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Epstein-Barr: Researchers accelerate vaccine efforts against mono, virus linked to MS

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Perhaps you have never heard of the Epstein-Barr virus. But he knows everything about you.

Your luck is living inside of you right now. About 95% of American adults become infected at some point in their lives. And once infected, the virus stays with you.

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

This viral family “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.”

While childhood Epstein-Barr infections are typically mild, exposure in teenagers and young adults can lead to infectious mononucleosis, a weeks-long illness that sickens 125,000 Americans a year, causing sore throats, swollen glands, and extreme tiredness. While Epstein-Barr spends most of his time sleeping, he can wake up again during stressful times or when his immune system is down. 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 vaccines against Epstein-Barr, or EBV. But several leaps in medical research lately have given the quest more urgency and more hope for success. Just last year, two experimental vaccine studies reached human clinical trials.

What changed?

First, the Epstein-Barr virus has been shown to pose an even greater threat. New research firmly 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, Science published the results of a 20-year landmark study of 10 million military personnel that provided the strongest evidence that Epstein-Barr can trigger MS. The new study found that people infected with Epstein-Barr were 32 times more likely to develop MS than people who were not infected.

And shedding new light on the mechanisms that may explain this correlation, a separate group of scientists has published a study in Nature describing how the virus can cause an autoimmune reaction that leads to MS. The disease, which usually occurs between the ages of 20 and 40, impairs communication between the brain and other parts of the body and is often manifested by recurrent fatigue, blurred vision, muscle weakness, and difficulty with balance and coordination. At worst, MS can lead to slurred speech and paralysis.

Reinforcing the newly discovered urgency, several recent studies suggest that Epstein-Barr virus reactivation is also related to some long-lived covid cases where patients often experience persistent symptoms resembling mononucleosis.

And it’s crucial for momentum: Advances in vaccinology fueled by the pandemic, including mRNA technology used in some covid vaccines, could accelerate the development of other vaccines, including those against Epstein-Barr, he said. National School of Tropical Medicine at Baylor College of Medicine. Hotez co-created a low-cost, unpatented covid vaccine called Corbevax.

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

A professor at the Lewis Katz School of Medicine at Temple University, Dr. Ralph Horwitz said that eliminating Epstein-Barr would require all healthy children to be vaccinated, even if their risk of developing cancer or multiple sclerosis is small.

Before exposing children to the potential risks of a new vaccine, he said, scientists need to answer fundamental questions about MS. For example, why would a virus that infects nearly everyone cause a small proportion of disease? And what roles do stress and other environmental conditions play in this equation?

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

Researchers may continue to investigate the mysteries surrounding Epstein-Barr and MS even as vaccine studies continue, Hotez said. Hotez said that more studies are needed to understand which populations can benefit most from a vaccine, and that it is known once again that such a vaccine could be used in patients at highest risk, such as organ transplant recipients, rather than being universally applied. to all young people.

“Now that we know that Epstein-Barr is so tightly linked to MS, we could save many lives if we develop the vaccine now,” Damania said, “rather than waiting 10 years” until every 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 Opko Health, a Miami-based biotech company; Fred Hutchinson Cancer Center in Seattle; and California’s City of Hope National Medical Center.

Scientists have tried to develop a vaccine against Epstein-Barr for decades, but the complexity of the virus has been hampered. Clinical immunologist and principal investigator of NIAID’s trial, Dr. Jessica Durkee-Shock said of Epstein-Barr “a master at evading the immune system.”

Cancers associated with both MS and Epstein-Barr develop years after people are infected. Therefore, a trial designed to find out whether a vaccine can prevent these diseases would take decades and a lot of money.

Moderna researchers initially focus on a more easily measurable goal: preventing mononucleosis, which doubles the risk of multiple sclerosis. Mono develops only a month or so after people are infected with Epstein-Barr, so scientists won’t have to wait long for results.

Mono on its own can be incredibly destructive, keeping students out of the classroom and enlisted soldiers out of training for weeks. In about 10% of cases, disabling fatigue lasts for six months or more. In 1% of cases, patients develop complications, including hepatitis and neurological problems.

For now, clinical trials for Epstein-Barr vaccines are taking adults only. “In the future, the perfect vaccine will be given to a young child,” Durkee-Shock said. “And it will protect them for their entire lives and prevent them from getting mono or any other complications from the Epstein-Barr virus.”

Tested for safety in 40 volunteers, the NIAID vaccine is built around ferritin, an iron storage protein that can be manipulated to expose an important viral protein to the immune system. Like a cartoon Transformer, the ferritin nanoparticle self-forms what looks like a “little iron soccer ball,” Durkee-Shock said. “This approach, in which many copies of the EBV protein are imaged on a single particle, has proven successful for HPV and other vaccines, including the hepatitis B vaccine.”

Moderna’s experimental vaccine, which has been tried in about 270 people, works more like the company’s covid vaccine. Both transmit snippets of a virus’s genetic information in molecules called mRNA inside a lipid nanoparticle or a small oil bubble. Sumana Chandramouli, senior director of infectious diseases and research program leader at Moderna, said she hopes to learn from each of Moderna’s dozens of mRNA vaccines in development and apply those lessons to Epstein-Barr.

“What the Covid vaccine has shown us is that mRNA technology is well tolerated, very safe and extremely 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. Hotez said this rapid loss of antibodies could be related specifically to the coronavirus and its rapidly evolving new strains. But if mRNA technology has inherent diminished immunity, this could severely limit future vaccines.

Designing a vaccine against Epstein-Barr is also more complex than covid. Epstein-Barr virus and other herpes viruses are relatively large, four to five times larger than the coronavirus SARS-CoV-2 that causes covid. And while the coronavirus uses just one protein to infect human cells, the Epstein-Barr virus uses many proteins, four of which are included in the Moderna vaccine.

Previous experimental Epstein-Barr vaccines targeting a viral protein reduced the rate of infectious mononucleosis but failed to prevent viral infection. UNC virologist Damania said targeting multiple viral proteins may be more effective at preventing infection.

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