Epstein-Barr virus (EBV), commonly known as mononucleosis or mono, is a very common virus that infects more than 90% of adults worldwide. While EBV usually causes a mild illness called infectious mononucleosis in older children and young adults, it can also lead to several cancers. Development of an effective vaccine against EBV has been a long-standing goal in the medical research field. Recent progress in vaccine development looks promising to offer protection against this potentially dangerous virus.
The EBV Problem
EBV is a herpes virus that remains in the body for life after initial infection. It belongs to the gammaherpesvirinae subfamily of herpesviruses. The virus is primarily transmitted through saliva and causes infectious mononucleosis, popularly known as mono or the kissing disease. Initial symptoms of mono include fever, sore throat, swollen lymph nodes and fatigue. While most people recover fully from mono within a few weeks or months, the virus then hides in B cells in a dormant or latent form.
In some cases, long-term infection with Epstein-Barr virus (EBV) has been linked to cancers like Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma and gastric carcinoma. EBV is estimated to account for up to 1-2% of all cancers worldwide. Other associated diseases include multiple sclerosis. Currently there are no approved vaccines against EBV. Development of an effective vaccine has been challenging due to the ability of the virus to establish lifelong latent infection.
Emergence of Monovaccine
In a major breakthrough, researchers have developed a novel vaccine approach called monovaccine that targets a specific EBV protein called gp350. This protein plays a crucial role in allowing the virus to enter and infect B cells. The monovaccine contains specifically purified gp350 protein that stimulates the immune system to produce antibodies against this viral coat protein.
In early clinical trials, the monovaccine has shown promising results with no significant safety issues. Those who received the experimental vaccine generated high levels of anti-gp350 antibodies in their blood. These antibodies were able to block EBV from entering and infecting B cells in laboratory experiments. Researchers believe that by inhibiting the initial infection of B cells, the monovaccine may stop EBV from establishing latent viral reservoirs in the body. This could help prevent EBV-associated diseases in the long run.
Phase 2 Clinical Trials
Encouraged by the Phase 1 safety and immunogenicity data, researchers have now advanced the monovaccine to Phase 2 clinical trials. The goal of these studies is to further evaluate the vaccine’s ability to produce an immune response and explore optimal dosing strategies. One of the Phase 2 trials is currently underway in China, enrolling over 200 healthy adult volunteers between 18-25 years of age who are EBV seronegative, meaning they have not been previously infected.
Participants receive either a single dose or two doses of the experimental monovalent gp350 vaccine or placebo at different dose levels. The primary outcome is to analyze vaccines’ capacity to induce anti-gp350 antibody levels after vaccination and determine the best dose for future efficacy studies. Other measurements include assessing antibody persistence over time and vaccine reactogenicity or side effects. Preliminary results are expected by late 2023, which will help delineate the best dose and regimen of the monovaccine.
Moving Towards Efficacy Trials
If the Phase 2 trials continue to demonstrate an acceptable safety profile along with strong induction of protective anti-gp350 antibodies, researchers aim to conduct larger Phase 3 efficacy studies. These definitive studies would evaluate whether the monovaccine can successfully prevent acute infection or disease following EBV exposure. They would need to enroll thousands of young adults who are seronegative for EBV in areas where the virus is commonly found.
Participants would be randomized to receive either the vaccine or placebo and then monitored over time to see if the vaccine offers any protection against developing infectious mononucleosis from natural EBV exposure compared to the control group. Additional long term follow up may assess if the vaccine lowers incidence of EBV-associated cancers. Successful Phase 3 efficacy data could potentially support licensure of the first approved prophylactic EBV vaccine worldwide.
If approved, the monovaccine may help curb the enormous disease burden caused by EBV in populations worldwide. It can offer protection to high-risk groups like transplant recipients against EBV reactivation and associated illnesses. The vaccine may also benefit individuals at increased risk of EBV-linked cancers. Development of an effective EBV vaccine has long eluded researchers. The monovaccine’s novel antigen-specific approach targeting the essential gp350 protein offers hope that the goal of an EBV vaccine may soon become reality. With continuing clinical testing, this first-in-class EBV immunization could transform prevention against infectious mononucleosis and EBV-driven malignancies globally.