9 August 2023
A cutting-edge vaccine candidate developed by QIMR Berghofer has achieved potent and durable immune protection against Epstein–Barr virus (EBV) in pre-clinical models, a breakthrough that could prevent the type of severe viral infection known to be a leading cause of several diseases including multiple sclerosis and various cancers.
The early findings have been published in the prestigious journal Nature Communications.
EBV is a member of the herpes virus family. It is carried by around 95 percent of the population. Most of us are unaware of the virus lying dormant in our bodies. Infection usually occurs in early childhood causing very mild symptoms.
However, in some people EBV can lead to severe illness. Those who catch the virus later in life as teens or young adults can develop infectious mononucleosis, or glandular fever, which is a major risk factor for a number of diseases and cancers.
A landmark study published last year established that EBV is likely the leading cause of multiple sclerosis (MS), an incurable neurological disease where the body’s own immune system mistakenly attacks the protective coating around the nerves causing debilitating symptoms.
Preventing EBV-associated infectious mononucleosis could potentially lead to the prevention of MS in the future, but despite worldwide research efforts there is still no vaccine available.
The new QIMR Berghofer vaccine candidate potentially offers a breakthrough approach that combines two powerful arms of the immune system to target the virus in both acute and latent infection.
Although further work is needed, the vaccine is potentially complementary to ATA188, a cell-based therapy that targets the root cause of multiple sclerosis and is currently in advanced Phase 2 clinical development by Atara Biotherapeutics.
QIMR Berghofer’s Professor Rajiv Khanna AO, who led the development of the vaccine and is also collaborating with Atara on ATA188, said the study shows the vaccine could provide effective, long-term protection against EBV.
“Other vaccine efforts have focused on inducing neutralising antibodies against the virus which blocks infection of immune B cells during primary acute infection.
“But EBV in its latent state hides inside B cells, turning them into tiny virus factories ready to divide and spread whenever our immune defences are down. It is our killer T cells that detect and control these infected B cells.
“Our vaccine formulation induces that killer T cell immune response as well as the neutralising antibody immune response.
“We think that in susceptible individuals, EBV-infected B cells travel to the brain and cause inflammation and damage. If we can prevent this at an early stage of infection then the infected B cells can’t go on to cause the development of secondary disease like MS,” Professor Khanna said.
The study found the vaccine induced potent and persistent humoral (antibody) and cellular (killer T cell) immunity in pre-clinical models during primary and latent EBV infection. This immune response also eliminated or significantly delayed the growth of EBV-positive lymphoma tumour cells in laboratory models.
The research involved international collaboration with biotechnology company Elicio Therapeutics.
Study co-author and Elicio Therapeutics Chief Scientific Officer Dr Peter DeMuth said the company’s Amphiphile vaccine adjuvant, AMP-CpG was used to deliver the vaccine effectively into the lymph nodes where the early immune response is activated.
“We are excited about this data. Pre-clinical validation suggests that it not only demonstrates an exciting opportunity for a potential EBV vaccine, but also validates the utility of the AMP platform to improve lymph node immune activation resulting in potent immune responses against historically challenging pathogens,” Dr DeMuth said.
“This will be beneficial in potentially providing protection against EBV-infection and the development of EBV-associated diseases.”
Nearly 3 million people around the world live with MS, including more than 33 thousand Australians. The disease causes symptoms including debilitating fatigue, loss of mobility, pain and brain fog.
As well as the causal link to multiple sclerosis, EBV is associated with diseases and cancers including Hodgkin’s lymphoma and nasopharyngeal cancer. The virus can be life-threatening in immunocompromised patients such as transplant recipients.
Lead author Dr Vijayendra Dasari from QIMR Berghofer said it was rewarding to see so many years of research getting to this stage of development.
“QIMR Berghofer has been researching the role of EBV in disease and cancer for decades. It is a really proud moment for us to see all of this work coming together, with this vaccine now heading towards the next important stages of development,” Dr Dasari said.
The research was funded by biopharmaceutical company Atara Biotherapeutics, which is supporting the development, in collaboration with QIMR Berghofer, of a novel EBV-vaccine composition involving a different, clinically validated adjuvant.
QIMR Berghofer’s Tumour Immunology Group, led by Professor Khanna, is making significant progress in vaccine design technology that can generate T-cell immunity against disease-causing viruses. This platform was used to develop the new EBV vaccine candidate, and has previously led to a potential preventative vaccine for human cytomegalovirus (CMV). The team is also working on a therapeutic vaccine to treat patients with human papillomavirus (HPV)-related cancers.
The research paper is available at this link https://www.nature.com/articles/s41467-023-39770-1 with DOI number 10.1038/s41467-023-39770-1