- The new Epstein-Barr virus (EBV) vaccine targets multiple parts of the virus.
- It induces strong, long-lasting immunity in two vital arms of the immune system.
- The results in laboratory models support the progression to human clinical trials.
Why do we need an EBV vaccine?
Infection with EBV has long been recognised as a risk factor for multiple sclerosis (MS).
A recent study of over 10 million US military personnel provided the strongest evidence yet that EBV is necessary, but not sufficient on its own, for the development of MS.
EBV infection can occur without symptoms, particularly during childhood, but is responsible for glandular fever (infectious mononucleosis) in some individuals. It is also a major risk factor for certain cancers.
An effective EBV vaccine could play an important role in blocking the development of autoimmune diseases such as MS, as well as EBV-associated cancers.
The new study by researchers at QIMR Berghofer, published in the prestigious journal Nature Communications, describes a new EBV vaccine that is highly effective in laboratory models.
Understanding the phases of EBV infection
EBV typically infects humans via the throat and then enters an inactive or dormant phase.
Periodic reactivation of the virus releases infectious viral particles, remaining a lifelong presence, with ~95% of adults infected worldwide.
EBV produces various proteins during the different stages of infection.
Parts of these proteins are recognised by the human immune system to initiate killing of the virus in the body.
Progress towards an EBV vaccine
There is no medical intervention currently licensed for the prevention or treatment of EBV infection.
However, two Phase I clinical trials are currently underway, testing safety and the immune response induced by two EBV vaccines. These are an mRNA vaccine (Moderna) and a nanoparticle vaccine (NIH). Additionally, another nanoparticle vaccine is being studied.
Two of these vaccines are based on a viral protein called gp350, which stimulates a strong antibody response against the virus.
Strong antibody responses (produced by immune “B cells”) are an important first-line defence against acute infection with EBV.
A previous EBV vaccine based on gp350 successfully prevented the development of glandular fever in Phase 2 clinical trials, although it was not able to prevent infection.
Ongoing research has highlighted the importance of a second arm of the immune system, dependent on immune “T cells”, in long-term effective control of this virus.
What did the Australian researchers do?
The Australian team used several strategic design elements to create a more effective EBV vaccine.
Firstly, they used components from several EBV viral proteins to achieve wide immune coverage across various stages of EBV infection. This approach also aimed to stimulate both arms of the immune system.
Whilst they used gp350 to stimulate a strong antibody response, the team genetically engineered a protein called “EBVpoly” to activate T cells.
Composed of 20 protein fragments from eight distinct EBV proteins, “EBVpoly” was engineered into a single molecule resembling “beads on a string.”
The different EBV components are preferentially recognised by the immune systems of different ethnic groups, enhancing the vaccine’s global potential.
Finally, an adjuvant, a vaccine ingredient that helps boost immune responses, was incorporated, with a specific focus on directing the vaccine to the lymph nodes – a critical site for immune response activation.
What did the researchers find?
The new EBV vaccine induced strong responses against EBV in both arms of the immune system.
The vaccine was effectively targeted to the lymph nodes by the adjuvant, and immune responses in the lymph nodes were enhanced.
Both arms of the immune response to the vaccine were long-lasting, and detected beyond six months.
Furthermore, the vaccine effectively prevented the spread of an EBV-related cancer in a laboratory model.
What does this mean for people with MS?
This study represents a major advance towards an effective EBV vaccine for human use.
MS Australia is delighted to have supported the EBV MS Research Program at QIMR Berghofer in its infancy in partnership with MS Queensland, and congratulates them on this significant achievement.
Given that EBV is a major risk factor for developing MS , an effective vaccine that prevents EBV infection in humans may also have an important role in preventing the onset of MS.
Although the extent of EBV’s involvement in ongoing disease activity in MS remains unclear, the pursuit of therapeutic vaccines to treat MS is an area of active investigation.
