To date, Epstein-Barr virus (EBV) has escaped the attentions of vaccines and therapeutics. That EBV should be so shy frustrates scientists, who are well aware of EBV’s depredations. EBV is nearly ubiquitous in adults, and it is associated with serious health impacts—not just with infectious mononucleosis, but also with B-cell lymphomas, epithelial cell malignancies, and multiple sclerosis.

To bring EBV vulnerabilities to light, scientists based at the National Institute of Allergy and Infectious Diseases (NIAID) and the Walter Reed Army Institute of Research focused on an EBV glycoprotein complex called gH/gL. It is expressed on EBV’s surface and is essential to EBV’s success because it facilitates fusion of virus membrane with host cells. If gH/gL vulnerabilities could be identified and exploited, EBV itself could be crippled.

The scientists developed a panel of human monoclonal antibodies (mAbs) that targeted five distinct antigenic sites on EBV gH/gL. Then the scientists evaluated how well the mAbs blocked virus-cell fusion in human B cells and epithelial cells, and in a humanized mouse EBV challenge model. The results of this work appeared in the journal Immunity, in an article titled, “Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition.”

“[Each of our six mAbs] prevented infection of epithelial and B cells,” the article’s authors wrote. They added that one of the experimental mAbs, mAB 769B10, provided “near-complete protection against viremia and lymphoma in a humanized mouse EBV challenge model.”

Analyzing the structure of the mAbs and their two surface proteins using X-ray crystallography and advanced microscopy, the researchers identified multiple sites of vulnerability on the virus to target.

“Our findings,” the article’s authors concluded, “provide structural and antigenic knowledge of the viral fusion machinery, yield a potential therapeutic antibody to prevent EBV disease, and emphasize gH/gL as a target for herpesvirus vaccines and therapeutics.”

EBV is one of the most common human viruses. After an EBV infection, the virus becomes dormant in the body but may reactivate in some cases. People with weakened immune systems, such as transplant recipients, are more likely than immunocompetent people to develop severe symptoms and complications from EBV infection.

In the current study, the scientists, led by the NIAID’s Jeffrey I. Cohen, MD, emphasized that their findings highlight viable EBV vaccine targets and the potential for the experimental mAbs to be used alone or in combination to prevent or treat EBV infection in immunocompromised patients most susceptible to severe EBV-related disease. The scientists also indicated that additional research with mAb 769B10 is planned.

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