Introduction
Yellow fever vaccine is a live, attenuated viral vaccine that provides active immunization against yellow fever, a potentially fatal mosquito-borne viral hemorrhagic fever endemic in tropical areas of Africa and South America. The vaccine contains the 17D-204 strain of yellow fever virus and has been in use since the 1930s, representing one of the most effective vaccines ever developed.
Mechanism of Action
The yellow fever vaccine contains live, attenuated yellow fever virus (17D strain) that replicates in vaccinated individuals. This replication stimulates both humoral and cellular immune responses. The vaccine induces neutralizing antibodies that provide protection against wild-type yellow fever virus infection. The immune response typically provides protection within 10 days in 90% of vaccinees and within 30 days in 99% of vaccinees.
Indications
- Primary immunization against yellow fever for persons aged 9 months and older living in or traveling to endemic areas
- Laboratory personnel who might be exposed to yellow fever virus
- Requirement for entry into certain countries according to International Health Regulations
- Revaccination every 10 years for continued protection (though some evidence suggests longer-lasting immunity)
Dosage and Administration
- Standard dose: 0.5 mL subcutaneous injection
- Administration: Subcutaneous injection in the upper arm
- Primary immunization: Single dose
- Booster: Every 10 years for continued protection (though WHO now states that a single dose may provide lifelong protection for most individuals)
- Special populations:
- Infants: Not recommended under 6 months; recommended 9-12 months in endemic areas - Elderly: Standard dosing with careful risk-benefit assessment - Immunocompromised: Generally contraindicated
Pharmacokinetics
- Absorption: The attenuated virus replicates locally and systemically after subcutaneous administration
- Distribution: The vaccine virus spreads to local lymph nodes and then systemically
- Metabolism: The vaccine virus replicates in host cells similar to wild-type virus but with attenuated pathogenicity
- Elimination: The vaccine virus is cleared by the immune system within 2-3 weeks post-vaccination
- Duration of immunity: Neutralizing antibodies persist for decades, possibly lifelong
Contraindications
- History of severe allergy to vaccine components (eggs, chicken proteins)
- Age <6 months
- Symptomatic HIV infection or CD4 count <200/mm³
- Primary immunodeficiencies
- Thymus disorder associated with abnormal immune function
- Malignant neoplasms affecting bone marrow or lymphatic systems
- Immunosuppressive and immunomodulatory therapies
- Pregnancy (except when travel to endemic area is unavoidable)
Warnings and Precautions
- Yellow fever vaccine-associated neurologic disease (YEL-AND): Rare (0.8 per 100,000 doses)
- Yellow fever vaccine-associated viscerotropic disease (YEL-AVD): Rare but serious (0.4 per 100,000 doses), higher risk in elderly
- Administer with caution to persons with asymptomatic HIV infection and CD4 counts 200-499/mm³
- Consider deferral during breastfeeding if infant <9 months
- Higher risk of serious adverse events in persons ≥60 years
- Not recommended for persons with history of thymus dysfunction
Drug Interactions
- Other live vaccines: Should be administered simultaneously or separated by ≥4 weeks
- Immunosuppressive agents: Corticosteroids, chemotherapy, radiation therapy may reduce vaccine effectiveness
- Immune globulins: May interfere with vaccine effectiveness if administered concurrently
- Antimalarials: No known interactions, but often administered to travelers to endemic areas
Adverse Effects
Common (≥10%):
- Injection site reactions (pain, redness, swelling)
- Low-grade fever
- Headache
- Myalgia
Less common (1-10%):
- Fatigue
- Mild rash
- Malaise
Rare but serious (<0.01%):
- Immediate hypersensitivity reactions
- Yellow fever vaccine-associated neurologic disease (encephalitis, Guillain-Barré syndrome)
- Yellow fever vaccine-associated viscerotropic disease (multi-organ system failure)
Monitoring Parameters
- Post-vaccination: Observe for 15 minutes for immediate hypersensitivity reactions
- Monitor for fever and systemic symptoms for 5-10 days post-vaccination
- International Certificate of Vaccination should be completed and provided to patient
- Serologic testing not routinely recommended to confirm immunity
- Monitor for delayed adverse events for 30 days post-vaccination
Patient Education
- Vaccine provides protection within 10 days for most recipients
- Common side effects include sore arm, mild fever, and headache
- Seek medical attention for high fever, severe headache, confusion, or unusual bleeding after vaccination
- Keep vaccination record (International Certificate of Vaccination) for travel requirements
- Protection is long-lasting; booster may be needed every 10 years for certificate purposes
- Continue mosquito bite prevention measures even after vaccination
- Inform healthcare providers of recent vaccination if seeking care for febrile illness
References
1. Staples JE, Bocchini JA Jr, Rubin L, Fischer M. Centers for Disease Control and Prevention. Yellow fever vaccine booster doses: Recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(23):647-650.
2. World Health Organization. Yellow fever vaccine: WHO position paper – June 2013. Wkly Epidemiol Rec. 2013;88(27):269-283.
3. Monath TP, Gershman M, Staples JE, Barrett ADT. Yellow fever vaccine. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 6th ed. Philadelphia, PA: Saunders Elsevier; 2013:870-968.
4. Lindsey NP, Rabe IB, Miller ER, Fischer M, Staples JE. Adverse event reports following yellow fever vaccination, 2007-13. J Travel Med. 2016;23(5):taw045.
5. CDC Yellow Book 2024: Health Information for International Travel. Centers for Disease Control and Prevention.
6. Manufacturer's prescribing information: YF-VAX® (Yellow Fever Vaccine)