Australian vaccine breakthrough offers hope against EBV-associated cancers and MS

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An Australian-developed vaccine candidate developed at QIMR Berghofer has achieved potent and durable immune protection against Epstein–Barr virus (EBV).

The early findings, published in the journal Nature Communications, suggest the vaccine candidate could prevent the type of severe viral infection known to be a leading cause of several diseases, including multiple sclerosis and various cancers.

EBV is carried by around 95 per cent of the population. Most are unaware of the virus lying dormant in their bodies. Infection usually occurs in early childhood, causing very mild symptoms. However, in some people, it can lead to severe illness.

The new QIMR Berghofer vaccine candidate potentially offers a breakthrough approach combining two powerful arms of the immune system to target the virus in acute and latent infection.

Although further work is needed, the vaccine is potentially complementary to ATA188. This cell-based therapy 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 vaccine's development 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,” said Professor Khanna.

The study found the vaccine-induced potent and persistent antibody and cellular 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,” said Dr DeMuth.

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

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,” said Dr Dasari.

The research was funded by Atara Biotherapeutics, which is supporting the development, in collaboration with QIMR Berghofer, of a novel EBV-vaccine composition involving a different, clinically validated adjuvant.