Testing the genomic stability of the Brazilian yellow fever vaccine strain using next-generation sequencing data

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.

The Present and Future of Yellow Fever Vaccines

“…There have been a number of papers on next-generation sequencing (NGS) of the 17D vaccine that suggest NGS could be used potentially as part of quality control of the vaccine [ 21 , 24 , 25 , 26 , 27 , 28 ]. However, at the present time, regulators use NGS to look for adventitious agents, and standardizing NGS for quality control of the vaccine would require careful discussion.…”

Genome stability assessment of PRRS vaccine strain with new ARTIC-style sequencing protocol

“…Since their first introduction in 2000, Porcilis ® PRRS (MSD Animal Health) vaccines against PRRSV-1 have been preferred vaccines for the active immunisation of sows and growing pigs ( 6 ). In general, safety monitoring of vaccines is important during manufacturing, however, information on the genetic stability of vaccine strains in different batches is limited ( 7 , 8 ). The quasispecies nature of live virus based vaccines poses additional challenges.…”

Bioinformatics in Latin America: ISCB-LA SOIBIO RMB Symposium 2020

“…However, as the virus evolves and acquires mutations, researchers must ensure that vaccines still work against the new strains or quasi-species. Araújo Serrão de Andrade [9] study vaccine efficiency by presenting a pipeline to analyse 20 genomes of the Yellow Fever Virus of the 17DD vaccine strain which is only produced in Brazil. The study shows that there is genetic stability in the Brazilian vaccine and provides a platform that can be used to test genetic variability and stability for other vaccines.…”