General Identification

Live, attenuated yellow fever virus

Vaccine Strain Characteristics

• The only approved vaccine for use worldwide is a live, attenuated virus derived from the original lot, 17D yellow fever virus strain, created by passing the wild-type virus repeatedly in cultures attenuate its virulent properties while ensuring it would induce immunity to the virus in the vaccine recipient.
  • There are two 17D strains in use today (with 99.9% sequence homology):[13]
    • 17D-204: found in the U.S. licensed vaccine (YF-Vax^TM), and in Stamaril^TM which is produced in France and licensed in 44 non-U.S. countries.
    • 17DD: manufactured in Brazil
• The attenuation process used minced chick embryo cultures (no brain or spinal cords included), and the final passage prior to human use was in embryonated eggs.
• The vaccine comprises quasi-species as the vaccines are not plaque-purified and contain heterogeneous subpopulations with differing mouse-brain neurovirulence.

Non-Virus Constituents in the Vaccine

• No antibiotics or preservatives are part of any yellow fever vaccine manufactured worldwide.
• The vaccine is lyophilized for storage and must be reconstituted before use.
  • It must be administered within 60 minutes of reconstitution to ensure potency and to avoid bacterial contamination.
• Manufacturer variability: salt, buffers, and stabilizer excipients.
  • Stabilizers are needed to maintain potency.
    • U.S. and U.K. (YF-Vax^TM): sorbitol and porcine gelatin for stabilization.
    • France (Stamaril^TM): sugars, amino acids, and divalent cations for stabilization.

Viremia following 17D Yellow Fever Vaccination

• 17D vaccine induces minimal virus titers in circulating blood instead of the high virus titers that were seen in natural yellow fever virus infection.
  • Similar onset to natural infection: ~ day 4 following inoculation, ends about neutralizing antibody appearance day 8 or 9 (see Immune Response below).
• Vaccine titers are below the threshold for uptake by the mosquito virus vector of yellow fever.
  • Thought to explain the low risk of maternal-fetal transmission and low rates of neurotropic and viscerotropic vaccine adverse effects.