As links to MS dipen, researchers accelerate efforts to develop an Epstein-Barr

Maybe you haven’t heard of the Epstein-Barr virus. But it knows all about you.

Chances are, it’s living inside of you right now. About 95% of American adults are infected at some point in their lives. And once infected, the virus stays with you.

Most viruses, like influenza, just come and go. A healthy immune system attacks them, kills them and prevents them from making you sick again. Epstein-Barr and its cousins, including the viruses that cause chickenpox and herpes, can hibernate inside your cells for decades.

This viral family has “evolved with us for millions of years,” said Blossom Damania, a virologist at the University of North Carolina-Chapel Hill. “They know all the secrets of your body.”

Although childhood Epstein-Barr infections are usually mild, exposure in teens and young adults can lead to infectious mononucleosis, a week-long illness that sickens 125,000 Americans a year, causing a sore throat, swollen glands, and extreme fatigue. And while Epstein-Barr spends most of its time asleep, it can reawaken during times of stress or when the immune system is off its game. These reactivations are linked to a long list of serious health conditions, including various types of cancer and autoimmune diseases.

Scientists have spent years developing a vaccine against Epstein-Barr, or EBV. But several recent leaps in medical research have given the search more urgency — and more hope for success. In just the past year, two experimental vaccine efforts have made it into human clinical trials.

What has changed?

First, the Epstein-Barr virus has been shown to pose a greater threat. New research strongly links it to multiple sclerosis, or MS, a potentially disabling chronic disease that affects more than 900,000 Americans and 2.8 million people worldwide.

In January the journal Science published the results of a groundbreaking 20-year study of 10 million military personnel that still provides the strongest evidence that Epstein-Barr can trigger MS. New study shows people infected with Epstein-Barr are 32 times more likely to develop MS.

And shedding new light on the mechanisms that may explain that correlation, a separate team of scientists has published a study in Nature that describes how viruses can trigger an autoimmune response that leads to MS. The disease, which usually strikes between the ages of 20 and 40, disrupts communication between the brain and other parts of the body and is often characterized by recurring episodes of extreme fatigue, blurred vision, muscle weakness and difficulty with balance and coordination. At its worst, MS can lead to impaired speech and paralysis.

Adding to the urgency of the new findings, several new studies have suggested that reactivation of the Epstein-Barr virus is also involved in some cases of prolonged Covid, a poorly understood condition in which patients experience chronic symptoms that often resemble mononucleosis.

And just as important for speed: Advances in vaccine science spurred by the pandemic, including the mRNA technology used in some Covid vaccines, could accelerate the development of other vaccines, including a vaccine against Epstein-Barr, said Dr. Peter Hotez, Ph.D. National School of Tropical Medicine at Baylor College of Medicine. Hotez co-developed a low-cost, patent-free Covid vaccine called Corbevax.

Some researchers question the need for a vaccine that targets a disease like MS that remains relatively rare while debilitating.

Lewis Katz School of Medicine Professor at Temple University. Eradicating Epstein-Barr would require vaccinating all healthy children, even if they are at low risk of developing cancer or multiple sclerosis, says Ralph Horvitz.

Before revealing the potential risks of a new vaccine to children, he said, scientists need to answer basic questions about MS. For example, why does a virus that affects almost everyone cause disease in a small fraction? And what role do stress and other environmental conditions play in that equation?

Immunologist Bruce Bebo, executive vice president of research at the National MS Society, said Epstein-Barr appears to be “necessary but not sufficient” to cause the disease, adding that the virus “could be the first in a string of dominoes.” “

Hotez said researchers can continue to explore the mysteries surrounding Epstein-Barr and MS, and even pursue vaccine efforts. More studies are needed to understand which populations might benefit most from a vaccine, and once more is known, Hotez said, such a vaccine could potentially be used in patients at highest risk, such as organ transplant recipients, rather than administered universally. To all young people.

“Now that we know that Epstein-Barr is very strongly linked to MS, if we develop a vaccine now we can save a lot of lives,” Damania said, adding that “rather than waiting 10 years” until each question is answered.

Moderna and the National Institute of Allergy and Infectious Diseases launched separate clinical trials of Epstein-Barr vaccines last year. Epstein-Barr vaccines are also in the early stages of testing at Miami-based biotech company Opko Health; Fred Hutchinson Cancer Center in Seattle; and City of Hope National Medical Center in California.

Scientists have sought to develop a vaccine against Epstein-Barr for decades only because of the complexity of the virus. Epstein-Barr is “a master of evading the immune system,” said Dr. Jessica Durkee-Schock, a clinical immunologist and principal investigator of the NIAID trial.

Both MS and cancers associated with Epstein-Barr develop many years after people become infected. So a trial designed to see if a vaccine can prevent these diseases would take decades and a lot of money.

Modern researchers are focusing primarily on a more easily measured goal: prevention of mononucleosis, which doubles the risk of multiple sclerosis. People develop psychosis only a month or so after contracting Epstein-Barr, so scientists don’t have to wait long for results.

Mono itself can be incredibly disruptive, keeping students out of class and military recruits out of training for weeks. In about 10% of cases, disabling fatigue lasts six months or more. In 1% of cases, patients develop complications including hepatitis and neurological problems.

For now, clinical trials of Epstein-Barr vaccination are enrolling only adults. “In the future, a small child will be given the perfect vaccine,” Durkee-Schock said. “And that will protect them for life, and prevent them from getting mono or any other complications from the Epstein-Barr virus.”

The NIAID vaccine, being tested for safety in 40 volunteers, is built around ferritin, an iron-storage protein that can be used to display an important viral protein in the immune system. Like the cartoon Transformers, ferritin nanoparticles self-assemble to look like a “little iron soccer ball,” Durkee-Schock said. “This approach, in which many copies of the EBV protein are displayed on a single particle, has proven successful for other vaccines, including the HPV and hepatitis B vaccines.”

Moderna’s experimental vaccine, being tested in about 270 people, works like the company’s Covid shot. Both deliver snippets of the virus’s genetic information, or tiny bubbles of fat, in molecules called mRNA inside a lipid nanoparticle. Moderna, which has dozens of mRNA vaccines in development, hopes to learn from each and apply those lessons to Epstein-Barr, said Sumana Chandramouli, senior director and leader of Moderna’s infectious disease research program.

“What the Covid vaccine has shown us is that mRNA technology is well tolerated, very safe and very effective,” Chandramouli said.

But mRNA vaccines have limitations.

Although they have saved millions of lives during the Covid pandemic, the levels of antibodies produced in response to mRNA vaccines decline after a few months. It’s possible that this rapid loss of antibodies is particularly related to the coronavirus and its rapidly evolving new strains, Hotez said. But if waning immunity is inherent to mRNA technology, it could seriously limit future vaccines.

Designing a vaccine against Epstein-Barr is more complicated than for Covid. Epstein-Barr virus and other herpes viruses are relatively large, four to five times larger than SARS-CoV-2, the coronavirus that causes Covid. And while the coronavirus uses only one protein to infect human cells, the Epstein-Barr virus uses many, including four in modern vaccines.

Earlier experimental Epstein-Barr vaccines targeting a viral protein reduced rates of infectious mononucleosis but failed to prevent viral infection. Targeting multiple viral proteins may be more effective in preventing infection, said Damania, the UNC virologist.

“If you close one door, the other door is still open,” Damania said. “You have to block infection in all cells to have a successful vaccine that prevents future infections.”

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