Teenage students and their parents often don’t know much about Epstein-Barr Virus infections. But mention the word “mono” and you’ll get an immediate reaction: “that’s bad stuff; something to stay away from.” Exactly. At the University of Minnesota Epstein-Barr Diseases Research Program, our prospective studies have shown that about 50 percent of freshmen at the universities of Minnesota and Iowa are naïve to EBV at the beginning of their first semester, however, 25 percent of them will acquire a primary EBV infection before the end of their second semester. The vast majority of these infections manifest as mono with a median duration of 17 days. For college students, mono is clearly an illness worth preventing. And this is, in part, why we’ve spent nearly the past two decades developing a prophylactic EBV vaccine.
About the vaccine
EBV initiates infection of B lymphocytes by binding its major surface glycoprotein (gp350) to CD21 on the B cell surface. Antibody against gp350 effectively blocks infection of B cells by EBV. Therefore, we have selected EBV gp350 to be the backbone of our vaccine. Because EBV is the first recognized human cancer virus, a whole live virus vaccine is not feasible. Thus, our vaccine is only a piece of the virus, which will be adjuvanted with a derivative of monophosphoryl lipid A. A similar vaccine was safe and prevented mono among Belgian college students, so our vaccine already has a positive track record.
Should this be a pediatric vaccine?
We think so, because a prophylactic vaccine needs to be given before primary infection. Research we’ve done both locally in collaboration with HealthPartners colleagues and nationally using samples from the National Health and Nutrition Examination Survey indicates that an EBV vaccine should be given about the time of school entry in order to protect the majority of vaccinees from getting mono. The high incidence of mono among college freshmen makes them ideal participants for the initial clinical trials, but children would be next in line.
Could EBV vaccine prevent more than mono?
Yes. EBV is the cause of a number of human cancers including Hodgkin’s lymphoma, lymphomas after organ or cell transplantation, gastric adenocarcinoma, and nasopharyngeal carcinoma. EBV is inextricably linked to autoimmune diseases, especially multiple sclerosis, but also lupus erythematosus, rheumatoid arthritis, and, recently, psoriasis. Since a history of mono is a risk factor for Hodgkin’s lymphoma and multiple sclerosis, and an EBV vaccine has been shown to prevent mono, it is logical to predict that a prophylactic EBV vaccine could prevent or reduce the incidence of all of the above-mentioned cancers and autoimmune disorders.
The development of a vaccine for human use is a slow process. We began this odyssey in 2002 and it’s still a work in progress. But there has been progress. In 2017, we obtained materials to create our candidate vaccine from an industrial partner. Soluble gp350 has been produced in the University of Minnesota Molecular and Cellular Therapeutics Laboratory and is ready for purification, after which preclinical testing can begin. We don’t want to overpromise, but a likely scenario is to complete purification and preclinical testing by summer 2020, and then apply to the FDA for an investigational new drug (IND) status by the end of 2020. If an IND is granted, we would launch clinical trials in summer 2021.
Henry “Hank” Balfour, MD, is a professor of Pediatrics, and Laboratory Medicine and Pathology at the University of Minnesota Medical School where he has been researching the prevention and treatment of herpesvirus infections for the past 50 years.