Immunovirology

Andreas Suhrbie Staff
Funding
Collaborators
Key Publications
Patents
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Lab Head: Associate Professor Andreas Suhrbier

The Immunovirology lab is developing and exploiting knowledge about interactions between viruses and the immune system to develop novel strategies against diseases including HIV and cancer. The lab has helped to develop a number of novel patented therapeutic technologies in collaboration with Australian and overseas pharmaceutical companies.

The Kunjin replicon technology
In collaboration with Dr Khromykh (UQ) we have developed the Kunjin replicon technology, which is being commercialised by a start-up company Replikun Biotech Pty Limited www.peplin.com. The technology is based on the Australian Flavivirus Kunjin and is being tested for potential utility for HIV and Ebola vaccines, cancer gene therapy and protein production applications. The replicon system can be delivered by DNA, RNA or virus like particles and has been shown to induce potent long lasting CD8+ cytotoxic T lymphocyte responses in animal models. This RNA-based vector system has the unique feature of being non-cytopathic, thus transfected cells do not undergo apoptosis ensuring extended antigen expression and dsRNA "danger signals". The replicon RNA continues to replicate itself to produce high mRNA copy numbers thereby providing high level antigen expression.

SerpinB2 / Plasminogen Activator Inhibitor Type-2
We are beginning unravel the physiological role of SerpinB2, aka Plasminogen Activator Inhibitor Type-2 (PAI-2). Although this Serpin is traditionally viewed as an inhibitor of the extracellular urokinase Plasminogen Activator, we have accumulated considerable evidence that SerpinB2 has intracellular activites. We have shown that SerpinB2 has an intranuclear activity that inibits the calpain-mediated degradation of the retinoblastoma tumour suppressor protein. SerpinB2 is also induced by HIV-1 infection of macrophages, and SerpinB2 expression can regulate transcription from the HIV-1 LTR. We are currently investigating the role of cytoplasmic SerpinB2 and its potential role in regulating inflamation.

Ross River virus disease and related studies
Ross River virus (RRV) causes a principally arthritic disease in up to 8000 Australians annually. Evidence from our lab and others strongly suggests that the disease is caused by the persistent productive infection of macrophages in the joints of RRV disease (RRVD) patients. We have shown that nearly all RRVD patients recover within 3-6 months, with patients suffering long term disease (>6-12 months) found to have other concurrent conditions. Thus the popular perception that this is a disease that lasts for years is very likely incorrect.

In collaboration with Dr Suresh Mahalingam (University of Canberra) we are utilising a mouse model of RRVD to understanding how the virus causes disease. Currently we believe the disease is an immune pathology associated with over-activated macrophages. A major new initiative involves work on Chikungunya virus disease funded by ACITH, where we seeking to understand the disease process and develop new intervesions.

Collaborative research with the Australian Antarctic division has resulted in the collection of multiple new viruses from Macquarie Island, which are currently being sequenced.

Contract R&D in the Immunovirology Laboratory
The Immunovirology Laboratory continues to undertake contract R&D for a number of Australian and international pharmaceutical companies. Customers have included Bavarian Nordic (Denmark), Aventis (France), NewBiomed Pika (Singapore), CSL Ltd., C-Bio Ltd., Virax Holdings Ltd. and Peplin Ltd. (Australia). We have recently helped establish and patent the mechanism of action of PEP005, the new anticancer drug from Peplin Ltd., and Cpn10 the new antiinflammatory drug from C Bio Ltd.

Staff

Labhead:	Dr Andreas Suhrbier
Postdocs:	Dr Grant Darnell Dr Wayne Schroder Dr Itaru Anraku Dr Sarah-Jane Cozzi
Lab Manager:	Joy Gardner
Research Assistants:	Thuy TT Lee Blake Fergusson
PhD scholars:	Paweena Rattanasena Lee Major
Visiting scientists:	Dr Alex Khromykh Dr Robert Slade	a.khromykh@mailbox.uq.edu.au rslade@scu.edu.au

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Funding

NH&MRC
National Cancer Institute, NIAID, USA.
Australian Centre for International & Tropical Health & Nutrition

Collaborators

Dr A. Khromykh,University of Queensland, QLD
Dr Suresh Mahalingam, University of Canberra, ACT
Dr T. Antalis, University of Maryland, USA
Dr Robert Medcalf, Monash University, Australia
Dr Angel Cid-Arregui, Deutsches Krebsforshungszentrum, Heidelberg, Germany
Dr Ranjeny Thomas, Diamentina Institute, Brisbane

Current Commercial associations

Peplin Biotech, Brisbane, Qld., Australia
C-Bio, Brisbane, Qld., Australia
Virax Holdings Ltd, Victoria, Australia

Key Publications

Chang DC, Liu WJ, Anraku I, Clark DC, Pollitt CC, Suhrbier A, Hall RA, Khromykh AA.Single-round infectious particles enhance immunogenicity of a DNA vaccine against West Nile virus.Nat Biotechnol. 2008 Apr 20; [Epub ahead of print] [pubmed abstract]

Elliott SL, Suhrbier A, Miles JJ, Lawrence G, Pye SJ, Le TT, Rosenstengel A, Nguyen T, Allworth A, Burrows SR, Cox J, Pye D, Moss DJ, Bharadwaj M. Phase I trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis. J Virol. 2008 Feb;82(3):1448-57. [pubmed abstract]

Challacombe JM, Suhrbier A, Parsons PG, Jones B, Hampson P, Kavanagh D, Rainger GE, Morris M, Lord JM, Hoang-Le D,Le TTT, and Ogbourne SM. Neutrophils are a key component of the anti-tumor efficacy of topical chemotherapy with 3-ingenyl angelate. J Immunol 177(11):8123-32. [pubmed abstract]

Darnell GA, Schroder WA, Gardner J, Harrich D, Yu H, Antalis TA, Medcalf RL, Warrilow D and Suhrbier A. 2006. SerpinB2 is an inducible host factor involved in enhancing HIV-1 transcription and replication. J Biol Chem 281(42):31348-58. [pubmed abstract]

Pijlman GP, Suhrbier A, Khromykh AA. 2006. Kunjin virus replicons: an RNA-based, non-cytopathic viral vector system for protein production, vaccine and gene therapy applications. Expert Opin Biol Ther 6(2):135-45. [pubmed abstract]

Johnson BJ, Le TT, Dobbin CA, Banovic T, Howard CB, Flores Fde M, Vanags D, Naylor DJ, Hill GR, Shurbier A. Heat shock protein 10 inhibits lipopolysaccharide-induced inflammatory mediator production. J Biol Chem. 2005 Feb 11;280(6):4037-47. [pubmed abstract]

Ogbourne SM, Suhrbier A, Jones B, Cozzi SJ, Boyle GM, Morris M, McAlpine D, Johns J, Scott TM, Sutherland KP, Gardner JM, Le TT, Lenarczyk A, Aylward JH, Parsons PG. Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res. 2004 Apr 15;64(8):2833-9. [pubmed abstract]

Suhrbier A, La Linn M. Suppression of antiviral responses by antibody-dependent enhancement of macrophage infection. Trends Immunol. 2003 Apr; 24(4): 165-8 [pubmed abstract]

Darnell GA, Antalis TM, Johnstone RW, Stringer BW, Ogbourne SM, Harrich D, Suhrbier A. Inhibition of retinoblastoma protein degradation by interaction with the serpin plasminogen activator inhibitor 2 via a novel consensus motif. Mol Cell Biol. 2003 Sep; 23(18): 6520-32 [pubmed abstract]

Harvey TJ, Anraku I, Linedale R, Harrich D, Mackenzie J, Suhrbier A, Khromykh AA. Kunjin virus replicon vectors for human immunodeficiency virus vaccine development. J Virol. 2003 Jul; 77(14): 7796-803 [pubmed abstract]

Woodberry T, Gardner J, Elliott SL, Leyrer S, Purdie DM, Chaplin P, Suhrbier A. Prime boost vaccination strategies: CD8 T cell numbers, protection, and Th1 bias. J Immunol. 2003 Mar 1; 170(5): 2599-604 [pubmed abstract]

A. D. Mylonas, A. M. Brown, T. L. Carthew, B. McGrath, D. M. Purdie, N. Pandeya, P. C. Vecchio, L. G. Collins, I. D. Gardner, F. J. DeLooze, E. Reymond, A. Suhrbier. 2002. The natural history of Ross River virus induced epidemic polyarthritis. Med J Aust. 177; 356-360 [pubmed abstract]

May La Linn, J. Gardner, D. Warrilow, G. A. Darnell, C. R. McMahon, I. Field, A. D. Hyatt, R. W. Slade, A. Suhrbier 2001. An arbovirus of marine mammals; a new alphavirus isolated from the elephant seal louse, Lepidophthirus macrorhini. J. Virol. 75: 4103-9 [pubmed abstract]

A.D. Hislop, M.F. Good, L. Mateo, J. Gardner, M.H. Gatei, R.C.W. Daniel, B.V. Meyers, M.F. Lavin and A. Suhrbier. 1998. Vaccine-induced cytotoxic T lymphocytes protect against retroviral challenge. Nature Medicine 4 (10);1193 - 1196 [pubmed abstract]

T.M. Antalis, May La Linn, K. Donnan, L. Mateo, J. Gardner, J.L. Dickinson, K. Buttigieg and A. Suhrbier. 1998. The serpin Plasminogen Activation Inhibitor Type-2 protects against viral cytopathic effects by constitutive interferon ab priming. J. Exp. Med. 187:1799-1811 [pubmed abstract]

S. Thomson, R. Khanna, J. Gardner, S. R. Burrows, B. Coupar, D. J. Moss, A. Suhrbier. 1995. Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T cells: Implications for vaccine design. PNAS USA 92; 5845-5849 [pubmed abstract]

Patents

PCT/AU2005/000041
Chaperonin 10 modulation of cytokine and chemokine secretion.
Inventors: B. Johnson, A. Suhrbier.
Applicant: CBio Ltd.
Commercialised - YES

PCT/AU02/01598
Flavivirus Vaccine System
Inventors - A.A. Khromykh, A. Suhrbier
Applicant - Queensland Department of Health
Commercialised - YES

PCT/AU01/00678/79 & 80
Therapeutic agents - I, II, III
Inventors - J.H. Aylward, P.G. Parsons, A. Suhrbier, K.A. Turner
Applicant - Peplin Biotech Ltd.
Commercialised - YES

WO0123577
Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis b virus sequences
Inventors - P. Langlade-Demoyen, M.L. Michel, H. Firat, F. Lemonnier, A. Suhrbier
Applicant - Institute Pasteur, Paris, France
Commercialised - NO

WO004863024/8/2000
Immunogenic Complexes and methods relating Thereto II
Inventors - D. Drane, J. Cox, A. Suhrbier
Applicant - CSL Ltd.
Commercialised - YES

WO9603144/EP076996308/02/1996
Polyepitope vaccines.
Inventors - A. Suhrbier, S. Thomson, R. Khanna, S.R. Burrows, B. Coupar, D.J. Moss
Applicant - CRC for Vaccine Technology
Commercialised - YES

WO9524925/US586945309/02/1999
Cytotoxic T-cell epitopes
Inventors - D.J. Moss, S. Burrows, R. Khanna, B. Kerr, A. Suhrbier
Applicant - CRC for Vaccine Technology
Commercialised - YES