Phase I clinical trial of Moderna mRNA vaccine for Epstein-Barr virus starting at UMass Chan

Katherine Luzuriaga, MD
Katherine Luzuriaga, MD

UMass Chan Medical School researchers are embarking on a clinical trial of an mRNA vaccine by Moderna against the Epstein-Barr virus (EBV), a common cause of infectious mononucleosis. EBV has also been associated with several autoimmune disorders and has been implicated in the development of several cancers, including Burkitt and Hodgkin’s lymphomas.

The study, called the Eclipse Trial, is a randomized, observer-blind, placebo-controlled, dose-ranging Phase I clinical trial in 18- to 30-year-old healthy adults. Study participants will be randomly assigned to one of four arms: one for each of three doses of the investigational vaccine and one placebo.

The investigational vaccine targets four glycoprotein antigens on the virus particle, using the same type of mRNA vaccine platform used for mRNA COVID vaccines.

Currently there is no approved vaccine for the highly contagious EBV, according to Katherine Luzuriaga, MD, the UMass Memorial Health Chair in Biomedical Research; professor of molecular medicine, pediatrics and medicine; director of the UMass Center for Clinical and Translational Science; and vice provost for clinical and translational research.

“In addition to using the mRNA platform, this vaccine differs from other EBV vaccines in development because it incorporates four glycoproteins expressed on the virus’ external surface that are used by the virus to enter cells,” said Dr. Luzuriaga, principal investigator for the study at UMass Chan. “The goal is to raise robust immune responses to a broader range of proteins used by the virus for cell entry, in order to protect against infection and mononucleosis disease.”

Researchers anticipate enrolling around 270 participants across 15 sites nationwide. UMass Chan investigators are ready to start screening. Individuals interested in participating in the study can learn more here

EBV replicates in the epithelial cells of the tonsils and is easily secreted in saliva. EBV is an extremely common infection, with 95 percent of the world’s population infected by their 40s. While the majority of study participants will be EBV seronegative, a small number of EBV seropositive individuals will be enrolled to determine whether the vaccine can boost or broaden EBV-specific immune responses and control of viral shedding.

Most primary infections in young children produce either minor or no symptoms.

“However, if you get Epstein-Barr infection as an older child or adult, you’re much more likely to have acute infectious mononucleosis, which consists of fever, pharyngitis and swelling of your lymph glands. Many individuals also experience profound malaise and fatigue that can linger even after the acute symptoms have subsided,” Luzuriaga said.

Previous research by Luzuriaga and Eclipse Trial co-investigator John L. Sullivan, MD, professor emeritus of molecular medicine, found that 30 percent of entering first-year students at UMass Amherst did not show antibodies to EBV in their blood and thus were susceptible to infection. Within two years, half of those susceptible students tested positive for the virus. Other investigators have reported similar data from other college campuses.

“If you multiply that across U.S. college campuses, it’s a pretty significant problem,” Sullivan said. “Students can miss a lot of school in the acute phase of disease, and some have prolonged symptoms that keep them out of many of the activities of daily living. So, there is a lot of interest in an effective EBV vaccine.”

In addition to Luzuriaga and Dr. Sullivan, other UMass Chan investigators include Nicole Theodoropoulos, MD, associate professor of medicine; Jesica Pagano-Therrien, PhD, assistant professor of nursing; and Margaret McManus, MPH, lead study coordinator. The clinical trial will be conducted in the UMass Chan Center for Clinical Research, which provides expert support for the conduct of early-stage vaccine trials.