maria; Dominguez Cardosa, Magda

    2012-01-01

    A descriptive and cross-sectional study was carried out in 30 females infected with the human papilloma virus, attended in the office of Immunology of the Specialty Polyclinic belonging to 'Saturnino Lora' Provincial Clinical Surgical Teaching Hospital in Santiago de Cuba, from June 2009 to June 2010, in order to characterize them according to immune response. To evaluate the humoral and cellular immune response rosetting assay and quantification of immunoglobulins were used respectively. Women between 25-36 years of age (40 %) infected with this virus, especially those coming from urban areas, prevailed in the series, and a significant decrease of the cellular response as compared to the humoral response was evidenced

  9. Vestibular syndrome due to a choroid plexus papilloma in a ferret.

    Science.gov (United States)

    van Zeeland, Yvonne; Schoemaker, Nico; Passon-Vastenburg, Maartje; Kik, Marja

    2009-01-01

    A 6-year-old, castrated male ferret (Mustela putorius furo) was presented with progressive neurological signs consisting of a right-sided head tilt and ataxia. Neurological examination revealed hemiparesis and absence of proprioception on the right side, consistent with central vestibular syndrome. Measurement of blood glucose excluded hypoglycemia due to insulinoma. Contrast-enhanced computed tomography revealed the presence of an intracranial mass, consistent with either granuloma or neoplasia. Palliative treatment with prednisolone yielded no improvement. At postmortem examination, a final diagnosis of a choroid plexus papilloma originating from the fourth ventricle was made. This is the first report of such a tumor in a ferret.

  10. Human Papilloma Virus Awareness, Knowledge and Vaccine Acceptance among Norwegian Adolescents

    OpenAIRE

    Stafne, Tina

    2014-01-01

    Background: Human papilloma virus (HPV) is a virus that causes genital warts and a range of different cancer types. Vaccination against HPV was introduced in Norway in 2009, for girls in the 7th grade, as a part of the Norwegian Childhood Vaccination Program. There has been much discussion about the HPV-vaccine before and after the vaccine introduction. The uptake of HPV-vaccination is lower (67-75%) than for other vaccines. The lower vaccine uptake may be explained by lack of information abo...

  11. Human papilloma virus: An etiological and prognostic factor for oral cancer?

    Science.gov (United States)

    Lafaurie, Gloria I; Perdomo, Sandra J; Buenahora, María R; Amaya, Sandra; Díaz-Báez, David

    2018-05-01

    The increasing prevalence of human papilloma virus (HPV)-positive oral tumors can be considered an epidemic. Although the incidence of HPV cervical cancer is decreasing, the incidence of oral cavity and oropharyngeal cancers associated with HPV is increasing. The presence of certain HPV genotypes could be a predictor of future oral cancer lesions, although lesions associated with HPV could be less aggressive and exhibit a higher survival rate. In the present study, we review the most important biologic, clinic, epidemiologic, and prognostic factors associated with HPV infection and oral cancer. © 2018 John Wiley & Sons Australia, Ltd.

  12. “Saving lives”: Adapting and adopting Human Papilloma Virus (HPV) vaccination in Austria

    Science.gov (United States)

    Paul, Katharina T.

    2016-01-01

    Vaccination against the sexually transmitted Human Papilloma Virus (HPV), a necessary agent for the development of cervical cancer, has triggered much debate. In Austria, HPV policy turned from “lagging behind” in 2008 into “Europe's frontrunner” by 2013. Drawing on qualitative research, the article shows how the vaccine was transformed and made “good enough” over the course of five years. By means of tinkering and shifting storylines, policy officials and experts disassociated the vaccine from gender, vaccine manufacturers, and youth sexuality. Ultimately, the HPV vaccine functioned to strengthen the national immunization program. To this end, preventing an effective problematization of the extant screening program was essential. PMID:26921834

  13. Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy.

    Science.gov (United States)

    Jastreboff, A M; Cymet, T

    2002-04-01

    Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed.

  14. 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 ...

  15. Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.

    Science.gov (United States)

    Panagopoulou, Maria; Lambropoulou, Maria; Balgkouranidou, Ioanna; Nena, Evangelia; Karaglani, Makrina; Nicolaidou, Christina; Asimaki, Anthi; Konstantinidis, Theocharis; Constantinidis, Theodoros C; Kolios, George; Kakolyris, Stylianos; Agorastos, Theodoros; Chatzaki, Ekaterini

    2017-04-01

    Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.

  16. Modification of endoscopic medial maxillectomy: a novel approach for inverted papilloma of the maxillary sinus.

    Science.gov (United States)

    Ghosh, A; Pal, S; Srivastava, A; Saha, S

    2015-02-01

    To describe modification to endoscopic medial maxillectomy for treating extensive Krouse stage II or III inverted papilloma of the nasal and maxillary sinus. Ten patients with inverted papilloma arising from the nasoantral area underwent diagnostic nasal endoscopy, contrast-enhanced computed tomography scanning of the paranasal sinus and pre-operative biopsy of the nasal mass. They were all managed using endoscopic medial maxillectomy and followed up for seven months to three years without recurrence. Most patients were aged 41-60 years at presentation, and most were male. Presenting symptoms were nasal obstruction, mass in the nasal cavity and epistaxis. In each case, computed tomography imaging showed a mass involving the nasal cavity and maxillary sinus, with bony remodelling. The endoscopic medial maxillectomy approach was modified by making an incision in the pyriform aperture and removing part of the anterolateral wall of the maxilla bone en bloc. Modified endoscopic medial maxillectomy providing full access to the maxillary and ethmoid sinuses is described in detail. This effective, reproducible technique is associated with reduced operative time and morbidity.

  17. Health Belief Model Scale for Human Papilloma Virus and its Vaccination: Adaptation and Psychometric Testing.

    Science.gov (United States)

    Guvenc, Gulten; Seven, Memnun; Akyuz, Aygul

    2016-06-01

    To adapt and psychometrically test the Health Belief Model Scale for Human Papilloma Virus (HPV) and Its Vaccination (HBMS-HPVV) for use in a Turkish population and to assess the Human Papilloma Virus Knowledge score (HPV-KS) among female college students. Instrument adaptation and psychometric testing study. The sample consisted of 302 nursing students at a nursing school in Turkey between April and May 2013. Questionnaire-based data were collected from the participants. Information regarding HBMS-HPVV and HPV knowledge and descriptive characteristic of participants was collected using translated HBMS-HPVV and HPV-KS. Test-retest reliability was evaluated and Cronbach α was used to assess internal consistency reliability, and exploratory factor analysis was used to assess construct validity of the HBMS-HPVV. The scale consists of 4 subscales that measure 4 constructs of the Health Belief Model covering the perceived susceptibility and severity of HPV and the benefits and barriers. The final 14-item scale had satisfactory validity and internal consistency. Cronbach α values for the 4 subscales ranged from 0.71 to 0.78. Total HPV-KS ranged from 0 to 8 (scale range, 0-10; 3.80 ± 2.12). The HBMS-HPVV is a valid and reliable instrument for measuring young Turkish women's beliefs and attitudes about HPV and its vaccination. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  18. A proposal to reduce the risk of transmission of human papilloma virus via transvaginal ultrasound.

    Science.gov (United States)

    Combs, C Andrew; Fishman, Alan

    2016-07-01

    Three steps must be followed to prevent the transmission of infection via a contaminated transvaginal ultrasound probe: cleaning the probe after every use, high-level disinfection, and covering the probe with a single-use barrier during the examination. There may be critical flaws in at least 2 of these steps as they are currently practiced. First, 2 widely used disinfectants, glutaraldehyde and orthophthalaldehyde, have recently been found to be ineffective at neutralizing human papilloma virus type 16 and type 18. Second, commercial ultrasound probe covers have an unacceptable rate of leakage (8-81%) compared to condoms (0.9-2%). We recommend the use of a sonicated hydrogen peroxide disinfectant system rather than aldehyde-type disinfectants. We recommend that the probe be covered with a condom rather than a commercial probe cover during transvaginal ultrasound examination. Combined with probe cleaning, these 2 steps are estimated to result in an 800 million- to 250 billion-fold reduction in human papilloma virus viral load, which should translate to greatly enhanced patient safety. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Human papilloma virus 16/18: Fabricator of trouble in oral squamous cell carcinoma.

    Science.gov (United States)

    Zil-E-Rubab; Baig, Saeeda; Zaman, Uzma; Lucky, Mohammad Haris

    2018-04-01

    To find out the association between Human Papilloma Virus (HPV) genotypes 16/18 in Pakistani patients with oral squamous cell carcinoma (OSCC). DNA from oral rinse of 300 subjects was taken. The subjects included 100 cases with OSCC and 200 controls. Samples were analyzed by both conventional and real time PCR using "HPV consensus Gp5+/Gp6+ and HPV 16, 18 specific primers". Out of 300 persons, 74/300 (25%) were found to be infected with HPV: "46/100(46%) from cases and 74/200(14%) from controls". The distribution was: HPV16, 6/300 (8%): 4/100 (9%) from OSCC group and 2/200 (8%) from controls while HPV 18 was 9/300(12%): 5/100(11%) from cases and 4/200(16%) from controls. Out of 300 subjects, 26(35%) were infected by "both HPV 16/18 (23(50%) from cases and 3(12%) from controls". Persons who were infected with HPV 16&18 had higher chances to develop OSCC as compared to those who didn't have HPV 16/18 (AOR: 21.4, 95% CI: 5.73 - 80.8). The exposure to high risk strains of Human papilloma virus (16/18) in combination can be fabricotor of trouble (p<0.001, Adjusted odds ratio; 21.42) in OSCC. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  20. Human papilloma virus testing in oropharyngeal squamous cell carcinoma: what the clinician should know.

    Science.gov (United States)

    Mirghani, Haïtham; Amen, Furrat; Moreau, Frederique; Guigay, Joel; Ferchiou, Malek; Melkane, Antoine E; Hartl, Dana M; Lacau St Guily, Jean

    2014-01-01

    High risk Human Papilloma virus (HR-HPV) associated oropharyngeal cancers are on the increase. Although, the scientific community is aware of the importance of Human Papilloma Virus (HPV) testing, there is no consensus on the assays that are required to reliably identify HR-HPV related tumors. A wide range of methods have been developed. The most widely used techniques include viral DNA detection, with polymerase chain reaction (PCR) or In Situ Hybridization, and p16 detected by immunohistochemistry. However, these tests provide different information and have their own specific limitations. In this review, we summarize these different techniques, in light of the recent literature. p16 Overexpression, which is an indirect marker of HPV infection, is considered by many head and neck oncologists to be the most important marker for patient stratification. We describe the frequent lack of concordance of this marker with other assays and the possible reasons for this. The latest developments in HPV testing are also reported, such as the RNAscope™ HPV test, and how they fit into the existing framework of techniques. HPV testing must not be considered in isolation, as there are important interactions with other parameters, such as tobacco exposure. This is an important and rapidly evolving field and is likely to become pivotal to staging and choice of treatment of oropharyngeal carcinoma in the future. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Possible non-sexual modes of transmission of human papilloma virus.

    Science.gov (United States)

    Sabeena, Sasidharanpillai; Bhat, Parvati; Kamath, Veena; Arunkumar, Govindakarnavar

    2017-03-01

    There is strong evidence to suggest vertical and horizontal modes of transmission of human papilloma virus (HPV), an established etiologic agent of cervical cancer. Infants, children, and adults can acquire both high-risk and low-risk infections by birth or by close contact even though HPV is mainly transmitted sexually. A thorough review of the literature was performed to assess the possible non-sexual modes of transmission of HPV. An electronic search of databases for review articles, cross-sectional studies, cohort studies, and case reports on non-sexual modes of transmission among sexually unexposed women and children was carried out using search terms such as "human papilloma virus, HPV, transmission, horizontal transmission, vertical transmission, and fomites". Articles published between 1983 and 2015 were retrieved. Epidemiological and clinical data support various non-sexual modes of transmission especially at the time of birth and by close contact. Even though the role of fomites in the transmission of HPV is not well established, HPV-DNA positivity has been reported in transvaginal ultrasound probes and colposcopes after routine disinfection. Awareness needs to be spread among the public about alternate modes of transmission. For a proper understanding of the exact natural history of HPV infection acquired via the non-sexual route, long-term prospective studies need to be undertaken. © 2017 Japan Society of Obstetrics and Gynecology.

  2. Human papilloma virus vaccination in Nepal: an initial experience in Nepal.

    Science.gov (United States)

    Singh, Yogendra; Shah, Aarti; Singh, Meeta; Verma, Sheela; Shrestha, Bhakta Man; Vaidya, Prabhu; Nakarmi, Radha Pyari; Shrestha, Surendra Bb

    2010-01-01

    Cervical cancer is the most common cancer among women in Nepal. Human papilloma virus (HPV) infection, a recognized cause of cervical cancer, is very common in sexually active women and HPV vaccination has been recommended as a prophylactic therapy. If HPV infection is prevented by the HPV vaccination to the adolescent girls, cervical cancer is also prevented. We received 3,300 vials of quadrivalent human papilloma virus (types 6, 11, 16, 18) recombinant vaccine (Gardasil; Merck and Co.) as a gift from the Australian Cervical Cancer Foundation (ACCF) which has a mission to provide life-saving HPV cervical cancer vaccines for women in developing countries, who cannot otherwise afford vaccination. HPV vaccine was offered to 1,096 of 10 to 26 year aged girls attending 17 secondary schools. In total, 1,091 (99.5%) received the second dose and 1,089 (99.3%) received the third dose of the vaccine. The remaining 5 girls at second dose and 2 girls at third dose remained unvaccinated. No serious vaccine related adverse events were reported except mild pain at the injection site in 7.8% of the vaccine recipients. High cost and low public awareness are the key barriers for successful implementation of the vaccination program in resource limited developing countries. In conclusion, HPV vaccine is safe with high acceptability in Nepalese school girls. However a large population study for longer follow up is warranted to validate the findings of this vaccination program.

  3. Concurrent fibroadenoma and intraductal papilloma - A recurring complex lesion in a premenarcheal girl.

    Science.gov (United States)

    Alessandrini, Lara; Gobbi, Dalia; Zanon, Giovanni Franco; Dall'Igna, Patrizia; Cecchetto, Giovanni; Alaggio, Rita

    2013-02-15

    Breast diseases are rare in childhood and adolescence, most lesions being fibroadenomas and papillomas. We report the case of an 11-year old girl with a complex breast lesion with hybrid features of fibroadenoma and intraductal papilloma with an early recurrence. Microscopically, the lesion was composed of dilated ducts showing intraluminal papillary projections with small to broad fibrovascular stalks. The typical leaf-like appearance of fibroadenoma was determined by the presence at the periphery of ducts compressed and distorted by the prominent stromal component. Despite its florid epithelial hyperplasia and mild cytological atypia (more evident in the relapse), immunohistochemical staining for p63 and smooth muscle actin highlighted a continuum outer myoepithelial layer, confirming the non-invasive appearance of the lesion. Two pathogenetic links have been hypothesized: one is based on the morphological continuum between these two entities, which may represent different evolutive stages in the same lesion; the other is based on epithelial/mesenchymal interactions. The possible malignant transformation of such complex lesion is also discussed, along with its differential diagnoses. The relevance of this case lies in its rarity, as well as in the therapeutic strategies related to its biological potential and to the necessity of a conservative treatment, due to the young age of the patient. Copyright © 2012. Published by Elsevier GmbH.

  4. Association of human papilloma virus with atypical and malignant oral papillary lesions.

    Science.gov (United States)

    McCord, Christina; Xu, Jing; Xu, Wei; Qiu, Xin; Muhanna, Nidal; Irish, Jonathan; Leong, Iona; McComb, Richard John; Perez-Ordonez, Bayardo; Bradley, Grace

    2014-06-01

    This study aimed to examine atypical and malignant papillary oral lesions for low- and high-risk human papillomavirus (HPV) infection and to correlate HPV infection with clinical and pathologic features. Sections of 28 atypical papillary lesions (APLs) and 14 malignant papillary lesions (MPLs) were examined for HPV by in situ hybridization and for p16 and MIB-1 by immunohistochemistry; 24 conventional papillomas were studied for comparison. Low-risk HPV was found in 10 of 66 cases, including 9 APLs and 1 papilloma. All low-risk HPV-positive cases showed suprabasilar MIB-1 staining, and the agreement was statistically significant (P < .0001). Diffuse p16 staining combined with high-risk HPV was not seen in any of the cases. A subset of HPV(-) APLs progressed to carcinoma. Oral papillary lesions are a heterogeneous group. Low-risk HPV infection is associated with a subset of APLs with a benign clinical course. Potentially malignant APLs and MPLs are not associated with low- or high-risk HPV. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Validation of the Turkish Cervical Cancer and Human Papilloma Virus Awareness Questionnaire.

    Science.gov (United States)

    Özdemir, E; Kısa, S

    2016-09-01

    The aim of this study was to determine the validity and reliability of the 'Cervical Cancer and Human Papilloma Virus Awareness Questionnaire' among fertility age women by adapting the scale into Turkish. Cervical cancer is the fourth most commonly form seen among women. Death from cervical cancer ranks third among causes and is one of the most preventable forms of cancer. This cross-sectional study included 360 women from three family health centres between January 5 and June 25, 2014. Internal consistency showed that the Kuder-Richardson 21 reliability coefficient in the first part was 0.60, Cronbach's alpha reliability coefficient was 0.61 in the second part. The Kaiser-Meyer-Olkin value of the items on the scale was 0.712. The Barlett test was significant. The confirmatory factor analysis indicated that the model matched the data adequately. This study shows that the Turkish version of the instrument is a valid and reliable tool to evaluate knowledge, perceptions and preventive behaviours of women regarding human papilloma virus and cervical cancer. Nurses who work in the clinical and primary care settings need to screen, detect and refer women who may be at risk from cervical cancer. © 2016 International Council of Nurses.

  6. [Knowledge of human papilloma virus (HPV) and acceptance of vaginal self-sampling among Mexican woman].

    Science.gov (United States)

    Hernández-Márquez, Clara I; Salinas-Urbina, Addis A; Cruz-Valdez, Aurelio; Hernández-Girón, Carlos

    2014-01-01

    To analyze the relationship between the level of knowledge about human papilloma virus and the acceptance of vaginal self-sampling as a cervical cancer diagnostic test among Mexican women who have already experienced vaginal self-sampling at home. A structured questionnaire consisting of 22 questions was applied to 690 women in the state of Morelos who had taken a vaginal self-sample at home. The aspects explored were the level of knowledge about transmission of the human papilloma virus, identification of the virus as a necessary cause of cervical cancer, and clinical manifestations of infection and treatment. A knowledge index was constructed, identifying the relationship between the index and the women's acceptance of self-sampling, and their degree of trust in the procedure. The statistical analysis included a logistic regression with estimates of measures of association and their respective 95% confidence intervals. The level of knowledge about human papillomavirus showed a positive association with the degree of acceptance of vaginal self-sampling (OR 2.9; 95% CI 1.0-5.01) and the women's level of confidence (OR 2.9; 95% CI 1.8-4.67). The level of knowledge increased with level of education and was higher in younger women. In order for women with an increased risk of cervical cancer to continue participating in vaginal self-sampling, they must be well informed about the virus. This is especially true for older women, those with lower levels of education, and those in lower socioeconomic levels.

  7. Examining a possible association between human papilloma virus (HPV) vaccination and migraine: results of a cohort study in the Netherlands

    NARCIS (Netherlands)

    T.M.S.-V. Klooster (T. M. Schurink-van’t); M.A.J. de Ridder (Maria); J.M. Kemmeren (Jeanet); J. van der Lei (Johan); F.W. Dekker (Friedo); M.C.J.M. Sturkenboom (Miriam); H.E. de Melker (Hester)

    2015-01-01

    textabstractSince the introduction of the bivalent human papilloma virus (HPV) vaccine in the Netherlands, migraine has been reported as a notable event in the passive safety surveillance system. Research on the association between HPV vaccination and migraine is needed. Therefore, potential

  8. TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients

    NARCIS (Netherlands)

    Braakhuis, B.J.M.; Rietbergen, M.M.; Buijze, M.; Snijders, P.J.F.; Bloemena, E.; Brakenhoff, R.H.; Leemans, C.R.

    2014-01-01

    Objective Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. Methods TP53 mutations

  9. Human papilloma virus DNA and p53 mutation analysis on bladder washes in relation to clinical outcome of bladder cancer.

    NARCIS (Netherlands)

    Moonen, P.M.J.; Bakkers, J.M.J.E.; Kiemeney, L.A.L.M.; Schalken, J.A.; Melchers, W.J.G.; Witjes, J.A.

    2007-01-01

    OBJECTIVES: High-risk human papilloma virus (HPV) types stimulate degradation and deactivation of protein associated with the p53 tumour suppressor gene via the ubiquitin-dependent pathway. For a long time, changes of the p53 tumour suppressor gene have been correlated with poor clinical outcome in

  10. A rare case of anal carcinosarcoma with human papilloma virus infection in both biphasic tumor elements: An immunohistochemical, molecular and ultrastructural study.

    Science.gov (United States)

    Hickman, Richard A; Bradshaw, Azore-Dee; Cassai, Nicholas; Neto, Antonio Galvao; Zhou, David; Fu, Tinghao; Lee, Peng; Pei, Zhiheng; Wieczorek, Rosemary

    2016-12-01

    Carcinosarcoma of the anus is rare and has yet to be reportedly associated with the keratinocyte-specific Human Papilloma Virus (HPV). We describe a case of anal carcinosarcoma with HPV infection in both the epithelial and mesenchymal components of the tumor by immunohistochemistry, chromogenic in-situ hybridization (CISH) and further supported by electron microscopy (EM). Microscopic examination of the tumor showed nests of poorly-differentiated invasive squamous cell carcinoma with basaloid features intermixed with a hypercellular, atypical spindle cell proliferation. Immunohistochemistry demonstrated that the epithelial component was positive for AE1/AE3, p63, CK5/6 and p16, whilst the mesenchymal component was positive for smooth muscle actin, vimentin, and focally positive for desmin and p16, consistent with carcinosarcoma. The tumor was negative for GATA-3, CK7 and CK20. CISH demonstrated that the tumor was positive for high risk HPV (subtype 16/18) in both tumor components. EM further supported the presence of intracellular virus particles (~50 nm) that is compatible with HPV infection. Infection of both epithelial and mesenchymal tumor components by HPV has not been previously observed in the gastrointestinal tract. This finding may represent initial epithelial HPV infection with subsequent divergent tumoral differentiation and suggests the presence of viral replication in both biphasic tumor components.

  11. [The implementation of polymerase chain reaction technique: the real time to reveal and differentiate the viruses of human papilloma of high carcinogenic risk].

    Science.gov (United States)

    Andosova, L D; Kontorshchikova, K N; Blatova, O L; Kudel'kina, S Iu; Kuznetsova, I A; Belov, A V; Baĭkova, R A

    2011-07-01

    The polymerase chain reaction technique was applied in "real time" format to evaluate the occurrence rate and infection ratio of various genotypes of human papilloma of high carcinogenic risk in virus-positive women and contact persons. The examination sampling consisted of 738 women aged of 17-50 years. The examination results permitted to establish high percentage of infection of 546 patients (74%) by carcinogenic papilloma viruses. The analysis of detection rate of various genotypes of human papilloma of high carcinogenic risk established that the 56th and 16th types of high carcinogenic risk are revealed more often than others--in 33% and 15.4% correspondingly. In males, first place in occurrence rate is for those types of virus of human papilloma: the 56th n = 10 (33.3%), 16th n = 3 (10%), 45th n = 3 (10%), 51th n = 3 (10%). The rest of genotypes are detected in 3-7% cases.

  12. 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

  13. 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

  14. 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

  15. 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...

  16. 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...

  17. 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.

  18. Knowledge levels of adolescent girls about human papilloma virus and its vaccine.

    Science.gov (United States)

    Çetin, Orkun; Verit, Fatma Ferda; Keskin, Seda; Zebitay, Ali Galip; Deregözü, Ayşegül; Usta, Taner; Yücel, Oğuz

    2014-06-01

    The aim of our study was to evaluate the level of knowledge of the adolescent girls who presented to our clinic about human papilloma virus (HPV) infection and HPV vaccine. Five hundred and one adolescent girls aged between 13 and 18 years who presented to the gynecology outpatient clinic between March 2012 and March 2013 were asked to answer the questions of the questionnaire about HPV and HPV vaccine. The "Participant Information Form" and "HPV Information Assessment Form" were used by examination of the related literature by the investigators. The data obtained were entered into the computer using the SPSS 16.5 program and evaluated. Descriptive statistics were shown with mean, standard deviation, number and percentage values. The mean age of 501 subjects who were included into the study was 15.92 years. 390 subjects (77.8%) who were included in the study had no information about HPV. 111 subjects (22.2%) stated that they heard of HPV before or had information about HPV. The mean age of the subjects who had information about human papilloma virus was found to be 16.52 years. The mean age of 390 subjects (77.8%) who had no information about human papilloma virus was 15.75 years. It was found that only one of the subjects (0.9%) was vaccinated with HPV vaccine. When the subjects who did not wish to be vaccinated were asked for the reason, 40.9% stated that the reason was inadequate information, 26.4% stated that the reason was high cost, 16.4% stated that the reason was the fact that they did not consider themselves at risk and 16.4% stated that the reason was the fact that they were afraid of side effects. In our study, it was found that the adolescent girls who constituted our study group had insufficient information about HPV and HPV vaccine. Verbal, written and visual communication tools and internet should be used intensively and efficiently for the objective of introducing HPV vaccine and teaching the precautions related with prevention of cervix cancer in

  19. A simple ductal mammary papilloma in a male maned wolf (Chrysocyon brachyurus).

    Science.gov (United States)

    Cassali, Geovanni D; Bertagnolli, Angélica C; Ferreira, Enio; Malta, Marcelo C C

    2009-01-01

    A 1-cm-diameter nodule was identified in the left inguinal mammary gland of a 9-year-old male maned wolf (Chrysocyon brachyurus). The mass was surgically excised and examined histologically. Microscopically, the neoplasm consisted of papillary proliferations of epithelial cells on well-defined fibrovascular stalks. A myoepithelial layer was located between the single layer of epithelial cells and the fibrovascular stalk. This histologic appearance was compatible with a diagnosis of simple ductal mammary papilloma. Immunohistochemical staining was positive for p63, cytokeratins AE1/AE3, and estrogen receptors. The clinical and histologic observations in the present case indicate that male maned wolves may develop mammary tumors that are similar to those observed in domestic dogs and humans.

  20. Inverted papilloma of lacrimal sac invading into the orbit: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Alistair W Hardy

    2015-01-01

    Full Text Available Inverted papilloma (IP is a sinonasal tumor of benign etiology with local invasion and malignant potential. IP arising in lacrimal sac invading the orbit is extremely rare with only one case reported so far. The presented case appears to be the second such case reported in the literature. A 60-year-old Caucasian male presented with a medial canthal mass and epiphora. Incisional biopsy confirmed a transitional neoplasm. The lesion was completely excised enbloc with clear margins by using a Weber-Ferguson incision; orbital clearance and nasolacrimalfossa clearance was achieved via a medial maxillectomy. Enbloc resection of orbital and nasolacrimal parts of the tumor with clear margins is recommended.

  1. Low Grade Peritoneal Mucinous Carcinomatosis Associated with Human Papilloma Virus Infection: Case Report

    Science.gov (United States)

    Gatalica, Zoran; Foster, Jason M.; Loggie, Brian W.

    2008-01-01

    Pseudomyxoma peritonei is a clinical syndrome characterized by peritoneal dissemination of a mucinous tumor with mucinous ascites. The vast majority of the pseudomyxoma peritoneis are associated with mucinous neoplasms of the appendix. We describe a case of pseudomyxoma peritonei associated with mucinous adenocarcinoma of the cervix in a 60-year-old woman. The patient developed low grade mucinous peritoneal carcinomatosis 8 years after hysterectomy for cervical adenocarcinoma. No other primary mucinous tumor was identified and peritoneal carcinomatosis tested positive for high-risk human papilloma virus (HPV), showing both integrated and episomal pattern. HPV has been previously associated with development of cervical carcinomas (both squamous and mucinous) but neither has cervical adenocarcinoma nor HPV been implicated in development of pseudomyxoma peritonei. To the best of our knowledge, this is the first description of HPV-associated malignancy presenting as pseudomyxoma peritonei. PMID:18925701

  2. Oropharyngeal cancer and human papilloma virus: evolving diagnostic and management paradigms.

    Science.gov (United States)

    Buckley, Lisa; Gupta, Ruta; Ashford, Bruce; Jabbour, Joe; Clark, Jonathan R

    2016-06-01

    The significant increase in human papilloma virus (HPV)-associated oropharyngeal carcinoma (OPC) over recent years has lead to a surge in research and an improved understanding of the disease. Most patients with HPV-associated OPC present with cystic nodal metastases with a small primary tumour, and respond well to all treatment modalities including primary surgery and primary chemoradiotherapy. Current research is evaluating treatment de-escalation to reduce long-term treatment-associated morbidities. Transoral robotic surgery (TORS) is particularly relevant as the transoral approach allows small primary tumours to be removed with lower morbidity than traditional surgical approaches. The current American Joint Committee on Cancer staging system for oropharyngeal cancer does not appropriately stratify HPV-associated OPC; hence, alternative risk stratification and staging classifications are being proposed. © 2015 Royal Australasian College of Surgeons.

  3. Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

    Science.gov (United States)

    Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

    2015-01-01

    Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management. PMID:26483987

  4. A physician's reflection on the moral use of human papilloma virus vaccine.

    Science.gov (United States)

    Burke, Greg F

    2016-08-01

    Controversies often surround the use of vaccines, particularly among the pediatric population. Often, the possible temporal relationship between vaccination and subsequent disease is at the center of the controversy. However, others have questioned the moral status of the human papilloma virus (HPV) vaccine because of some instances of state coercion and also the possibility that the vaccine may promote promiscuity. This article addresses the moral status of the HPV vaccine from the perspective of a primary care physician and father of four daughters. Lay Summary: Parents are often asked by pediatricians for permission to vaccinate their children under the age of consent against the sexually transmitted virus HPV. This article addresses the medical and moral concerns about vaccination with some guiding principles to assist in a final decision.

  5. Attitudes towards Human Papilloma Virus Vaccination in the Latin American Andean Region.

    Science.gov (United States)

    Nwanodi, Oroma

    2017-09-08

    This commentary explores the distribution of human papilloma virus (HPV) and HPV-related diseases, and factors affecting attitudes towards HPV, HPV-related diseases, and HPV vaccination in the Latin American Andean region. Lack of knowledge of HPV, known negative attitudes or incorrect assumptions about HPV, HPV-related diseases, and HPV vaccination provide a basis upon which to develop targeted HPV awareness and preventive health media campaigns. For maximal effect, media campaigns should use the internet, radio, and television to address health care providers, parents, and students. Additional programming can be developed for clinics to use in-house with their clients. Ministries of Education, Finance, and Health all have roles to play to increase national HPV, HPV-related diseases, and HPV vaccination awareness.

  6. Human Papilloma Virus and oral cancer: Narrative review of the literature.

    Directory of Open Access Journals (Sweden)

    Alejandra Fernández

    2014-09-01

    Full Text Available The Human Papilloma Virus (HPV infection is now more common sexually transmitted diseases, with an incidence of 5.5 million worldwide, with 85% of the carrier of this virus adult population. Their oncogenic potential and increased oral lesions associated with oral HPV infection have led us to make a narrative of the literature on the role of HPV in oral cancer, especially types 16 and 18. Here we refer to the possible routes of infection, oncogenic mechanisms, both benign and potentially malignant oral lesions associated with the infection, different methods used for detection, prediction and prevention of infection. We stress the importance of the role of the dentist to identify individuals considered high risk and ease of performing detection in the oral cavity, through a quick and easy method as exfoliative cytology.

  7. Attitudes towards Human Papilloma Virus Vaccination in the Latin American Andean Region

    Directory of Open Access Journals (Sweden)

    Oroma Nwanodi

    2017-09-01

    Full Text Available This commentary explores the distribution of human papilloma virus (HPV and HPV-related diseases, and factors affecting attitudes towards HPV, HPV-related diseases, and HPV vaccination in the Latin American Andean region. Lack of knowledge of HPV, known negative attitudes or incorrect assumptions about HPV, HPV-related diseases, and HPV vaccination provide a basis upon which to develop targeted HPV awareness and preventive health media campaigns. For maximal effect, media campaigns should use the internet, radio, and television to address health care providers, parents, and students. Additional programming can be developed for clinics to use in-house with their clients. Ministries of Education, Finance, and Health all have roles to play to increase national HPV, HPV-related diseases, and HPV vaccination awareness.

  8. Choroid plexus papilloma in an adult ewe – a case report

    Directory of Open Access Journals (Sweden)

    Jose María González

    2013-01-01

    Full Text Available Primary neoplasms of the central nervous system have been rarely reported in sheep. A three-year-old Rasa Aragonesa ewe was admitted to the small ruminant external consultancy at the Veterinary Faculty of University of Zaragoza, Spain. Clinical, haematological and neurological examinations were performed. Neurological examination showed signs of ataxia, hyperextension of the right front limb and abnormal postural reactions. The animal was unable to stand and walk, even with help. Patellar and flexor reflexes were normal and superficial sensation was present but decreased. Humanitarian sacrifice was carried out one month later. Gross and histopathological findings revealed a choroid plexus papilloma located in the fourth ventricle of the brain. To the authors’ knowledge this is the first description of this neoplastic disorder in sheep.

  9. Detection of human papilloma virus in the tonsils of children undergoing tonsillectomy

    Directory of Open Access Journals (Sweden)

    Kátia Moreira Xavier Ribeiro

    Full Text Available Human papilloma virus (HPV is related to respiratory mucosal diseases, such as recurrent respiratory papillomatosis, as well as to upper-respiratory-tract malignancies. There are few reports concerning the prevalence of HPV in the upper respiratory tract of non-affected individuals. We examined the prevalence of HPV in the tonsils of children of the general population scheduled for tonsillectomy. Samples were taken from the tonsils of 100 children undergoing tonsillectomy and were then tested for HPV with the polymerase chain reaction (PCR technique, utilizing the generic primers MY09 and MY 11. The study excluded children known to have HPV and HIV-related diseases. Parents and legal guardians completed a standardized socio-demographic questionnaire. The questionnaire revealed that 84% of the mothers had at least one risk factor for genital HPV. None of the tonsil samples were positive for HPV. Apparently HPV does not commonly colonize the tonsils of children undergoing routine tonsillectomy.

  10. Prevalence of human papilloma virus infection in pregnant Turkish women compared with non-pregnant women.

    Science.gov (United States)

    Aydin, Y; Atis, A; Tutuman, T; Goker, N

    2010-01-01

    We aimed to find a prevalence of human papilloma virus (HPV) in order to define the 100 genotypes and subset of 14 oncogenic genotypes in pregnant Turkish women and to compare these with non-pregnant women. Cervical thin-prep specimens were obtained from 164 women in the first trimester pregnancy and 153 non pregnant women. 29.2% of pregnant versus 19.6% of non-pregnant Turkish women had at least one of the 100 types of HPV infection--a statistically significant difference. The rate of 14 high-risk HPV genotype infections was significantly higher in pregnant (14.6) compared to non-pregnant Turkish women (9.6%). Pregnant Turkish women are at higher risk for all HPV infections including high-risk cervical cancer genotypes.

  11. Attitude of Israeli mothers with vaccination of their daughters against human papilloma virus.

    Science.gov (United States)

    Ben Natan, Merav; Aharon, Osnat; Palickshvili, Sharon; Gurman, Vicky

    2011-02-01

    The purpose of the study is to examine whether the model based on the Theory of Reasoned Action (TRA) succeeds in predicting mothers' intention to vaccinate their daughters against the human papilloma virus infection. Questionnaires were distributed among convenience sample of 103 mothers of daughters 18 years and younger. Approximately 65% of mothers intend to vaccinate their daughters. Behavioral beliefs, normative beliefs, and level of knowledge had a significant positive effect on mothers' intention to vaccinate their daughters. High levels of religiosity were found to negatively affect mothers' intention to vaccinate their daughters. The TRA combined with level of knowledge and level of religiosity succeeds in predicting mothers' behavioral intentions regarding vaccinating daughters. This indicates the significance of nurses' roles in imparting information and increasing awareness among mothers. Copyright © 2011. Published by Elsevier Inc.

  12. Determination of knowledge of Turkish midwifery students about human papilloma virus infection and its vaccines.

    Science.gov (United States)

    Genc, Rabia Ekti; Sarican, Emine Serap; Turgay, Ayse San; Icke, Sibel; Sari, Dilek; Saydam, Birsen Karaca

    2013-01-01

    Human papilloma virus (HPV) is one of the most common sexually transmitted agents and its infection is the most established cause of cervical cancer. Midwives play a key position in the implementation of cervical cancer. This descriptive study aimed to determine the level of knowledge concerning HPV and HPV vaccination among 268 midwifery students. Data were collected between November 15 and 30, 2011, through a self-reported questionnaire. The mean age of participants was 20.75 ± 1.60. Among all students, 44.4% had heard of HPV, while 40.4% had heard of HPV vaccinatiob. The relationship between the midwifery student knowledge on HPV and HPV vaccine and their current educational year was significant (p=0.001). In conclusion midwifery students have moderate level of knowledge about HPV and its vaccine and relevant information should be included in their teaching curriculum.

  13. Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck.

    Science.gov (United States)

    Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

    2015-01-01

    Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management.

  14. Human Papilloma Virus in Oral Squamous Cell Carcinoma - The Enigma Unravelled.

    Science.gov (United States)

    Khot, Komal P; Deshmane, Swati; Choudhari, Sheetal

    2016-03-01

    Squamous cell carcinoma of the head and neck (HNSCC) has long been regarded as a disease entity having a remarkable incidence worldwide and a fairly onerous prognosis; thus encouraging further research on factors that might modify disease outcome. Squamous cell carcinomas encompass at least 90% of all oral malignancies. Several factors like tobacco and tobacco-related products, alcohol, genetic predisposition and hormonal factors are suspected as possible causative factors. Human papilloma virus (HPV), the causal agent of cervical cancer also appears to be involved in the aetiology of oral and oropharyngeal cancer. HPVpositive squamous cell carcinoma (SCC) seems to differ from HPV-negative SCC. Many questions about the natural history of oral HPV infection remain under investigation. The aim of this review is to highlight the current understanding of HPV-associated oral cancer with an emphasis on its prognosis, detection and management.

  15. Exploring the link between human papilloma virus and oral and oropharyngeal cancers

    Directory of Open Access Journals (Sweden)

    Shailesh R Khode

    2014-01-01

    Full Text Available Squamous cell carcinoma involving the oral cavity (OC and oropharynx regions are a major cause of morbidity and mortality world-wide. The recent discovery of a strong association between human papilloma virus (HPV infection and OC and oropharyngeal (OP cancer has prompted world-wide research into the exact etiology and pathogenesis of these cancers in relation to the HPV. HPV-positive OC/OP cancers generally present at a relatively advanced stage (by virtue of cervical nodal involvement and are more commonly seen in younger patients without significant exposure to alcohol or tobacco. These factors are implicated in prognosis, regardless of HPV association. In this article, we review the biology and epidemiology, risk factors, association, molecular analyses, treatment response and prognosis of HPV-related cancers. Role of HPV vaccination in HPV-related OC/OP cancers has also been discussed.

  16. "Saving lives": Adapting and adopting Human Papilloma Virus (HPV) vaccination in Austria.

    Science.gov (United States)

    Paul, Katharina T

    2016-03-01

    Vaccination against the sexually transmitted Human Papilloma Virus (HPV), a necessary agent for the development of cervical cancer, has triggered much debate. In Austria, HPV policy turned from "lagging behind" in 2008 into "Europe's frontrunner" by 2013. Drawing on qualitative research, the article shows how the vaccine was transformed and made "good enough" over the course of five years. By means of tinkering and shifting storylines, policy officials and experts disassociated the vaccine from gender, vaccine manufacturers, and youth sexuality. Ultimately, the HPV vaccine functioned to strengthen the national immunization program. To this end, preventing an effective problematization of the extant screening program was essential. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

  17. Systematic meta-analysis on association of human papilloma virus and oral cancer.

    Science.gov (United States)

    Chaitanya, Nallan C S K; Allam, Neeharika Satya Jyothi; Gandhi Babu, D B; Waghray, Shefali; Badam, R K; Lavanya, Reddy

    2016-01-01

    Oral cancer is a disease with complex etiology. There is a strong evidence for the role of smoking, alcohol, genetic susceptibility, and indications that DNA viruses could also be involved in oral cancer. Recognized initially as sexually transmitted agent, human papilloma virus (HPV) is now considered a human carcinogen. Papilloma viruses are epitheliotropic viruses. A strong association of cervical cancer has been implicated with high-risk HPV16 and HPV18 infections, establishing the viral pathogenesis of the carcinoma. The etiopathogenesis is still unclear referring mainly to conflicting evidences in the detection of such viruses in oral carcinoma in spite of few studies suggesting their positive correlation. This systematic meta-analysis aimed to provide evidence-based analysis of literature relating oral cancer and HPV, along with identification of reliable diagnostic methodology for identifying HPV in oral and oropharyngeal cancer. A systematic review was performed using PubMed (from the year 1995 to 2015), Medline, Cochrane, ScienceDirect, and the Internet search. Reviewed literature included randomized control trials, cross sectional and cohort studies. Pooled data were analyzed by calculating relative risk and odds ratios (ORs), using a binary random-effects model. Out of 1497 cases, 588 patients were positive for HPV DNA, detected by various methods. About 39.27% of case samples were positive for HPV DNA. The calculated OR was 2.82 and 95% confidence interval, which showed significantly an increased risk of HPV among case group when compared to that of controls. The present meta-analysis suggests a potentially significant casual relation between HPV and oral and oropharyngeal cancers.

  18. Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

    Science.gov (United States)

    Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

    1994-07-01

    We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

  19. Knowledge and Attitudes About Human Papilloma Virus (HPV) Vaccination and Cervical Cancer Screening Among Women in Rural Uganda

    Science.gov (United States)

    2016-06-15

    1- Knowledge and attitudes about Human Papilloma Virus (HPV) vaccination and cervical cancer screening among women in rural Uganda Authors...vaccination among parents/guardians of the vaccinated girls and to assess the attitudes to HPV vaccination among parents/guardians of the vaccinated girls...general attitude towards HPV vaccination was positive among mothers though there is still need for the populations to appreciate HPV and cervical

  20. Giant magnetoimpedance-based microchannel system for quick and parallel genotyping of human papilloma virus type 16/18

    Science.gov (United States)

    Yang, Hao; Chen, Lei; Lei, Chong; Zhang, Ju; Li, Ding; Zhou, Zhi-Min; Bao, Chen-Chen; Hu, Heng-Yao; Chen, Xiang; Cui, Feng; Zhang, Shuang-Xi; Zhou, Yong; Cui, Da-Xiang

    2010-07-01

    Quick and parallel genotyping of human papilloma virus (HPV) type 16/18 is carried out by a specially designed giant magnetoimpedance (GMI) based microchannel system. Micropatterned soft magnetic ribbon exhibiting large GMI ratio serves as the biosensor element. HPV genotyping can be determined by the changes in GMI ratio in corresponding detection region after hybridization. The result shows that this system has great potential in future clinical diagnostics and can be easily extended to other biomedical applications based on molecular recognition.

  1. Factors associated with future commitment and past history of human papilloma virus vaccination among female college students in northern Taiwan

    OpenAIRE

    Kuo, Ping-Fen; Yeh, Ying-Tse; Sheu, Shuh-Jen; Wang, Tze-Fang

    2014-01-01

    Objective To investigate factors influencing commitment to human papilloma virus (HPV) vaccination and prior vaccination among female college students in northern Taiwan. Methods A quota sample of 400 female college students was recruited from nine colleges in northern Taiwan during March 2013. Of these, 398 completed the self administered questionnaire which was designed based on the health promotion model. Results The results showed that factors associated with prior vaccination behavior we...

  2. Knowledge of Saudi female university students regarding cervical cancer and acceptance of the human papilloma virus vaccine

    OpenAIRE

    Al-Shaikh, Ghadeer K.; Almussaed, Eman M.; Fayed, Amel A.; Khan, Farida H.; Syed, Sadiqa B.; Al-Tamimi, Tahani N.; Elmorshedy, Hala N.

    2014-01-01

    Objectives: To assess the level of knowledge regarding cervical cancer and the acceptance of the human papilloma virus (HPV) vaccine among Saudi female students in health colleges. Methods: This cross-sectional study of a convenient sample encompassed 1400 students in Health Colleges at Princess Nora Bint Abdul Rahman University, Riyadh, Saudi Arabia was conducted between December 2013 and February 2014. A self-administrated questionnaire was distributed to all participants. Data collected in...

  3. Knowledge and perception of human papilloma virus vaccine among the antenatal women in a Nigerian tertiary hospital

    OpenAIRE

    Agida, Teddy E.; Akaba, Godwin O.; Isah, Aliyu Y.; Ekele, Bissalla

    2015-01-01

    Background: Cervical cancer is a major health problem globally, especially in sub-Saharan Africa, Nigeria inclusive. One of the preventive measures is the vaccination of teenagers against oncogenic human papilloma virus. The aim of this study was to find out the level of knowledge mothers possess about these vaccines and their willingness to administer vaccination to their teenage girls. Materials and Methods: This was a cross-sectional descriptive study of 255 consecutive women attending ant...

  4. 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.

  5. Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8- and UV-light induced skin carcinogenesis.

    Science.gov (United States)

    Deshmukh, Jayesh; Pofahl, Ruth; Pfister, Herbert; Haase, Ingo

    2016-09-06

    Overexpression and increased activity of the small Rho GTPase Rac1 has been linked to squamous cell carcinoma of the epidermis and mucosa in humans. Targeted deletion of Rac1 or inhibition of Rac1 activity in epidermal keratinocytes reduced papilloma formation in a chemical skin carcinogenesis mouse model. However, a potential role of Rac1 in HPV- and UV-light induced skin carcinogenesis has not been investigated so far, solar UV radiation being an important carcinogen to the skin.To investigate this, we deleted Rac1 or modulated its activity in mice with transgenic expression of Human papilloma virus type-8 (HPV-8) in epidermal keratinocytes. Our data show that inhibition or deletion of Rac1 results in reduced papilloma formation upon UV-irradiation with a single dose, whereas constitutive activation of Rac1 strongly increases papilloma frequency in these mice. Surprisingly, we observed that, upon chronic UV-irradiation, the majority of mice with transgenic expression of HPV-8 and epidermis specific Rac1 deletion developed squamous cell carcinomas. Taken together, our data show that Rac1 exerts a dual role in skin carcinogenesis: its activation is, on one hand, required for HPV-8- and UV-light induced papilloma formation but, on the other, suppresses the development of squamous cell carcinomas.

  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. High-risk human papilloma virus in archival tissues of oral pathosis and normal oral mucosa

    Directory of Open Access Journals (Sweden)

    Raghu Dhanapal

    2015-01-01

    Full Text Available Objectives: Oral cancer ranks third among all cancers in the Indian population. Human papilloma virus (HPV plays a significant role in oral carcinogenesis. Population-based subtype variations are present in the HPV prevalence. This study gives an emphasis on the parameters to be considered in formalin fixed paraffin embedded tissues for polymerase chain reaction (PCR-based research work. Materials and Methods: Cross-sectional study on archival paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC, epithelial dysplasia, and normal oral mucosa surrounding impacted tooth was amplified by PCR for the E6 gene of HPV type 16 and E1 gene of HPV type 18. Results: HPV 18 was positive in three OSCC cases. There was no statistically significant association of the positivity of HPV with the age, gender or habit. The HPV positive patients had a tobacco habit and were of a younger age group. Conclusion: The presence of HPV in carcinomatous tissue highlights the possible role of HPV in carcinogenesis and archival paraffin embedded tissue specimen can be used for this analysis. Recent studies on genomic analyses have highlighted that the HPV positive tumors are a separate subgroup based on genomic sequencing. The results of a larger retrospective study will help further in our understanding of the role of HPV in carcinogenesis, this study could form the baseline for such follow-up studies.

  8. High Risk Human Papilloma Virus Genotypes in Kurdistan Region in Patients with Vaginal Discharge.

    Science.gov (United States)

    Hussein, Nawfal R; Balatay, Amer A; Assafi, Mahde S; AlMufty, Tamara Abdulezel

    2016-01-01

    The human papilloma virus (HPV) is considered as the major risk factor for the development of cervical cancer. This virus is of different genotypes and generally can be classified into high and low risk types. To determine the rate of high risk HPV genotypes in women with vaginal discharge and lower abdominal pain in Kurdistan region, Iraq. Cervical swabs were taken from 104 women. DNA was extracted and the polymerase chain reaction (PCR) technique was used to determine the presence of high risk genotypes. It was found that 13/104 (12.5%) of the samples were positive for high risk HPV genotypes. Amongst those who were positive, 4/13 (30.7%) were typed as genotype 16 and 7/13 (53.8%) showed mixed genotyping. On the other hand, genotypes 53 and 56 were found in only one sample each. High risk HPV genotypes are not uncommon and further community based study is needed to determine the prevalence of HPV and its genotypes and plan for prevention of infection.

  9. Endoscopic modified medial maxillectomy for treatment of inverted papilloma originating from the maxillary sinus.

    Science.gov (United States)

    Erbek, Selim S; Koycu, Alper; Buyuklu, Fuat

    2015-05-01

    Endoscopic approaches have become an alternative to external approaches in the treatment of sinonasal inverted papillomas (IPs) in recent years. The aim of this study was to analyze the outcomes of endoscopic modified medial maxillectomy preserving the nasolacrimal duct and the inferior turbinate in selected IP cases. Medical charts of patients diagnosed with IP originating from the maxillary sinus between July 2008 and August 2013 were reviewed. Eight patients who had undergone endoscopic modified medial maxillectomy were included in the study. Attachment of IP was located on the medial wall of the maxillary sinus in all cases. The nasolacrimal duct was preserved in all of the patients. The inferior turbinate was completely preserved in 5 patients, and the anterior part of the inferior turbinate was preserved in 3 patients. The mean follow-up period of the patients was 30.8 months (12-60  mo). None of the patients had recurrence or major complications. The postoperative complaints were minor hemorrhagic discharge and crusting for the first few weeks. Endoscopic modified medial maxillectomy preserving the nasolacrimal duct and the inferior turbinate provides good surgical and functional outcomes in selected IP cases.

  10. Variability of intraductal papillomas of the mammary gland: Clinical, roentgenologic and morphologic investigations

    International Nuclear Information System (INIS)

    Rummel, W.

    1974-01-01

    The radiodiagnostical method of choice is the galactographic technique. However, a specific X-ray image of the papilloma does not exist. The galactographic technique has to be adapted to the surgical and histologic one. Only by combining these three techniques good results can be achieved. It is not possible to draw conclusions from the colour of the pathologic discharge about the type and character of the pathologic process. Contrary to the findings documented in the literature, we were able to diagnose with our technique not only small tumours, but also tumours situated in the periphery of the lactiferous duct. Because of our investigations it is no longer possible to maintain and keep the strict division of the proliferative changes occurring at the lactiferous duct walls. In this study, the most significant morphologic results are described in detail. In all patients with pathologic discharge of the mammary gland, the so-called papillo-carcinoma was found only in one case. As clinical consequence it has therefore to be demanded that in all women with the symptom of pathologic mamillary discharge first of all the origin of this discharge has to be localised by means of galactography. Only the individual morphologic picture of a proliferative change of the lactiferous duct provides some prognostic value. The prerequisites for such an individual assessment are differentiated roentgenologic, surgical and histological techniques. (orig./MG) [de

  11. Analysis of human papilloma virus in oral squamous cell carcinoma using p16: An immunohistochemical study

    Science.gov (United States)

    Patil, S.; Rao, R. S.; Amrutha, N.; Sanketh, D. S.

    2014-01-01

    Aims: The aim of this study is to evaluate the expression of human papilloma virus (HPV) in oral squamous cell carcinoma (OSCC) and to correlate the association of HPV in histological grades of OSCC using p16 (p16INK4a) immunohistochemistry (IHC). Subjects and Methods: This study consists of 30 histological diagnosed cases of OSCC (10-well-differentiated oral squamous cell carcinoma [WDOSCC], 10-moderately differentiated oral squamous cell carcinoma [MDOSCC] and 10-poorly differentiated oral squamous cell carcinoma [PDOSCC]). The sections were subjected to IHC procedure using p16. Two parameters in immunohistochemical p16 expression were evaluated by 3 observers based on the criteria by Galgano M. Tetal (2010) (a) percentage of p16 positive cases (b) pattern of p16 staining in various grades of OSCC. Statistical Analysis Used: Kappa test. Results: Totally, 30 samples of 0SCC, p16 positivity was noted in 26/30 (86.66%). Of 26 positive cases, p16 staining was positive in 7/10 (70%) of WDOSCC, 9/10 (90%) in MDOSCC and, 10/10 (100%) PDOSCC. Incidentally, we also found single dispersed cell staining in WDOSCC, patchy staining in MDOSCC and more diffuse staining pattern predominant in PDOSCC. Conclusions: Our study revealed an association between HPV and OSCC. Diffuse staining pattern was noted in PDOSCC, which in turn depicts the increase viral overload, which might have an influence on its aggressive behavior. PMID:24818098

  12. Genetic Mutation and Exosome Signature of Human Papilloma Virus Associated Oropharyngeal Cancer

    Science.gov (United States)

    Kannan, Anbarasu; Hertweck, Kate L.; Philley, Julie V.; Wells, Robert B.; Dasgupta, Santanu

    2017-01-01

    Human papilloma virus-16 (HPV-16) associated oropharyngeal cancer (HPVOPC) is increasing alarmingly in the United States. We performed whole genome sequencing of a 44 year old, male HPVOPC subject diagnosed with moderately differentiated tonsillar carcinoma. We identified new somatic mutation in MUC16 (A.k.a. CA-125), MUC12, MUC4, MUC6, MUC2, SIRPA, HLA-DRB1, HLA-A and HLA-B molecules. Increased protein expression of MUC16, SIRPA and decreased expression of HLA-DRB1 was further demonstrated in this HPVOPC subject and an additional set of 15 HPVOPC cases. Copy number gain (3 copies) was also observed for MUC2, MUC4, MUC6 and SIRPA. Enhanced expression of MUC16, SIRPA and HPV-16-E7 protein was detectable in the circulating exosomes of numerous HPVOPC subjects. Treatment of non-tumorigenic mammary epithelial cells with exosomes derived from aggressive HPVOPC cells harboring MUC16, SIRPA and HPV-16-E7 proteins augmented invasion and induced epithelial to mesenchymal transition (EMT) accompanied by an increased expression ratio of the EMT markers Vimentin/E-cadherin. Exosome based screening of key HPVOPC associated molecules could be beneficial for early cancer diagnosis, monitoring and surveillance. PMID:28383029

  13. The role of human papilloma virus and herpes viruses in the etiology of nasal polyposis.

    Science.gov (United States)

    Koçoğlu, Mücahide Esra; Mengeloğlu, Fırat Zafer; Apuhan, Tayfun; Özsoy, Şeyda; Yilmaz, Beyhan

    2016-02-17

    The aim of this study was to investigate the etiological role of human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6) and -7 (HHV-7) in the occurrence of nasal polyposis. Nasal polyp samples from 30 patients with nasal polyposis and normal nasal mucosa from 10 patients without nasal polyps were obtained. DNA was extracted from tissues. Real-time polymerase chain reaction was performed for all runs. No HSV-1, HSV-2, or VZV was detected in the samples. Among the patient samples, EBV and HHV-7 DNA were detected in 18 (60%), HHV-6 was detected in 20 (66.7%), and HPV was detected in 4 (13.3%) samples. Among the controls, CMV DNA was positive in one (10%). EBV was positive in 5 (50%), HHV-6 and HHV-7 were positive in 7 (70%), and HPV was positive in 2 (20%) samples. No significant difference was found among the groups with any test in terms of positivity. The association of Herpesviridae and HPV with the pathogenesis of nasal polyps was investigated in this study and no relationship was found. Thus, these viruses do not play a significant role in the formation of nasal polyps.

  14. Comparison of Three Different Commercial Kits for the Human Papilloma Virus Genotyping.

    Science.gov (United States)

    Lim, Yong Kwan; Choi, Jee-Hye; Park, Serah; Kweon, Oh Joo; Park, Ae Ja

    2016-11-01

    High-risk type human papilloma virus (HPV) is the most important cause of cervical cancer. Recently, real-time polymerase chain reaction and reverse blot hybridization assay-based HPV DNA genotyping kits are developed. So, we compared the performances of different three HPV genotyping kits using different analytical principles and methods. Two hundred positive and 100 negative cervical swab specimens were used. DNA was extracted and all samples were tested by the MolecuTech REBA HPV-ID, Anyplex II HPV28 Detection, and HPVDNAChip. Direct sequencing was performed as a reference method for confirming high-risk HPV genotypes 16, 18, 45, 52, and 58. Although high-level agreement results were observed in negative samples, three kits showed decreased interassay agreement as screening setting in positive samples. Comparing the genotyping results, three assays showed acceptable sensitivity and specificity for the detection of HPV 16 and 18. Otherwise, various sensitivities showed in the detection of HPV 45, 52, and 58. The three assays had dissimilar performance of HPV screening capacity and exhibited moderate level of concordance in HPV genotyping. These discrepant results were unavoidable due to difference in type-specific analytical sensitivity and lack of standardization; therefore, we suggested that the efforts to standardization of HPV genotyping kits and adjusting analytical sensitivity would be important for the best clinical performance. © 2016 Wiley Periodicals, Inc.

  15. A review of the use of human papilloma virus (HPV) in cervical screening.

    Science.gov (United States)

    Crossley, B; Crossley, J

    2017-07-01

    Using key words online databases were searched to identify relevant publications to review the use of Human papilloma virus (HPV) in cervical screening. The mode of cervical screening in the UK has been decided but implementation plans have yet to be announced. The protracted uncertainty surrounding the initial announcement to move to HPV primary screening together with the lack of a national steer has resulted in a flight of staff which threatens the provision of the current and future service. The transition will be a challenging time but analysis of data from more than 176,000 women has shown clear evidence of a reduction in the incidence of cancer where HPV testing is used. There will however, be a population of women who are cytologically negative but high-risk HPV positive and the management of these women will be key to maximising the benefits of HPV primary screening. As cervical cytology becomes increasingly rare its effectiveness and role in cervical screening will come under scrutiny and we must ensure the specificity of reporting is maintained in order for it to survive.

  16. Prevalence of Oral Human Papilloma Virus in Healthy Individuals in East Azerbaijan Province of Iran

    Science.gov (United States)

    SEIFI, Sharareh; ASVADI KERMANI, Iraj; DOLATKHAH, Roya; ASVADI KERMANI, Atabak; SAKHINIA, Ebrahim; ASGARZADEH, Mohammad; DASTGIRI, Saeed; EBRAHIMI, Ayoub; ASGHARI HAGGI, Arezou; NADRI, Mahsa; ASVADI KERMANI, Touraj

    2013-01-01

    Background: Human papilloma virus causes benign and malignant abnormalities in different part of the body. The link between high risk types of HPV and some anogenital and aerodigestive tract cancer is well established. Oral HPV infection plays a role in developing oropharyngeal squamous cell carcinoma. We studied the prevalence of oral HPV in healthy individuals and its relative risk factors. Methods: Saliva samples of 114 healthy subjects were collected for HPV DNA analysis. Volunteers completed questionnaires and signed a written consent. For data analysis descriptive statistic, chi square test and odds ratio was used. Results: The frequency of oral HPV in healthy individuals was 6.1 %(seven participant).The most frequent type was HPV-18 in five of them. HPV-6 and HPV-66 each was detected in one case. Relation of oral HPV positivity to demographic features and risk factors was not statistically significant. Conclusions: The prevalence of oral HPV infection in our community is the same as many other communities of developing countries, stressing that HPV-18 were the dominant type. PMID:23514804

  17. Diagnostic Algorithm to Reflect Regressive Changes of Human Papilloma Virus in Tissue Biopsies

    Science.gov (United States)

    Lhee, Min Jin; Cha, Youn Jin; Bae, Jong Man; Kim, Young Tae

    2014-01-01

    Purpose Landmark indicators have not yet to be developed to detect the regression of cervical intraepithelial neoplasia (CIN). We propose that quantitative viral load and indicative histological criteria can be used to differentiate between atypical squamous cells of undetermined significance (ASCUS) and a CIN of grade 1. Materials and Methods We collected 115 tissue biopsies from women who tested positive for the human papilloma virus (HPV). Nine morphological parameters including nuclear size, perinuclear halo, hyperchromasia, typical koilocyte (TK), abortive koilocyte (AK), bi-/multi-nucleation, keratohyaline granules, inflammation, and dyskeratosis were examined for each case. Correlation analyses, cumulative logistic regression, and binary logistic regression were used to determine optimal cut-off values of HPV copy numbers. The parameters TK, perinuclear halo, multi-nucleation, and nuclear size were significantly correlated quantitatively to HPV copy number. Results An HPV loading number of 58.9 and AK number of 20 were optimal to discriminate between negative and subtle findings in biopsies. An HPV loading number of 271.49 and AK of 20 were optimal for discriminating between equivocal changes and obvious koilocytosis. Conclusion We propose that a squamous epithelial lesion with AK of >20 and quantitative HPV copy number between 58.9-271.49 represents a new spectrum of subtle pathological findings, characterized by AK in ASCUS. This can be described as a distinct entity and called "regressing koilocytosis". PMID:24532500

  18. Expectation prior to human papilloma virus vaccination: 11 to 12-Year-old girls' written narratives.

    Science.gov (United States)

    Forsner, M; Nilsson, S; Finnström, B; Mörelius, E

    2016-09-01

    Expectations prior to needle-related procedures can influence individuals' decision making and compliance with immunization programmes. To protect from human papilloma virus (HPV) and cervical cancer, the immunization needs to be given before sexual debut raising interest for this study's aim to investigate how 11 to 12-year-old girls narrate about their expectations prior to HPV vaccination. A total of 27 girls aged 11 to 12 years participated in this qualitative narrative study by writing short narratives describing their expectations. The requirement for inclusion was to have accepted HPV vaccination. Data were subjected to qualitative content analysis. Findings showed the following expectations: going to hurt, going to be scared and going to turn out fine. The expectations were based on the girls' previous experiences, knowledge and self-image. The latent content revealed that the girls tried to transform uneasiness to confidence. The conclusion drawn from this study is that most girls of this age seem confident about their ability to cope with possible unpleasantness related to vaccinations. However, nurses need to find strategies to help those children who feel uneasy about needle-related procedures. © The Author(s) 2015.

  19. Human papilloma virus positive oropharyngeal squamous cell carcinoma: a growing epidemic.

    Science.gov (United States)

    Panwar, Aru; Batra, Rishi; Lydiatt, William M; Ganti, Apar Kishor

    2014-03-01

    The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing despite a decrease in tobacco use. Almost 20-30% of patients with OPSCC do not have the traditional risk factors of smoking and alcohol use and in a vast majority of these patients, the human papilloma virus (HPV) appears to drive the malignant transformation. HPV induced malignant transformation is attributed to two viral oncogenes and their non-structural protein products (E6 and E7). These two proteins appear to affect carcinogenesis by their inhibitory effects on p53 and retinoblastoma proteins (Rb). Patients with HPV mediated OPSCC seem to have a better prognosis compared to their non-HPV counterparts. However, in the absence of strong evidence, standard of care at this time for OPSCC does not differ based on HPV status. Current research is focused on the role of de-escalation of treatment and elucidation of prognostic markers in this unique population. This review focuses on the pathogenesis of HPV mediated OPSCC and details the current evidence in the management of these patients. Published by Elsevier Ltd.

  20. No Evidence of Human Papilloma Virus Infection in Basal Cell Carcinoma

    Science.gov (United States)

    Nahidi, Yalda; Meibodi, Naser Tayyebi; Meshkat, Zahra; Esmaili, Habibollah; Jahanfakhr, Samaneh

    2015-01-01

    Background: Basal cell carcinoma (BCC) is the most common skin cancer among whites, and several risk factors have been discussed in itsdevelopment and progress. Detection of human papilloma virus (HPV) deoxyribonucleic acid (DNA) BCCs in some studies suggests that the virus may play a role in the pathogenesis of this disease. Several molecular studies showed conflicting reports. Aims: The purpose of this study was to investigate the association between HPV and BCC using polymerase chain reaction (PCR). Materials and Methods: HPV DNA detection was done for 42 paraffin-embedded tissue specimens of BCC and 42 normal skin samples around the lesions by PCR using GP5+/GP6+ primers. Results: HPV DNA was not found in any of the 42 samples of BCC, and only one normal skin sample around the lesions was positive for HPV DNA by PCR. Conclusion: In this study, no statistically significant difference was seen between the presence of HPV DNA in BCC and normal skin around the lesion, and HPV is not likely to have an important role in pathogenesis of BCC. PMID:26288402