Infectious Diseases, Pathogen of the Month, Vaccines, Viruses

Kissing Mono Goodbye: Why We Need an Epstein-Barr Virus Vaccine

Author Chandana Balasubramanian , 12-Apr-2023

Mononucleosis, which is also referred to as “mono,” “the kissing disease,” “infectious mononucleosis (IM),” or “glandular fever”, is a viral infection that causes lifelong or prolonged illness in adolescents and young adults [1]. The Epstein-Barr Virus (EBV), responsible for causing most cases of mono, is associated with several cancers and autoimmune diseases. According to the latest research [2], people who get mono may have a 32 times higher risk of getting multiple sclerosis, a debilitating neurological disease. Since there is no vaccine available, it is especially important to educate the public about the nature of the virus, modes of transmission, and ways to protect yourself and those that you love [3]. 


EBV accounts for over 90% of mono cases worldwide. (Cytomegalovirus [CMV] is the second leading cause [4].) EBV belongs to the Herpesviridae family of viruses, which are more colloquially known as herpes viruses. The specific genus to which EBV belongs is  Lymphocryptovirus. The International Agency for Research on Cancer classifies EBV as a Group I carcinogen (cancer-causing agent) due to its association with various lymphatic and epithelial cancers [5]. 


According to the Centers for Disease Control and Prevention (CDC), at least one in four adolescents and young adults develop infectious mononucleosis due to EBV infections. Mono is contagious and can spread from one person to another through contact with bodily fluids, including saliva, blood, and semen from an infected person [6]. 

Deaths due to mononucleosis are rare [1]. The viral infection is usually self-limiting. It usually resolves itself without treatment [7]. However, mono-related complications can be fatal. These include neurological complications, airway obstructions, spleen ruptures, inflammation, and damage to the heart muscle. Cardiac arrhythmias, liver failure, secondary bacterial infections, and low platelet counts are other possible manifestations of mono.



Mononucleosis was first described in 1885 by Nil Filatov, a famous Russian pediatrician [8]. In 1889, a German doctor named Emil Pfeiffer described a similar condition characterized by fever, sore throat, enlarged spleen, and swollen lymph nodes and liver. He called it “glandular fever.” Deaths due to glandular fever or similar conditions were subsequently reported by other physicians.  

In 1920, Thomas Peck Sprunt and Frank Alexander Evans coined the term “infectious mononucleosis” to refer to what had previously been called glandular fever [9]. Around that same time, the colloquialism “kissing disease” came into use. This was due to the fact that this particular disease was spread through saliva [10]. 

During the 1940s, clinicians became aware of the potential dangers of mono. In 1944, death from a spleen rupture, one of the complications of mononucleosis, was reported for the first time. In 1953, a review of 38 mono-associated deaths was published by Sidney Leibowitz. 

At the University of Bristol, in 1964, Michael Epstein, Yvonne Barr, and Bert Achong found EBV in Burkitt’s lymphoma cells. (Burkitt lymphoma is lymphatic cancer named after an Irish doctor, Denis Parsons Burkitt.) Werner and Gertrude Henle linked the pathogen with infectious mononucleosis in 1968 at the Children’s Hospital of Philadelphia [9,11]. 

In 1970, H.G. Penman, a pathologist from the University of Otago medical school in Dunedin, New Zealand, published a comprehensive review of 87 mono-related deaths. He found that only 20 out of 87 reported cases were actually caused by mononucleosis. This review specifies that fatalities due to mono are rare, but the possibility cannot be overlooked [9].



Mono is usually a mild illness. About 20% of patients will experience tiredness for about two months. Around 13% experience persistent fatigue for about six months, and about 1% of patients develop neurologic, hematologic, or hepatic complications [12]. 

EBV, the primary causative agent, is present in over 95% of the adult population worldwide [7]. Like all herpes viruses, EBV also causes lifelong infection and latent infection of B lymphocytes [1].

The viral infection does not usually manifest itself clinically during childhood. In high-income countries, the incidence increases in adolescence and early adulthood and falls gradually by the time a person reaches 35. In low-income countries, symptomatic mono is uncommon, even though many children are infected with EBV in childhood [7]. It frequently occurs in first-degree siblings and same-sex twins [10].  

United States

In 2016, the annual incidence of mononucleosis in the US was about 500 cases per 100,000 population [7]. The incidence was almost 30 times higher among Caucasians than among Black populations [10]. Approximately 15% of all lymphoma patients in the US, including those with Burkitt and Hodgkin lymphoma, have a form of the disease that is associated with EBV [13]. 


In China, children are usually infected during their early childhood. According to the information provided by China’s national pediatric patient medical record database, around 24,120 hospitalized children were diagnosed with IM (mono) between 2016 and 2020. Around 14,386 patients were male, accounting for about 59.64% of all cases. The remaining 9,734 (40.36%) patients were female. Children aged between one and three accounted for 41.75% of cases. Four to six-year-olds accounted for 38.45% of cases, and seven to 12-year-olds accounted for 17.89%.. The remaining 1.44% of cases were infants under 12 months old [14]. 

Scandinavia and Africa

In Scandinavian and African countries, most IM-associated complications, mainly lymphomas, are caused by EBV infection. Around 1 in 800 people in the Scandinavian countries developed Hodgkin lymphoma about four years (median time) following the onset of EBV-associated infectious mononucleosis. Also, around 85% of Burkitt lymphoma cases in Africa were found to be EBV-positive.

How is it spread?


EBV, one of the most common causes of mononucleosis, spreads from person to person through direct contact with bodily fluids, including saliva, blood, and semen. The infected person can spread the infection  before the onset of symptoms.

EBV spreads in the following ways: 

  • Through direct contact with saliva from an infected person via kissing, use of cups and utensils, or toothbrushes.
  • Indirect contact with the saliva of an infected person. Such saliva may be left on surfaces such as countertops.
  • Receiving an organ donation from an infected person.
  • Through semen when an uninfected person is involved in sexual activity with an infected person [6,15]. 

Biology of the disease


The EBV virus primarily infects the lymphatic system. When the virus enters the body, it begins affecting the mouth and throat. The virus then enters the bloodstream and replicates within B-cells (a type of white blood cell). This replication also occurs in the epithelial cells lining the pharynx and parotid (salivary) duct [16]. 

For people with mono, the infected B-cells replicate uncontrollably and then spread the infection throughout the entire lymphatic system [10]. This can lead to swollen lymph nodes, sore throat, fever, and other symptoms. 

After someone is first infected with the EBV virus, they may develop a latent infection. This means the virus does not cause symptoms but remains in the body, specifically in memory B-lymphocytes. It can cause various forms of lymphoma, including Hodgkin, non-Hodgkin, or nasopharyngeal carcinoma (cancer that starts in the upper part of the throat behind the nose). It can also cause chronic fatigue syndrome and multiple sclerosis (MS) – a disease that affects the central nervous system [17].



It takes around 4-6 weeks for symptoms of mono to appear after getting infected. 

The following are the common symptoms of mononucleosis:

  • Tiredness
  • Fever
  • Headache
  • Body pains
  • Swollen lymph nodes in the neck and armpits
  • Swollen liver (less common)
  • Swollen spleen (less common)
  • Rashes


A patient will develop symptoms gradually, and not all appear simultaneously. On average, people recover within 2-4 weeks. However, some may experience tiredness for several weeks [6].

The viral load remains high in salivary secretions for up to six months after the illness’s onset. It will continue to shed in the oropharynx for up to 18 months after clinical recovery [10].


The following are some early and late complications of EBV viral infection:

Early complications:

  • Hepatitis (inflammation in the liver)
  • Spleen rupture  
  • Airway obstruction (nasopharyngeal and palatal tonsils)


Late complications:

  • Lymphoproliferative cancers
  • Multiple sclerosis
  • Rheumatoid arthritis
  • Chronic active EBV infection [4]



Mononucleosis is usually diagnosed based on symptoms. Laboratory tests are generally not needed. Sometimes, a simple blood test capturing the following metrics is used to confirm infectious mononucleosis caused by EBV:

  • Lymphocyte (white blood cell) count – more than normal
  • Lymphocyte (white blood cell) appearance – looking unusual 
  • Neutrophils or platelets count – lower than normal
  • Liver function – abnormal [6].


Healthcare providers will conduct a physical examination and check for swollen lymph nodes in the neck or signs of a swollen liver or spleen. 

Symptoms of mono are sometimes mistaken for the flu or strep throat. 



Currently, there are no treatments available for mono. Supportive or symptomatic care is taken to relieve pain and discomfort experienced by patients. These include the following:

  • Drinking more fluids
  • Rest
  • Taking over-the-counter medications like ibuprofen or acetaminophen for fever and body pains [6].



There are currently no vaccines to protect against infectious mononucleosis. However, a few preventive measures can help control the spread of the infection. 

In general, it is best to avoid the following: 

  • Kissing people who are infected
  • Sharing drinks, food, or other personal items (including cups, spoons, and toothbrushes with infected people)
  • Receiving blood or organs from infected individuals
  • Sexual contact with infected people
  • Contact sports with people who have a mono infection [6].


Vaccine research on EBV is woefully behind. However, there has been progress. In May 2022, the National Institute of Allergy and Infectious Diseases (NIAID) launched an early-stage (Phase 1) study to find an effective vaccine against the Epstein-Barr virus. Other clinical studies are underway to find more effective treatments against infections caused by EBV.

The GIDEON difference


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Learn more about infectious mononucleosis on the GIDEON platform.


[1] K. F. Macsween and D. H. Crawford, “Epstein-Barr virus-recent advances,” Lancet Infect. Dis., vol. 3, no. 3, pp. 131–140, 2003.

[2] A. Fugl and C. L. Andersen, “Epstein-Barr virus and its association with disease – a review of relevance to general practice,” BMC Fam. Pract., vol. 20, no. 1, 2019.

[3] G. Niedobitek, N. Meru, and H. J. Delecluse, “Epstein-Barr virus infection and human malignancies,” Int. J. Exp. Pathol., vol. 82, no. 3, pp. 149–170, 2001.

[4] CDC, “About Mono (Infectious Mononucleosis),” Centers for Disease Control and Prevention (CDC), 23-Jan-2023. [Online]. Available: 

[5] M. De Paor, K. O’Brien, T. Fahey, and S. M. Smith, “Antiviral agents for infectious mononucleosis (glandular fever),” Cochrane Database Syst. Rev., vol. 12, no. 12, p. CD011487, 2016.

[6] S. Soran, “The association of Epstein-Barr virus infection with progress of cancer and immune defects,”, 2017. [Online]. Available: 

[7] E. G. Donald and B. M. Gregoire, “The Dark Side of MONO,” Academic Journal of Pediatrics and Neonatology, vol. 5, no. 3, 2017.

[8] M. Saljoughian and PhD Department of Pharmacy Alta Bates Summit Medical Center Berkeley, “Diagnosing and treating mononucleosis,”, 19-May-2017. [Online]. Available: 

[9] J. I. Cohen, “Vaccine development for Epstein-Barr virus,” Adv. Exp. Med. Biol., vol. 1045, pp. 477–493, 2018.

[10] M. Liu et al., “Epidemiological characteristics and disease burden of infectious mononucleosis in hospitalized children in China: A nationwide retrospective study,” Virol. Sin., vol. 37, no. 5, pp. 637–645, 2022.

[11] J. I. Cohen, “Epstein-barr virus vaccines,” Clin. Transl. Immunology, vol. 4, no. 1, p. e32, 2015.   

[12] CDC, “About Epstein-Barr virus (EBV),” Centers for Disease Control and Prevention (CDC), 03-Oct-2022. [Online]. Available: 

[13] M. H. Ebell, “Epstein-Barr virus infectious mononucleosis,” [Online]. Available: 

[14] E. Visser, D. Milne, I. Collacott, D. McLernon, C. Counsell, and M. Vickers, “The epidemiology of infectious mononucleosis in Northern Scotland: a decreasing incidence and winter peak,” BMC Infect. Dis., vol. 14, no. 1, p. 151, 2014.

[15] K. Bjornevik et al., “Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis,” Science, vol. 375, no. 6578, pp. 296–301, 2022.

[16] “NIH launches clinical trial of Epstein-Barr virus vaccine,” National Institutes of Health (NIH), 06-May-2022. [Online]. Available: 

[17] J. B. Harford, “Viral infections and human cancers: the legacy of Denis Burkitt: Review,” Br. J. Haematol., vol. 156, no. 6, pp. 709–718, 2012.

Chandana Balasubramanian

Chandana Balasubramanian is an experienced healthcare executive who writes on the intersection of healthcare and technology. She is the President of Global Insight Advisory Network, and has a Masters degree in Biomedical Engineering from the University of Wisconsin-Madison, USA.

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