YF-VAX�, Yellow Fever Vaccine, for subcutaneous use, is prepared by culturing the 17D-204 strain of yellow fever virus in living avian leukosis virus-free (ALV-free) chicken embryos. The vaccine contains sorbitol and gelatin as a stabilizer, is lyophilized, and is hermetically sealed under nitrogen. No preservative is added. The vaccine must be reconstituted immediately before use with the sterile diluent provided (Sodium Chloride Injection USP � contains no preservative). YF-VAX vaccine is formulated to contain not less than 4.74 log10 plaque forming units (PFU) per 0.5 mL dose throughout the life of the product. YF-VAX vaccine is a slight pink-brown suspension after reconstitution.
The vial stoppers for YF-VAX vaccine and diluent are not made with natural rubber latex.
Yellow fever is an acute viral illness caused by a mosquito-borne flavivirus. The clinical spectrum of yellow fever is highly variable, from subclinical infection to overwhelming pansystemic disease. Yellow fever has an abrupt onset after an incubation period of 3 to 6 days, and usually includes fever, prostration, headache, photophobia, lumbosacral pain, extremity pain (especially the knee joints), epigastric pain, anorexia, and vomiting. The illness may progress to liver and renal failure, and hemorrhagic symptoms and signs caused by thrombocytopenia and abnormal clotting and coagulation may occur. The case-fatality rate of yellow fever varies widely in different studies and may be different for Africa compared to South America, but is typically 20% or higher. Jaundice or other gross evidence of severe liver disease is associated with higher mortality rates. (1)
Two live, attenuated yellow fever vaccines, strains 17D-204 and 17DD, were derived in parallel in the 1930s. Historical data suggest that these "17D vaccines" have identical safety and immunogenicity profiles. Despite a marked reduction in the world-wide incidence of yellow fever in the last five decades due to the extensive use of 17D vaccines and mosquito eradication programs, at least seven tropical South American countries (Bolivia, Brazil, Colombia, Ecuador, French Guiana, Peru, and Venezuela) and much of sub-Saharan Africa (2) currently experience yellow fever epidemics. However, the actual areas of yellow fever virus activity far exceed the infected zones officially reported for epidemics. Approximately 200,000 yellow fever cases have been reported to occur world-wide each year. Six fatalities from yellow fever were reported between 1996 and July 2002, among unimmunized American and European travelers who visited rural areas within the yellow fever endemic zone. (3) (4) (5) (6) (7) (8)
Vaccination with 17D strain viruses is predicted to elicit an immune response identical in quality to that induced by wild-type infection. This response is presumed to result from initial infection of cells in the dermis or other subcutaneous tissues near the injection site, with subsequent replication and limited spread of virus leading to the processing and presentation of viral antigens to the immune system, as would occur during infection with wild-type yellow fever virus. The humoral immune response to the viral structural proteins, as opposed to a cell-mediated response, is most important in the protective effect induced by 17D vaccines. Yellow fever antibodies with specificities that prevent or abort infection of cells are detected as neutralizing antibodies in assays that measure the ability of serum to reduce plaque formation in tissue culture cells. The titer of virus neutralizing antibodies in sera of vaccinees is a surrogate for efficacy. A log10 neutralization index (LNI, measured by a plaque reduction assay) of 0.7 or greater was shown to protect 90% of monkeys from lethal intracerebral challenge. (9) This is the definition of seroconversion adopted for clinical trials of yellow fever vaccine. The standard has also been adopted by the World Health Organization (WHO) for efficacy of yellow fever vaccines in humans. (10)
The neutralizing antibody response to 17D vaccines has been evaluated in several uncontrolled studies since the late 1930s. In 24 studies conducted world-wide between 1962 and 1997 using 17D vaccines involving a total of 2,529 adults and 991 infants and children, the seroconversion rate was greater than 91% in all but two studies and never lower than 81%. There were no significant age-related differences in immunogenicity. (1)
YF-VAX vaccine is recommended for active immunization of persons 9 months of age and older in the following categories:
Persons Living in or Traveling to Endemic Areas
While the actual risk for contracting yellow fever during travel is probably low, variability of itineraries and behaviors and the seasonal incidence of disease make it difficult to predict the actual risk for a given individual traveling to a known endemic or epidemic area. Persons greater than or equal to 9 months of age traveling to or living in areas of South America and Africa where yellow fever infection is officially reported at the time of travel should be vaccinated. Vaccination is also recommended for travel outside the urban areas of countries that do not officially report the disease but that lie in a yellow fever endemic zone.
International Travel
Yellow fever vaccination may be required for international travel. Some countries in Africa require evidence of vaccination from all entering travelers and some countries may waive the requirements for travelers staying less than 2 weeks that are coming from areas where there is no current evidence of significant risk for contracting yellow fever. Some countries require an individual, even if only in transit, to have a valid International Certificate of Vaccination if the individual has been in countries either known or thought to harbor yellow fever virus. The certificate becomes valid 10 days after vaccination with YF-VAX vaccine. (2) (21)
In no instance should infants less than 9 months of age receive yellow fever vaccine, because of the risk of encephalitis (see CONTRAINDICATIONS and ADVERSE REACTIONS sections).
Laboratory Personnel
Those laboratory personnel who might be exposed to virulent yellow fever virus or to concentrated preparations of the yellow fever vaccine strain by direct or indirect contact or by aerosols should be vaccinated. (2)
Primary Vaccination
For all eligible persons, a single subcutaneous injection of 0.5 mL of reconstituted vaccine (formulated to contain not less than 4.74 log10 PFU throughout the life of the product) should be administered. Immunity develops by the 10th day after primary vaccination. (11) (25) (46)
Booster Doses
Re-immunization with 17D vaccine is recommended every 10 years for those at continuing risk of exposure and is required by International Health Regulations. (23) Revaccination boosts antibody titer, although evidence from several studies suggests that yellow fever vaccine immunity persists for at least 30 to 35 years and probably for life, (47) and epidemiologic data suggest that a single infection with wild-type yellow fever virus provides lifelong immunity against illness due to subsequent exposure.
