The Epstein-Barr virus is one of the most ubiquitous viruses that infect humans. Around 95% of humans are infected by the virus, so it is probably the most common virus, at least for humans. However, I bet most people haven’t heard of it and are unaware that they have the virus floating around in their bodies.
How did you catch it? It spreads through the saliva, so it could have been from your mother when she shared some of her food with you. Or it could have been from sharing a milkshake while on a date. Or maybe you got it when you kissed your date. In fact, if you caught the virus in this last scenario — as a teen or young adult — then the Epstein-Barr virus may have triggered mononucleosis, or the “kissing disease,” in which a massive immune response against the pathogen causes weeks of sore throat, fever, and debilitating fatigue.
The Epstein-Barr virus is so pervasive, and the outcomes are so minor, you might be wondering why we need a vaccine. The problem is that the outcomes aren’t all that minor — rare, but very serious, outcomes are frequently observed because so many individuals are infected by the disease.
This article will examine what the Epstein-Barr virus is, and why it is so dangerous. Hopefully, it will be obvious why we need a vaccine.
What is the Epstein-Barr virus?
The Epstein-Barr virus (EBV), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family and is one of the most common viruses in humans. For those who are interested in these things, the virus is a double-stranded DNA virus.
As I mentioned above, infection by the virus occurs by the oral transfer of saliva, but it also can be from genital secretions. Most people who are infected by the Epstein-Barr virus gain adaptive immunity against the virus.
For unknown reasons, the Epstein-Barr virus hits harder the later you get it in life. If you first caught the virus as a baby or young child, as most people do, the initial infection was likely mild, if not asymptomatic. But it does not disappear.
So it might appear to be an unremarkable virus that can be ignored. Except, it does something that makes it more dangerous.
EBV infects B cells of the immune system and epithelial cells. Once the virus’ initial lytic infection is brought under control by the immune system, the Epstein-Barr virus latency persists in the individual’s B cells for the rest of their life. While hiding there, it is mostly benign. Mostly.
An article, published on 3 March 2022, in the Atlantic describes how the Epstein-Bar virus does its damage.:
In particular, EBV infects a type of lymphocyte called a B cell, each of which is born to recognize a different hypothetical enemy. If a certain B cell never finds its matching enemy, it dies as part of the body’s ruthless culling of useless immune cells. If it does find a match, however, the B cell divides and transforms into memory B cells, which will remain to guard against infection for the rest of a person’s life.
EBV’s genius is that it co-opts this normal process. It manipulates infected B cells into thinking they have been activated, so that they turn into long-lasting memory B cells where the virus can hide for decades. (All herpesviruses in the family have this unusual ability to become latent, though they hide out in different types of cells. The chicken-pox virus, for example, uses nerve cells, sometimes coming out to cause shingles.) Occasionally, EBV emerges from its hiding place, replicating just enough to get by. If it replicates too little, it won’t find another host before getting shut down by the immune system. If it replicates too much, it risks harming its current host. The virus and immune system are in constant balance, each holding the other in check.
This makes it a very dangerous virus.
What does the virus do to us?
Now, this is where we see that the Epstein-Barr virus is not as innocuous as it would seem. It does stick around until it causes something. I’m just going to list out some of the research which shows how the virus is linked to many serious medical conditions:
- A 2022 article showed that an EBV infection is linked to a 32X increase in risk of developing multiple sclerosis (MS), which is probably an autoimmune disorder that destroys the myelin sheath of nerves. A 2022 study, published in Nature, shows possible causation to the correlation between the virus and MS. According to the article, some multiple-sclerosis patients have antibodies that bind both an EBV protein and a protein in the brain, which is erroneously targeted by the immune system.
- Furthermore, the virus may be linked to other autoimmune disorders such as dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, and transverse myelitis (which I wrote about here).
- EBV may be linked to that triggers type 1 diabetes.
- About 200,000 cases of cancer a year are linked to an EBV infection.
- EBV is linked to malignant lymphoproliferative diseases such as Burkitt lymphoma, hemophagocytic lymphohistiocytosis, and Hodgkin’s lymphoma.
- EBV is also linked to nasopharyngeal cancer and stomach cancer. In all, it plays a role in 1.5 percent of cancers globally.
Knowing what we know about the virus, that it sticks around in the B cells for the rest of your life or attack epithelial cells, this makes sense. Autoimmune diseases may be linked to these B-cells that are under the “control” of EBV. Of course, nasopharyngeal and stomach cancers usually arise in epithelial cells, the other place of attack for the virus.
Even though the Epstein-Barr virus may appear to be a boring disease that we should ignore, like the flu (except you shouldn’t ignore the flu), it appears to be much more dangerous because even rare events, like cancer or multiple sclerosis, show up in big numbers because so many people are infected with the virus.
And that leads us to vaccines.
EBV vaccines
Now that you know how dangerous an EBV infection can be, lucky for us, there are two vaccines in clinical trials right now that may block an EBV infection.
The first one, from Moderna (yes THAT Moderna that makes one of the mRNA vaccines for COVID-19), is also an mRNA vaccine. The vaccine is currently in a phase 1 clinical trial which should be completed in June 2023.
The second one, from the National Institutes of Health, is also in a phase 1 clinical trial which should be completed in July 2025. As opposed to the mRNA technology used by Moderna, this vaccine is a more “traditional” vaccine using antigens directly from the Epstein-Barr virus.
Of course, both vaccine candidates are in phase 1 clinical trials, so we are many years from the vaccines being available for us. The endpoints for both vaccines are the prevention of mononucleosis and infection by the virus. We probably won’t know if they prevent cancer or autoimmune diseases until much later after millions of people get the vaccine. But if it does prevent EBV, then we probably will see a reduction in all of those EBV-related conditions.
This will be similar to the HPV vaccine. We knew that the vaccine stopped HPV infections and HPV was linked to cancer. However, it took 10 years after the launch of the vaccine to begin to see a vast reduction in cancer cases.
It’s too bad, because of how many cancers, multiple sclerosis diagnoses, and autoimmune disorders could be prevented by this new vaccine. But we do have hope.
Citations
- Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, Elledge SJ, Niebuhr DW, Scher AI, Munger KL, Ascherio A. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022 Jan 21;375(6578):296-301. doi: 10.1126/science.abj8222. Epub 2022 Jan 13. PMID: 35025605.
- Farrell PJ. Epstein–Barr Virus and Cancer. Annual Review of Pathology: Mechanisms of Disease 2019 14:1, 29-53.
- Khan G, Fitzmaurice C, Naghavi M, Ahmed LA. Global and regional incidence, mortality and disability-adjusted life-years for Epstein-Barr virus-attributable malignancies, 1990-2017. BMJ Open. 2020 Aug 30;10(8):e037505. doi: 10.1136/bmjopen-2020-037505. PMID: 32868361; PMCID: PMC7462312.
- Kuri A, Jacobs BM, Vickaryous N, Pakpoor J, Middeldorp J, Giovannoni G, Dobson R. Epidemiology of Epstein-Barr virus infection and infectious mononucleosis in the United Kingdom. BMC Public Health. 2020 Jun 12;20(1):912. doi: 10.1186/s12889-020-09049-x. PMID: 32532296; PMCID: PMC7291753.
- Lanz TV, Brewer RC, Ho PP, Moon JS, Jude KM, Fernandez D, Fernandes RA, Gomez AM, Nadj GS, Bartley CM, Schubert RD, Hawes IA, Vazquez SE, Iyer M, Zuchero JB, Teegen B, Dunn JE, Lock CB, Kipp LB, Cotham VC, Ueberheide BM, Aftab BT, Anderson MS, DeRisi JL, Wilson MR, Bashford-Rogers RJM, Platten M, Garcia KC, Steinman L, Robinson WH. Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM. Nature. 2022 Jan 24. doi: 10.1038/s41586-022-04432-7. Epub ahead of print. PMID: 35073561.
- Nagafuchi S. Regulation of Viral Infection in Diabetes. Biology (Basel). 2021 Jun 13;10(6):529. doi: 10.3390/biology10060529. PMID: 34199246; PMCID: PMC8231782.
- Rezk SA, Zhao X, Weiss LM. Epstein-Barr virus (EBV)-associated lymphoid proliferations, a 2018 update. Hum Pathol. 2018 Sep;79:18-41. doi: 10.1016/j.humpath.2018.05.020. Epub 2018 Jun 6. PMID: 29885408.
- Toussirot E, Roudier J. Epstein-Barr virus in autoimmune diseases. Best Pract Res Clin Rheumatol. 2008 Oct;22(5):883-96. doi: 10.1016/j.berh.2008.09.007. PMID: 19028369.
