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Experimental monoclonal antibodies show promise against Epstein-Barr virus: October 27, 2022

SWAlexander

Senior Member
Messages
1,898
If EBV is the only culprit for ME/CFS, there is hope.

The German Ärzteblatt (medical magazine) reported:

Google translation.
Monoclonal antibody protects against Epstein-Barr virus infection
Bethesda/Maryland – US researchers have discovered monoclonal antibodies that can neutralize the Epstein-Barr virus (EBV). A monoclonal antibody protected mice from infection and lymphoma, according to the report in Immunity (2022; DOI: 10.1016/j.immuni.2022.10.003).

The herpes virus, discovered in 1964 by the English virologist Michael Epstein and his colleague Yvonne Barr in cell cultures of Burkitt's lymphoma, is one of the most successful pathogens. About 90% of all people become infected with EBV, mostly in childhood and adolescence, which, like other herpes viruses, leads to lifelong persistence.
Acute infections with EBV trigger the mostly mild glandular fever. The latent infections are associated with certain types of cancer, such as Hodgkin's lymphoma, but also with autoimmune diseases such as multiple sclerosis.

In people with a weakened immune system, such as organ transplant recipients or recipients of stem cell therapies, an acute infection can lead to a life-threatening lymphoproliferative disease in which the infected B cells spread to internal organs and also to the brain.

So far there is no vaccine that could protect against EBV infection. However, a team led by Jeffrey Cohen from the "National Institute of Allergy and Infectious Diseases" in Bethesda/Maryland has now succeeded in detecting antibodies in the blood of EBV-positive people that neutralize the EBV surface proteins gB and gH. The genes of a total of 6 antibodies were isolated from B cells and used in recombinant cells to produce monoclonal antibodies.

The laboratory tests showed that the monoclonal antibodies protect human B cells and the epithelial cells of the pharyngeal mucosa - the main portal of entry in humans - from infection. By analyzing the structure of the antibodies and their two surface proteins, the researchers identified several vulnerabilities on the virus that would also be suitable targets for vaccines that would need to produce endogenous antibodies against these targets.
In a first animal study, one of the 6 antibodies called mAb 769B10 was able to completely protect mice from infection. The antibody also prevented the mice from developing EBV lymphoma.

If the effect is confirmed in further studies, the monoclonal antibody could protect transplant recipients from infection or slow down the course of a lymphoproliferative disease.

It could also fund the development of a vaccine that would not only protect children from glandular fever, but could potentially reduce their risk of developing lymphoma or autoimmune disease later in life. This would also provide evidence for the involvement of EBV in these diseases.
https://www.aerzteblatt.de/nachrich...huetzt-vor-Infektionen-mit-Epstein-Barr-Virus

Reference to:
Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition

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
 

SWAlexander

Senior Member
Messages
1,898
Reading Experimental monoclonal antibodies show promise against Epstein-Barr virus
https://www.nih.gov/news-events/new...odies-show-promise-against-epstein-barr-virus

There is no clear stipulation if the EBV vaccine could eradicate active or latent infection.
I my understanding in summary:
The Epstein-Barr virus (EBV) vaccine, which is currently under development, aims primarily to prevent the initial infection with EBV. This is significant because EBV is known to cause infectious mononucleosis and is associated with several types of cancer and autoimmune diseases. However, the effectiveness of an EBV vaccine in eradicating active or latent infections in individuals who are already infected is less clear.
  1. Preventing Initial Infection: The primary goal of the EBV vaccine is to prevent the initial infection. By stimulating an immune response that can recognize and neutralize the virus, the vaccine could significantly reduce the incidence of EBV-related diseases. This is crucial because once EBV infects a person, it usually remains in the body in a latent form.
  2. Active Infection: For those who are currently experiencing an active EBV infection, the vaccine's role is less certain. An active infection means the virus is replicating and causing symptoms. Vaccines generally are not designed to treat active infections, but to prevent them.
  3. Latent Infection: EBV can remain latent in the body for a lifetime without causing symptoms. During latency, the virus is present in a dormant state and is less likely to be affected by the immune response triggered by a vaccine. Therefore, the ability of a vaccine to impact a latent EBV infection is not well established and is a subject of ongoing research.
  4. Therapeutic Vaccines: A different type of vaccine, known as a therapeutic vaccine, is designed to treat existing infections or diseases. Research into therapeutic vaccines for EBV is ongoing, but this is a separate area of study from preventive vaccines.
In summary, while an EBV vaccine could potentially prevent new infections, its effectiveness against active or latent infections in those already infected remains an area of active research and development. The future of EBV management may involve both preventive vaccines and therapeutic strategies.
 

Hoosierfans

Senior Member
Messages
400
If I’m reading all of the above correctly — and someone please correct me — this development could lead to two things;

1. Development of an EBV vaccine (but is already in the works by others) as @SWAlexander discusses, which will protect uninfected individuals; AND

2. Therapeutic monoclonal antibody therapy for those already infected, which could be utilized in latent EBV driven diseases such as MS, ME/CFS and EBV driven cancers.
 

SWAlexander

Senior Member
Messages
1,898
already infected, which could be utilized in latent EBV driven diseases such as MS, ME/CFS and EBV driven cancers.
I know there is a contradiction:
"There is no clear stipulation if the EBV vaccine could eradicate active or latent infection."
Yesterday, I sent out some requests to confirm about protection for "those already infected, which could be utilized in latent EBV driven diseases". I hope NIH will confirm this statement and provide a protocol.

I asked the same question two years ago about Polio vaccine for people with post-Polio. I never received an answer.
 
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Hoosierfans

Senior Member
Messages
400
@SWAlexander i think there’s TWO possible therapies that could come out of this, as I read the information. The first is the development of a vaccine (again, already in the works but this work may create another vaccine or a broader range single vaccine).

The second is some kind of monoclonal antibody therapy that is given post infection / inflammatory condition like Humira, Ajovy, Frexalimab (in development for MS), Rituximab etc etc etc. From this list, it appears that there are plenty of monoclonal antibodies aimed at treating existing viral infections (Ebola, CMV, COVID)

https://en.m.wikipedia.org/wiki/List_of_therapeutic_monoclonal_antibodies

In other words, I’m not asking if the vaccine would be effective / useful for existing infections, but rather if this development means that they could develop a therapeutic MAB treatment for existing infections. That’s what I’m trying to clairfy — that my understand of this breakthrough is correct.
 

SWAlexander

Senior Member
Messages
1,898
understand of this breakthrough is correct
This is what I understand. Please understand that I'm not the author of this scientific paper, I'm only the messenger.

There is additional news.
"A fascinating new study on catalytic antibodies and their possible link to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome/(ME/CFS). In this study, researchers (one of them Ron Davis) explored the presence of catalytic antibodies in ME/CFS patients, focusing on their ability to break down 𝐌𝐲𝐞𝐥𝐢𝐧 𝐁𝐚𝐬𝐢𝐜 𝐏𝐫𝐨𝐭𝐞𝐢𝐧 (𝐌𝐁𝐏). The rationale lies in the common symptoms between ME/CFS and Multiple Sclerosis (MS), especially muscle weakness and nerve pain associated with demyelination."

If you like read the whole thread:
 
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SWAlexander

Senior Member
Messages
1,898
mononucleosus they did not know a virus existed?
Maybe the definition EBV did not exist. The herpes simplex virus I (HSV-1) strain behind facial herpes arose 5000 years ago during the Bronze Age. Herpes was not found to be a virus until the 1940s.
However German pathologist Hugo Ribbert observed CMV in 1881.

Even though EBV was mentioned by Dr. Komaroff at the CFIDS Association of America Research Conference held on 17th-18th November 1990 at Charlotte, North Carolina, no further research was done then. We are still at the same unknown place without a marker. https://www.investinme.org/Article422-2 Grey Information about ME-CFS.shtml
 
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