The Epstein-Barr virus (EBV) is one of the most widespread members of the herpesvirus family worldwide. It stands as the primary cause of infectious mononucleosis, typically acquired during adolescence. EBV infection has also been linked to the development of several autoimmune conditions such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis, as well as an elevated risk of cancers. This is because once infected, the virus persists in a latent form within the immune system, potentially leading to serious complications in immunocompromised individuals, where the virus can reactivate.
Among the glycoproteins involved in the virus’s entry into B lymphocytes are gp350 and gp42. The latter interacts with the gH/gL complex, a fundamental step for cellular infection.
Various research teams at the University of Washington and the Fred Hutchinson Cancer Center have evaluated the possibility of preventing infection using monoclonal antibodies, that is, lab-produced antibodies specifically directed against a molecular target.
Earlier studies had demonstrated that some of these antibodies could protect animal models from infection; however, the initial attempts in humans using the murine monoclonal antibody 72A1 revealed immunogenicity issues, as patients developed antibodies against the drug itself and, in some instances, hypersensitivity reactions.
To overcome this limitation, the study authors used genetically modified mice to produce antibodies with essentially human characteristics. By immunizing these animals with recombinant glycoproteins gp350 and gp42, they obtained two monoclonals directed against gp350 and eight directed against gp42. The results showed that the antibodies neutralize the virus by blocking the early stages of B cell infection.
Study Findings
The findings suggest that these antibodies could limit infection and reduce the risk of viremia in high-risk individuals, a hypothesis that will need confirmation in clinical trials. In particular, the monoclonal antibody directed against gp42 demonstrated strong preventive efficacy in the preclinical model: passive transfer before exposure to the virus in humanized mouse models prevented viremia, splenomegaly, and the presence of viral DNA in tissues, indicating results compatible with high protection from infection in the experimental model.
Antibodies directed against gp350, however, provided only partial protection.
Overall, the researchers suggest that gp42 represents one of the most promising targets for developing new preventive strategies against Epstein-Barr virus and that fully human monoclonal antibodies could eventually be used as prophylaxis in high-risk patients, particularly those with compromised immune systems and organ transplant recipients.
Study
Chhan C, Lang K, Davis A …Transgenic mouse-derived human monoclonal antibodies targeting EBV gp350 and gp42 provide basis for therapeutic developmentCell Reports Medicine, 7
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