mRNA-1189 Epstein-Barr Virus Vaccine

Moderna Inc. messenger RNA (mRNA) vaccine candidate mRNA-1189 contains four mRNAs that encode Epstein-Barr Virus (EBV) envelope glycoproteins (gH, gL, gp42, gp220), which mediate viral entry into B-cells (a type of immune system cells) and epithelial surface cells, the primary targets of EBV infection. mRNA-1189 seeks to prevent the development of infectious mononucleosis and EBV infection. The viral proteins in mRNA-1189 are expressed in their native membrane-bound form for recognition by the Human Immune System. Similar to Moderna's CMV vaccine candidate (mRNA-1647), mRNA-1189 contains four mRNAs that encode EBV envelope glycoproteins (gH, gL, gp42, gp220), which mediate viral entry into B-cells (a type of immune system cells) and epithelial surface cells, the major targets of EBV infection.

While EBV infection in early childhood is predominantly asymptomatic, primary infection in adolescence can lead to infectious mononucleosis (IM), a clinical syndrome including fever, fatigue, sore throat, and lymphadenopathy. IM can debilitate patients for weeks to months, sometimes requiring hospitalization for severe complications such as splenic rupture and significant airway compromise. In the long term, EBV is associated with certain lymphoproliferative disorders, a higher risk of developing cancers and autoimmune diseases, and an approximately 32-fold increased risk of developing multiple sclerosis.

On January 5, 2022, Moderna announced the first participant had been dosed in the Phase 1 study of mRNA-1189 (mRNA-1189-P101), known as Eclipse. The primary purpose of the Phase 1 study is to assess the safety and tolerability of mRNA-1189 in healthy adults ages 18 to 30. Moderna expects to enroll approximately 270 participants (estimated completion date 2025-06-18). The ClinicalTrials.gov identifier is NCT05164094. The Company confirmed on May 4, 2022, that it expects to test the vaccine in patients with multiple sclerosis and transplant patients to prevent post-transplant lymphoproliferative disorder.

As of November 2023, the U.S. Food and Drug Administration (FDA) had not authorized an EBV vaccine.

Massachusetts-based Moderna's capabilities and mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology, and manufacturing. It has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases, and autoimmune diseases. To learn more, visit www.modernatx.com.

mRNA-1189 EBV Vaccine Indication

The Epstein-Barr virus is a herpesvirus family member. Over 90% of the adult population globally has been infected by the Epstein-Barr virus. Potential future indications may be the prevention of EBV reactivation in other conditions, such as post-transplant lymphoproliferative disease. EBV is a common viral infection, with 83% of Americans seropositive by 19 years. It is spread through bodily fluids (e.g., saliva). EBV is responsible for approximately 90% of the one million cases of IM each year in the U.S. As a latent virus, EBV remains in the body for life after infection and can lead to lifelong medical conditions, which causes significant direct and indirect costs to the healthcare system. For example, EBV is associated with a 4- to 10-fold risk of developing multiple sclerosis and the development of certain lymphoproliferative disorders, cancers, and autoimmune diseases.

EBV is also associated with other malignancies, including gastric carcinoma, nasopharyngeal carcinoma, and Burkitt lymphoma. Overall, EBV is estimated to have caused ~1-2% of all global cancers in 2021 and is responsible for 140-200,000 deaths per year (est.). In addition, EBV also causes Post-transplant lymphoproliferative disorder, a potentially fatal complication affecting allogeneic hematologic stem cell transplant recipients and, to a lesser extent, solid organ transplants.

"Epstein-Barr Virus is one of the most common viral infections in the world. Although it causes infectious mononucleosis, which impacts millions of adolescents globally, no vaccine is currently available. As a result, adolescents who develop infectious mononucleosis are frequently absent from school for weeks and even months at a time, impacting the quality of their education and their families," said Stéphane Bancel, CEO of Moderna.

Epstein-Barr Virus Myocarditis in Children

Cardiovascular involvement is an uncommon but severe complication of Epstein–Barr virus infection. EBV is a common cause of myocarditis in children. Clinicians need to look for symptoms beyond those of typical mononucleosis and follow up on any subsequent clinical changes.

Epstein-Barr Virus and Multiple Sclerosis

Multiple sclerosis is likely caused by infection with the Epstein-Barr virus, according to a study published by Harvard T.H. Chan School of Public Health researchers on January 13, 2022. Scientists, led by Alberto Ascherio from the Harvard TH Chan School of Public Health, examined more than 10m blood samples from U.S. military personnel collected over 20 years and identified that those who became infected with EBV were 32 times more likely to develop MS later. 

Epstein-Barr Virus and Cancer

Researchers estimated that EBV-related cases from six cancers accounted for over 200,000 new cases and 130,000 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of diseases that could benefit from an EBV-specific therapeutic.

mRNA-1189 EBV Vaccine News 2023

February 14, 2023 - A Phase 1 Clinical Study of an EBV candidate vaccine, mRNA-1189, with 272 participants, was updated. The estimated Completion Date is June 24, 2023.

March 24, 2022 - Moderna Inc. confirmed conducting a Phase 1 trial in the expansion phase following a favorable initial safety review. Additionally, a therapeutic vaccine (mRNA-1195) against long-term EBV sequelae, such as MS and post-transplant lymphoproliferative disease, is in preclinical development.

January 13, 2022 - A longitudinal analysis revealed a high prevalence of EBV associated with multiple sclerosis. The risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. In addition, serum levels of the neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS, suggesting EBV is the leading cause of MS.

January 5, 2022 - Moderna announced today that they had dosed their first participant in Eclipse, a phase 1 study of their EBV vaccine candidate. Stéphane Bancel, Chief Executive Officer of Moderna. "The start of this Phase 1 study is a significant milestone as we continue to advance mRNA vaccines against latent viruses, which remain in the body for life after infection and can lead to chronic medical conditions. Moderna is committed to developing a portfolio of first-in-class vaccines against latent viruses for which there are no approved vaccines today, including vaccines against CMV, EBV, and HIV. Our research team is working to bring even more vaccines against latent viruses to the clinic. We believe these vaccines could have a profound impact on the quality of health for hundreds of millions of people around the world."

mRNA-1189 EBV Vaccine Clinical Trials

Clinical Trial NCT05164094: A Study of an Epstein-Barr Virus Candidate Vaccine, mRNA-1189, in 18- to 30-Year-Old Healthy Adults. Participants will receive three intramuscular (IM) injections of mRNA-1189 at Dose Level 1 on Days 1, 57, and 169. Last Update Posted: February 14, 2023. Contact: Moderna Clinical Trials Support [email protected].