Yellow fever vaccine

Noreen A. Hynes, M.D., M.P.H., D.T.M.&H.
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VACCINE TYPE

General Identification

Live, attenuated yellow fever virus

Vaccine Strain Characteristics

  • The only approved vaccine for use world-wide 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):[12]
      • 17D-204: found in the U.S. licensed vaccine (YF-VaxTM) as well as StamarilTM 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 is comprised of a 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.
      • UK and U.S. (YF-VaxTM): sorbitol and porcine gelatin for stabilization.
      • France (StamarilTM): sugars, amino acids, and divalent cations for stabilization.

Viremia following 17D Yellow Fever Vaccination

  • 17D vaccine induces minimal virus titers in circulating blood as opposed to the high virus titers seen in natural yellow fever virus infection.
    • Similar onset to natural infection: ~ day 4 following inoculation, ends about the time of 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.

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VACCINE TYPE

General Identification

Live, attenuated yellow fever virus

Vaccine Strain Characteristics

  • The only approved vaccine for use world-wide 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):[12]
      • 17D-204: found in the U.S. licensed vaccine (YF-VaxTM) as well as StamarilTM 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 is comprised of a 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.
      • UK and U.S. (YF-VaxTM): sorbitol and porcine gelatin for stabilization.
      • France (StamarilTM): sugars, amino acids, and divalent cations for stabilization.

Viremia following 17D Yellow Fever Vaccination

  • 17D vaccine induces minimal virus titers in circulating blood as opposed to the high virus titers seen in natural yellow fever virus infection.
    • Similar onset to natural infection: ~ day 4 following inoculation, ends about the time of 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.

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Last updated: February 10, 2020