New EBV Antibodies Could Help Block Epstein-Barr Virus Infection

The Epstein-Barr virus (EBV) ranks among the most widespread viruses globally and is believed to be present in 95 percent of adults. In most cases, people experience no clear symptoms.

However, EBV is not simply a temporary infection.

After entering the body, EBV can remain there for life. It has associations with several cancers, multiple sclerosis and other serious health complications.

Scientists have now identified a potentially promising new method of tackling it.

EBV antibodies target proteins used to infect B cells

In February, researchers from the Fred Hutchinson Cancer Center and the University of Washington in the US created antibodies aimed at two proteins found on the surface of EBV particles.

The proteins enable the virus to gain entry to B cells, a form of white blood cell with a crucial role in the immune system.

Stopping these proteins from working could prevent EBV from establishing infection initially, and might also stop it reactivating later in life.

In tests involving mice with human-like immune systems, one of the antibodies protected the animals against EBV infection.

This research also addresses a longstanding obstacle in developing EBV antibodies. Because the virus attacks the body so extensively, it is exceptionally difficult to find the particular immune cells that fight it and use them as the basis for antibodies.

"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," said biochemist Andrew McGuire at the time.

"We decided to use new technologies to try to fill this knowledge gap and we ended up taking a critical step toward blocking one of the world's most common viruses."

A particularly clever element of the method involved mice bred to make genetically human antibodies. Should the research eventually progress to injections in people, this increases the likelihood that the antibodies will be accepted by the human body.

When the mice encountered the two EBV proteins, gp350 and gp42, their cells produced the specific immune response the scientists sought, making it possible to generate tightly targeted antibodies.

In total, the team isolated 10 new antibodies in the laboratory: two directed at gp350 and eight at gp42. When examined in live mice, one of these antibodies offered especially encouraging protection against EBV.

"Not only did we identify important antibodies against Epstein-Barr virus, but we also validated an innovative new approach for discovering protective antibodies against other pathogens," said pathobiologist Crystal Chhan.

"As an early-career scientist, it was an exciting finding and has helped me appreciate how science often leads to unexpected discoveries."

Potential protection for transplant recipients

When EBV produces noticeable illness in people, it commonly begins as infectious mononucleosis, or glandular fever. It then persists in a dormant, non-infectious form, but can become considerably more dangerous, particularly for people with weakened immune systems.

One potential use for these antibodies could be in the hundreds of thousands of organ and bone marrow transplants carried out annually. Such procedures require immunosuppression, which may make recipients susceptible to EBV.

EBV-driven post-transplant lymphoproliferative disorders (PTLD) are a particular concern. In these conditions, lymphocytes - again, the B cells - may multiply uncontrollably, causing life-threatening cancers.

A dose of the newly identified antibodies could potentially restrain this uncontrolled growth.

"Preventing EBV viremia has strong potential to reduce the incidence of PTLD and limit the need to reduce immunosuppression," said infectious disease physician Rachel Bender Ignacio.

Preventing infection may be especially useful in transplants involving children, who may not yet have encountered EBV.

Next steps for EBV treatment and vaccine research

Considerably more research is needed before a treatment becomes available, but the discovery of new ways to prevent EBV infecting human immune cells is encouraging. The next step is to move towards human safety testing and clinical trials.

Other researchers are also developing an EBV vaccine.

"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," said McGuire.

The research was published in Cell Reports Medicine.

This article was fact-checked and edited by Fiona MacDonald. Although we take pride in our process, we are only human. If you notice an error, please let us know.