Japanese Encephalitis Vaccine - Drug Monograph

Introduction

Japanese encephalitis (JE) vaccine is an immunization agent used to prevent Japanese encephalitis, a potentially severe viral infection caused by the Japanese encephalitis virus (JEV). JE is the leading vaccine-preventable cause of encephalitis in Asia, with an estimated 68,000 clinical cases annually. The vaccine provides active immunization against JEV, which is transmitted through the bite of infected Culex mosquitoes.

Mechanism of Action

Japanese encephalitis vaccines work by stimulating the immune system to produce antibodies against the Japanese encephalitis virus. The inactivated Vero cell-derived vaccine (IXIARO) contains purified, inactivated JE virus particles that cannot cause disease. Upon administration, antigen-presenting cells process the vaccine antigens and present them to T-cells, initiating both humoral and cellular immune responses. This results in the production of virus-neutralizing antibodies and memory B-cells that provide protection against future JEV exposure.

Indications

• Primary immunization for persons aged ≥2 months traveling to or residing in JE-endemic areas
• Laboratory workers with potential exposure to JEV
• Booster doses for persons at continued risk of JEV infection
• Recommended for travelers spending ≥1 month in endemic areas during JE virus transmission season

Dosage and Administration

• Primary series for persons ≥3 years: 0.5 mL intramuscularly at days 0 and 28
• Primary series for children 2 months to <3 years: 0.25 mL intramuscularly at days 0 and 28
• Booster dose: 0.5 mL (all ages) at ≥12 months after primary series if ongoing exposure risk exists

• Administer intramuscularly in the deltoid muscle (adults) or anterolateral thigh (infants)
• Do not administer intravenously, intradermally, or subcutaneously
• Complete primary series at least 1 week prior to potential JEV exposure

• Pregnancy: Consider if benefit outweighs risk; limited safety data
• Lactation: Generally considered compatible with breastfeeding
• Immunocompromised: May have reduced immune response; consider timing with immunosuppressive therapies

Pharmacokinetics

As a vaccine, Japanese encephalitis vaccine does not follow typical pharmacokinetic parameters. The immune response develops over several weeks following administration:

• Onset of immunity: Protective antibody levels typically develop within 1-2 weeks after completing primary series
• Peak antibody response: Occurs approximately 4-6 weeks after second dose
• Duration of immunity: At least 1 year after primary series; booster doses extend protection
• Seroconversion rates: >96% in adults and children after primary series

Contraindications

• History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine
• History of severe allergic reaction to previous dose of JE vaccine
• Moderate or severe acute illness with or without fever (defer until recovery)

Warnings and Precautions

• Syncope: Can occur following vaccination; observe patients for 15 minutes post-vaccination
• Apnea: Monitor infants born prematurely for apnea for 48-72 hours after vaccination
• Guillain-Barré syndrome: Theoretical risk; benefits generally outweigh risks
• Altered immunocompetence: May have reduced immune response
• Multiple vaccinations: Can be administered simultaneously with other vaccines using different injection sites

Drug Interactions

• Immunosuppressive therapies: (corticosteroids, chemotherapy, biologics) may diminish immune response
• Other vaccines: No clinically significant interactions when administered simultaneously with different injectable vaccines
• Immunoglobulins: May interfere with immune response if administered concurrently; separate administration by ≥3 months
• Antimalarials: No known interactions, but consider timing with malaria prophylaxis

Adverse Effects

• Injection site reactions: pain, tenderness, redness, swelling
• Systemic: headache, myalgia, fatigue, fever

• Nausea, vomiting
• Influenza-like illness
• Rash, pruritus

• Allergic reactions (urticaria, angioedema)
• Neurological events (seizures, encephalitis) - causal relationship not established

Monitoring Parameters

• Pre-vaccination: Screen for contraindications and precautions
• Post-vaccination: Observe for immediate adverse reactions for 15-30 minutes
• Immune response: Consider serologic testing in immunocompromised patients if concern about adequate response
• Surveillance: Monitor for delayed adverse events through vaccine adverse event reporting systems

Patient Education

• Complete the full two-dose series for optimal protection
• Schedule vaccination at least 1 week before travel to endemic areas
• Expect mild side effects; use analgesics/antipyretics for discomfort if needed
• Continue mosquito bite prevention measures (repellents, protective clothing, bed nets)
• Seek medical attention for severe reactions including difficulty breathing, tachycardia, or dizziness
• Keep vaccination record for future reference
• Booster doses may be needed if ongoing risk exists

References

1. Centers for Disease Control and Prevention. (2021). Japanese Encephalitis ACIP Vaccine Recommendations. MMWR, 68(2), 1-33. 2. World Health Organization. (2015). Japanese encephalitis vaccines: WHO position paper. Weekly Epidemiological Record, 90(9), 69-88. 3. FDA. (2021). IXIARO® prescribing information. Valneva USA, Inc. 4. Hoke, C. H., et al. (1988). Protection against Japanese encephalitis by inactivated vaccines. New England Journal of Medicine, 319(10), 608-614. 5. Tauber, E., et al. (2007). Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial. The Lancet, 370(9602), 1847-1853. 6. Fischer, M., et al. (2010). Japanese encephalitis prevention and control: advances, challenges, and new initiatives. Emerging Infectious Diseases, 16(1), 1-7.