Previous EBV Projects funded by MS Australia

This project investigated whether Epstein-Barr virus (EBV) may be the cause of MS through studying the effect of autologous haematopoietic stem cell transplant (AHSCT), a highly effective MS therapy, on an individual’s immune response to EBV. 

The project investigated whether EBV reactivates after AHSCT, as has been suggested by one prior study. The project determined whether people with MS who have undergone AHSCT who develop a new immune system capable of rapidly controlling EBV are more likely to have a sustained response to treatment. 

This research has direct implications on  

1. Understanding of the role EBV plays in causing MS.
2. Treatment of people with MS.  

This knowledge will help clinicians alter the way in which AHSCT is performed (e.g., with anti-viral or cellular therapies) to better control EBV if it is shown to be relevant to disease remission. 

A remarkable amount of evidence has shown that certain white blood cells, called B cells, are involved in the development and progression of MS as well as MS relapses. B cells are also the target of Epstein Barr Virus (EBV). EBV infects about ~90% of the population and is thought to infect 100% of people with MS, and is strongly connected with the risk of developing MS. However, the mechanisms through which EBV contributes to MS are largely unknown and there are currently no effective antiviral medications for this virus.

Following an infection, EBV remains in the body, hiding out in B cells but largely controlled by the body. The presence of EBV in B cells causes them to grow, potentially contributing to the development and progression of MS.

This project aims to test the effects of targeting three important EBV viral genes to reduce the amount of EBV in B cells as well as reducing the virus’ ability to continue hijacking B cells leading to their growth.

Targeting the most effective viral genes in B cells could lead to new ways to limit EBV in people with MS, and better control of the B cells that are known to contribute to MS.

MS is a condition where a person's immune system mistakenly attacks the fatty, protective layer, called myelin, around nerves in the brain and spinal cord. The resulting damage can cause a range of symptoms and disability. 

Why the immune system mistakenly attacks the body is unknown. Dr Trend and her team investigated whether there are any intrinsic differences between immune cell functions in people with MS compared to people without MS. She did this by examining immune cells from the blood of people with MS and those without MS.  

The team examined whether cells from people with MS are primed to give a more inflammatory response when exposed to antibodies (small proteins produced by the immune system that bind foreign substances that invade the body and activate the immune system) compared to those who do not have MS.  

The team also investigated whether people at an early MS stage have the same responses to antibodies as those with more advanced disease. 

Epstein Barr Virus (EBV) has long been implicated in the development of MS. Professor Sanjay Swaminathan and his team have recently found evidence that many genes that are associated with MS also are involved in the body’s ability to fight off an EBV infection.

This might go some way to explain the link between MS and EBV. By finding out how EBV interacts with these genes may help us block an EBV infection and improve someone’s MS. Specifically, this group has found that one protein from the virus hijacks some of the human genes in the immune cells they infect.

Research has shown a link between the development of MS and infection with Epstein–Barr virus (EBV). The majority of healthy adults are infected with EBV, which infects a subset of white blood cells called B cells. Once a person becomes infected with EBV, they carry the virus in their B cells for the rest of their life. In most cases, the virus is kept in check by another type of white blood cell, called T cells.  T cells can recognise and kill virus-infected cells. Previous studies by Professor Pender’s research group have shown that people with MS have a reduced number of T cells capable of killing EBV-infected B cells, compared with healthy people. We have proposed that this allows EBV-infected B cells to accumulate in the central nervous system, where they promote an immune attack on the nervous system, leading to the development of MS. This clinical trial is evaluating the safety and feasibility of using a patient’s own EBV-specific T cells to treat progressive MS.

In total, ten patients (five with primary progressive MS and five with secondary progressive MS) will be recruited from Professor Pender’s MS clinic at the Royal Brisbane and Women’s Hospital. Once a patient provides their consent to participate in the project, a range of assessments are done to determine if they meet the eligibility criteria of the trial. After eligibility is confirmed, a blood sample is collected from the participant and the white blood cells are isolated so that the EBV-specific T cells can be grown in the laboratory.  Once these cells have multiplied, they are frozen at four different doses, ready for intravenous infusion back into the patient. We are administering four increasing doses to reduce the risk of aggravating central nervous system inflammation.

Safety and tolerability of this immunotherapy will be measured using clinical examination, a battery of neurological assessments, blood testing, monitoring of vital signs, magnetic resonance imaging of the brain and spinal cord, cerebrospinal fluid analysis, and assessing changes in neurological symptoms.

A large body of evidence indicates that infection with Epstein-Barr virus (EBV) has a role in MS. Prof Pender has shown that people with MS have decreased immunity to EBV which could allow the accumulation of EBV-infected cells in the brain and the subsequent development of MS. This project will look at specific immune cells involved with the response to EBV infection known as CD8 T cells.

The first stage will characterise the CD8 T cell response to EBV-infected cells and investigate the role of other factors such as genetics in the altered EBV response in MS. This will hopefully lead to knowledge regarding the cause of this lower immunity against EBV in people with MS. The second stage will determine whether the alterations in the EBV immune response increases as the duration of MS increases. The final stage will determine the relationship between the CD8 T cells and other factors related to the level of EBV infection.

This project will investigate the consequence of impaired immunity to MS and will lay the foundation for preventing and curing MS by controlling EBV infection.