Epstein-Barr Virus Biology

Denis Moss Patents
Staff
Funding
Collaborators
Key Recent Publications
Go to Glossary

Lab Head: Prof Denis Moss
denisM@qimr.edu.au

Epstein-Barr virus (EBV) causes glandular fever and is associated with a number of cancers, including lymphomas in transplant patients and a relatively common form of cancer in the back of the nose called nasopharyngeal carcinoma. The EBV Biology laboratory has a broad interest in all aspects of the biology of the virus and is closely linked with other EBV laboratories within the Division.

Research Highlights

Definition of the components of the immune system that protect from EBV infection. In particular this laboratory has established the principle that "killer T cells" (CTL) are the main immune parameter responsible for controlling the long-term latent EBV infection that all immune individuals carry for life.
Successfully treated patients with post-transplant lymphoproliferative disease by adoptively transferring patient "killer T cells" following expansion in the test tube.
" Began a trial with nasopharyngeal carcinoma patients using adoptive immunotherapy following peptide stimulation in the test tube
" Collaborated in a program designed to formulate vaccine preparation for the treatment of EBV-related diseases

Nasopharyngeal carcinoma (NPC)

NPC is a form of cancer which occurs mostly in the back of the nose or neck, and is most common in males from SE Asia. Common risk factors for the development of NPC include:

The EBV Biology laboratory is:

Monitoring the immune response to EBV in NPC patients to aid in the diagnosis and treatment of NPC tumours
Producing an NPC vaccine
Attempting to grow EBV immune cells in the test tube to treat NPC patients. This is complicated as the NPC tumour cells express few EBV proteins, making it difficult for the immune system to recognise and destroy the tumour cells.

Patents

International Patent on EBV cytotoxic T cell epitopes (Patent number WO9524925)
This patent includes a worldwide patent on 12 EBV CTL epitopes and proposed to be used in any future vaccine designed to control EBV-associated diseases.
Inventors: DJ Moss, SR Burrows, R Khanna, J Burrows, A Suhrbier
PCT/AU95/00461
Granted in USA, Australia, New Zealand, South Africa

International Patent on EBV polyepitope (Patent number WO9603144)
This patent includes a new design for CTL based vaccines aimed at preventing multiple diseases with a single vaccine.
Inventors: A Suhrbier, S Thomson, R Khanna, SR Burrows, DJ Moss
PCT/AU95/00140
Granted in New Zealand, Australia, South Africa.

International Patent on EBV cytotoxic T cell epitopes (Patent number WO974544)
This patent includes a worldwide patent on 6 EBV CTL epitopes and proposed to be used in any future vaccine designed to control EBV-associated diseases.
Inventors: R Khanna, B Kerr, IS Misko, SR Burrows, DJ Moss
PCT/AU97/00328
Granted in New Zealand, Australia, South Africa.

Staff

Labhead:	Professor Denis Moss
Research Officer:	Dr Viviana Lutzky
Research Assistants:	Pauline Crooks Monika Corban Michelle Martinez Leanne Morrison Simone Cross
Clinical Trial Coordinator:	Natasha Stevens
Masters Student (clinical trainee):	Mark Smith

To see staff contact details, please type name below and hit Enter

Funding

The National Health and Medical Research Council - Program Grant
The Queensland Cancer Fund
Cell-based Therapy Grant from Atlantic Philanthropies(QIMR)
Rodney Williams Memorial Fund

Collaborators

Prof. William Coman, Princess Alexandra Hospital, UQ.
Accessing archival material to determine the presence of EBV DNA in head and neck malignancies.
Dr. Benedict Panizza, Greenslopes Private Hospital, Prof. William Coman, Princess Alexandra Hospital, UQ, Dr. David Chin, QIMR & Princess Alexandra Hospital, UQ.
Studying EBV specific CTL response in patients with Nasopharyngeal Carcinoma for potential immunotherapy development.
Dr John Nicolls, Hong Kong University
Collaborating on a project to treat NPC patients by adoptive immunotherapy

Key Publications

White CA, Thomson SA, Cooper L, Van-Endert PM, Tampe R, Coupar B, Qui L, Parsons PG, MOSS DJ and Khanna R.(1998) Constitutive transduction of peptide transporter and HLA genes restores antigen processing function and cytotoxic T cell-mediated immune recognition of human melanoma cells. Int. J. Cancer 75: 590-595. [pubmed abstract]

Khanna R, Busson P, Burrows SR, Raffoux C, MOSS DJ, Nicholls J and Cooper L. (1998). Molecular characterisation of antigen processing function in nasopharyngeal carcinoma (NPC): Evidence for efficient presentation of Epstein-Barr virus cytotoxic T cell epitopes by NPC cells. Cancer Research 58:310-314.[pubmed abstract]

Thomson SA, Burrows SR, Misko I, MOSS DJ, Coupar B and Khanna R. (1998). Targeting a polyepitope protein incorporating multiple class II-restricted viral epitopes to the secretory/endocytic pathway facilitates immune recognition by CD4+ cytotoxic T lymphocytes: A novel approach to vaccine design. J. Virol. 73:2246-2252 [free full text article]

Thomson SA, Sherritt MA, Medveczky J, Elliott SL, MOSS DJ, Fernando GJP, Brown LE and Suhrbier A. (1998). Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination. J. Immunol. 160:1717-1723. [free full text article]

Peh CA, Burrows SR, Barnden M, Khanna R, Cresswell P, MOSS DJ and McCluskey J. 1998. HLA B27-restricted antigen presentation in the absence of tapasin reveals polymorphism in generic mechanisms of HLA class I-peptide loading. Immunity 8:531-542. [pdf]

Silins SL, Cross SM, Krauer K, MOSS DJ, Schmidt CW and Misko IS. (1998). Functional link for T Cell expansions in healthy adults: evidence that persistent Epstein-Barr virus infection causes major TcR perturbations in the peripheral blood repertoire. J. Clin. Invest. 15:1551-1558. [free full text article]

Khanna R, Bell S, Sherritt M, Burrows SR, Galbraith A, Rafter L, Falk MC, Douglass J, Williams T, Elliott SL and MOSS DJ. (1999). Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in a solid organ transplant patient with post transplant lymphoproliferative disease. Proc. Nat. Acad. Sci. U.S.A. 96,10391-10396. [free full text article]

Burrows SR, Khanna R and MOSS DJ. (1999). Direct alloreactivity by human cytotoxic T lymphocytes can be inhibited by altered peptide ligand antagonism. Blood 93:1020-1024. [free full text article]

Burrows SR, Khanna R, Silins S and MOSS DJ. (1999). The influence of anti-viral T cell responses on the alloreactive repertoire. Immunol. Today 20:203-207. [pubmed abstract]

Faulkner GC, Burrows SR, Khanna R, MOSS DJ, Bird AG and Crawford DH. (1999). X-linked agammaglobulinaemia patients are not infected with Epstein-Barr virus: implications for the biology of the virus. J. Virol. 73:1555-1564. [free full text article]

Bharadwaj M, Parsons PG and MOSS DJ. (2000). Cost efficient quantification of enzyme-linked immunospot (ELISPOT). Biotechniques 30:36-38.

MOSS DJ, Burrows SR, Silins SL, Misko I and Khanna R. (2000). The Immunology of Epstein-Barr Virus Infection. Philos. Trans. Royal Society 356:475-488.[pubmed abstract]

Bharadwaj M, Burrows SR, Burrows JM, MOSS DJ, Catalina M and Khanna R. (2001). Longitudinal dynamics of antigen-specific CD8+ cytotoxic T lymphocytes following primary EBV infection. Blood 98: 2588-2589.[free full text article]

Bharadwaj M, Sherritt M, Khanna R, MOSS, DJ. (2001). Contrasting Epstein Barr virus specific cytotoxic T cell responses to HLA A2 restricted epitopes in humans and HLA transgenic mice: implications for vaccine design. Vaccine 19:3769-3777. [pubmed abstract]

Silins SL, Sherritt MA, Silleri JM, Cross SM, Elliott SL, Bharadwaj M, Le TTT, Morrison LE, Khanna R, MOSS DJ, Suhrbier AS, Misko IS. (2001). Asymptomatic primary EBV infection occurs in the absence of blood T cell repertoire perturbations despite high levels of systemic viral load. Blood 15:3739-3744. [free full text article]

Bharadwaj M, Moss DJ. Epstein-Barr virus vaccine: a cytotoxic T-cell-based approach. Expert Review of Vaccines 2002 Dec;1(4):467-76. [pubmed abstract]

Sherritt MA, Bharadwaj M, Burrows JM, Morrison LE, Elliott SL, Davis JE, Kear LM, Slaughter RE, Bell SC, Galbraith AJ, Khanna R, Moss DJ. Reconstitution of the latent T lymphocyte response to Epstein-Barr virus is coincident with long-term recovery from post transplant lymphoma following adoptive immunotherapy. Transplantation 75(9): 1556-1560 (2003). [pubmed abstract]

Davis, J. E., Sherritt, M. A., Bharadwaj, M., Morrison, L.E., Elliott, S. L. Kear, L.M., Maddicks-Law, J., Kotsimbos, T., Gill, D., Malouf, M., Falk, M.., Khanna, R. and Moss, D. J. (2004). Determining virological, serological and immunological parameters of EBV infection in the development of PTLD. Intern.Immunol.16:983-989 [pubmed abstract]

Tellam, J., Connolly, G., Green, K., Miles, J., Moss, D. J., Burrows, S. R. and Khanna, R., (2004) Endogenous processing of CD8+ T cells epitopes from Epstein-Barr virus encoded nuclear antigen 1. J. Exp. Med.199:1421-1431. [pubmed abstract]

Khanna, R., Moss, D.J and Gandhi, M., and. (2005). Technology insight: applications of emerging immunotherapeutic strategies for Epstein-Barr virus-associated malignancies. Nature Clinical Practice Oncology. 2: 138-149. [pubmed abstract]

Tscharke, DC., Woo, WP., Sakala, IG., Sidney J., Sette, J., Moss, DJ., Bennink, JR., Karupiah G., Yewdell1,JW.(2006) Poxvirus CD8+ T cell determinants and cross-reactivity in BALB/c mice J Virol 80, 6318-6323. [pubmed abstract]