Scientists have zeroed in on a way to disarm an incurable virus that infects nearly every American.
Cancer researchers at the Fred Hutchinson Cancer Center and the University of Washington in the US developed antibodies that bind to Epstein-Barr virus particles and block them from attaching to crucial immune cells.
In experiments with mice carrying human-like immune systems, one of those antibodies protected the animals from Epstein-Barr virus (EBV) infection, estimated to affect 95 percent of American adults.
EBV is a common virus from the herpes family. It is best known for causing infectious mononucleosis, often called ‘mono’ or the ‘kissing disease.’ Most people get infected with EBV at some point in their lives, often during childhood, with mild or no symptoms.
Once someone catches it, the virus stays in the body for life, usually remaining dormant, but it can sometimes reactivate, often due to stress or a weakened immune system.
It can sometimes lead to symptoms like fatigue or swollen glands. In rare cases, chronic or severe reactivation has been linked to certain autoimmune diseases, such as multiple sclerosis or lupus, and some cancers, like Hodgkin’s lymphoma or nasopharyngeal cancer, especially in people with suppressed immune systems.
EBV was the first virus discovered to cause cancer in humans. It is linked to about 358,000 new cancer cases and 209,000 deaths every year.
Andrew McGuire, biochemist and co-researcher, said: ‘After many years of searching for a viable way to protect against Epstein-Barr virus, this is a significant stride for the scientific community and the people at the highest risk of complications from this virus.’
The hallmark symptom of EBV is chronic fatigue, sometimes lasting for weeks or months. Other signs include sore throat, swollen lymph nodes in the neck and armpits, headache and enlarged spleen (stock)
Researchers set out to develop fully human antibodies that can prevent EBV infection, especially in high-risk organ transplant patients who can develop a deadly blood cancer if infected.
The researchers used genetically engineered mice that produced human antibodies rather than mouse antibodies.
They immunized the mice with two EBV surface proteins, then collected the cells in mice that produced antibodies and fused them with cancer cells to create hybridomas, or immortal cell lines that produce a single type of antibody.
They screened these antibodies to find ones that could block EBV from infecting B cells in lab dishes.
After immunizing the mice with two EBV proteins, gp350 and gp42, they identified two antibodies against gp350 and eight against gp42.
These are fully human antibodies, meaning they could be safer for patients than mouse-derived ones.
McGuire said: ‘Finding human antibodies that block Epstein-Barr virus from infecting our immune cells has been particularly challenging because, unlike other viruses, EBV finds a way to bind to nearly every one of our B cells.’
The gp350 antibodies stop the virus by blocking its attachment to a docking site on immune cells. The gp42 antibodies block a different docking site called HLA class II.
Both approaches prevent the virus from getting inside cells.
The gp42 antibody fully protected all the mice, with results showing none had virus in their spleens. The gp350 antibody only offered partial protection, with some mice still showing signs of infection.
This makes gp42 a promising candidate for protecting high-risk patients, such as organ transplant recipients who are vulnerable to EBV-related cancers.
Currently, there are no approved vaccines or specific treatments for EBV. This discovery provides strong candidates to advance human trials, potentially filling that gap for the first time.
Organ transplant recipients and people with weakened immune systems are very vulnerable to EBV-related cancers.
This discovery, detailed in Cell Reports Medicine, offers a potential preventive treatment; giving them the gp42 antibody before they get sick could block EBV infection and stop these cancers from developing.
The idea is that these antibodies could be given to the hundreds of thousands of people who get organ or bone marrow transplants every year. Because transplant patients need drugs that weaken their immune system, they become especially prone to EBV infection.
However, if antibodies can block or reduce EBV infection early, it might lower the risk of developing conditions linked to EBV later in life.
