Progress in Prophylactic and Therapeutic EBV Vaccine Development Based on Molecular Characteristics of EBV Target Antigens

Abstract

Epstein-Barr virus (EBV) was discovered in 1964 in the cell line of Burkitt lymphoma and became first known human oncogenic virus. EBV belongs to the Herpesviridae family, and is present worldwide as it infects 95% of people. Infection with EBV usually happens during childhood when it remains asymptomatic; however, in adults, it can cause an acute infection known as infectious mononucleosis. In addition, EBV can cause wide range of tumors with origins in B lymphocytes, T lymphocytes, and NK cells. Its oncogenicity and wide distribution indicated the need for vaccine development. Research on mice and cultured cells as well as human clinical trials have been in progress for a few decades for both prophylactic and therapeutic EBV vaccines. The main targets of the vaccines are EBV envelope glycoproteins such as gp350 and EBV latent genes. The long wait for the EBV vaccine is due to the complexity of the EBV replication cycle and the wide range of its host cells. Although some strategies such as the use of dendritic cells and recombinant Vaccinia viral vectors have shown success, ongoing clinical trials using mRNA-based vaccines as well as new delivery systems as nanoparticles are yet to show the best choice of vaccine target and its production strategy.

Keywords: EBV and immune response; EBV mRNA vaccine; EBV replication cycle; prophylactic EBV vaccine; therapeutic EBV vaccine.

Figure 1

Structure of EBV virion; stressed glycoproteins gp350, gHgL, gp42, and gB are required for attachment and fusion with B lymphocytes during primary infection.

Figure 2

Development of the production strategy of the EBV prophylactic vaccine based on gp350 protein.

Figure 3

EBV vaccine designed with mRNA-1189, with a group of five different mRNAs coding for glycoproteins needed for virus attachment and fusion, incorporated into lipid nanoparticles. Translated proteins are displayed on the surface of B lymphocytes, which induces the production of neutralizing antibodies.