The Eastern Equine Encephalitis Vaccine: What You Need To Know

Eastern equine encephalitis (EEE)

Eastern equine encephalitis (EEE), also called eastern equine encephalomyelitis, is a disease with varying severity that can affect a number of different species, including humans. In general, encephalitis or encephalomyelitis is an inflammation of the brain, generally caused by pathogens such as viruses, bacteria or fungi.¹ The name of the condition is slightly misleading since not everyone contracting EEE actually develops encephalitis.

EEE was first found in horses (hence the ‘equine’ in the name) between 1913 and 1914 in the USA but was later found to also occur in humans.² In 1938, the first human case of EEE was confirmed.³ The most severe cases of EEE often prove fatal in both horses (75 - 90%) and humans (30 - 41%). ^4,5,6,7

Frequency of eastern equine encephalitis (EEE)

Thankfully, the incidence rate of EEE among humans is rather low. On average, 11 people per year are reported to develop EEE in the US. From 2003 to 2022, the United States saw 186 cases of severe EEE, resulting in 167 hospitalizations and 78 deaths.⁸ Nevertheless, occasionally there are higher occurrences of severe EEE, like the most recent one in 2019 with 38 severe EEE cases, 17 of which proved fatal.⁸ 

Cause of eastern equine encephalitis (EEE)

Eastern Equine Encephalitis (EEE) is caused by Eastern Equine Encephalitis Virus (EEEV).^{2, 3} EEEV is not to be confused with two of its distinct yet similarly named relatives, namely the western equine encephalitis virus (WEEV) and the Venezuelan equine encephalitis virus (VEEV). Both of them can cause similar symptoms, yet EEEV is the most dangerous of the three of them since EEEV is more effective at causing illness after infection.⁹

Transmission of eastern equine encephalitis virus (EEEV)

Through mosquitoes

The mosquito known as Culiseta melanura primarily maintains the population of EEEV by mainly feeding on wild birds and thereby passing EEEV from one bird to the next, allowing the virus to effectively propagate inside these birds. Other mosquitoes such as Culex erraticus and Coquillettidia perturbans feed on both birds and mammals including horses and humans, thereby acquiring EEEV from infected wild birds and then transmitting them to humans and horses (making these mosquitoes so-called ‘bridge’ vectors).^10,11 Since EEEV is carried and transmitted by an insect (=arthropod), it is characterised as an arthropod-borne virus or arbovirus.

Both humans and horses are considered ‘dead-end’ hosts. That means that EEEV is unable to multiply well enough in the blood of these hosts to allow an EEEV-free mosquito to infect itself with EEEV and then pass it along to other hosts. Consequently, the presence of an EEEV infected horse or human does not increase the risk of infection for other nearby horses or humans.¹² 

Through organ transplantation and blood transfusion

However, incurring an EEEV infection via organ transplantation is possible. It has been reported that an EEEV positive organ donor infected 3 organ recipients with EEEV.¹² Additionally, it is believed that receiving a blood transfusion with blood from an EEEV-positive donor is likely to transmit the virus from donor to the recipient. Therefore, patients with a positive EEEV infection are discouraged from donating blood for 4 months after acquiring the illness.¹³ 

Geographical occurrence of eastern equine encephalitis virus (EEEV) 

The different species of mosquitoes capable of carrying and transmitting EEEV can mostly be found in the eastern part of the United States, namely near freshwater hardwood swamps in the Great Lakes region and the Gulf Coast and Atlantic states and also in the Caribbean.^8,14 That is the main reason EEEV infections are so rare because only very few people live near the swamps. The people who live or visit the area are at a greater risk of EEEV infection, especially when engaging in outdoor activities.⁸

Asymptomatic and symptomatic eastern equine encephalitis (EEE)

It has been estimated that only 4 - 5% of humans infected by EEEV will develop EEE with symptoms while the other 95 - 96% will have asymptomatic EEE ( without any symptoms). Furthermore, people under the age of 15 and over the age of 50 are most likely to incur severe forms of EEE when infected.8 People develop symptoms between 4 and 10 days after the bite of the infected mosquito carrying EEEV (which is the incubation period).¹⁵

Symptoms of eastern equine encephalitis (EEE)

Mild symptoms in humans include fever, joint pain, body aches and chills. This milder version can last for 1 to 2 weeks and patients with this condition tend to make a complete recovery as long as the central nervous system (brain and spinal cord) is not affected.¹⁵ 

Some infected people can develop EEEV-induced viral meningitis (infection of the membranes surrounding and protecting the brain and spinal cord by a virus)¹⁶ or viral encephalitis (infection of the brain by a virus)¹ if the virus spreads to the central nervous system. These neurological cases of EEE can show a plethora of symptoms including headache, fever, drowsiness, diarrhoea, vomiting and changes in behaviour, seizures and even coma. Regrettably, it is estimated that a third of all the people with an EEEV-induced encephalitis pass away.¹⁵ This occurs normally between 2 to 10 days after the patients show signs of the neurological EEE disease.

Consequences of EEE-induced encephalitis

The two-thirds who manage to survive this serious condition are often left with long-lasting impairments such as slightly to strongly diminished mental capacity, cranial nerve dysfunction (damage to one or several of the 12 cranial nerves), paralysis, fits and personality disorders (e.g. borderline or antisocial personality disorder¹⁷). Those with grave impairments often need ongoing care for several years.¹⁵ Incurring and surviving an EEEV infection is believed to bestow life-long protection against re-infection by EEEV but does not grant any protection against similar viruses such as western equine encephalitis virus (WEEV).⁸ 

Diagnosis for eastern equine encephalitis (EEE)

Generally, the diagnosis of eastern equine encephalitis (EEE) can be performed in a number of ways^15,18:

1.  Signs and symptoms consistent with symptomatic EEE
2. Living or having been in an area where EEEV is abundant
3. Having stung by mosquitoes that could potentially carry EEEV
4. Detecting antibodies against EEEV or other viruses causing similar symptoms (e.g. WEEV or VEEV) in

• Blood
• Cerebrospinal fluid (colourless fluid found in the brain and spinal cord)

Treatments for eastern equine encephalitis (EEE)

Unfortunately, there is no medication available yet to combat EEEV directly. The only thing that can be done currently is to try to alleviate the occurring symptoms as best as possible.^{13, 15}

Patients developing EEV-induced meningitis (infection of the membranes surrounding and protecting the brain and spinal cord¹⁶) or encephalitis (infection of the brain¹) require hospitalisation. That way, the resulting symptoms can be better managed and the patients can receive nursing care. It also allows healthcare professionals to keep a close eye on EEEV encephalitis patients who are at risk of developing seizures, increased intracranial pressure (heightened pressure around and on the brain¹⁹) and the inability to keep their airways open leading to serious breathing difficulties.^13,15 

Due to the lack of specific treatment to eradicate EEEV directly, the development of a vaccine would be a big step towards preventing the occurrence of EEE in general and the severe, neurological cases of EEE in particular. 

Prevention of eastern equine encephalitis

Due to the lack of both cure and vaccine for EEE, the best way to protect yourself is to prevent mosquito bites as much as possible in areas where EEE can be found. Protective measures include²⁰

• Using insect repellents applied directly onto skin
• Wearing loose-fitting and long-sleeved clothing completely covering arms and legs
• Spraying those items of clothing and others (such as socks and boots) with 0.5% permethrin (repels and kills mosquitoes) → protection still maintained even after multiple washes
• Sleeping in rooms with adequate ventilation; door and window screens and air conditioning 
• Alternatively or additionally, sleeping under a (ideally permethrin-treated) mosquito tent

There is one additional tip that only applies to people living in these areas and not just visiting. Mosquitoes lay their eggs in stagnant water. Therefore, it is a risk allowing water to gather near one’s home. It is recommended to empty out any outside items accumulating water every week. This final measure is to make it difficult for the mosquitoes to lay their eggs in close proximity.²⁰

Eastern equine encephalitis virus (EEEV) as a biological weapon

The discovery of an EEE vaccine is especially important given its s potential to be used as a bioweapon. It was shown in mice that EEEV is far more dangerous when present as an aerosol (droplets or particles which are suspended in the air).²¹ As an airborne agent, EEEV’s infection rate, probability to invade the central nervous system (brain and spinal cord) and mortality rate increase to 100 percent.²² Thankfully, that is not something that occurs in nature. An EEEV aerosol would need to be either manufactured on purpose (biological weapon) or created accidentally (as it happened with an WEEV aerosol due to a laboratory accident).²³

Developing a human vaccine for eastern equine encephalitis (EEE)

Although an EEEV vaccine for horses is commercially available, an EEEV vaccine for humans has not been approved so far. Given that there is no specialised treatment for EEE, a vaccine would go a long way to mitigate the risk, especially for the most severe forms of EEE. The search for such a human EEEV vaccine has been going on for over 80 years and 10 more recent promising candidates have been successfully tested in animal models. Unfortunately, finding and testing a vaccine for a virus such as EEEV faces one main challenge, namely the financial kind. Since EEEV outbreaks tend to be rather small and occur rarely, there appears to be less incentives to invest in the discovery and testing of an EEEV vaccine for humans.²⁴ That is especially true because it has been estimated that establishing and licensing a new vaccine could take between 5 and 18 years and the cost would amount to about $500 million.²⁵

Despite that, EEEV is more likely to get a vaccine than viruses with similar characteristics. The first reason is that it can be potentially used as a bioweapon, which is a grave concern, especially for the military. The second reason is that the people who survive EEEV-induced neurological disease (meningitis¹⁶ or encephalitis¹) often require expensive long-term care, likely putting a financial strain on both the patients and healthcare providers .²⁴

A promising human vaccine candidate for eastern equine encephalitis (EEE)

Intriguingly, a vaccine called the WEVEE VLP (= western, eastern, and Venezuelan equine encephalitis virus-like particle) vaccine successfully passed phase I clinical trials 4 years ago and the results were published.²⁶ As the name suggests, it is designed to protect against EEEV, WEEV and VEEV (all three encephalitic alphaviruses, therefore the vaccine is trivalent) and consists of virus-like particles (VLPs) of these alphaviruses. 

Virus-like particles (VLP) vaccines

These particles are called virus-like because they look exactly like these viruses from the outside but they do not contain any genetic material.²⁴ Therefore, due to their striking similarity, an injection with these VLPs will cause the human immune system to react in precisely the same way as it would if it was encountering the actual viruses. The immune defence mounted against VLPs would thereby also grant immunity against the real viruses found in the wild. 

Using VLPs instead of weakened living (live-attenuated) viruses is safer because live-attenuated viruses still possess their genetic material.²⁴ This means they can still potentially multiply uncontrollably and cause severe disease if someone’s immune system is sufficiently weakened for whatever reason.²⁷

Phase I clinical trials

Phase I of clinical trials involves testing a new medicine in healthy people to determine any side effects and the best dose to use in treatment. Ultimately, phase I shows to a certain extent if a new drug is suitable and safe for use in humans.²⁸ 

Results of the WEVEE VLP vaccine phase I clinical trial

During the trial, 2 injections of the WEVEE VLP vaccine were given, 8 weeks apart. The vaccine was found to produce only mild side effects.²⁶ These included tenderness and mild pain at the injection site, headache, malaise (feeling unwell or ill), chills, nausea, joint pain and myalgia (muscle pain²⁹). By the 12th week, the study participants who were given either a high concentration of the vaccine or a lesser concentration coupled with an immune reaction booster ( = adjuvant) developed neutralising antibodies in quantities that would most likely grant outstanding protection against EEEV, WEEV and VEEV infection.²⁶ 

All in all, the WEVEE VLP vaccine has shown great potential and appears to be a very promising EEEV vaccine candidate that will hopefully also be tested in phase II and phase III clinical trials in the foreseeable future. 

FAQ’s

Is there a vaccine for eastern equine encephalitis?

No, there is currently no human vaccine for eastern equine encephalitis but there is one available for horses.

What is eastern equine encephalitis?

Eastern equine encephalitis (EEE) is an illness by the eastern equine encephalitis virus (EEEV). EEE is mostly harmless but can lead to very serious symptoms including coma and death.

How rare is eastern equine encephalitis?

In the USA, an average of 11 cases of EEE are reported per year.

What is the mortality rate for eastern equine encephalitis?

The mortality of EEE in general is fairly low. About 4 - 5% of people infected by EEEV develop EEE with symptoms and only some of them will develop encephalitis (infection and inflammation of the brain) which is a serious complication. Roughly 33% of the patients with this grave condition do not recover.

Where can you get eastern equine encephalitis?

Eastern equine encephalitis is caused by the eastern equine encephalitis virus (EEEV) which is transmitted via the sting of infected mosquitoes.

Summary

Eastern equine encephalitis (EEE) is a disease caused by the eastern equine encephalitis virus (EEEV). Mosquitos in the east of the US and in the Caribbean can carry EEEV and infect horses and humans when feeding on them. Most EEEV infections in humans produce no or only mild symptoms but in some cases, it can lead to grave symptoms including coma and death. Furthermore, survivors of severe cases of EEE are often left with long-term debilitations. There is currently no EEEV vaccine and also no specific treatment to combat EEE. Therefore, it is recommended to employ preventive measures to avoid being stung by mosquitos when living or travelling in these areas. A promising EEEV vaccine candidate was successfully tested in phase I clinical trials in 2020, so there is hope that there will be an EEEV vaccine in the not-too-distant future. That might prove especially vital since EEEV has the potential to be used as a bioweapons.