New EBV-targeted vaccine induces durable immune response in mice

Researchers have developed a vaccine against the Epstein-Barr virus (EBV) — a leading environmental risk factor for multiple sclerosis (MS) — that induced durable immune responses in mice.

If it’s moved to the clinic, the vaccine could help prevent infections that drive MS and certain cancers, according to the authors.

“We are excited about this data,” said Peter DeMuth, PhD, chief scientific offer at Elicio Therapeutics, in a press release. “This will be beneficial in potentially providing protection against EBV-infection and the development of EBV-associated diseases.” Elicio collaborated in the vaccine’s development.

The report, “Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice,” was published in Nature Communications.

A member of the herpes virus family, EBV is one of the most common viruses worldwide, infecting about 95% of people at some point in their lives. Infection is usually asymptomatic or causes cold-like symptoms, but it can also cause infectious mononucleosis, or mono, which may accompany more severe symptoms such as fever, fatigue, sore throat, and rash.

The virus works by infecting B-cells, the immune cells responsible for producing antibodies. After an active infection, it lives dormant, or latent, in a person’s body for the rest of their lives — although it can reactivate later on.

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Link between MS, EBV

Last year, a landmark study established EBV as a leading cause of MS, raising the risk of the neurodegenerative disease by 32 times. That discovery was closely followed by another groundbreaking study that showed that similarities between EBV and proteins could underlie the link, so that immune cells trying to fight the virus would instead end up attacking nerve tissue.

These findings and others linking EBV to MS and certain cancers have garnered significant interest in developing vaccines.

“We think that in susceptible individuals, EBV-infected B-cells travel to the brain and cause inflammation and damage,” said Rajiv Khanna, PhD, who led the development of the vaccine used in the recent study. “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.”

Khanna is also the director of the Center for Immunotherapy and Vaccine Development at QIMR Berghofer Medical Research Institute, Australia.

Most vaccines being developed for EBV work to target the virus in its active state. By increasing the body’s production of virus-neutralizing antibodies, they would prevent it from invading B-cells in the first place.

Phase 1 trials for such vaccines are currently underway, led by the National Institutes of Health (NCT04645147) and Moderna (NCT05164094).

“But EBV in its latent state hides inside B-cells, turning them into tiny virus factories ready to divide and spread whenever our immune defenses are down,” Khanna said.

Inducing killer T-cells’ immune response

For this reason, Khanna and his colleagues developed a candidate that targets both the active and latent forms of EBV.

Specifically, it targets killer T-cells, another type of immune cell, which can identify infected B-cells and kill them, reducing the number of B-cells where latent EBV can be found.

“Our vaccine formulation induces that killer T-cell immune response as well as the neutralizing antibody immune response,” Khanna said.

The vaccine also includes an adjuvant, an ingredient that’s sometimes added to a vaccine to boost an immune response and make it more effective. The one used here was developed by Elicio and helps the vaccine reach the lymph nodes, where early immune responses occur.

In preclinical experiments, the vaccine was found to potently induce the production of antibodies that could neutralize EBV, in addition to producing killer T-cell immune responses.

Immune responses driven by the vaccine began to decline after seven weeks, but were sustained at levels above nonimmunized animals for at least seven months.

These responses also eliminated or delayed the growth of EBV-positive tumor cells in preclinical models of EBV-associated cancer, demonstrating its potential to prevent EBV-associated disease.

The study was funded by Atara Biotherapeutics, which is developing an investigational EBV-targeted therapy called ATA188 for progressive and relapsing forms of MS.

Khanna is collaborating with Atara to develop ATA188, which contains T-cells than can selectively identify and destroy EBV-infected cells in the brain and spinal cord. An EBV-targeted vaccine could possibly complement a treatment like ATA188, according to the scientists.

“Collectively, the data presented here clearly demonstrate that EBV protein subunit vaccine … can generate robust virus-specific … immunity which is persistent,” the researchers wrote. “These studies provide an important platform for future clinical assessment of this vaccine formulation in human volunteers.”