Vernon K Ward

University of Otago, Taieri, Otago Region, New Zealand

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Publications (66)204.94 Total impact

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    ABSTRACT: Virus-like particles (VLPs) are an effective means of establishing both prophylactic and therapeutic immunity against their source virus or heterologous antigens. The particulate nature and repetitive structure of VLPs makes them ideal for stimulating potent immune responses. Epitopes delivered by VLPs can be presented on MHC-II for stimulation of a humoral immune response, or cross-presented onto MHC-I leading to cell-mediated immunity. VLPs as particulate subunit vaccine carriers are showing promise in preclinical and clinical trials for the treatment of many conditions including cancer, autoimmunity, allergies and addiction. Supporting the delivery of almost any form of antigenic material, VLPs are ideal candidate vectors for development of future vaccines.
    Therapeutic delivery 11/2014; 5(11):1223-40.
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    ABSTRACT: The norovirus NS6 protease is a key target for anti-viral drug development. Noroviruses encode a 2,200 amino acid polyprotein which is cleaved by this critical protease at five defined boundary substrates into six mature non-structural proteins. Studies of the human norovirus NS6 protease, in the context of a full ORF1 polyprotein, have been severely hampered because human noroviruses are not culturable. Thus, investigations into the human norovirus NS6 protease have been largely restricted to in vitro assays using E. coli-expressed, purified enzyme. The NS6 protease is formed of two distinct domains joined by a linking loop. Structural data suggests that domain 2 of the protease possesses substantial substrate binding pockets which form the bulk of the interactions with the non-structural boundaries and largely dictate boundary specificity and cleavage. We have constructed chimeric murine norovirus genomes carrying individual domains from the human norovirus protease and demonstrated by cell transfection that, chimeric human norovirus proteases have functional activity in the context of the full-length ORF1 polyprotein. Whilst domain 2 confers boundary specificity, our data suggests that an inter-domain interaction exists within human norovirus NS6 protease which influences cleavage of specific substrates. This study also shows that chimeric murine noroviruses provide improved models for studying human norovirus protein function in the context of a full ORF1 polyprotein.
    The Biochemical journal. 10/2014;
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    ABSTRACT: Internalization of peptides by antigen presenting cells is crucial for the initiation of the adaptive immune response. Mannosylation has been demonstrated to enhance antigen uptake through mannose receptors, leading to improved immune responses. In this study we test the effect of surface mannosylation of protein-based virus-like particles (VLP) derived from Rabbit hemorrhagic disease virus (RHDV) on uptake by murine and human antigen presenting cells. A monomannoside and a novel dimannoside were synthesized and successfully conjugated to RHDV VLP capsid protein, providing approximately 270 mannose groups on the surface of each virus particle. VLP conjugated to the mannoside or dimannoside exhibited significantly enhanced binding and internalization by murine dendritic cells, macrophages and B cells as well as human dendritic cells and macrophages. This uptake was inhibited by the inclusion of mannan as a specific inhibitor of mannose specific uptake, demonstrating that mannosylation of VLP targets mannose receptor-based uptake. Consistent with mannose receptor-based uptake, partial retargeting of the intracellular processing of RHDV VLP was observed, confirming that mannosylation of VLP provides both enhanced uptake and modified processing of associated antigens.
    PLoS ONE 08/2014; 9(8):e104523. · 3.53 Impact Factor
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    ABSTRACT: Investigations into human norovirus infection, replication and pathogenesis, as well as the development of potential antiviral agents, have been restricted by the lack of a cell culture system for human norovirus. To date, the optimal cell culture surrogate virus model for studying human norovirus biology is the murine norovirus (MNV). In this report we generate a tetracycline-regulated, inducible eukaryotic cell system expressing the entire MNV ORF1 polyprotein. Once induced, the MNV ORF1 polyprotein was faithfully processed to the six mature non-structural proteins that predominately located to a discrete perinuclear region, as has been observed in active MNV infection. Furthermore, we found that expression of the ORF1 polyprotein alone was sufficient to induce apoptosis, characterised by caspase-9 activation and survivin down-regulation. This cell line provides a valuable new tool for studying MNV ORF1 non-structural protein function, screening for potential antiviral agents and acts as a proof-of-principle for such systems to be developed for human noroviruses.
    PLoS ONE 01/2014; 9(3):e90679. · 3.53 Impact Factor
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    ABSTRACT: Noroviruses are an emerging threat to public health, causing large health and economic costs, including at least 200,000 deaths annually. The inability to replicate in cell culture or small animal models has limited the understanding of the interaction between human noroviruses and their hosts. However an alternative strategy to gain insights into norovirus pathogenesis is to study murine norovirus (MNV-1) that replicates in cultured macrophages. While the innate immune response is central to the resolution of norovirus disease, the adaptive immune response is required for viral clearance. The specific responses of infected macrophages and dendritic cells to infection drive the adaptive immune response, with chemokines playing an important role. In this study we have conducted microarray analysis of RAW264.7 macrophages infected with MNV-1 and examined the changes in chemokine transcriptional expression during infection. While the majority of chemokines showed no change, there was specific up-regulation in chemokines reflective of a bias towards a Th1 response, specifically CCL2, CCL3, CCL4, CCL5, CXCL2, CXCL10 and CXCL11. These changes in gene expression were reflected in protein levels as determined by ELISA assay. This virus-induced chemokine response will affect the resolution of infection and may limit the humoral response to norovirus infection.
    Virus Research 12/2013; · 2.83 Impact Factor
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    ABSTRACT: 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.
    PLoS ONE 06/2013; 8(6):e66866. · 3.53 Impact Factor
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    ABSTRACT: Virus-like particles (VLP) from rabbit hemorrhagic disease virus (RHDV) can be used as a scaffold to facilitate the delivery of antigens to induce cell-mediated immune responses. In this study, we investigated the immune response to lymphocytic choriomeningitis virus-derived peptide antigen (gp33) delivered by RHDV VLP. The gp33 peptides were incorporated into the VLP in 2 different forms, either recombinantly expressed inside the VLP (VLP-gp33r) or chemically coupled to the surface of the VLP (VLP-gp33c). We showed that VLP-gp33r induced a greater level of cytotoxicity than VLP-gp33c against gp33-coated target cells in vivo. Both VLP, when delivered as prophylactic vaccines, inhibited the growth of Lewis' lung carcinoma tumors expressing gp33 (LL-LCMV) in mice to a similar degree. Studies to investigate the mechanism induced by these VLP showed that 2 CD11c DC subsets, CD8α and CD8α, acquired VLP in vivo and in vitro, and VLP-gp33r were cross-presented by both these subsets to prime CD8 T cells through a TAP-independent, endosomal recycling pathway. Depletion of Langerin DC in vivo before and after vaccination with VLP-gp33r, lead to reduced cytotoxicity implicating these cells in the induction of cytotoxic effector cells. These results suggest that recombinant VLP expressing tumor peptides targeted to Langerin DC may have clinical application. Finally we found that VLP-gp33r were more effective antitumor vaccines than VLP-gp33c when delivered therapeutically. The findings of this study suggest the potential of VLP as a platform for delivery of tumor-associate antigen and elicit protective immunity against tumors.
    Journal of immunotherapy (Hagerstown, Md.: 1997) 11/2012; · 3.20 Impact Factor
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    ABSTRACT: Virus-like particles (VLP) are effective vehicles for delivery of heterologous antigen to antigen-presenting cells. However VLP alone are insufficiently stimulatory to generate the signals required to facilitate effective priming of naïve T cells. We show that the VLP derived from rabbit hemorrhagic disease virus can bind the galactose-containing adjuvant α-galactosylceramide to form a composite particle for co-delivery of antigen and adjuvant to the same antigen-presenting cell. Vaccination with VLP and α-galactosylceramide activated splenic iNKT cells to produce IFN-γ and IL-4, led to the generation of antigen-specific T cells that protected prophylactically against subcutaneous tumor challenge, and was more effective at generating anti-tumor immune responses than either component individually. These data demonstrate a novel method for immunopotentiating VLP to increase their efficacy in the generation of anti-tumor responses via the innate ligand recognition properties of calicivirus-derived nanoparticles.
    Journal of Controlled Release 02/2012; 159(3):338-45. · 7.63 Impact Factor
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    ABSTRACT: Human noroviruses are highly infectious viruses that cause the majority of acute, non-bacterial epidemic gastroenteritis cases worldwide. The first open reading frame of the norovirus RNA genome encodes for a polyprotein that is cleaved by the viral protease into six non-structural proteins. The first non-structural protein, NS1-2, lacks any significant sequence similarity to other viral or cellular proteins and limited information is available about the function and biophysical characteristics of this protein. Bioinformatic analyses identified an inherently disordered region (residues 1-142) in the highly divergent N-terminal region of the norovirus NS1-2 protein. Expression and purification of the NS1-2 protein of Murine norovirus confirmed these predictions by identifying several features typical of an inherently disordered protein. These were a biased amino acid composition with enrichment in the disorder promoting residues serine and proline, a lack of predicted secondary structure, a hydrophilic nature, an aberrant electrophoretic migration, an increased Stokes radius similar to that predicted for a protein from the pre-molten globule family, a high sensitivity to thermolysin proteolysis and a circular dichroism spectrum typical of an inherently disordered protein. The purification of the NS1-2 protein also identified the presence of an NS1-2 dimer in Escherichia coli and transfected HEK293T cells. Inherent disorder provides significant advantages including structural flexibility and the ability to bind to numerous targets allowing a single protein to have multiple functions. These advantages combined with the potential functional advantages of multimerisation suggest a multi-functional role for the NS1-2 protein.
    PLoS ONE 02/2012; 7(2):e30534. · 3.53 Impact Factor
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    ABSTRACT: Tumour cell lysates are an excellent source of many defined and undefined tumour antigens and have been used clinically in immunotherapeutic regimes but with limited success. We conjugated Mel888 melanoma lysates to rabbit haemorrhagic disease virus virus-like particles (VLP), which can act as vehicles to deliver multiple tumour epitopes to dendritic cells (DC) to effectively activate antitumour responses. Virus-like particles did not stimulate the phenotypic maturation of DC although, the conjugation of lysates to VLP (VLP-lysate) did overcome lysate-induced suppression of DC activation. Lysate-conjugated VLP enhanced delivery of antigenic proteins to DC, while the co-delivery of VLP-lysates with OK432 resulted in cross-priming of naïve T cells, with expansion of a MART1(+) population of CD8(+) T cells and generation of a specific cytotoxic response against Mel888 tumour cell targets. The responses generated with VLP-lysate and OK432 were superior to those stimulated by unconjugated lysate with OK432. Collectively, these results show that the combination of VLP-lysate with OK432 delivered to DC overcomes the suppressive effects of lysates, and enables priming of naïve T cells with superior ability to specifically kill their target tumour cells.
    British Journal of Cancer 12/2011; 106(1):92-8. · 5.08 Impact Factor
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    ABSTRACT: Iridoviruses (IV) are nuclear cytoplasmic large DNA viruses that are receiving increasing attention as sublethal pathogens of a range of insects. Invertebrate iridovirus type 9 (IIV-9; Wiseana iridovirus) is a member of the major phylogenetic group of iridoviruses for which there is very limited genomic and proteomic information. The genome is 205,791 bp, has a G+C content of 31%, and contains 191 predicted genes, with approximately 20% of its repeat sequences being located predominantly within coding regions. The repeated sequences include 11 proteins with helix-turn-helix motifs and genes encoding related tandem repeat amino acid sequences. Of the 191 proteins encoded by IIV-9, 108 are most closely related to orthologs in IIV-3 (Chloriridovirus genus), and 114 of the 126 IIV-3 genes have orthologs in IIV-9. In contrast, only 97 of 211 IIV-6 genes have orthologs in IIV-9. There is almost no conservation of gene order between IIV-3, IIV-6, and IIV-9. Phylogenetic analysis using a concatenated sequence of 26 core IV genes confirms that IIV-3 is more closely related to IIV-9 than to IIV-6, despite being from a different genus of the Iridoviridae. An interaction between IIV and small RNA regulatory systems is supported by the prediction of seven putative microRNA (miRNA) sequences combined with XRN exonuclease, RNase III, and double-stranded RNA binding activities encoded on the genome. Proteomic analysis of IIV-9 identified 64 proteins in the virus particle and, when combined with infected cell analysis, confirmed the expression of 94 viral proteins. This study provides the first full-genome and consequent proteomic analysis of group II IIV.
    Journal of Virology 06/2011; 85(15):7900-11. · 4.65 Impact Factor
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    ABSTRACT: Effective vaccines and immunotherapies against cancer require professional antigen-presenting cells to cross-present exogenous antigen to initiate cytotoxic T-cell responses to destroy tumors. Virus-like particles (VLPs), containing tumor antigens, which can immunize against cancers, are cross-presented by dendritic cell (DC) but the mechanism by which this occurs is not fully understood. Here, we used VLPs, derived from rabbit hemorrhagic disease virus (RHDV) with both murine and human DCs, to elucidate these pathways. We have employed inhibitors to demonstrate that these VLPs are taken up by clathrin-dependent macropinocytosis and phagocytosis before being degraded in acidic lysosomal compartments. VLP-derived peptides are loaded onto major histocompatibility complex I that have been recycled from the cell surface. Antigen-coupled VLPs and murine ovalbumin-specific and human melanoma-associated antigen recognized by T cells (MART-1)-specific CD8(+) T cells were used to demonstrate cross-presentation via this alternate, receptor recycling pathway, which operated independently of the proteasome and the transporter-associated with antigen presentation. Finally, we found that cross-presentation of VLPs in vivo was not confined to CD8α(+) DC subsets. These data define the cross-presentation pathway for RHDV VLPs and may lead to improved cancer immunotherapies.
    Immunology and Cell Biology 01/2011; 89(6):681-8. · 4.21 Impact Factor
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    ABSTRACT: Our previous structural studies on intact, infectious murine norovirus 1 (MNV-1) virions demonstrated that the receptor binding protruding (P) domains are lifted off the inner shell of the virus. Here, the three-dimensional (3D) reconstructions of recombinant rabbit hemorrhagic disease virus (rRHDV) virus-like particles (VLPs) and intact MNV-1 were determined to approximately 8-A resolution. rRHDV also has a raised P domain, and therefore, this conformation is independent of infectivity and genus. The atomic structure of the MNV-1 P domain was used to interpret the MNV-1 reconstruction. Connections between the P and shell domains and between the floating P domains were modeled. This observed P-domain flexibility likely facilitates virus-host receptor interactions.
    Journal of Virology 03/2010; 84(11):5836-41. · 4.65 Impact Factor
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    ABSTRACT: The lightbrown apple moth (Epiphyas postvittana) is a leafroller pest that damages horticultural crops in New Zealand. This paper documents the establishment of a primary cell line from neonate E. postvittana larvae to facilitate the development of E. postvittana nucleopolyhedrovirus (EppoNPV) for control of this pest. The cell line was cultured for 36 passages and a clonal derivative designated EpN1.10 was generated that had a doubling time of 36h at 21 degrees C. The EpN1.10 cell line allowed for recovery of EppoNPV from transfected genomic DNA and virus passage, as determined by occlusion body production and restriction endonuclease analysis.
    Journal of Invertebrate Pathology 02/2010; 104(2):147-9. · 2.60 Impact Factor
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    ABSTRACT: The painted apple moth (PAM), Teia anartoides (Walker) (Lepidoptera: Lymantriidae) made a recent incursion into New Zealand. A nucleopolyhedrovirus (NPV), Orgyia anartoides NPV (OranNPV), originally isolated from PAM in Australia, was tested for its pathogenicity to PAM and a range of non-target insect species found in New Zealand, to evaluate its suitability as a microbial control for this insect invader. Dosage-mortality tests showed that OranNPV was highly pathogenic to PAM larvae; mean LT50 values for third instars ranged from 17.9 to 8.1 days for doses from 102 to 105 polyhedral inclusion bodies/larva, respectively. The cause of death in infected insects was confirmed as OranNPV. Molecular analysis established that OranNPV can be identified by PCR and restriction digestion, and this process complemented microscopic examination of infected larvae. No lymantriid species occur in New Zealand; however, the virus had no significant effects on species from five other lepidopteran families (Noctuidae, Tortricidae, Geometridae, Nymphalidae and Plutellidae) or on adult honeybees. Thus, all indications from this initial investigation are that OranNPV would be an important tool in the control of PAM in a future incursion of this species into New Zealand.
    Journal of Applied Entomology 01/2010; 134(1):61 - 71. · 1.70 Impact Factor
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    ABSTRACT: Baculoviruses are ubiquitous insect viruses well known for their use as bioinsecticides, gene therapy vectors, and protein expression systems. Overexpression of recombinant proteins in insect cell culture utilizes the strong promoter of the polyhedrin gene. In infected larvae, the polyhedrin protein forms robust intracellular crystals called polyhedra, which protect encased virions for prolonged periods in the environment. Polyhedra are produced by two unrelated families of insect viruses, baculoviruses and cypoviruses. The atomic structure of cypovirus polyhedra revealed an intricate packing of trimers, which are interconnected by a projecting N-terminal helical arm of the polyhedrin molecule. Baculovirus and cypovirus polyhedra share nearly identical lattices, and the N-terminal region of the otherwise unrelated baculovirus polyhedrin protein sequence is also predicted to be alpha-helical. These results suggest homology between the proteins and a common structural basis for viral polyhedra. Here, we present the 2.2-A structure of baculovirus polyhedra determined by x-ray crystallography from microcrystals produced in vivo. We show that the underlying molecular organization is, in fact, very different. Although both polyhedra have nearly identical unit cell dimensions and share I23 symmetry, the polyhedrin molecules are structurally unrelated and pack differently in the crystals. In particular, disulfide bonds and domain-swapped N-terminal domains stabilize the building blocks of baculovirus polyhedra and interlocking C-terminal arms join unit cells together. We show that the N-terminal projecting helical arms have different structural roles in baculovirus and cypovirus polyhedra and conclude that there is no structural evidence for a common evolutionary origin for both classes of polyhedra.
    Proceedings of the National Academy of Sciences 12/2009; 106(52):22205-10. · 9.81 Impact Factor
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    ABSTRACT: The Tetraviridae is a family of non-enveloped positive-stranded RNA insect viruses that is defined by the T=4 symmetry of virions. We report the complete Euprosterna elaeasa virus (EeV) genome sequence of 5698 nt with no poly(A) tail and two overlapping open reading frames, encoding the replicase and capsid precursor, with approximately 67% amino acid identity to Thosea asigna virus (TaV). The N-terminally positioned 17 kDa protein is released from the capsid precursor by a NPGP motif. EeV has 40 nm non-enveloped isometric particles composed of 58 and 7 kDa proteins. The 3'-end of TaV/EeV is predicted to form a conserved pseudoknot. Replicases of TaV and EeV include a newly delineated VPg signal mediating the protein priming of RNA synthesis in dsRNA Birnaviridae. Results of rooted phylogenetic analysis of replicase and capsid proteins are presented to implicate recombination between monopartite tetraviruses, involving autonomization of a sgRNA, in the emergence of bipartite tetraviruses. They are also used to revise the Tetraviridae taxonomy.
    Virology 11/2009; 397(1):145-54. · 3.28 Impact Factor
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    ABSTRACT: Host cell and virus gene expression were measured five days after per os inoculation of 3rd instar lightbrown apple moth (LBAM) larvae with the Epiphyas postvittana nucleopolyhedrovirus (EppoNPV). Microarray analysis identified 84 insect genes that were up-regulated and 18 genes that were down-regulated in virus-infected larvae compared with uninfected larvae. From the 134 viral open reading frames represented on the microarray, 81 genes showed strong expression. Of the 38 functionally identifiable regulated insect genes, 23 coded for proteins that have roles in one of five processes; regulation of transcription and translation, induction of apoptosis, and maintenance of both juvenility and actin cytoskeletal integrity. Of the 34 functionally identifiable viral genes that were most strongly expressed, 12 had functions associated with these five processes, as did a further seven viral genes which were expressed at slightly lower levels. A survey of the LBAM-expressed sequence tag library identified further genes involved in these processes. In total, 135 insect genes and 38 viral genes were analysed by quantitative polymerase chain reaction. Twenty-one insect genes were strongly up-regulated and 31 genes strongly down-regulated. All 38 viral genes examined were highly expressed. These data suggest that induction of apoptosis and regulation of juvenility are the major 'battlegrounds' between virus and insect, with the majority of changes observed representing viral control of insect gene expression. Transcription and translational effects seem to be exerted largely through modulation of mRNA and protein degradation. Examples of attempts by the insect to repel the infection via changes in gene expression within these same processes were, however, also noted. The data also showed the extent to which viral transcription dominated in the infected insects at five days post inoculation.
    Insect Molecular Biology 10/2009; 18(5):635-48. · 2.98 Impact Factor
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    ABSTRACT: Recombinant virus-like particles (VLP) expressing heterologous tumor antigens have recently been investigated for use as vaccines. We have chemically conjugated ovalbumin (OVA) or OVA-derived CD4 (OTII) and CD8 (OTI) epitopes, to rabbit hemorrhagic disease virus (RHDV) VLP. VLP conjugated with OVA were able to cross-prime CD8+ cells from OT1 mice transgenic for the OVA T cell receptor. VLP.OTI was able to induce higher antigen-specific cytotoxicity in vivo than VLP mixed with either the protein or the peptide. Furthermore we have shown that the growth of the aggressive B16.OVA melanoma in mice was significantly delayed in those animals that had been vaccinated with VLP.OVA or with VLP coupled with both OTI and OTII peptides prior to the introduction of the tumor. Neither VLP.OTI nor VLP.OTII alone were capable of inhibiting tumor growth. This work suggests that RHDV VLP offer a versatile scaffold for multiple vaccine epitopes, enabling cross-presentation of the antigen to elicit potent cell-mediated and anti-tumor responses.
    Vaccine 09/2008; 26(42):5334-7. · 3.49 Impact Factor
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    ABSTRACT: Viruses have traditionally been studied as pathogens, but in recent years they have been adapted for applications ranging from drug delivery and gene therapy to nanotechnology, photonics, and electronics. Although the structures of many viruses are known, most of their biophysical properties remain largely unexplored. Using Brillouin light scattering, we analyzed the mechanical rigidity, intervirion coupling, and vibrational eigenmodes of Wiseana iridovirus (WIV). We identified phonon modes propagating through the viral assemblies as well as the localized vibrational eigenmode of individual viruses. The measurements indicate a Young's modulus of approximately 7 GPa for single virus particles and their assemblies, surprisingly high for "soft" materials. Mechanical modeling confirms that the DNA core dominates the WIV rigidity. The results also indicate a peculiar mechanical coupling during self-assembly of WIV particles.
    Physical Review E 09/2008; 78(2 Pt 1):021907. · 2.33 Impact Factor

Publication Stats

923 Citations
204.94 Total Impact Points

Institutions

  • 1998–2014
    • University of Otago
      • Department of Microbiology and Immunology
      Taieri, Otago Region, New Zealand
  • 2012
    • Malaghan Institute
      Wellington, Wellington, New Zealand
  • 2006
    • AgResearch
      Hamilton City, Waikato, New Zealand
  • 2005
    • Wright-Patterson Air Force Base
      Dayton, Ohio, United States
  • 2002
    • Leiden University Medical Centre
      • Department of Medical Microbiology
      Leiden, South Holland, Netherlands
  • 1991–1997
    • University of California, Davis
      • Department of Entomology
      Davis, CA, United States
  • 1995
    • CSU Mentor
      Long Beach, California, United States
  • 1989
    • Oxford Institute for Energy Studies
      Oxford, England, United Kingdom