
An electron micrograph showing three EBV virions in red-orange. Credit: NIAID
Key points:
- Researchers generated two monoclonal antibodies—A10 and 4C12—that target the gp42 protein the Epstein-Barr virus (EBV) uses to infect B cells.
- A10 blocked a receptor binding site on the protein and provided protection against EBV infection in mice.
- Future studies will examine if A10 can be used safely and effectively in humans who have not been infected with EBV, who have immunodeficiency conditions, or who received transplants.
Researchers examined interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein to reveal novel targets that can guide treatment. Their discovery, published in Immunity, provides new insights for EBV vaccine development.
Following infection, EBV remains in the body permanently—typically in B lymphocytes. In some cases, EBV can lead to B-cell, gastric, or nasopharyngeal cancers or raise the risk of developing multiple sclerosis. Despite nearly 95% of the world’s population being infected with EBV, no EBV vaccine or treatment exists.
Now, researchers are investigating the viral protein gp42 that EBV uses to infect B cells to find potential treatment targets. They generated two gp42-specific mAbs—A10 and 4C12—and used X-ray crystallography to visualize their interaction with gp42. They found that the two mAbs interacted with distinct, non-overlapping sites on gp42 with A10 blocking a receptor binding site and 4C12 interfering with a membrane fusion site.
A vaccine or antibody-treatment capable of inhibiting gp42 binding would prevent infection and the virus’s ability to persist in cells. To bring this closer to reality, the researchers tested A10, 4C12, and other mAbs in mice to probe their ability to prevent EBV infection and EBV lymphomas. They found that A10 provided nearly complete protection against EBV infection and none of the mice developed lymphoma. Nearly all the mice with other mAbs became infected and some developed lymphoproliferative disease or lymphoma.
Future studies will examine if A10 is safe and effective for use in humans. The team expects A10 could be used for people who have not been infected with EBV, people with immunodeficiency conditions, or people receiving transplants. The team also hopes to identify other vulnerable sites on gp42 that can inform future vaccine design.