A Frontier in EBV Vaccine Research: mRNA-Based Immunization with gp350, gp42, and gL Glycoproteins

Epstein-Barr virus (EBV), an extremely common herpesvirus that affects 95% of the adult population, has been implicated in various medical conditions, including infectious mononucleosis, cancers, and autoimmune diseases, yet there is no working vaccine approved for it. Demonstrated by their success in combatting SARS-CoV-2, which became a pandemic-level health-threat in 2020, Messenger RNA (mRNA) vaccines offer a streamlined process that could expedite the development of an EBV vaccine. After providing an overview of mRNA vaccines and their applications, this paper discusses candidate EBV glycoproteins gp350, gp42, and gL for the development of a vaccine, selected based on the criteria of protein abundance, functional importance, stage of EBV infection, presence on the viral envelope, and role in immune evasion. The engineering process for these candidate mRNA vaccines involved the insertion of signal sequences, transmembrane domains, 5’ and 3’ untranslated regions, and poly (A) tails to ensure protein expression and localization. Potential next steps and their merits are discussed regarding mRNA synthesis. Immunofluorescence, Western blotting, and Enzyme-Linked Immunosorbent Assay ELISA) are suggested to visualize protein expression, confirm localization, and quantify protein levels, respectively. Subsequent steps and their obstacles are discussed, including in vitro testing on human cell lines, animal models, and human trials. This paper explores three candidate vaccines with the potential to reduce the prevalence of the elusive pathogen EBV and its associated diseases. Its findings lay the groundwork for developing mRNA vaccines targeting EBV-associated diseases, offering a promising avenue for research in the fields of preventive medicine and immunology.