Developing vaccines against Epstein-Barr virus

By Rachel Arthur contact

- Last updated on GMT

Pic:getty/hailshadow
Pic:getty/hailshadow

Related tags: Epstein-Barr Virus, Vaccines

Last week the US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, launched a clinical trial to investigate a preventative vaccine for Epstein-Barr virus (EBV). It’s part of growing efforts to create a vaccine against the virus.

EBV is a member of the herpes virus family and one of the most common human viruses. It is spread through bodily fluids, primarily saliva. An estimated 125,000 cases of infectious mononucleosis occur each year in the US. Most people will get infected with EBV at some point in their life and will not have any symptoms. So why the interest in a vaccine?

Around 10% of those people who are infected with EBV develop fatigue lasting six months or longer. Around 1% of all EBV-infected individuals develop serious complications, including hepatitis, neurologic problems, or severe blood abnormalities.

As a latent virus, EBV also is associated with several malignancies - including stomach and nasopharyngeal cancers and Hodgkin and Burkitt lymphomas - as well as autoimmune diseases, such as systemic lupus erythematosus.

Furthermore, a landmark study published earlier this year built on years of research linking EPV to multiple sclerosis. Using data from millions of US military recruits over a 20-year period, the researchers determined that EBV infection greatly increased the risk of subsequent multiple sclerosis​ and that it preceded development of the disease.

NIH trial

There are currently no authorized vaccines against EBV, and only two studies to test an investigational EBV vaccine have taken place in more than a decade, notes the NIH.

But recent research into its implications in serious diseases – as well as the advances in mRNA and other tech – are spurring candidates into development.

While linking EBV to MS has helped spur interest in the development of vaccines, it has also supported other research into treatments for MS. Atara Biotherapeutics, for example, is developing a first-of-its-kind T-cell immunotherapy​ in the hope of not only slowing decline but also helping patients regain function previously lost to the disease.

“A vaccine that could prevent or reduce the severity of infection with the Epstein-Barr virus could reduce the incidence of infectious mononucleosis and might also reduce the incidence of EBV-associated malignancies and autoimmune diseases,”​ noted NIAID Director Anthony S. Fauci, M.D, as it launched the early-stage clinical study of its vaccine candidate.

Led by principal investigator Jessica Durkee-Shock, M.D., of NIAID’s Laboratory of Infectious Diseases, the NIH study will evaluate the safety and immune response of an investigational EBV gp350-Ferritin nanoparticle vaccine with a saponin-based Matrix-M adjuvant from Novavax. The experimental vaccine was developed by the Laboratory of Infectious Diseases in collaboration with NIAID’s Vaccine Research Center.

The vaccine works by targeting EBV glycoprotein gp350, which is found on the surface of the virus and virus-infected cells. EBV gp350 is also the primary target for neutralizing antibodies found in the blood of people naturally infected with EBV. Ferritin, a natural iron storage protein found in cells of all living species, is considered a promising vaccine platform because it can display proteins from the targeted virus in a dense array on its surface. The adjuvant is intended to enhance the immune response induced by the investigational vaccine.

The study​ will enroll 40 healthy volunteer adults ages 18 to 29 years, half of whom have evidence of prior EBV infection and half of whom do not have evidence of prior EBV infection.​ 

Participants will receive three doses (at 0, 30 days and 180 days) and the trial will last four years.

Harnessing mRNA advances

Meanwhile, Moderna announced in January that it had dosed the first participant in a Phase 1 study of its mRNA EBV vaccine.

The company's vaccine candidate against EBV (mRNA-1189) is being developed to prevent EBV-induced mononucleosis and potentially EBV infection.

Similar to Moderna's cytomegalovirus (CMV) vaccine candidate (mRNA-1647), mRNA-1189 contains four mRNAs that encode EBV envelope glycoproteins (gH, gL, gp42, gp220), which mediate viral entry into B-cells (a type of immune system cells) and epithelial surface cells, the major targets of EBV infection.

The Phase 1 randomized, observer-blind, placebo-controlled study of mRNA-1189 is being conducted at around 15 sites in the US. The primary purpose of the Phase 1 study is to assess safety and tolerability of mRNA-1189 in healthy adults ages 18 to 30. Moderna expects to enroll approximately 270 participants.

The EBV virus vaccine joins Moderna’s focus on developing vaccines against latent viruses: which now include vaccines against, shingles, CMV and human immunodeficiency virus (HIV).

Related topics: Bio Developments

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