Abstract
The live attenuated yellow fever (YF) vaccine was developed in the 1930s. Currently, the 17D and 17DD attenuated substrains are used for vaccine production. The 17D strain is used for vaccine production by several countries, while the 17DD strain is used exclusively in Brazil. The cell passages carried out through the seed-lot system of vaccine production influence the presence of quasispecies causing changes in the stability and immunogenicity of attenuated genotypes by increasing attenuation or virulence. Using next-generation sequencing, we carried out genomic characterization and genetic diversity analysis between vaccine lots of the Brazilian YF vaccine, produced by BioManguinhos–Fiocruz, and used during 11 years of vaccination in Brazil. We present 20 assembled and annotated genomes from the Brazilian 17DD vaccine strain, eight single nucleotide polymorphisms and the quasispecies spectrum reconstruction for the 17DD vaccine, through a pipeline here introduced. The V2IDA pipeline provided a relationship between low genetic diversity, maintained through the seed lot system, and the confirmation of genetic stability of lots of the Brazilian vaccine against YF. Our study sets precedents for use of V2IDA in genetic diversity analysis and in silico stability investigation of attenuated viral vaccines, facilitating genetic surveillance during the vaccine production process.
Highlights
Yellow fever virus (YFV) causes an acute febrile disease affecting humans and non-human primates called yellow fever (YF) [1]
Using next-generation sequencing, we carried out genomic characterization and genetic diversity analysis between vaccine lots of the Brazilian YF vaccine, produced by BioManguinhos–Fiocruz, and used during 11 years of vaccination in Brazil
The comparison of all 17DD vaccine lots revealed low genetic variation, with an average nucleotide identity of 99.8% and amino acid identity values ranging from 99.9% to 100%
Summary
Yellow fever virus (YFV) causes an acute febrile disease affecting humans and non-human primates called yellow fever (YF) [1]. While the live attenuated 17D-204 vaccine is manufactured in the USA, France, China, Senegal and Russia [7] and used worldwide [6], the 17DD substrain is produced and distributed exclusively in Brazil by BioManguinhos (Oswaldo Cruz Foundation, Fiocruz), which is linked to the Brazilian Ministry of Health. It supplies the YF 17DD vaccine to other countries in South America and Africa [8]
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