Yellow Fever Vaccine

Introduction Overview

Generic Name

yellow fever vaccine

Brand Name

YF-Vax
Stamaril

Dosage Form

Subcutaneous powder for injection

Drug Class

Viral vaccines

Pharmacokinetics

Absorption:
The yellow fever vaccine is administered subcutaneously, providing direct delivery into the subcutaneous tissue where immune cells such as dendritic cells and macrophages reside. Upon injection, the live-attenuated virus contained in the vaccine infects local cells and begins replication, although at a significantly reduced level compared to wild-type virus, thus stimulating the immune system without causing disease. This local replication is essential for antigen presentation and subsequent induction of immunity. There is rapid uptake by antigen-presenting cells in the local lymphatic tissue, facilitating prompt immune activation. The vaccine is not absorbed into the systemic circulation in the classical pharmacokinetic sense, as it relies primarily on localized replication and immune stimulation.

Distribution:
Following subcutaneous administration, the vaccine virus remains mostly localized to the injection site and regional lymph nodes where antigen presentation occurs. Limited systemic dissemination of the attenuated virus does occur to stimulate a protective immune response, but the viral particles do not establish widespread viremia in healthy individuals. In immunocompromised patients, there may be a higher risk of systemic spread. The vaccine’s viral components interact with immune cells within lymphoid tissues, especially the lymph nodes and spleen, to effectively prime adaptive immune responses including generation of neutralizing antibodies.

Metabolism:
The live-attenuated yellow fever virus in the vaccine undergoes limited replication following administration to present viral antigens to the immune system. The metabolic degradation is accomplished by host cellular processes and immune-mediated clearance mechanisms. Viral particles are processed by antigen-presenting cells and viral proteins are degraded via proteasomal and lysosomal pathways, leading to presentation of viral peptides on MHC molecules for T-cell activation. The attenuated virus does not undergo classical hepatic metabolism, but its elimination is essentially dependent on host immune surveillance and cellular clearance.

Elimination:
Elimination of the vaccine virus occurs through the host’s immune responses. Cytotoxic T lymphocytes, neutralizing antibodies, and innate immune mechanisms progressively clear the attenuated virus from the host. No significant shedding or prolonged persistence has been documented in immunocompetent individuals. The vaccine virus is ultimately eliminated by cellular destruction, phagocytosis, and degradation. The live vaccine virus does not accumulate or persist chronically; the immune system eliminates it over days to weeks while establishing enduring immunity.

Clinical Implications:
The pharmacokinetic profile underscores the importance of a competent immune system for vaccine efficacy and safety. Immunocompromised persons may have delayed clearance of the vaccine virus and increased risk of vaccine-associated complications like viscerotropic or neurotropic disease. Vaccine timing with respect to potential exposure is critical, as immunity develops approximately 10 days post-vaccination. The localized nature of vaccine virus replication and immune activation explains the minimal systemic adverse effects in most recipients.

Dosage Forms

Available Dosage Forms:
- Subcutaneous powder for injection provided as a lyophilized (freeze-dried) vaccine powder which must be reconstituted with a sterile diluent prior to administration.

Dosages for Adults and Adolescents:
- Standard dose: 0.5 mL administered subcutaneously as a single injection.
- Booster doses may be administered at least 10 years after the initial vaccination to individuals at continued or increased risk of exposure to yellow fever virus.

Specific Patient Populations:
- Pediatric patients 9 months of age and older: 0.5 mL subcutaneously as a single dose, similar to adult dosing.
- Children under 9 months: Contraindicated due to risk of vaccine-associated viscerotropic disease.
- Immunocompromised patients or those with special risk factors (e.g., hematopoietic stem cell transplant recipients, HIV-infected patients, pregnant women) may require additional doses if exposed continuously or without adequate immune response.
- Older adults (≥60 years): Vaccination is generally recommended only if at high risk for exposure because of increased risk of adverse events.

Clinical Guidelines:
-The vaccine is typically administered at least 10 days before travel to endemic areas to allow adequate immune response development.
-Multiple dose regimens may be tailored based on immune status, risk profile, and local health authority recommendations.

Storage and Handling:
-The lyophilized vaccine must be stored refrigerated and protected from light.
-Reconstitution must be performed aseptically immediately before administration using recommended diluents.

Mechanism Of Action

The yellow fever vaccine is a live attenuated viral vaccine derived from the 17D strain of yellow fever virus. The vaccine functions primarily by mimicking natural infection, thereby stimulating the immune system to develop robust and durable immunity without causing disease.

Upon subcutaneous administration, the attenuated virus infects host cells, particularly antigen-presenting cells such as dendritic cells. This limited replication produces viral antigens within host cells that are processed and presented on major histocompatibility complex (MHC) molecules. This antigen presentation activates CD4+ helper T cells and CD8+ cytotoxic T cells along with B cells, initiating both cellular and humoral immune responses.

The humoral response is characterized by production of neutralizing antibodies directed against viral envelope glycoproteins, predominantly the E protein, which block viral attachment and entry upon subsequent exposure. These neutralizing antibodies confer long-term immunity and are the main correlates of protection. Cellular immunity also contributes by eliminating infected cells during any future exposure.

Comparatively, yellow fever vaccine shares immunological mechanisms with other live attenuated viral vaccines, such as measles and varicella vaccines, relying on attenuation to provide sufficient replication for immune priming without virulence. Extensive clinical trials and epidemiologic studies have demonstrated that a single dose induces protective immunity in approximately 99% of recipients within 10 days, lasting at least 10 years, often lifelong.

Furthermore, ongoing research explores the molecular basis of attenuation in the 17D strain focusing on mutations that reduce neurovirulence and viscerotropism, contributing to its excellent safety profile. The vaccine also exhibits cross-protection to some degree against flaviviruses due to conserved antigenic epitopes, though this is clinically limited.

Pharmacological Actions

Induces active immunity against yellow fever virus by stimulating both humoral and cellular immune responses.
Utilizes live attenuated yellow fever virus (17D strain) to mimic natural infection without causing disease.
Elicits production of neutralizing antibodies targeting viral envelope proteins to prevent viral entry.
Activates antigen-presenting cells and T-lymphocytes, facilitating immunological memory formation.
Provides long-lasting protection, typically 10 years or more, often lifelong after a single dose.
Reduces morbidity and mortality from yellow fever by preventing viral replication and systemic infection.
Recommended by health authorities for individuals traveling to or residing in endemic regions.
Used in occupational settings to protect laboratory personnel at risk of yellow fever virus exposure.
Live vaccine with limited replication predominantly localized to injection site and regional lymph nodes.
Induces vaccine-virus clearance through host immune mechanisms to prevent persistence.
May provide partial cross-immunity to related flaviviruses through conserved antigenic sites.
Vaccination results in immunological memory, allowing rapid response upon exposure to wild virus.
Boosters enhance immunity in individuals with waning antibody levels or ongoing exposure risk.
Has a rapid onset of immunity, with protective antibody titers developing within 10 days.
Does not treat active yellow fever infection; used solely for prophylaxis.

Therapeutic Or Clinical Uses

Prevention of yellow fever infection in individuals traveling to or living in endemic areas of Africa and South America.
Immunization of laboratory workers or researchers with potential occupational exposure to yellow fever virus.
Required documentation for international travel to countries with yellow fever endemicity, as proof of vaccination.
Used in outbreak control to prevent spread of yellow fever in epidemic situations.
Administered to individuals aged 9 months and older, with contraindications below this age.
Recommended for pregnant women at high risk of exposure after risk-benefit assessment.
May be given as a booster dose for individuals previously vaccinated and at continued exposure risk.
Pre-exposure prophylaxis to reduce incidence of the potentially fatal viral hemorrhagic fever.
Part of national immunization programs in endemic countries to prevent yellow fever morbidity and mortality.
Used to confer herd immunity during mass vaccination campaigns in endemic regions.
Protects against yellow fever-associated viscerotropic and neurotropic disease by preventing infection.
Reducing the public health and economic burdens associated with yellow fever outbreaks.
Immunizes travelers and military personnel deployed in yellow fever endemic zones.
Supports global control and eventual elimination efforts for yellow fever virus transmission.
Important in preventing international spread of yellow fever through infected travelers.

Side Or Adverse Effects

Common side effects include mild to moderate fever following vaccination.
Injection site reactions such as pain, redness, swelling, tenderness, and induration may occur.
Headache is frequently reported in the first few days post-vaccination.
Muscle and joint pain, as well as general fatigue and weakness, can be experienced transiently.
Nausea and vomiting are occasionally observed.
Severe allergic reactions (anaphylaxis) are rare but can involve hives, breathing difficulty, and facial swelling.
Yellow fever vaccine-associated viscerotropic disease (YEL-AVD), a rare but serious systemic illness resembling wild yellow fever, typically occurs within 10 days post-vaccination.
Yellow fever vaccine-associated neurotropic disease (YEL-AND), involving encephalitis or meningoencephalitis, can rarely occur, especially in older adults.
Neurologic symptoms such as confusion, seizures, neck stiffness, and cranial nerve palsies have been reported in very rare cases.
Severe hypersensitivity may be more common in individuals with egg allergies due to vaccine production methods.
Rare occurrences of Guillain-Barré syndrome and other autoimmune neurologic disorders have been reported.
Bruising or unusual bleeding can be a manifestation of systemic adverse reactions.
Transient decreases in urine output and jaundice are clinical signs indicative of serious adverse events.
Older adults (≥60 years) have an increased risk of serious vaccine-related adverse reactions.
Local adverse reactions resolve without intervention typically within several days.

Precautions

Do not administer to individuals with a history of severe allergic reaction to yellow fever vaccine or its components, including egg or chicken protein allergy unless benefits outweigh risks and desensitization protocols are implemented.
Contraindicated in infants younger than 9 months due to increased risk of vaccine-associated viscerotropic disease.
Use caution in immunocompromised patients, including those with HIV/AIDS, cancer, leukemia, lymphoma, or those on immunosuppressive therapy such as corticosteroids.
Patients with thymus gland disorders or those who have undergone thymectomy should be evaluated carefully prior to vaccination.
Assess history of neurologic disorders or prior adverse reactions to vaccines before administration.
Pregnant women should generally avoid vaccination unless travel to high-risk areas is essential and benefits justify risks.
Breastfeeding should be deferred if the infant is under 9 months old; safety in breastfeeding mothers requires clinical judgment.
Patients with bleeding or clotting disorders should be vaccinated cautiously to avoid bleeding complications.
Inform patients about potential post-vaccination symptoms and advise they seek medical attention if severe adverse effects develop.
Wait until resolution of acute febrile or moderate/severe illness before administering the vaccine.
Monitor elderly patients carefully due to increased risk of adverse events.
Consider use of smaller divided doses and close monitoring in egg-allergic individuals when vaccination is necessary.
Inquire about prior seizure disorders and neurologic symptoms to identify potential risks.
Advise patients to carry their International Certificate of Vaccination for 10 years after vaccination as proof of immunization when traveling.
Patients should disclose all recently received vaccines or immune-modifying medications prior to vaccination.

Warnings

Do not administer booster doses if a life-threatening allergic reaction occurred with previous yellow fever vaccination.
Rare but potentially fatal vaccine-associated viscerotropic disease (YEL-AVD) can occur, presenting with multi-organ failure resembling wild-type infection.
Vaccine-associated neurotropic disease (YEL-AND) involving encephalitis or meningoencephalitis is a rare serious adverse event.
The vaccine is contraindicated in infants below 9 months due to safety concerns.
Pregnant and immunocompromised individuals require careful risk-benefit assessment before vaccination.
Severe hypersensitivity reactions, including anaphylaxis, may occur and require emergency interventions.
Older adults are at increased risk for serious adverse effects and should be vaccinated only if at high risk of exposure.
False-positive serologic tests for rabies or Japanese encephalitis may occur after vaccination.
Immunization should be postponed in patients with acute severe febrile illness.
Ensure proper storage and reconstitution to maintain vaccine potency and effectiveness.
International travel regulations may require documented vaccination for entry to endemic countries.
Continuous monitoring and reporting of adverse events are advised to maintain vaccine safety surveillance.
Administer in settings equipped to manage potential hypersensitivity reactions.
Pregnant women should receive vaccination only if clearly indicated to prevent maternal and fetal morbidity from yellow fever infection.
Concomitant use with immunosuppressive therapy may reduce vaccine effectiveness and increase adverse event risk.

Contraindication

History of life-threatening allergic reaction to any component of the yellow fever vaccine, including eggs or chicken protein.
Known severe hypersensitivity to a previous dose of yellow fever vaccine.
Age less than 9 months due to high risk of vaccine-associated viscerotropic disease.
Severe immunodeficiency states, including HIV/AIDS with severe immunosuppression, leukemia, lymphoma, or cancers involving the bone marrow or lymphatic system.
Patients on immunosuppressive therapy such as high-dose corticosteroids, chemotherapy, or drugs for autoimmune disorders without medical clearance.
Individuals with thymus gland disease or those who have undergone thymectomy.
Pregnant women unless risks of disease exposure outweigh potential vaccine risks.
Active febrile illness or moderate to severe infection until recovery.
Known bleeding disorders posing risk for subcutaneous injections without medical supervision.
Patients with a history of neurologic complications related to previous yellow fever vaccination.
Individuals who have received other live vaccines within a specified interval without clearance.
Presence of Guillain-Barré syndrome or other immune-mediated neurologic disorders without medical advice.
Severe egg allergy unamenable to desensitization protocols.

Drug Interactions

Concurrent or recent administration of other live vaccines may interfere with immune response; timing should be coordinated accordingly.
Immunosuppressive drugs, including corticosteroids, chemotherapy agents, and biologics used in autoimmune disorders, can reduce vaccine effectiveness and increase risk of adverse effects.
Cancer treatments that suppress immune function may diminish immune response to the vaccine.
Medications used to prevent organ transplant rejection may impair vaccine-induced immunity and increase susceptibility to vaccine virus replication.
Psoriasis treatments affecting immune function may alter vaccine safety profile and efficacy.
Vaccination shortly after blood product administration may compromise immunogenicity due to circulating antibodies.
No significant direct pharmacokinetic drug interactions, but immunomodulatory drugs impact vaccine response.
Other vaccines administered concomitantly require assessment to avoid overlapping side effects or immune interference.
Herbal and over-the-counter immune stimulants or suppressants may theoretically affect immune response.
Live vaccines should generally not be administered during antiviral therapy targeting yellow fever virus, though rarely applicable.
Vaccination may yield false-positive serologic tests for rabies and Japanese encephalitis viruses, complicating interpretation of diagnostic assays.
Interactions with antibiotics or antiparasitic agents are not documented but clinical assessment advised.
Caution advised when combining with medications that affect coagulation due to risk of injection site bleeding.
Vitamins and dietary supplements with immunomodulatory effects have no known significant interactions but clinical monitoring is prudent.
Consider timing of vaccinations relative to immunosuppressive therapies to optimize efficacy and safety.

Preparations Of The Drug

YF-Vax: Licensed yellow fever vaccine produced as a lyophilized powder requiring reconstitution.
Stamaril: Another licensed live attenuated yellow fever vaccine formulated similarly as a freeze-dried preparation.
Provided in single-dose vials for reconstitution with sterile diluent immediately prior to subcutaneous injection.
Stored refrigerated at 2°C to 8°C, protected from light, and discarded if reconstituted vaccine is not used promptly.
Supplied in packaging appropriate for clinical, travel, and occupational immunization settings.
Diluent provided separately, containing sterile water or sodium chloride for injection.
Packaging may include an international vaccination certificate (yellow card) to document administration.
Manufactured following stringent quality control to ensure live virus attenuation and potency.
Administered by healthcare professionals trained in vaccine reconstitution and injection techniques.
Typically available through public health programs, travel clinics, and hospital immunization services.
May be supplied alongside information leaflets detailing contraindications, precautions, and side effects.
Multiple manufacturers produce the vaccine under various regulatory authorities with comparable efficacy.
Used widely in endemic countries and recommended by global health organizations such as WHO and CDC.
Distribution protocols ensure cold chain maintenance from production to point of administration.
Not available as an oral or intramuscular product; subcutaneous injection is the only approved route.