Status: approved; marketed

Organizations involved:

Sanofi Pasteur Inc. – Manuf.; R&D; Tech.; USA mark.

Sanofi Pasteur S.A. – Intl. mark.; Parent

Rockefeller Institute – R&D; Tech.

Cross ref.: See also the entry above for a similar yellow fever virus vaccine.

Description: Yellow Fever Virus Vaccine, Live or YF-VAX is a lyophilized (freeze-dried) formulation of live attenuated yellow fever virus strain 17D. The vaccine is manufactured from cultures of the 17D strain of yellow fever virus (using a seed virus of a fixed-passage level) in avian leukosis virus-free live chicken embryos (eggs). The tissues are homogenized, the supernatant fluid removed by centrifugation, sorbitol and gelatin (bovine source) are added as stabilizer, and vials are filled, lyophilized, and hermetically sealed under nitrogen. No preservatives are added. YF-VAX is formulated to contain not less than 5.04 Log10 (1 x 105.04 or over 100,000) Plaque Forming Units (PFU) of live virus per 0.5 mL dose.

YF-VAX is considered “one of the safest live virus vaccines ever developed,” with over 300 million doses having been administered since the 1930s. The vaccine is also considered the most effective vaccine, with a single injection generally providing 100% lifelong protection in recipients.

YF-VAX is packaged in single and 5-dose vials. The vaccine is reconstituted for subcutaneous injection immediately before use with the provided sterile diluent (Sodium Chloride Injection USP, containing no preservatives). The live vaccine is temperature sensitive. It is shipped in containers with dry ice. The vaccine is be stored at temperatures between 5˚C (41˚F) and -30˚C (-22˚F), preferably frozen below 0˚C (32˚C).

Note, Japanese encephalitis vaccine, rDNA/Acambis (ChimeriVax-JE; see related entry) uses the yellow fever virus 17D strain as a recombinant vector.

Nomenclature: Yellow Fever Vaccine/Sanofi [BIO]; Yellow Fever Vaccine [BIO FDA]; YF-VAX [TR]; Yellow Fever Vaccine USP [USP]

History: Development of chicken egg chorioallantoic membrane culture enabled development of live yellow fever vaccines, which first became available by 1935.

A yellow fever virus vaccine, not FDA approved, was used by the defense/war department starting in 1942 (during WW II) to vaccinate military personnel in the Pacific theater. This vaccine contained human serum, some of which was later found to be contaminated with hepatitis B virus (HBV). This mass vaccination program resulted in the largest known point source outbreak of hepatitis B virus infection, and vaccination was halted. Serological studies have shown that 330,000 people may have been infected [See the New England Journal of Medicine, 316(16), p. 965-70, April 16, 1987].

The 17D strain of attenuated yellow fever virus was developed by Dr. M. Theiler, Rockefeller Institute (now Rockefeller University), winner of a Nobel prize for studies of yellow fever. The virus is derived from the Asibi strain, named for a resident of Ghana wit very mild symptoms and from whom samples were obtained in 1927.

Companies.: YF-VAX was developed and is manufactured by Aventis Pasteur Inc., now Sanofi Aventis Inc., CBER/FDA lic. no. 1277. It is marketed in the U.S. by Sanofi Aventis Inc., and internationally by Sanofi Aventis S.A.

In spring 2007, it was reported that Sanofi Pasteur is investing €200m in expanding manufacturing capacity at its Val de Reuil, France, facility that includes manufacture of yellow fever vaccine (but, apparently, not vaccine for the U.S. market, since the U.S. product, from FDA documentation, is manufactured at Swiftwater, PA, facilities).

FDA class: Biologic PLA

CBER class: Viral And Rickettsial Vaccines

Approvals: Date = 19530522; first approval, PLA; granted to Merrell-National Labs.

Date = 19780103; first approval, according to CBER/FDA database; However, an FDA approval letter on this date reports that the license was revoked and granted (reisssued) to the new owner, Connaught Labs. Inc. (CLI)

Date = 19840215; PLA supplement; Indication = change in potency of the reconstituted final container vaccine at release to be at least 2,000 mouse LD50 per human dose

Date = 19991209; Indication = license revoked from CLI and reissued to new owner, Aventis Pasteur Inc.

Date = 20080212; BLA supplement (STN: BL 103915/5086); Indications: = changes to the package insert:

a) CONTRAindications: addition of postponement of vaccinations in case of an acute febrile disease.

b) PRECAUTIONS, Pregnancy Category C: changes in statements for use of the vaccine in pregnant women.

c) PRECAUTIONS, Nursing Mothers: changes in statement for use of the vaccine during lactation.

d) ADVERSE REACTIONS: addition of rare neurological symptoms.

Indications: [portion of the "INDICATIONS AND USAGE” section from product insert/labeling]:

YF-VAX (Yellow Fever Vaccine) is recommended for all persons ≥9 months of age travelling to or living in areas where yellow fever infection is reported or yellow fever vaccination is required.

Infants 4 to 9 months of age and pregnant women should be considered for immunization only if they are travelling to high-risk areas, travel cannot be postponed and a high level of prevention against mosquito exposure is unfeasible. In no circumstances should infants <4 months of age be given yellow fever vaccine because of the risk of encephalitis after vaccination which may occur in as many as 1% of infants <3 months of age.1,2 (See CONTRAindications: and WARNINGS.)

The vaccine is recommended for all travellers passing through or living in countries in Africa, Central America and South America where yellow fever infection is officially reported. It is also recommended for travel outside the urban area of countries that do not officially report yellow fever but lie in the yellow fever “endemic zones.”

Yellow fever vaccination is required by law upon entry to certain countries irrespective of the traveller’s country of origin, and in other countries when travellers are coming from endemic areas. In some cases, vaccination against yellow fever is recommended, although not required by law, e.g., if yellow fever has been reported in the country of destination. In some Asian and other tropical countries where yellow fever does not exist but the transmitting mosquito is found, vaccination is required for arrivals from an endemic country to prevent importation of the disease. Current information on the countries for which an International Certificate of Vaccination is required can be obtained from local health departments.

Laboratory personnel who might be exposed to virulent yellow fever virus by direct or indirect contact or by aerosols also should be vaccinated.

For simultaneous administration of other vaccines see PRECAUTIONS.

Under the International Health Regulations the validity period of the certificate of vaccination or revaccination is 10 years beginning 10 days after vaccination.

Market: The 2007 Average Wholesale Price (AWP) is $336.43/5-dose vial, with a Direct Price (Manufacturer’s discount price) of $$280.36; and $420.54/5 single-dose vials, with a Direct Price of $350.45.

The Sanofi Pasteur list price (Jan. 2006) is $340.24/five 1-dose vials and $272.20/5-dose vial.

R&D: Acambis plc is developing ChimeriVax-JE in collaboration with Sanofi Aventis S.A. (see entry #224). This is a live Japanese encephalitis virus vaccine using YF 17D as a recombinant viral vector.