Experimental Monoclonal Antibodies Show Promise Against Epstein-Barr Virus

A panel of investigational monoclonal antibodies (mAbs) targeting different sites of the Epstein-Barr virus (EBV) blocked infection when tested in human cells in a laboratory setting. Moreover, one of the experimental mAbs provided nearly complete protection against EBV infection and lymphoma when tested in mice. The results appear online today in the journal Immunity. Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, in collaboration with researchers from Walter Reed Army Institute of Research, led the study.

https://www.nih.gov/news-events/new...ional monoclonal,lymphoma when tested in mice

 

Highlights

• •
  Six human mAbs target five distinct sites on EBV gH/gL
• •
  Some of these antigenic sites match sites of vulnerability on other herpesviruses
• •
  Each mAb neutralizes EBV infection and blocks virus-cell fusion
• •
  mAb 769B10 inhibits viremia and prevents lymphoma in an animal EBV challenge model

Summary
Epstein-Barr virus (EBV) is nearly ubiquitous in adults. EBV causes infectious mononucleosis and is associated with B cell lymphomas, epithelial cell malignancies, and multiple sclerosis. The EBV gH/gL glycoprotein complex facilitates fusion of virus membrane with host cells and is a target of neutralizing antibodies. Here, we examined the sites of vulnerability for virus neutralization and fusion inhibition within EBV gH/gL. We developed a panel of human monoclonal antibodies (mAbs) that targeted five distinct antigenic sites on EBV gH/gL and prevented infection of epithelial and B cells. Structural analyses using X-ray crystallography and electron microscopy revealed multiple sites of vulnerability and defined the antigenic landscape of EBV gH/gL. One mAb provided near-complete protection against viremia and lymphoma in a humanized mouse EBV challenge model. Our findings 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


https://www.cell.com/immunity/fulltext/S1074-7613(22)00544-1?_returnURL=https://linkinghub.elsevier.com/retrieve/pii/S1074761322005441?showall=tru

 

Hopefully, an antiviral that is effective against EBV may prevent the progression to ME after being infected. If the ongoing trials of Moderna’s mRNA vaccine also demonstrate its efficacy, we could have a long awaited toolbox against EBV-induced ME/CFS, cancers, MS, and possibly other diseases that are (for now unknowingly) linked to it. This would be a major achievement.

 

I'd like to see a study on EBV and ME similar to the MS one. Maybe EBV is a requirement to get ME as well.

 

Wouldn’t you just keep getting reinfected with EBV?

 

Yes, I would too.

 

Can you expand on this? I've missed something

 

I think there are realistic concerns about what this treatment might achieve.

If it removes virus that may improve the acute illness.

On the other hand if it makes the virus invisible to the immune system then you may not mount a healthy immune response. The immune response to EBV is unusual and has three phases. In the first phase the virus colonises B cells and expands them almost like a lymphoma. In the second phase cytotoxic T cells learn to recognise B cells infected with virus and kill them. In the third phase T cells keep a constant control over the constant re-infection of a small proportion of B cells with the virus never being fully cleared.

If virus was made invisible to T cells then the second phase might be blocked and the lymphoma-like proliferation might just get out of hand. This might not occur because the T cells recognise fragments of virus proteins presented to them by infected B cells in a way that might not be interfered with by monoclonals. I think it is quite likely that the monoclonal treatment will turn out to be a useful way of controlling severe acute infection. Whether it has any other benefit seems a bit doubtful. If the virus is inside cells the monoclonals are unlikely to get at it. So once the treatment is over you are pretty much back to the situation we are all in now - low level hidden infection.