The Epstein-Barr virus (EBV) persists for life in the human body after a primary infection. Most often, the infection has no consequences, but the virus can also cause severe illness and is associated with the development of certain tumors and autoimmune diseases. For this reason, it is logical to consider vaccination against EBV, even if the infection is without consequences in the majority of cases. At least at the present time, where the exact individual relationships between EBV infection and disease onset are still unclear, this seems to me to be a sensible approach to potentially prevent EBV-associated diseases.
For this, a vaccine would first have to be developed – and then one would need a very long breath to observe whether the incidence of EBV-associated diseases decreases. From my point of view, it would also make sense to vaccinate very early in life, as the vast majority of individuals are infected in childhood and adolescence, which places special safety requirements on a vaccine.
Vaccine against different antigens needed
The development of a vaccine against EBV is anything but trivial. The central problem in developing a protective vaccine against EBV is that the virus goes through various phases (see The Epstein-Barr Virus (EBV) – Facts and Considerations for Vaccination (2)). After infection, it is in a latent phase in infected B-cells and multiplies together with these infected B-cells during their cell division. It is to be assumed that the virus proteins, which are expressed in the latent phase, are particularly important for the development of various diseases – especially for tumor development. From the latent phase, the virus can be reactivated and enter the so-called lytic phase, in which new virus particles are formed and released. In both phases, EBV produces a very different repertoire of virus proteins. Since the immune response in healthy EBV-infected people also targets proteins of both phases, antigens from both phases would have to be used in vaccine development.
In search of the appropriate vaccine
To this day, there is still no approved vaccine against the Epstein-Barr virus. Initially, vaccine studies were conducted targeting the EBV surface protein gp350, which however only prevented the infection of B-cells, but not that of epithelial cells with EBV. Therefore, subsequent efforts focused on a vaccine response against the viral glycoproteins gH and gL, which can also protect endothelial cells from infection. New approaches to vaccine development include VLP-based (virus-like particle) EBV vaccines and the use of mRNA technology. Newer approaches have in common that a multitude of epitopes (small amino acid sequences that trigger an immune response) were included in the vaccine formula. Each epitope targets proteins expressed by EBV at different stages of its life cycle. Additionally, work is being done intensively on new adjuvants that increase the effectiveness of the vaccines. Successful trials have been conducted on mice using this new vaccine strategy, showing that the vaccine induced antibodies that could prevent the virus from penetrating B-cells and triggered a killer T-cell immune response that destroyed infected B-cells (Dasari V et al. Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice. Nat Commun. 2023;14(1):4371). It is unknown how the long-term effectiveness of the vaccine for protection against EBV-associated diseases looks like. Therefore, human studies will ultimately be needed to better understand the long-term effectiveness.
Even though it is still a long way off, it should be noted that the vaccines currently being developed have the potential to prevent EBV-related diseases – and this could mean a significant breakthrough in MS in the long term, as there is undoubtedly a strong link between EBV and MS.