The first antibody of its kind blocks the Epstein-Barr virus, which 95% of people carry.

Most people have Epstein-Barr virus (EBV). Sometimes people are not aware that the virus is present in their body;penetrates immune cells and persists.

First-of-its-kind antibody blocks Epstein-Barr virus - carried by 95% of people.

Most people have Epstein-Barr virus (EBV).Sometimes people don't know they have this virus in their bodies.It lives in immune cells and stays there all the time.Although EBV does not cause illness in most people (most people live without signs or symptoms of infection), for many people in the world today, including people with weakened immune systems, EBV has been linked to the development of various cancers and serious complications.

However, a new class of antibodies developed in the laboratory may eventually provide a way to prevent the EBV virus from causing disease.

Researchers at the Fred Hutch Cancer Center have created genetically engineered human monoclonal antibodies that can block EBV infection in mice with the human immune system.The research, published in Cell Reports Medicine00035-2, is an important step toward the development of new treatments that protect high-risk transplant recipients and other people affected by EBV infection.

Epstein-Barr virus infects about 95% of the world's population.It causes infectious mononucleosis.It is also linked to multiple sclerosis, autoimmune diseases, and about 358,000 cases of cancer, resulting in about 209,000 deaths.

Containing the virus has proven extremely difficult.

Inhibits the penetration of immune cells

According to Andrew McGuire, Ph.D., a biochemist and cell biologist in Fred Hutch's Vaccines and Infectious Diseases Division, “We have not been able to find any human antibodies that will prevent EBV from attaching to our immune cells.Unlike many other viruses, EBV has evolved greatly to connect to all the broader B cells.”

Therefore,Dr. McGuire and his colleagues decided to use new techniques to fill this knowledge gap.

Based on recent studies, EBV engages cells efficiently by deploying specific surface proteins and thus successfully infects and integrates into the B cell population. GP350 and GP42 are two viral proteins that act as molecular switches to bind and access the virus to human immune cells.

to create antibodies that can inhibit these stepsThe research team used a genetically engineered mouse model that carried human antibody genes.These mice were able to produce antibodies that closely mimicked the antibodies that humans produce.This reduces the chance of future antibody-mediated immune reactions.

Using this model, the scientists generated a total of ten different types of antibodies, including two antibodies against gp350 and eight antibodies against gp42.These antibodies blocked all human B cells to prevent the virus from attaching to receptors on the surface of human B cells.

Structural analysis of these antibodies also provides additional information about regions of the EBV-encoded protein that can be targeted for candidate vaccine development.

"Through our research, we have identified several important antibodies against Epstein-Barr virus. We have also demonstrated a new and effective way to detect antibodies against other viruses," said Crystal Chhan, Ph.D.candidate at the University of Virginia's McGuire Laboratory.

Protection against human rodents

Among the antibody candidates, one of the most promising has been found to be an antibody against gp42, a protein required by EBV to successfully enter immune cells.In studies using humanized mice (mice with human immune systems), infusions of this antibody provided significant protection against EBV after mice were exposed to the virus.

Evidence suggests a therapeutic potential for patients receiving organ and/or bone transplants.

About 128,000 people in the United States receive a solid organ or bone marrow transplant each year.By taking drugs to suppress the immune system (eg immunosuppressants), these patients allow EBV to become active again or spread.

One of its most important complications is called post-transplant lymphoproliferative disorder (PTLD), a type of aggressive lymphoma that is often associated with EBV.

Risks and Medical Needs of Transplantation

"Post-transplant lymphoproliferative disorders (PTLD), primarily EBV-associated lymphomas, are a common source of morbidity and mortality after organ transplant surgery," said Rachel Bender Ignacio, MD, MPH, professor and infectious disease specialist at the Fred Hutchinson Research School at the University of Washington.

"The ability to prevent EBV viremia can significantly reduce the incidence of PTLD while decreasing the need to reduce immunosuppressive therapy, ultimately supporting the continued function of transplants and improving patient outcomes. Therefore, the development of a way to prevent EBV viremia is one of the most significant unmet needs in transplant medicine," he added.

Because many children receiving transplants have not been previously exposed to EBV and are therefore not immune to the virus, they are expected to benefit more than adults.

Uncertainty in results

Although the results of this study were satisfactory, there are still many uncertainties. First, the study uses a humanized mouse model to evaluate the effectiveness of antibody therapy. For example, it does not model many aspects of EBV infection in humans. Murine epithelial cells cannot be infected by EBV, so tissue protection from antibody treatment cannot be assessed outside of immune cells.

Second, the virus was administered intravenously (IV).Given the frequency of EBV infections in transplant patients, the route of administration is likely to be different in the clinical setting.

In addition, the small sample size and variability in antibody levels precluded a reliable comparison of the two treatments.

Ultimately, clinical trials must be completed to prove whether the antibodies are safe and effective in humans.

Aim for optimal treatment

The researchers believe that patients could receive prophylactic antibody infusions before or after transplantation to prevent EBV infection and/or reactivation.

The Fred Hutchinson Cancer Research Center has also filed for antibody-related patent protection and is working with numerous collaborators and industry partners to facilitate the continued development of antibody therapy.Initial testing will include a safety study using healthy volunteers, followed by studies involving patients at high risk of developing EBV-associated PTLD.

"There has been growing momentum to take our findings and create a therapy that will have a tremendous impact on the lives of patients receiving organ transplants," adds McGuire."After many, many years of searching for an effective method to prevent EBV infection, we believe this is a major step forward for both the scientific community and those at highest risk for complications from EBV."

The research results are available online in the journal Cell Reports Medicine00035-2).

The original story "First antibody of its kind blocks Epstein Barr virus - carried by 95% of people" was published by The Brighter Side of News.

Like this emotional story?Get the bright side of the news.