Insights into the interplay between Epstein‐Barr virus (EBV) and multiple sclerosis (MS): A state‐of‐the‐art review and implications for vaccine development

Article

Author: Shaygannejad, Vahid ; Mohammadzamani, Mahtab ; Ebrahimi, Narges ; Thapa, Sangharsha ; Yazdan Panah, Mohammad ; Mirmosayyeb, Omid ; Kazemzadeh, Kimia ; Chand, Swati

AbstractBackground and AimsMultiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). MS results from an inflammatory process leading to the loss of neural tissue and increased disability over time. The role of Epstein Barr Virus (EBV), as one of the most common global viruses, in MS development has been the subject of several studies. However, many related questions are still unanswered. This study aimed to review the connection between MS and EBV and provide a quick outline of MS prevention using EBV vaccination.MethodsFor this narrative review, an extensive literature search using specific terms was conducted across online databases, including PubMed/Medline, Scopus, Web of Science, and Google Scholar, to identify pertinent studies.ResultsSeveral studies proved that almost 100% of people with MS showed a history of EBV infection, and there was an association between high titers of EBV antibodies and an increased risk of MS development. Various hypotheses are proposed for how EBV may contribute to MS directly and indirectly: (1) Molecular Mimicry, (2) Mistaken Self, (3) Bystander Damage, and (4) Autoreactive B cells infected with EBV.ConclusionGiven the infectious nature of EBV and its ability to elude the immune system, EBV emerges as a strong candidate for being the underlying cause of MS. The development of an EBV vaccine holds promise for preventing MS; however, overcoming the challenge of creating a safe and efficacious vaccine presents a significant obstacle.

04 Jun 2021·The Journal of Infectious DiseasesQ2 · MEDICINE

Maternal Epstein-Barr Virus-Specific Antibodies and Risk of Infection in Ugandan Infants

Q2 · MEDICINE

Article

Author: McGuire, Andrew T ; Krantz, Elizabeth M ; Casper, Corey ; Ortego, Michael ; Sholukh, Anton M ; Cohen, Jeffrey I ; Bu, Wei ; Irvine, Michael ; Nguyen, Hanh ; Huang, Meei-Li ; Orem, Jackson ; Minab, Rana ; Gantt, Soren ; Wall, Abigail

AbstractBackgroundEpstein-Barr virus (EBV) infection is a major cause of malignancy worldwide. Maternal antibody is thought to prevent EBV infection because it is uncommon in early infancy. Maternal HIV infection is associated with an increased incidence of EBV infection in exposed infants, which we hypothesized results from impaired transfer of EBV-neutralizing maternal antibodies.MethodsAmong Ugandan infants followed for EBV acquisition from birth, we measured antibody binding to EBV glycoproteins (gp350, gH/gL) involved in B-cell and epithelial-cell entry, as well as viral neutralization and antibody-dependent cellular cytotoxicity (ADCC) activity in plasma samples prior to infection. These serologic data were analyzed for differences between HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) infants, and for associations with incident infant EBV infection.ResultsHEU infants had significantly higher titers than HUU infants for all EBV-binding and neutralizing antibodies measured (P < .01) but not ADCC activity, which was similar between groups. No antibody measure was associated with a decreased risk of EBV acquisition in the cohort.ConclusionsOur findings indicate that in this cohort maternal antibody did not protect infants against EBV infection through viral neutralization. The identification of protective nonneutralizing antibody functions would be invaluable for the development of an EBV vaccine.

01 Nov 2020·Cellular and Molecular Life SciencesQ2 · BIOLOGY

Vaccination against the Epstein–Barr virus

Q2 · BIOLOGY

Review

Author: Münz, Christian ; Leung, Carol S ; Rühl, Julia

Epstein-Barr virus (EBV) was the first human tumor virus being discovered and remains to date the only human pathogen that can transform cells in vitro. 55 years of EBV research have now brought us to the brink of an EBV vaccine. For this purpose, recombinant viral vectors and their heterologous prime-boost vaccinations, EBV-derived virus-like particles and viral envelope glycoprotein formulations are explored and are discussed in this review. Even so, cell-mediated immune control by cytotoxic lymphocytes protects healthy virus carriers from EBV-associated malignancies, antibodies might be able to prevent symptomatic primary infection, the most likely EBV-associated pathology against which EBV vaccines will be initially tested. Thus, the variety of EBV vaccines reflects the sophisticated life cycle of this human tumor virus and only vaccination in humans will finally be able to reveal the efficacy of these candidates. Nevertheless, the recently renewed efforts to develop an EBV vaccine and the long history of safe adoptive T cell transfer to treat EBV-associated malignancies suggest that this oncogenic γ-herpesvirus can be targeted by immunotherapies. Such vaccination should ideally implement the very same immune control that protects healthy EBV carriers.

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Indication	Highest Phase	Country/Location	Organization	Date
Epstein-Barr Virus Infections	Preclinical	China	Chongqing Zhifei Biological Products Co., Ltd.	29 Oct 2023
Epstein-Barr Virus Infections	Preclinical	China	Sun Yat-Sen University Cancer Center	29 Oct 2023

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