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- Vernon Ward
Professor Vernon Ward
Viral pathogenesis, Molecular virology, Applied immunology, Host pathogen interactions
Viruses are well known for their ability to cause disease and there is an ongoing need to develop treatments for a range of viruses. Understanding the interactions between a virus and its host cell and the mechanisms of viral replication are important for the development of antiviral agents. In addition, the diversity of structure and replication found in viruses offers opportunities for exploiting the biology and properties of viruses for beneficial purposes. Our research investigates the replication of viruses and their interaction with the host for the development of antiviral agents and exploitation of virus properties for beneficial purposes.
Ward Lab 2019
(RHDV VLP cryoEM reconstruction image: Dr Tom Smith, Donald Danforth Centre, St Louis, MO, USA).
Our research group predominantly studies caliciviruses. Caliciviruses are small isometric RNA viruses with a single-stranded, positive-sense RNA genome. There are a wide range of viruses in the Caliciviridae family with members infected a wide range of animals in many different environments.
Two well-studied groups of caliciviruses are the noroviruses, well-known for their ability to cause gastrointestinal disease, and lagoviruses, well-known for their ability to cause disease in rabbits and other lagomorphs.
The research group has a long standing interest in insect viruses and continues to routinely use the baculovirus insect cell expression system for the production of recombinant proteins.
Globally, there are an estimated 699 million illnesses and over 200,000 deaths attributed to noroviruses annually. Norovirus infections result in $US60.3 billion in societal costs and $US4.2 billion in direct healthcare cost (Bartsch et al, 2016, PLoS One 11, e0151219). There is a clear need for rapid treatment in semi-closed environments such as hospitals, the military and aged care facilities, and where patients are immunosuppressed, such as during transplantation. There are no vaccines or direct-acting antiviral agents for noroviruses with this further complicated by the episodic emergence of pandemic strains through recombination and drift. There is an urgent need for norovirus antivirals that can be administered at the first sign of symptoms and as a prevention for spread.
Despite new systems becoming available, human noroviruses remain challenging to replicate in culture. The use of viral replicons and model viruses such as the murine norovirus continue to be important for investigating viral replication, host-pathogen interactions and the development of anti-viral agents. These systems will complement new human norovirus culture systems as they become more prevalent.
Goals of this research:
- To increase our understanding of the role(s) and mechanisms of action of viral proteins during viral replication.
- To identify targets and systems for the development of antiviral agents against noroviruses.
This research is supported by an MBIE Endeavour Programme Grant, The Maurice Wilkens Centre for Molecular Biodiscovery, the William Sherriff Trust and the University of Otago.
Rabbit hemorrhagic disease Virus-like Particles (RHDV VLP)
The over-expression of the major capsid protein(s) of a range of viruses leads to the assembly of Virus-Like Particles (VLP). A well known example is the Human papilloma virus VLP that is used as a vaccine against papillomavirus infection and cervical cancer. VLP are excellent particulate vaccines.
Our interest in VLP is to use these complex particles as carriers for subunit vaccines. We were looking for a VLP that would not meet pre-existing immunity in preclinical experiments or during clinical application. We did not want to use VLP that might complicate future vaccination regimes. We wanted to be able to generate both humoral and cell-mediated immunity to provide a broadly applicable vaccine delivery platform.
We have developed the VLP derived from RHDV as a vaccine carrier for immune epitopes and proteins. This carrier is suitable for cross-presentation of MHC-I epitopes to the immmune system for the generation of cell-mediated immunity and is an effective carrier of epitopes for antibody generation through multiple delivery routes.
Goals of this research:
- To develop and modify RHDV as a carrier for a range of molecules for applications benefiting from a nanoparticle format
- To develop RHDV as a carrier for cell-mediated immunity in tumour immunotherapy
Section of Epiphyas postvittana NPV occlusion body
Baculoviruses are a core competency of the laboratory with a long history of research of these viruses for biological control of insect pests. The laboratory uses the baculovirus expression vector system as a standard laboratory tool for the eukaryotic expression of recombinant proteins, including the RHDV VP60 protein for production of virus-like particles and various norovirus proteins
We also maintain an interest in insect iridoviruses.
- Kim, S.H., Mercer, A., Mitchell, A., de Miranda, J.R., Ward, V., Mondet, F., and Bostina, M. Viral infections induced alterations of antennal epithelium ultrastructure in honey bees. Journal of Invertebrate Pathology. 168:107252.(2019).
- Thomson, N. A., Howe, L., Weidgraaf, K., Thomas, D. G., Young, V., Ward, V. K., Munday, J. S. Fells catus papillomavirus type 2 virus-like particle vaccine is safe and immunogenic but does not reduce FcaPV-2 viral loads in adult cats. Veterinary Immunology and Immunopathology 213: 109888, doi.org/10.1016/j.vetimm.2019.109888 (2019).
- McSweeney, A., Davies, C., and Ward, V.K. Cell cycle arrest is a conserved function of norovirus VPg proteins. Viruses 11:217 (2019).
- Kramer, K., Al-Barwani, F, Baird, M.A., Young, V.L., Larsen, D.S., Ward, V.K. and Young, S.L. Functionalisation of virus-like particles enhances anti-tumour immune responses. Journal of Immunological Research. DOI: 10.1155/2019/5364632, 10 pages (2019).
- Donaldson, B., Lateef, Z., Walker, G.F., Young, S.L., and Ward, V.K. Virus-like particle vaccines: immunology and formulation for clinical translation. Expert Reviews Vaccines. 17:9, 833-849 (2018).
- Donaldson, B., Al-Barwani, F., Pelham, S.J., Young, K., Ward, V.K., and Young, S.L. Multi-target chimaeric VLP as a therapeutic vaccine in a model of colorectal cancer. Journal for ImmunoTherapy of Cancer. 5:69 (2017).
- Li, K., Donaldson, B., Young, V., Ward, V., Jackson, C., Baird, M., and Young, S.L. Adoptive cell therapy with CD4+ T help1 cells and CD8+ cytotoxic T cells enhance complete rejection of an established tumour, leading to generation of endogenous memory response to non-targeted tumour epitopes. Clinical and Translational Immunology. 6:e160 (2017)
- Nicholson, L.J., Mahar, J.E., Strive, T., Zheng, T., Holmes, E.C., Ward, V.K., and Duckworth, J.A. Benign rabbit calicivirus in New Zealand. Applied and Environmental Microbiology, 83:e00090-17 (2017).
- Lateef, Z., Gimenez, G., Baker, E.S., and Ward, V.K. Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role. BMC genomics, 18:39 (2017).
- Mahar, J.E., Nicholson, L., Eden, J.-S., Duchene, S., Kerr, P.J., Duckworth, J., Ward, V.K., Holmes, E.C., and Strive, T. Benign rabbit caliciviruses exhibit evolutionary dynamics similar to those of their virulent relatives. Journal of Virology 90:9317-9329, (2016)
- Davies, C. and Ward, V.K. Expression of the NS5 (VPg) protein of murine norovirus induces a G1/S phase arrest. PLoS ONE 11(8) e0161582 (2016).
- Slatter, T.L., Wilson, M., Tang, C., Campbell, H.G., Ward, V.K., Young, V.L., Van Ly, D., Fleming, N.I., Braithwaite, A.W., and Baird, M.A. Anti-tumor cytotoxicity induced by bone marrow-derived antigen presenting cells is facilitated by the tumor suppressor protein p53 via regulation of IL-12. OncoImmunology 5(3) e1112941, (2016)
- Donaldson, B., Al-Barwani, F., Young, V., Scullion, S., Ward, V., and Young, S. Virus-like particles, a versatile subunit vaccine platform. In: Advances in Delivery Science and Technology: Subunit Vaccine Delivery. Foged, C., Rades, T., Perrie, Y., and Hook, S. Eds. Springer, 2015 Chapter 9, pp159-180 [ISBN 978-1-4939-1417-3].
- Davies, C., Brown, C.B., Westphal, D., Ward, V.K. Murine norovirus replication induces a G0/G1 cell cycle arrest in asynchronous cells. Journal of Virology 89(11) 6057-6066, (2015).
- Chiu, E., Hijnen, M., Bunker, R., Boudes, M., Rajendren, C., Aizel, K., Olieric, V., Schulze-Briese, C., Mitsuhashi, W., Young, V., Ward, V.K., Bergoin, M., Metcalf, P., and Coulibaly, F. Strcutural basis for the virulence activity and in vivo crystallization of viral spindles. Proceedings of the National Academy of Sciences, USA. 112(13) 3973-3978, doi10.1073/pnas.1418798112 (2015).
- Herod, M.R., Prince, C.A., Skilton, R.J., Ward, V.K., Cooper, J.B., and Clarke, I.N. Structure-based design and functional studies of novel noroviral 3C protease chimeras offers insight into substrate specificity. Biochemical Journal, 464:461-472 (2014).
- Al-Barwani, F., Donaldson, B., Pelham, S., Young, S.L., and Ward, V.K. Antigen Delivery by virus-like particles for immunotherapeutic vaccination. Therapeutic Delivery, 5(11), 1223-1240 (2014).
- Al-Barwani, F., Young, S.L., Baird, M.A., Larsen, D.S., Ward, V.K. Mannosylation of virus-like particles enhances internalization by antigen presenting cells. PLoS ONE, 9(8): e104523 (2014).
- Herod, M.R., Salim, O., Skilton, R.J., Prince, C.A., Ward, V.K., Lambden, P.R., and Clarke, I.N. Expression of the Murine norovirus (MNV) ORF1 polyprotein is sufficient to induce apoptosis in an inducible virus-free cell model. PLoS one, 9(3):e90679 (2014).
- Waugh, E., Chen, A., Baird, M.A., Brown, C.B., and Ward, V.K. Characterization of the chemokine response of RAW264.7 cells to infection by murine norovirus. Virus Research 181:27-34 (2014).
- Sirotkin, S., Mermet, A., Bergoin, M., Ward, V., and Van Etten, J. Viruses as nanoparticles: structure versus collective dynamics. Physical Review E. 90: e022718 (2014).
- Jemon, K., Young, V., Wilson, M., McKee, S., Ward, V., Baird, M., Young, S., and Hibma, M. An enhanced heterologous virus-like particle for human papillomavirus Type 16 tumour immunotherapy. PLoS one 8(6):e66866 doi:10.1371/journal.pone.0066866 (2013).
- Li, K., Peers-Adams, A., Win, S.J., Scullion, S., Wilson, M., Young, V.L., Jennings, P., Ward, V.K., Baird, M.A., Young, S.L. Antigen incorporated in virus-like particles is delivered to specific dendritic cell subsets that induce an effective anti-tumor immune response in vivo. Journal of Immunotherapy, 36:11-19 (2013).
- McKee, S.J., Young, V.L., Clow, F., Hayman, C.M., Baird, M.A., Hermans, I.F., Young, S.L., Ward, V.K. Virus-like particles and a-galactosylceramide form a self-adjuvanting composite particle that elicits anti-tumor responses. Journal of Controlled Release 159:338-345 (2012).
- Baker, E.S., Luckner, S.R., Krause, K.L., Lambden, P.R., Clarke, I.N., Ward, V.K. Inherent structural disorder and dimerisation of murine norovirus NS1-2 protein. PloS one 7:e30534 (2012).
- Win, S.J., McMillan, D.G.G., Errington-Mais, F., Ward, V.K., Young, S.L., Baird, M.A., Melcher, A.A. Enhancing the Immunogenicity of Tumor Lysate-Loaded Dendritic Cell Vaccines by Canjugation to Virus-Like Particles. British Journal of Cancer 106:92-98 (2012).
- Win, S.J., Ward, V.K., Dunbar, P.R., Young, S.L., and Baird, M.A. Cross presentation of epitopes on virus-like particles by dendritic cells via the MHC-I receptor recycling pathway. Immunology and Cell Biology, 2011 doi:10.1038/icb.2010.161.
- Wong, C.K., Young, V.L., Kleffmann, T., and Ward, V.K. Genomic and proteomic analysis of Invertebrate Iridovirus Type 9. Journal of Virology 85:7900-7911 (2011).
- Dorrington, R.A. Gorbalenya, A.E., Gordon, K.H.J., Lauber, C., and Ward, V.K. Tetraviridiae. In: Virus Taxonomy: IXth Report of the International Committee on Taxonomy of Viruses. King, A.M.K., Lefkowitz, E., Adams, M.J. and Carstens, E.B. eds, Elsevier, 2011 pp1091-1102 [ISBN 978-0-12-384684-6].
- Katpally, U., Vocc, N.R., Cavazza, T., Taube, A., Rubin, J.R., Young, V.L., Stuckey, J., Ward, V.K., Virgin, H.W., Wobus, C.E., and Smith, T.J. High resolution cryo-electron microscopy structures of MNV-1 and RHDV reveals marked flexibility in the receptor binding domains. Journal of Virology 84: 5836-5841 (2010).
- Ward, V.K., Cooke, B., Strive, T. Rabbit hemorrhagic disease virus and other lagoviruses, In: Caliciviruses: Molecular and Cellular Virology, G. Hansman, J. Jiang and K.Y. Green eds, Horizon Scientific Press, (2010).
- Zeddam, J.-L., Gordon, K.H.J., Lauber, C., Felipe Alves, C.A., Luke, B.T., Hanzlik, T.N., Ward, V.K. and Gorbalenya, A.E. Euprosterna elaeasa virus genome sequence and evolution of the Tetraviridae family: Emergence of bipartite genomes and conservation of the VPg signal with the dsRNA Birnaviridae family. Virology 397:145-154 (2010).
- Williams, T., and Ward, V.K. Iridoviruses. In: Insect Virology. Caister Academic Press, Norfolk UK, Eds. S. Asgari and K. Johnson, Chapter 6, pp. 123-151 (2010).
- Markwick, N.P., Glare, T.R., Hauxwell, C., Li, Z., Poulton, J., Ward, J.M., Young, V.L., and Ward, V.K. The infectivity and host-range of Orgyia anartoides nucleopolyhedrovirus. Journal of Applied Entomology 134:61-71 (2010).
- Coulibaly, F., Chiu, E., Gutman, S., Rajendran, C., Haebel, P., Ikeda, K., Mori, H., Ward, V., Schulze-Briese, C., and Metcalf, P. The atomic structure of baculovirus polyhedra reveals the independent emergence of intracellular infectious crystals in DNA and RNA viruses. Proceedings of the National Academy of Sciences, USA 106:22205-22210 (2009).
Lab members and postgraduate students
The laboratory is actively involved in supporting postgraduate student research with 4 PhD students currently being supervised on projects associated with the research outlined above. There have been 69 research degree project completions for a range of degrees by students in the laboratory. There are currently 8 students and staff associated with the laboratory.
Some recent postgraduate completions
S. Dowlath, MSc(Distinction), Stabilised virus-like particles for vaccination, 2018.
S. Thomas, BSc(Hons 1st Class), Human norovirus VPg and the cell cycle, 2018.
G. McKenzie-Goldsmith BSc(Hons 1st Class), Human norovirus propol, 2018.
L Nicholson, PhD, Rabbit biocontrol, investigating the role of rabbit caliciviruses in the epidemiology of RHDV in NZ, 2017
B. Donaldson, PhD, Development of a virus-based cDNA library vaccine for colorectal cancer, 2017
C. Davies, PhD, Norovirus regulation of the cell cycle, 2016.
F. Al Barwani, PhD, Enhancing the functionality of RHDV nanoparticles, 2015
E. Waugh, PhD, The regulation of chemokines by murine norovirus, 2015
S. McKee, PhD, Enhancing the adjuvancy of virus-like particles for cancer immunotherapy, 2013
E. Baker, PhD, The NS1-2 protein of murine norovirus, 2012
S. Scullion, MSc (with Credit), Investigating cytotoxic T cell responses to RHDV virus-like particles, 2012
S. Win, PhD, The use of virus-like particles as immunotherapies for cancer, 2011
- New Zealand Representative, International Committee for the Taxonomy of Viruses
- I was the Head of Department of Microbiology & Immunology 2012-14
- I was Dean, School of Biomedical Sciences 2014-2019
- I am active in a range of University committees and projects