Phenotypic and Molecular Analyses of Yellow Fever 17DD Vaccine Viruses Associated with Serious Adverse Events in Brazil

The yellow fever (YF) 17D virus is one of the most successful vaccines developed to date. Its use has been estimated to be over 400 million doses with an excellent record of safety. In the past 3 years, yellow fever vaccination was intensified in Brazil in response to higher risk of urban outbreaks...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2001-11, Vol.290 (2), p.309-319
Main Authors: Galler, R., Pugachev, K.V., Santos, C.L.S., Ocran, S.W., Jabor, A.V., Rodrigues, S.G., Marchevsky, R.S., Freire, M.S., Almeida, L.F.C., Cruz, A.C.R., Yamamura, A.M.Y., Rocco, I.M., Travassos da Rosa, E.S., Souza, L.T.M., Vasconcelos, P.F.C., Guirakhoo, F., Monath, T.P.
Format: Article
Language:English
Subjects:
17DD vaccine virus
adverse events
Animals
Antibodies, Viral - blood
Brazil
Cercopithecus aethiops
Consumer Product Safety
Disease Models, Animal
Female
human vaccination
Humans
Macaca mulatta
Male
multiorgan failure
Phenotype
Sequence Analysis, DNA
Vaccination
vaccines
Vero Cells
Viremia
Yellow fever
Yellow Fever - prevention & control
Yellow Fever - virology
Yellow Fever Vaccine - adverse effects
Yellow Fever Vaccine - genetics
Yellow fever virus
Yellow fever virus - genetics
Yellow fever virus - growth & development
Yellow fever virus - physiology
YF vaccine
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Summary:The yellow fever (YF) 17D virus is one of the most successful vaccines developed to date. Its use has been estimated to be over 400 million doses with an excellent record of safety. In the past 3 years, yellow fever vaccination was intensified in Brazil in response to higher risk of urban outbreaks of the disease. Two fatal adverse events temporally associated with YF vaccination were reported. Both cases had features similar to yellow fever disease, including hepatitis and multiorgan failure. Two different lots of YF 17DD virus vaccine were administered to the affected patients and also to hundreds of thousands of other individuals without any other reported serious adverse events. The lots were prepared from the secondary seed, which has been in continuous use since 1984. Nucleotide sequencing revealed minor variations at some nucleotide positions between the secondary seed lot virus and the virus isolates from patients; these differences were not consistent across the isolates, represented differences in the relative amount of each nucleotide in a heterogeneous position, and did not result in amino acid substitutions. Inoculation of rhesus monkeys with the viruses isolated from the two patients by the intracerebral (ic) or intrahepatic (ih) route caused minimal viremia and no clinical signs of infection or alterations in laboratory markers. Central nervous system histological scores of rhesus monkeys inoculated ic were within the expected range, and there were no histopathological lesions in animals inoculated ih. Altogether, these results demonstrated the genetic stability and attenuated phenotype of the viruses that caused fatal illness in the two patients. Therefore, the fatal adverse events experienced by the vaccinees are related to individual, genetically determined host factors that regulate cellular susceptibility to yellow fever virus. Such increased susceptibility, resulting in clinically overt disease expression, appears to be extremely rare.
ISSN:0042-6822
1096-0341
DOI:10.1006/viro.2001.1168