The Epstein-Barr virus (EBV) is a very common virus, present in more than 90% of the adult human population. The initial infection is most often through saliva, in childhood or adolescence. The virus then penetrates to the level of the oropharynx where it infects epithelial cells and local B lymphocytes, before winning those of the whole organism. The infection can then manifest as infectious mononucleosis, also called kissing disease, which is generally mild and heals spontaneously. It can also remain asymptomatic but, in all cases, the virus will persist in the lymphocytes where its DNA genome is maintained in the form of an episome, without integrating into the cellular DNA. In this state, some viral genes continue to be expressed and contribute to the appearance of cancers, lymphomas (including Burkitt’s lymphoma and certain Hodgkin’s lymphomas) and cancer of the nasopharynx.
Multiple sclerosis (MS) is an autoimmune disease in which the myelin that surrounds nerve fibers and allows the transmission of nerve impulses is attacked by immune cells and gradually destroyed. MS is most often diagnosed in young adults, more frequently in women than in men. In France, 2,500 new cases are discovered each year and approximately 100,000 people are affected. A role of persistent EBV infection in the onset of MS has long been suspected, but no confirmation has yet been provided. The study that has just been published by an American team tells us that the prevalence of EBV is significantly higher in people with MS (1). The researchers looked at a cohort of more than 10 million young adults, serving military personnel, over a 20-year period. Over this period, 955 cases of MS were diagnosed. The risk of MS was found to increase 32-fold after infection with EBV, while no other viral infection was associated with an increased risk. Only one of the MS cases did not show anti-EBV antibodies when tested 3 months before diagnosis. In addition, blood levels of a product linked to nerve fiber degeneration, neurofilament light chains, were only increased in subjects who had been infected with EBV.
The researchers found no possible explanation for their findings among other factors that could potentially contribute to the onset of MS. In particular, they did not detect in those who presented with the disease any anomaly in the immune response that could both explain the onset of MS and independently facilitate EBV infection. They conclude that EBV is probably a main triggering factor for MS, even if the disease remains rare relative to the frequency of infections. The virus, which remains present, could also then be involved in the evolution of the disease. Therefore, antiviral treatments or a vaccine against EBV, aimed at preventing infectious mononucleosis, could also protect against the onset of MS and perhaps modify its evolution.
The development of such a vaccine is difficult and none of the projects carried out in other laboratories have resulted in an effective vaccine (2). The difficulties are numerous, between the absence of a satisfactory animal model (EBV is a strictly human virus) and the still imperfect knowledge of the biology of the virus and the mechanisms of infection. On the other hand, it is expected that different solutions and formulas will have to be found to prepare a prophylactic vaccine intended to prevent infection and perhaps several therapeutic vaccines capable of treating the diseases in which the virus is implicated. While several attempts have used viral proteins isolated or combined into virus-like particles, Moderna has used messenger RNA technology to develop a vaccine candidate that has begun a Phase 1 trial. The laboratory is counting on the possibility of causing this RNA to express four surface glycoproteins of the virus involved in the infection of cells, which would induce a broad immune response capable of preventing this infection and the subsequent installation of the virus.
It will of course be necessary to ensure that these proteins play no role in the triggering of cancers or the autoimmune mechanisms for which the virus is made responsible.
References
- K. BjornevikLongitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis.
- H. Gruffat. A vaccine against the Epstein-Barr virus: a reality for tomorrow, but for whom?