Medicine:Epstein–Barr virus vaccine
| Vaccine description | |
|---|---|
| Target disease | Epstein–Barr virus |
| Identifiers | |
| ChemSpider |
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(As of 2024), 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] In early 2023, Moderna began Phase I clinical trials of mRNA-1195.[citation needed]
References
- ↑ 1.0 1.1 "Antiviral agents for infectious mononucleosis (glandular fever)". The Cochrane Database of Systematic Reviews 2016 (12): CD011487. December 2016. doi:10.1002/14651858.CD011487.pub2. PMID 27933614.
- ↑ "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): 1749–1753. December 2007. doi:10.1086/523813. PMID 18190254.
- ↑ "Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis" (in EN). Science 375 (6578): 296–301. January 2022. doi:10.1126/science.abj8222. PMID 35025605. Bibcode: 2022Sci...375..296B.
- ↑ "A cohort study among university students: identification of risk factors for Epstein-Barr virus seroconversion and infectious mononucleosis". Clinical Infectious Diseases 43 (3): 276–282. August 2006. doi:10.1086/505400. PMID 16804839.
- ↑ "Phase I trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis". Journal of Virology 82 (3): 1448–1457. February 2008. doi:10.1128/JVI.01409-07. PMID 18032491.
- ↑ "Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults". Vaccine 25 (24): 4697–4705. June 2007. doi:10.1016/j.vaccine.2007.04.008. PMID 17485150.
- ↑ "WHO | Viral Cancers". https://www.who.int/vaccine_research/diseases/viral_cancers/en/index1.html.
- ↑ "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): 768–778. January 2004. doi:10.1128/JVI.78.2.768-778.2004. PMID 14694109.
- ↑ "Epstein-Barr virus and cancer: New tricks from an old dog". 2017-02-13. https://www.sciencedaily.com/releases/2017/02/170213131346.htm.
- ↑ "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. April 2018. doi:10.1016/j.immuni.2018.03.026. PMID 29669253.
- ↑ "First human antibody found to block Epstein-Barr virus" (in en-US). Fred Hutch. https://www.fredhutch.org/en/news/center-news/2018/04/first-human-antibody-found-to-block-epstein-barr-virus.html.
- ↑ 12.0 12.1 12.2 "Moderna Reports Third Quarter Fiscal Year 2021 Financial Results and Provides Business Updates". BioSpace. 4 November 2021. https://www.biospace.com/article/releases/moderna-reports-third-quarter-fiscal-year-2021-financial-results-and-provides-business-updates/.
- ↑ "Epstein-Barr virus (EBV) vaccine (mRNA-1189)". Moderna. February 25, 2021. https://investors.modernatx.com/static-files/834b6509-553f-4ee5-84e0-c198bbb850f0.
- ↑ "Moderna Announces First Participant Dosed in Phase 1 Study of its mRNA Epstein-Barr Virus (EBV) Vaccine". BioSpace. 5 January 2022. https://www.biospace.com/article/releases/moderna-announces-first-participant-dosed-in-phase-1-study-of-its-mrna-epstein-barr-virus-ebv-vaccine/.
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