Epstein–Barr virus vaccine

Epstein–Barr virus vaccine
Vaccine description
TargetEpstein–Barr virus
Identifiers
ChemSpider
  • none

As of 2021, a vaccine against Epstein–Barr virus was not yet available.[1][2] The virus establishes latent infection and causes infectious mononucleosis. There is also increasingly more evidence that EBV may be a trigger of multiple sclerosis.[3] It is a dual-tropic virus, meaning that it infects two different host cell types — in this case, both B cells and epithelial cells. One challenge is that the Epstein–Barr virus expresses very different proteins during its lytic and its latent phases. Antiviral agents act by inhibiting viral DNA replication, but as of 2016 there was little evidence that they are effective against Epstein–Barr virus, they are expensive, they risk causing resistance to antiviral agents, and (in 1% to 10% of cases) can cause unpleasant side effects.[1]

Several clinical trials for a vaccine were conducted in 2006–2008.[4][5][6] The viral proteins Gp350/220 are a primary target,[7] but this would only block infection of B cells, not epithelial cells. A vaccine called MVA-EL has been also proposed as a target for EBV-positive cancers, but this would only be effective in combating EBV-related cancers, not the EBV infection itself.[8] VLP (virus-like particle)-based EBV vaccines are also the subject of intensive research.[9]

In April 2018, the first human antibody that blocks Epstein-Barr Virus was discovered, called AMMO1.[10] It blocks glycoproteins gH and gL. This discovery defines new sites of vulnerability on Epstein-Barr Virus, and neutralizes the dual-tropic infection (stopping both infection of B cells and epithelial cells). It is the most promising discovery to date, as it is the first that may be able to block both B cell infection and epithelial infection.[11]

In 2021, Moderna announced two mRNA vaccine candidates targeting EBV: a prophylactic mRNA-1189 and a therapeutic mRNA-1195.[12] Regarding the mRNA-1189, the company said that the "vaccine encodes five glycoproteins to inhibit both mechanisms for viral entry into B cells (gp350 plus gH/gL/gp42), adds protection for epithelial cells (gH/gL), and includes gB for protection of all cells."[13] The viral proteins produced by the mRNA in this vaccine are expressed in their native form, bound to the cell membrane, where they are available for recognition by the immune system.[12] The company began Phase I clinical trials of mRNA-1189 on 5 January 2022.[14] The other candidate, mRNA-1195 vaccine, is being developed to prevent longer-term complications which may be caused by EBV and it contains additional antigens compared to mRNA-1189.[12] As of February 2022, mRNA-1195 is still in pre-clinical trials.

References

  1. 1 2 De Paor M, O'Brien K, Smith SM (2016). "Antiviral agents for infectious mononucleosis (glandular fever)". The Cochrane Database of Systematic Reviews. 12 (12): CD011487. doi:10.1002/14651858.CD011487.pub2. PMC 6463965. PMID 27933614.
  2. ↑ Sokal EM, Hoppenbrouwers K, Vandermeulen C, Moutschen M, Léonard P, Moreels A, et al. (December 2007). "Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults". The Journal of Infectious Diseases. 196 (12): 1749–53. doi:10.1086/523813. PMID 18190254.
  3. ↑ Bjornevik, Kjetil; Cortese, Marianna; Healy, Brian C.; Kuhle, Jens; Mina, Michael J.; Leng, Yumei; Elledge, Stephen J.; Niebuhr, David W.; Scher, Ann I.; Munger, Kassandra L.; Ascherio, Alberto (21 January 2022). "Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis". Science. doi:10.1126/science.abj8222.
  4. ↑ Crawford DH, Macsween KF, Higgins CD, Thomas R, McAulay K, Williams H, et al. (August 2006). "A cohort study among university students: identification of risk factors for Epstein-Barr virus seroconversion and infectious mononucleosis". Clinical Infectious Diseases. 43 (3): 276–82. doi:10.1086/505400. PMID 16804839.
  5. ↑ Elliott SL, Suhrbier A, Miles JJ, Lawrence G, Pye SJ, Le TT, et al. (February 2008). "Phase I trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis". Journal of Virology. 82 (3): 1448–57. doi:10.1128/JVI.01409-07. PMC 2224445. PMID 18032491.
  6. ↑ Moutschen M, Léonard P, Sokal EM, Smets F, Haumont M, Mazzu P, et al. (June 2007). "Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults". Vaccine. 25 (24): 4697–705. doi:10.1016/j.vaccine.2007.04.008. PMID 17485150.
  7. ↑ "WHO | Viral Cancers". Archived from the original on 24 March 2006. Retrieved 15 January 2009.
  8. ↑ Taylor GS, Haigh TA, Gudgeon NH, Phelps RJ, Lee SP, Steven NM, Rickinson AB (January 2004). "Dual stimulation of Epstein-Barr Virus (EBV)-specific CD4+- and CD8+-T-cell responses by a chimeric antigen construct: potential therapeutic vaccine for EBV-positive nasopharyngeal carcinoma". Journal of Virology. 78 (2): 768–78. doi:10.1128/JVI.78.2.768-778.2004. PMC 368843. PMID 14694109.
  9. ↑ "Epstein-Barr virus and cancer: New tricks from an old dog". www.sciencedaily.com. 13 February 2017. Retrieved 26 December 2017.
  10. ↑ Snijder J, Ortego MS, Weidle C, Stuart AB, Gray MD, McElrath MJ, et al. (April 2018). "An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus". Immunity. 48 (4): 799–811.e9. doi:10.1016/j.immuni.2018.03.026. PMC 5909843. PMID 29669253.
  11. ↑ "First human antibody found to block Epstein-Barr virus". Fred Hutch. Retrieved 1 December 2018.
  12. 1 2 3 "Moderna Reports Third Quarter Fiscal Year 2021 Financial Results and Provides Business Updates". BioSpace. 4 November 2021. Retrieved 1 February 2022.
  13. ↑ "Epstein-Barr virus (EBV) vaccine (mRNA-1189)". investors.modernatx.com. Moderna. 25 February 2021. Archived from the original on 21 January 2021. Retrieved 17 March 2021.
  14. ↑ "Moderna Announces First Participant Dosed in Phase 1 Study of its mRNA Epstein-Barr Virus (EBV) Vaccine". BioSpace. 5 January 2022. Retrieved 1 February 2022.
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