Epstein-Barr Virus (EBV) is a common human virus, infecting an estimated 90% of adults worldwide. It primarily spreads through saliva, often causing infectious mononucleosis, known as “mono.” While many infections are asymptomatic, especially in childhood, EBV’s widespread nature and diverse health implications have generated interest in developing a preventive vaccine.
Current Status of EBV Vaccine Development
Currently, no widely available or approved vaccine exists for Epstein-Barr Virus. Despite decades of research, an effective vaccine preventing EBV infection and its associated diseases has yet to reach clinical use. Earlier candidates, often targeting the viral protein gp350, reduced infectious mononucleosis but did not consistently prevent the viral infection itself.
Ongoing research explores various vaccine platforms and antigen targets. Several investigational vaccines are in early-stage clinical trials, including those from Moderna, NIAID, Modex, and EBViously. These trials assess the safety and immune response generated by new candidates.
Why an EBV Vaccine is Needed
An EBV vaccine is needed due to the wide range of health conditions linked to this common virus. While primary infection often causes no noticeable symptoms, especially in young children, it can lead to infectious mononucleosis (mono) in adolescents and adults. Mono causes extreme fatigue, fever, sore throat, and swollen lymph nodes, with fatigue potentially lasting for months.
Beyond acute illness, EBV is associated with several serious, though rarer, conditions. It is the first identified oncogenic virus, contributing to approximately 2% of global malignancies and over 200,000 cancer cases annually. These include Burkitt and Hodgkin lymphoma, nasopharyngeal carcinoma, and certain gastric cancers.
EBV infection is also implicated in various autoimmune diseases. These include Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Sjögren’s syndrome, and inflammatory bowel disease. Notably, EBV infection may increase the risk of developing MS by as much as 32-fold.
Challenges in Developing an EBV Vaccine
Developing an effective EBV vaccine presents scientific and logistical hurdles. The virus has a complex life cycle, existing in both lytic (active replication) and latent (dormant) phases, persisting lifelong within host B cells. This duality makes it difficult for a vaccine to target all viral forms and achieve comprehensive protection.
Selecting appropriate viral antigens is another challenge. While glycoprotein 350 (gp350) was a primary target in past efforts, it proved insufficient for complete protection. Researchers now explore including multiple viral glycoproteins (gH/gL, gB, gp42) and latency-associated proteins to elicit a broader immune response, encompassing neutralizing antibodies and T-cell activity.
The absence of a fully representative animal model for human EBV infection further complicates vaccine development. While some animal models, such as cottontop tamarins, have been used, they do not fully mimic all aspects of human infection, making it difficult to translate preclinical findings directly to humans. Additionally, clinical trials for EBV-associated cancers are challenging due to the long latency period between infection and disease, and a lack of clear surrogate markers for tumor prevention.
Promising Research and Future Outlook
Despite challenges, promising research advances the prospect of an EBV vaccine. Scientists are exploring innovative strategies, including subunit vaccines that utilize improved gp350 formulations such as multimeric forms, nanoparticles, and virus-like particles, designed to enhance immune responses.
The success of mRNA vaccine technology, highlighted during the COVID-19 pandemic, has accelerated development. Companies like Moderna are now testing mRNA vaccine candidates (e.g., mRNA-1189 and mRNA-1195) in clinical trials. These approaches aim to target multiple EBV antigens, including gH/gL, gB, gp42, and latency proteins, in addition to gp350, to elicit comprehensive protective immunity.
Ongoing Phase 1 and Phase 2 clinical trials represent significant steps. A successful vaccine could have a substantial public health impact by reducing the incidence of infectious mononucleosis, various associated cancers, and a range of autoimmune diseases.