Epstein-Barr is one of the world’s most common human viruses and the most frequent cause of infectious mononucleosis — the “kissing disease” that’s the scourge of college campuses.
But in rare cases, the Epstein-Barr virus, or EBV, can have more serious consequences. Researchers have linked it to cancers, including forms of lymphoma, and to the chronic neurological illness, multiple sclerosis.
The virus also has national security implications. Mononucleosis sidelines hundreds of young military service members each year, resulting in at least 2,797 weeks of lost duty time annually, according to the Defense Department.
Biotechnology and pharmaceutical companies are now working on experimental vaccines to ward off the Epstein-Barr virus, with at least two development efforts in Massachusetts. Moderna, the Cambridge biotech that created one of the world’s most successful COVID-19 shots, is testing an Epstein-Barr vaccine that uses the firm’s messenger RNA technology to stimulate immunity. The early-stage clinical trial has recruited adults ages 18 to 30 at sites across the country, including UMass Memorial Medical Center in Worcester.
ModeX Therapeutics, the Natick subsidiary of the Miami health care company OPKO Health, has developed a rival Epstein-Barr vaccine, tested it in laboratory mice, and hopes to begin clinical trials within two years. The pharmaceutical giant Merck in March paid OPKO Health $50 million for global rights to the experimental vaccine and could pay another $872.5 million — plus royalties — if the shot gets approved by the Food and Drug Administration.
A third vaccine, developed by the federal government, is in an early-stage trial. The National Institute of Allergy and Infectious Diseases, or NIAID, began testing the vaccine on adults between the ages of 18 and 29 more than a year ago. Like the Merck-OPKO shot, this vaccine uses an iron-storing blood protein called ferritin to deliver engineered proteins from the Epstein-Barr virus to stimulate an immune response.
Dr. Jessica Durkee-Shock, a NIAID immunologist and principal investigator for the government-sponsored trial, said that preventing mononucleosis is the “low-hanging fruit” for developers of Epstein-Barr vaccines.
“But I think my vision and the vision of a lot of people that work on EBV vaccines is that we’d love to prevent some of these more severe complications,” she said.
About 95 percent of adults in the US are infected by the Epstein-Barr virus at some point in their lives, although many never know it. It spreads easily through saliva, hence its nickname and prevalence among college students.
Mononucleosis can cause extreme fatigue, fever, sore throat, head and body aches, and swelling of the lymph nodes, liver, and spleen. An estimated 125,000 cases occur each year in the US, according to the National Institutes of Health. Although most people get better in two to four weeks, roughly 10 percent of patients experience fatigue lasting six months or longer.
“Infectious mononucleosis is a pretty nasty adolescent disease,” said Dr. Gary Nabel, who co-founded ModeX in 2020 and became OPKO’s chief innovation officer last year after OKPO bought the Natick startup for $300 million in stock. “Most people recover but some do have serious consequences.”
The most serious potential implications of an infection stem from a problematic trait that Epstein-Barr shares with several other viruses: it never disappears from the human body it infects.
EBV is a member of the herpesvirus family. Like the herpesvirus that causes chickenpox and shingles, it can remain dormant for years without causing symptoms and become reactivated if the immune system weakens.
Notably, patients on immune-suppressing drugs after an organ transplant are at risk for developing life-threatening forms of lymphoma driven by once-dormant EBV, according to Dr. Lindsey Baden, an infectious diseases specialist at Brigham and Women’s Hospital. Organ recipients who never had an EBV infection can also develop lymphoma if tissue from donors contained the virus.
That’s what happened to Jeff Schultz, 70, of Middleton. He underwent a 12-hour double lung transplant at Brigham & Women’s in January 2020 because his lungs were scarred from pulmonary fibrosis, a condition he attributed to drywall dust that he inhaled working as a general contractor. About a year after the transplant, he said, doctors detected EBV in a routine blood test.
A needle biopsy of a lymph node in Schultz’s neck indicated he had early-stage lymphoma, he said. He received infusions of cancer-fighting drugs for months at Dana-Farber Cancer Institute and is now in remission.
“I was EBV negative [before the double transplant] but most of the donor organs are positive,” said Schultz, who had never heard of the virus until doctors warned him about the possible complication prior to surgery.
Baden, the Brigham specialist, confirmed that most organ donors have the virus in their tissue. Doctors and patients weigh that risk against the dire consequences of forgoing transplant surgery. “We try to minimize the risk, but the alternative is you have lung failure,” he said.
For years, the US military has wanted an EBV vaccine to prevent service members from catching mononucleosis, said Durkee-Shock, the NIAID immunologist. But developing vaccines is expensive, and EBV is a challenging target, so pharmaceutical companies have had a limited appetite.
When pharmaceutical firms considered the potential market for a vaccine to prevent mononucleosis, said Nabel, co-founder of ModeX, “it was small, in the several-hundred-million-dollar range. That’s not a very compelling target for a drug company looking for a billion-dollar-a-year drug.”
The calculus appears to be changing due to a growing body of evidence that an Epstein-Barr infection can have dangerous consequences years late.
Since the 1960s, researchers have known that an EBV infection raises the risk of forms of cancer, including nasopharyngeal carcinoma — a rare malignancy that affects part of the throat — and gastric cancer. An effective EBV vaccine could prevent cancers similar to the way the human papillomavirus vaccine has been administered to children in an effort to lower rates of cervical cancer and other malignancies.
A recent study has only fueled interest in an EBV vaccine. Researchers at the Harvard T.H. Chan School of Public Health reported in January 2022 in the journal Science that the biggest risk factor for contracting multiple sclerosis appeared to be a prior infection with Epstein-Barr.
The study relied on data from more than 10 million US military recruits over a 20-year period. Researchers identified 955 young adults on active duty who were diagnosed with multiple sclerosis during their period of service. The risk of MS increased 32-fold after infection with EBV but was unchanged after infection with other viruses, according to the study.
The researchers acknowledged that an Epstein-Barr infection wasn’t the only risk factor for developing multiple sclerosis, a devastating disease of the central nervous system that afflicts nearly 1 million people in the US. There are also genetic factors. But the researchers said the data suggesting a link with EBV was compelling.
Dr. Katherine Luzuriaga, a principal investigator for the Moderna trial at UMass Chan Medical School and head of the Center for Clinical and Translational Science there, said that only a small fraction of people infected by EBV develop multiple sclerosis or cancers.
“But it’s significant enough,” she said, “that many people in the community have advocated for the development of an EBV vaccine.”
Jonathan Saltzman can be reached at firstname.lastname@example.org.