Kissing the Epstein-Barr virus goodbye?
Key text
This topic is sponsored by the Cooperative Research Centre for Vaccine Technology.
Glandular fever, a common disease in teenagers, is caused by the Epstein-Barr virus. Australian research on the Epstein-Barr virus has led to a glandular fever vaccine being trialled.
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Related publication: The Science of Immunisation: Questions and Answers
Like most good things in life, kissing can be hazardous to your health. Pucker up to someone and you risk infection with the Epstein-Barr virus, which causes glandular fever and other nasty diseases.
But we might not have to give up kissing just yet. A vaccine currently under development in Australian laboratories could help limit the dangers posed by this sometimes deadly virus.
How was the virus discovered?
In 1961, a surgeon working in Uganda, Denis Burkitt, presented the results of his research to staff at the Middlesex Hospital Medical School in Britain. He reported that the incidence of a certain tumour in African children had a geographic distribution corresponding to rainfall and temperature patterns.
The disease, which affects about 8 in every 100,000 children in parts of Africa and Papua New Guinea, quickly became known as Burkitt’s lymphoma. The influence of climate on its incidence seemed to suggest that some biological factor was involved. Three researchers, M.A. Epstein, Y.M. Barr and B.G. Achong, immediately began looking for possible cancer-causing viruses in samples of the tumour sent from Uganda to Britain.
In 1964, they identified the culprit using an electron microscope: a previously unknown member of the herpes family of viruses. Epstein and Barr were awarded the dubious honour of having the pathogen named after them.
What diseases does the virus cause?
The Epstein-Barr virus is thought to be responsible for a number of diseases in addition to glandular fever (otherwise known as infectious mononucleosis) and Burkitt’s lymphoma. One of these is nasopharyngeal carcinoma: this is a tumour of the nasal passages and throat which affects up to 2 per cent of people in southern China and also occurs in Southeast Asia, northern Africa and among Arctic peoples. It has been proposed as a possible cause of Hodgkin’s disease (a type of cancer affecting cells of lymph nodes).
Diseases caused by the virus are particularly common among people with reduced immunity. For example, the virus is associated with ‘post-transplant lymphoproliferative disease’, a tumour often found in organ transplant patients. The immune systems of such patients are usually suppressed artificially by drug therapy to help prevent the body from rejecting the new organ.
AIDS sufferers, who also have reduced immunity, commonly suffer from ‘oral hairy leukoplakia’, a condition involving considerable replication of the Epstein-Barr virus in cells along the edge of the tongue. And researchers have suggested that the high incidence of malaria in countries where Burkitt’s lymphoma is prevalent may also play a role in the disease by suppressing the body’s immune system.
Scientists don’t know why the virus causes a relatively mild disease like glandular fever in some people and malignant tumours in others. Some evidence suggests that genetic factors may play a role.
How is the virus spread?
People infected with the Epstein-Barr virus will retain it for life, but it may not make them sick. In fact, the virus infects almost everyone in developing countries and more than 80 per cent of people in developed countries. It is spread mainly via the transfer of saliva between individuals, which is the reason that glandular fever has been dubbed the ‘kissing disease’.
Most people are infected with the virus during childhood, probably by their mothers, and are usually not noticeably affected. On the other hand, people infected for the first time during or after adolescence (10–20 per cent of people living in developed countries) have a 50 per cent chance of contracting glandular fever.
How does the virus work?
The Epstein-Barr virus infects white blood cells known as B lymphocytes (B-cells). Infection with the Epstein-Barr virus develops first in the salivary gland. Large amounts of the virus are released in the saliva, enabling it to spread from one person to another.
Infection of B-cells with the virus causes them to proliferate. This proliferation is controlled by the immune system; if the correct immune response does not develop, individuals are at risk of developing a form of cancer.
The response of the body’s immune system
The Epstein-Barr virus produces about 100 different antigens (large protein molecules) during the active phase of the viral cycle. In contrast, only about 10 antigens are produced during the inactive phase: these include the Epstein-Barr virus nuclear antigens (EBNAs 1–6), and the latent membrane proteins (LMPs 1–3).
The heroes in the battle against the Epstein-Barr virus are white blood cells known as cytotoxic T lymphocytes (T-cells) (Box 1: Acquired immunity: Antibodies and T lymphocytes). These cells combine with certain antigens produced by the virus and kill cells that harbour it. Unfortunately, when the virus is associated with Burkitt’s lymphoma and nasopharyngeal carcinoma it appears to produce only one antigen – EBNA1. T-cells are unable to combine with this particular antigen and will not attack the infected cell. In such circumstances, the virus is able to ‘hide’ from the body’s immune system.
The search for a vaccine
As with most viruses, the best chance of defence against Epstein-Barr is vaccination. Yet a vaccine has been elusive, partly because the virus is so good at hiding.
To prevent Burkitt’s lymphoma or nasopharyngeal carcinoma, a vaccine would need to provide 100 per cent immunity or be capable of establishing a T-cell population that recognises EBNA1. Both tasks are extremely difficult. It may be possible, though, to produce a vaccine against glandular fever and post-transplant lymphoproliferative disease, since both produce antigens that are recognised by T-cells.
For several years, Australian scientists have been engaged on a project to produce such a vaccine. Based at the Queensland Institute of Medical Research within the Cooperative Research Centre for Vaccine Technology, they have conducted a trial with a prototype vaccine using human volunteers (Box 2: The future of vaccines).
One of the first steps in the development of the vaccine was to define the antigens of the virus that are important in the immune control of it. Antigens stimulate the manufacture of T-cells: if they – or their most important parts – could be introduced artificially to an individual, then the immune system might be ‘tricked’ into producing T-cells that would recognise the real antigen should infection occur.
The researchers were able to produce a peptide identical to part of the Epstein-Barr virus antigen EBNA3. This peptide formed the basis of the vaccine: by injecting it into patients, researchers hoped to ‘arm’ the body with T-cells in readiness for an invasion of the real disease.
The trial has been completed and scientists are now confident that the vaccine does not have any harmful effects on patients. Recipients didn't develop infectious mononucleosis, but being a small trial the vaccine's effectiveness in preventing disease could not be accurately assessed.
Another vaccine developed in Europe that is based on a surface protein of the virus, gp350, has successfully reduced Epstein-Barr infections in an 18-month trial. Attempts are also being made to grow and expand T-cells in the laboratory to help cure various forms of Epstein-Barr virus-induced cancers. This approach should be particularly useful for treating patients suffering from post-transplant lymphoproliferative disease.
Boxes
1. Acquired immunity: Antibodies and T lymphocytes
2. The future of vaccines
Related Academy material
The Science of Immunisation: Questions and Answers
This publication aims to address confusion created by contradictory
information in the public domain. It sets out to explain the current
situation in immunisation science, including where there is scientific consensus and where uncertainties exist. The Science of Immunisation: Questions and Answers was prepared by a Working Group and Oversight Committee made up of
Academy Fellows and other Australian scientists with internationally
recognised expertise in immunology.
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Interviews with Australian Scientists
Professor Frank Fenner (Microbiology and virology)
Professor Ian Frazer (Immunology)
Professor Gordon Ada (Microbiology)
Sir Gustav Nossal (Immunology)
Updated November 2012.