The winding road to discovery
A University of Minnesota researcher’s career-spanning odyssey in pursuit of a vaccine for the Epstein-Barr virus is finally paying off
It might seem like a random assortment of disorders: an illness called the “kissing disease,” an autoimmune condition that affects the brain and spine, and a type of blood cancer.
But mononucleosis (mono), multiple sclerosis (MS), and Hodgkin lymphoma do share a connection: close ties to the Epstein-Barr virus (EBV), one of the most common—and least understood—viruses in humans.
Long known as the cause of mono, EBV has more recently been revealed as a factor in more serious diseases like MS and cancer. Most people infected with EBV never experience chronic consequences. But for a small, unlucky group, the virus is able to maliciously tinker with a cell’s hardwiring, causing either abnormal immune responses that lead to autoimmune disorders or cancer-causing mutations.
Henry “Hank” Balfour Jr., MD, a University of Minnesota Medical School professor of laboratory medicine and pathology and of pediatrics, has been researching EBV for decades and is intimately familiar with its broad consequences. That’s why he’s spent the better part of two decades working to create a vaccine that prevents EBV infection—and perhaps mono, MS, and Hodgkin lymphoma, too.
“Nine out of 10 adults are infected with EBV, and most don’t realize they’ve been infected,” he says. “But EBV can set up housekeeping inside our cells and reactivate at any time … and then it can cause what we call EBV-spurred or chronic EBV diseases. For all those reasons, I embarked on a path in research to try to put together an EBV vaccine.”
Now, Balfour is on the cusp of bringing that vaccine to the public.
Starts and stops
A bit of history is necessary to fully understand the challenges Balfour has encountered during his mission to bring an EBV vaccine to life.
The Epstein-Barr virus was ﬁrst identiﬁed in 1964, and the idea of a vaccine was ﬁrst entertained in 1973. Fast forward to the 1990s, when a group of scientists created an experimental EBV vaccine. But due to a series of pharmaceutical company buyouts, the vaccine was never completely developed.
In the meantime, Balfour spent the bulk of the 1990s researching the intricacies of the EBV virus and the various ways it affects people, including those who are immunocompromised as well as those who are healthy.
Because of his research, Balfour was approached by a pharmaceutical company to resurrect the vaccine project. He worked with them from 2007 until 2016, trying to bring the vaccine to people through a clinical trial. But once again the project was derailed, this time because the sponsor withdrew support.
A PASSIONATE PARTNER
Cancer got personal in 1998, when Twin Cities newscaster Randy Shaver was diagnosed with stage IV Hodgkin lymphoma. Shaver was already helping those affected by the disease; his Randy Shaver Cancer Research and Community Fund was created in 1995 to support the Minnesota cancer community. But his treatment, recovery, and remission have made him even more committed to fueling cancer research.
Roseann Giovanatto-Shaver, Shaver’s wife and executive director of the charity, is a two-time melanoma survivor herself and a passionate supporter of cancer research. She met Henry “Hank” Balfour Jr., MD, more than 10 years ago. He told her about his EBV research and explained that the virus was connected to Hodgkin lymphoma.
Then Balfour told her about the long history of starts and stops that had characterized his work on the EBV vaccine, and about his ongoing trouble securing funding for the work. Without adequate financial support, the vaccine would never get to a clinical trial.
Giovanatto-Shaver was “fuming” when she learned about these roadblocks, she says. “I told told Hank, ‘I’ll do anything in my power to help with this.’”
And now, with the support of more than $266,000 from the Shaver fund, Balfour and his team are finally launching their hard-won clinical trial.
“Without their help, our clinical trial of the EBV vaccine could never have taken place,” Balfour says.
Then in early 2020, Balfour was approached by Jeffrey Cohen, MD, a researcher at the National Institute of Allergy and Infectious Diseases (NIAID).
“I contacted Dr. Balfour as he is, in my opinion, one of the world’s experts and a champion for development of an EBV vaccine,” Cohen says.
Cohen’s team had received FDA approval to conduct a clinical trial of an EBV vaccine, but they needed Balfour’s help. Finally, it looked like the vaccine might have a chance.
Balfour and his team at the U started screening potential participants for a phase I/II clinical trial in August. They hope to recruit 50 U of M undergraduate students—25 who will receive the vaccine and 25 who will receive a placebo—for a study that will kick off this fall.
Balfour points out that college students are an ideal population for the trial; studies show that about half of incoming freshmen haven’t been infected with EBV.
“This vaccine is meant to prevent EBV infections, so it has to be given to those who haven’t already gotten it,” he says.
The participants will be followed for two years to evaluate the safety of the vaccine, but Balfour is hoping to see some prevention capabilities as well.
“If our estimates are right, we have [a pretty good] chance of showing efficacy in that small group—a group at high risk for clinical infectious mono,” he says.
Of course, there’s more work to be done before an EBV vaccine becomes widely available, including studies involving larger numbers of participants that show both safety and effectiveness. But if the new clinical trial shows what he expects, Balfour says we could be looking at a future with signiﬁcantly reduced rates of mono, MS, and several types of cancer.
“The Epstein-Barr virus is extremely important in human health,” he says. “The disease burden can only be guesstimated, but it’s monstrous because the worldwide population is 90% infected by adulthood. So treatment is nice, but in infectious diseases, prevention is always better than treatment.”