Vaccine candidate offers hope against EBV-associated diseases

A cutting-edge vaccine candidate, developed at QIMR Berghofer Medical Research Institute, has achieved potent and durable immune protection against Epstein–Barr virus (EBV) in preclinical models — a breakthrough that could prevent the type of severe viral infection known to be a leading cause of several diseases and cancers. The findings have been published in the journal Nature Communications.

EBV is a member of the herpes virus family. It is carried by around 95% of the population, with most of us 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 (glandular fever), which is a major risk factor for a number of diseases and cancers — including Hodgkin’s lymphoma and nasopharyngeal cancer.

Indeed, a landmark study published in Science 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 including fatigue, loss of mobility, pain and brain fog. 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 offers a breakthrough approach that combines two powerful arms of the immune system to target the virus in both acute and latent infection. The vaccine is potentially complementary to ATA188, a cell-based therapy that targets the root cause of MS 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,” Khanna said.

“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.”

The study found the vaccine induced potent and persistent humoral (antibody) and cellular (killer T cell) immunity in preclinical 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. Elicio 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,” DeMuth said. “Preclinical 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.

“This will be beneficial in potentially providing protection against EBV infection and the development of EBV-associated diseases.”

Lead author Dr Vijayendra Dasari said it was rewarding to see so many years of research getting to this stage of development, noting that 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,” Dasari said.

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