Japanese Encephalitis (JE) vaccine

The Japanese encephalitis vaccine is a prescription medication belonging to the vaccine class.

The Japanese encephalitis vaccine is approved for protection against the Japanese encephalitis virus (a viral infection transmitted by mosquitoes) in adults and adolescents who are at least 17 years old, particularly for tourists visiting locations where the disease is prevalent or for military personnel deployed in affected areas.

It is a part of national routine immunization programmes in high-risk areas where the disease is prevalent.

The Japanese encephalitis (JE) vaccine is given intramuscularly. It is absorbed into the circulation and stimulates the production of defense-enhancing antibodies by the immune system. It undergoes an insignificant amount of metabolic processing and provides long-lasting protection against the JE virus.

The common side effects of the Japanese encephalitis vaccine include injection site pain, redness, cold symptoms, low-grade fever, back pain, chills and fatigue.

The Japanese encephalitis vaccine is available in the form of suspension for injections.

The Japanese encephalitis vaccine is available for travellers to at-risk areas in Japan, South Korea, China, India, Bangladesh, Thailand, Vietnam, and the United States.

The Japanese Encephalitis vaccine, belonging to the vaccine class, acts as an inactivated virus and is a sterile, lyophilized vaccine recommended to be administered intramuscularly or subcutaneously. To generate it, mice are intracerebrally inoculated with the Japanese encephalitis virus.

The specific mechanism by which JE vaccines work is still not fully known. According to animal model studies, the vaccine boosts the immune system to produce antibodies against the Japanese encephalitis virus, with a high probability of protecting the individual receiving it. Mice treated with human vaccination antisera performed challenge trials to evaluate the vaccine's effectiveness. These experiments showed that almost all mice protected against a potentially fatal Japanese encephalitis virus challenge had a Plaque Reduction Neutralisation Test titre of at least 1:10. This shows the vaccine's ability to trigger a protective immunological response.

The Japanese encephalitis vaccine is available in the form of suspension for injection.

Suspension for injection: To be administered parenterally, as applicable.

A healthcare professional administers the injectable JE vaccine. Typically, two doses are given several weeks apart, and booster shots may be needed for long-term protection, especially in high-risk areas for JE.

The Japanese Encephalitis (JE) vaccine can be used as follows:

• Adults travelling to Asia at a higher risk of acquiring the Japanese encephalitis virus (JEV) are advised to receive the active immunization vaccine.
• An active immunisation vaccine is advised for adults and children older than two months who are travelling to Asia and are at elevated risk of acquiring the Japanese encephalitis virus (JEV).

The Japanese Encephalitis (JE) vaccine can help support the following health benefits:

Prevention: The JE vaccination helps to prevent Japanese encephalitis, a condition caused by the JEV. Bites from mosquitoes typically spread this virus, and once it has been caught, it can cause severe brain inflammation, neurological symptoms, and, in very rare cases, death. People may substantially decrease their chance of acquiring this potentially fatal disease by receiving the JE vaccination. Since the illness can result in deadly neurological complications and long-term consequences, preventing Japanese encephalitis is essential for maintaining good health.

Mortality: Japanese encephalitis is fatal, especially in the elderly and young. The vaccination reduces the risk of JE-related death by protecting against the virus. This advantage is significant in areas where the disease is prevalent since it can significantly lower the number of mortalities caused by Japanese encephalitis.

Traveller Safety: The vaccine's protection is highly beneficial for anyone travelling or residing in regions with a high risk of an outbreak of Japanese encephalitis. Without immunization, travellers can acquire the virus, which can cause life-threatening sickness while travelling or afterwards.

Herd immunity: Public health benefits greatly from extensive JE vaccinations. The possibility for severe JE ramifications among them is reduced. It protects the person vaccinated and those individuals with weaker immune systems, children, the elderly, and vulnerable populations, reducing the burden on healthcare systems and improving overall community well-being.

The Japanese encephalitis vaccine is approved for its use in the following clinical indications:

• For adults, teenagers, kids, and babies two months and older who need an active vaccination against Japanese encephalitis.
• People who travel to or reside in areas with a high incidence of Japanese encephalitis, particularly for a prolonged period or during the peak transmission seasons.
• Individuals who handle the Japanese encephalitis virus in laboratories to lower the risk of occupational exposure.

Parenterally: The JE vaccine is given parenterally. The vaccine is injected into the anterolateral aspect of the thigh for children under two years old, which may be used as an injection site. In contrast, it is injected into the deltoid muscle for children over two years old and adults. It should never be administered intravascularly. When given concurrently with injectable vaccines, the shots have to be delivered using different syringes at different places. Following immunization, monitoring for at least 15 minutes for signs of any acute allergic reactions is essential.

In exceptional cases, the JE vaccine can also be given subcutaneously to individuals with thrombocytopenia or bleeding problems since bleeding might happen after an intramuscular injection. An inadequate reaction to the vaccination after subcutaneous delivery is possible.

It can be only given by a healthcare professional in a hospital setting or during routine immunization programs.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Suspension for injection: 0.5mL pre-filled syringe

Dosage Adjustment for Adult Patients

Active Immunization against Japanese Encephalitis Virus (JEV)

Before a possible JEV exposure, complete the primary immunization series at least one week in advance.

Primary dose

Ages 18 to 65: Two doses (0.5 mL each), administered seven or 28 days apart.

More than 66 years old: two 0.5 mL Intramuscularly doses scheduled 28 days apart.

Booster dose

If extra exposure or re-exposure to JEV is expected, a single 5-mL booster dose (third dose) may be administered at least 11 months after the primary immunization series is completed.

The Japanese Encephalitis vaccine is available in the form of suspension for injection.

Japanese Encephalitis vaccine should be used to prevent Japanese Encephalitis virus infections in high-risk individuals, along with no appropriate nutritional restrictions.

JE vaccine usually has little effect on dietary or food substances when administered. Consuming regular foods and drinks before and after receiving the vaccine is safe.

Staying well hydrated by drinking water or other fluids is commonly advised. Maintaining a balanced diet can help boost the body's immunological response to the vaccine and overall health during vaccination.

The dietary restriction should be individualized as per patient requirements.

Japanese Encephalitis vaccine may be contraindicated in the following conditions-

• Hypersensitivity (previous dose of JE vaccine or any of its components)
• Allergic to latex rubber
• Generalised urticaria
• Angioedema
• Hypersensitivity to thiomersal in children aged less than a year old.
• Guillain-Barré syndrome
• Severe immunosuppressive conditions like HIV/AIDS or those receiving immunosuppressive medications

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

• The JE vaccine should not be administered to anyone with a known severe allergy to any ingredients, including specific proteins or preservatives.
• If the individual has a moderately critical acute sickness (with or without fever), administration of the vaccine should be postponed.
• If an individual is receiving other vaccines simultaneously, healthcare providers should cautiously administer the vaccine, considering all the potential interactions and the intervals between vaccinations.
• It is recommended not to reconstitute or dilute the vaccine before administration.
• Japanese Encephalitis vaccine is not typically recommended during pregnancy unless there is a specific risk of exposure to the Japanese Encephalitis Virus.

There is no sufficient scientific evidence regarding the use and safety of the Japanese Encephalitis vaccine in the breastfeeding population.

There is no sufficient scientific evidence regarding the use and safety of the Japanese Encephalitis vaccine in concurrent use with any particular food.

The adverse reactions related to the Japanese Encephalitis vaccine can be categorized as

• Common: Pain, redness, swelling at the injection site, irritability and myalgia.
• Less common: GI disturbances like nausea and vomiting, weakness/fatigue, low-grade fever and dizziness.
• Rare: Fever, >104.9°F (most common in infants and children), allergic and neurological reactions.

The clinically relevant drug interactions of the Japanese Encephalitis vaccine are briefly summarized here:

• Immunosuppressants- The immunological response to Japanese Encephalitis vaccine may be suppressed by immunosuppressive treatments such as radiation, antimetabolites, alkylating agents, cytotoxic medicines, and corticosteroids (used in dosages larger than therapeutic doses).
• Other Vaccines- Multiple vaccinations, including the Japanese Encephalitis vaccine, given at the same time may increase the risk of adverse reactions. To reduce such a risk, medical professionals frequently adhere to vaccination regimens considering the time and space of vaccines.

The common side of the JE Vaccine includes the following-

• Diarrhoea
• Cough
• Flu symptoms
• Fever
• Pain or disease generally
• Headaches
• Pain in the joints
• Stomach pain
• Pain in the muscles
• Nausea
• Clogged nose
• Chills
• Stiff neck
• Sweating
• Inability to sleep
• Unusual weakness or fatigue
• Vomiting

The Japanese encephalitis (JE) Vaccine should be prudent in the following group of special populations.

• Pregnancy: There is no sufficient scientific evidence traceable regarding the use and safety of the JE vaccine for pregnant populations.
• Paediatrics: The Japanese encephalitis (JE) vaccine protects against Japanese encephalitis, a potentially severe and fatal medical condition, in pediatric populations. It protects children's health and well-being, especially in regions where the virus is prevalent.

Dosage Adjustment for Paediatric Patients

Active Immunization against Japanese encephalitis virus (JEV)

Less than two months: Safety and effectiveness have not been established

Before any possible JEV exposure, complete all vaccinations at least one week in advance.

Primary immunization series

Two months to less than three years: 2 doses of 0.25 mL intramuscularly administered 28 days apart

More than three years: 2 doses of 0.5 mL intramuscularly administered 28 days apart

Booster dose

If there is expected to be continued exposure or re-exposure to JEV, a booster dose (third dose) may be administered at least 11 months after the primary immunization series is completed.

From 14 months to three years, administer a single 0.25 mL booster dose.

Administer a single 0.5-mL booster dose to children under three years old.

• Geriatrics: There is no sufficient scientific evidence traceable regarding the use and safety of the JE vaccine for geriatric populations.

• Lactating mothers: There is no sufficient scientific evidence traceable regarding the use and safety of the JE vaccine for lactating mother populations.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Overdosage of the Japanese Encephalitis (JE) vaccine rarely occurs because healthcare professionals administer it according to specific or precise dosing guidelines.

There is no specific antidote or treatment for excessive intake of JE vaccine. Medical attention should be sought immediately when an overdose is suspected, followed by close monitoring for any adverse effects or allergic reactions. Supportive therapy may include pain relievers for discomfort or fever reducers if needed, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Pharmacodynamics of Japanese Encephalitis (JE) vaccine:

The Japanese encephalitis (JE) vaccine has a physiological mechanism that plays a role in its pharmacodynamics, involving its interaction with the immune system. It protects against the Japanese encephalitis virus, which can cause severe brain inflammation, by a specific action method. The vaccine acts as the antigen by incorporating a harmless viral component when delivered, either inactivated or weakened. The immune system's reaction to this antigen is triggered, resulting in the production of antibodies and the activation of immune cells. While the immune system develops memory cells to keep the virus's traits, these antibodies can identify and neutralise the virus. This immunological memory ensures an effective defence against Japanese encephalitis in the event of subsequent exposure.

Pharmacokinetics of Japanese Encephalitis (JE) vaccine:

Absorption: The JE vaccine is usually administered intramuscularly, after which the vaccine components are absorbed from the muscle tissue into the bloodstream.

Distribution: Once it reaches the bloodstream, the vaccine components, including inactivated virus particles or proteins, may be transported throughout the body. They stimulate the immune system's production of antibodies that are effective against the virus that causes Japanese encephalitis.

Metabolism: Unlike drugs, the JE vaccine does not involve metabolism processes because vaccines contain inert viral proteins, not active drugs. The vaccine's effectiveness comes from the body's immune response and antibody production against Japanese encephalitis virus infections.

Elimination: The vaccine's active ingredients are eliminated from the body, but the immunological memory is activated to provide long-term defence against the Japanese encephalitis virus and related diseases.

• Xin, Y Y et al. “Safety of a live-attenuated Japanese encephalitis virus vaccine (SA14-14-2) for children.” The American journal of tropical medicine and hygiene vol. 39,2 (1988): 214-7. doi:10.4269/ajtmh.1988.39.214
• Hegde, Nagendra R, and Milind M Gore. “Japanese encephalitis vaccines: Immunogenicity, protective efficacy, effectiveness, and impact on the disease burden.” Human vaccines & Immunotherapeutics vol. 13,6 (2017): 1-18. doi:10.1080/21645515.2017.1285472
• Kumar, Awanish et al. “Japanese encephalitis virus: Associated immune response and recent progress in vaccine development.” Microbial pathogenesis vol. 136 (2019): 103678. doi:10.1016/j.micpath.2019.103678

Data on non-clinical toxicity are limited.

No vaccine-related effects on pregnancy, fetal weight, survival, or offspring development were found in reproductive and pre-/post-natal toxicity research. However, only in the group getting two doses, not in the group receiving three doses, was partial ossification of the skeleton observed. It is still unclear whether or not this event results from the therapy.

• Inform the caregivers of the dosage and schedule for the vaccine, including any booster shots if needed.
• Inform the vaccination recipient, their parents, or their guardians whether they had any side effects from a prior dosage of the JE vaccine.
• Assure caregivers that JE immunizations are generally safe, with only minor, short side effects. Encouraging them to immediately report any unexpected or severe responses to the healthcare physician and, whenever applicable, to use reporting systems like the Vaccine Adverse Event Reporting System (VAERS)
• Inform caregivers of the recommended immunization schedule, which usually consists of two or three doses, depending on the vaccine brand used. Also, mention the ages at which the doses should be administered and give the Vaccine Information Statements, which must be disclosed before immunization by the National Childhood Vaccine Injury Act of 1986 about the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines), these resources are freely accessible.

http://www.cdc.gov/vaccines/schedules/hcp/index.html

https://www.cdc.gov/vaccines/vpd/j-enceph/

https://www.pediatriconcall.com/drugs/japanese-encephalitis-vaccine/684

https://www.indianpediatrics.net/oct2014/785 figure1.pdf

https://www.cdc.gov/vaccines/hcp/vis/vis-statements/je-ixiaro.html