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