EPSTEIN-BARR VIRUS

Kiss this disease good-bye!

What is Epstein-Barr Virus?

Epstein-Barr Virus or EBV, is a common infection that affects more than 90% of the world's
population. It is one of the herpes virus group, sharing the ability to remain latent or dormant
within the body and reactivate when the immune system is compromised or suppressed

What makes EBV different from other viruses?

What makes EBV unusual, and what is not commonly known, is that EBV is more than just a
'kissing disease'. EBV causes different diseases depending on which part of the world you live in,
unlike any other herpes virus.
In industrialised nations, EBV causes a debilitating but relatively harmless infection; a bout of
glandular fever is almost expected in adolescents, with the effect of disruption to studies for
months.
In developing countries, primary EBV infection mostly occurs in childhood and is generally without
symptoms, resulting in life-long latency and early development of immunity. 80% of people carry
latent EBV; a healthy immune system normally holds the virus in check, but the virus may be a
hazard to those with a compromised immune system such as in organ transplant patients or those
with HIV.
In Africa and Papua New Guinea, EBV is strongly associated with a number of human cancers
including Burkitt's Lymphoma - the most common childhood cancer in central Africa and one of the
most aggressive of all human cancers.
Further, in China and eastern Asia, nasopharyngeal carcinoma (NPC) is proving to display strong
associations with EBV; and post-transplant proliferative disease (PTLD) in transplant recipients and
certain types of Hodgkin's Disease (HD) in many developed countries is related to EBV.

How does the virus spread?

EBV is spread mainly through the transfer of saliva between individuals, hence the name the
'kissing disease'. People who contract EBV retain it for life, although it does not always cause
symptoms.
Most people are infected with the virus in childhood, probably by their mothers, and are usually not
noticeably affected. However, people infected for the first time during adolescence (10-20% of
people in developed countries) have a 50% chance of contracting glandular fever.

How does the virus work?

Research has shown that EBV appears only able to infect two major types of cells:
i. the outer cells of the salivary gland - enabling it to spread to new hosts; and
ii. white blood cells or B lymphocytes - enabling it to spread within the current host body.
If the immune system is suppressed or compromised, more severe disease states have a greater
chance of occurring as the body is unable to control the proliferation of the virus. These individuals
are at greater risk of developing one of the cancers associated with EBV.

Is there an EBV Vaccine?

No. As for most viruses, the best defense is through vaccination. Due to the complex nature of
EBV, there have not been any vaccines on the market able to provide adequate protection.

What is the strategy of the EBV Vaccine Project Team?

Based at the Queensland Institute of Medical Research, the CRC-VT's EBV team has identified a
number of key components within the proteins of the virus that enable the body to effectively
control the disease. These have been copied synthetically and used to create a prototype vaccine.
Using the Centre's PolytopeTM technology the vaccine formulation has been tested in human cells
and mice. It has demonstrated consistent activation of an appropriate immune response and shows
the potential to form the basis for a successful vaccine against glandular fever or post-transplant
lymphoproliferative disease.

What are the benefits of an EBV vaccine?

Aside from the life-saving and quality of life benefits associated with an EBV vaccine, there are
additional benefits that would affect the wider community.
The cost of a vaccine may be off-set by long-term benefits from decreased health care costs and
fewer days of lost productivity. A vaccine against infectious mononucleosis may also contribute to
the delayed onset of EBV, decreasing the incidence of diseases such as Burkitt's lymphoma insert
hyperlink to glossary in young African children.

How would a vaccine help transplant patients?

A donor organ may harbour latent EBV. When a patient is given immunosuppressive drugs to
prevent organ rejection, chronically infected cells in the organ can become cancerous and form
tumours.
The introduction of an EBV vaccine of this type would allow transplant patients to be immunised
before they receive an organ transplant. A primary requirement of such a vaccine is the activation
of a strong T-cell response (immune response associated with other types of T cells) to eliminate
hidden EBV-infected cells.
Given the enormous investment in any individual transplant, a vaccine that would allow recipients
to be immunised before receiving a donor organ and protect against the development of
lymphomas would potentially have a very wide market.

Would this vaccine protect against EBV-associated cancers?

The CRC-VT EBV Team is investigating the concept that a modification of the vaccine to glandular
fever may also be used to protect against nasopharyngeal carcinoma and Hodgkin's Disease. Such
a vaccine would boost the immune response to the parts of the virus that are displayed on the
surface of malignant cells.

Who is involved in this project?

This project involves collaboration between CRC-VT partners, QIMR and CSL Limited. The EBV
team is searching to enhance commercial partnerships on this exciting project, to further progress
the development of an EBV vaccine.

For links to more information on the EBV Project:

u See Research Program:
http://www.crc-vt.qimr.edu.au/research/passiveimmunity/ebv.html

u See Media Release: Cooperative Research a Fast Track to Development

http://www.crc-vt.qimr.edu.au/media/releases/ebv.rtf

u See Queensland Institute of Medical Research:

http://www.qimr.edu.au/research/labs/denism/index.html

u See Vaccine Solutions:

http://www.vaccine-solutions.com.au/tech_ebv.html

u See our Annual Report 2002/03, page 37:

http://www.crc-vt.qimr.edu.au/corporate/report/ar0203.pdf

Queensland Institute of Medical Research, The Bancroft Centre, 300 Herston Road, PO Royal Brisbane Hospital QLD 4029, Australia
Telephone 61 7 3362 0430 Facsimile 61 7 3362 0105 Email CRCVT@qimr.edu.au
QIMR, CSL Limited, ARCBS, The University of Melbourne, WEHI, CSIRO, Monash University, La Trobe University