The Yellow Fever Virus Vaccine Strain Genetic Stability Study

Yellow fever vaccine is a highly attenuated live virus vaccine.It was produced from the whole chicken embryo and has been uased safely for almost 50 years. In this study we want to inspect the genetic stability of the yellow fever vaccine through passing it in primary culture of chicken embryo fibroblasts (CEF), to provide some proofs for the advanced study of producing the yellow fever vaccine by CEF.We take the international standard for yellow fever vaccine 99/616 (NIBSC code) and yellow fever vaccine working seed lot 2006 (54) 0239 (BTBP code) as the seed for the passing. They are all 17D vaccine strains. Yellow fever vaccine 99/616 was derived from 17D-204 strain.The two seeds were passed respectively for 10 passages in CEF. We marked it with 99/616-CEF virus and YFVBJ-CEF virus and chosen the passages of 1,3,6 and 9 from the 99/616-CEF virus and the YFVBJ-CEF virus as the samples. We sequenced the strcture gene fragment including gene C, M and E of the samples. The sequenced sample also including the YFV, which was a commercial yellow fever vaccine of our country produced from chicken embryos with the working seed lot , BTBP code NO 2006 (54) 0239. The analysis of the sequencing datas involved three parts. The first part: Analysising the genetic stability of the 99/616-CEF virus . Comparison the nuocleotides sequence of the 99/616-CEF virus with the given nuocleotides sequence of the yellow fever vaccine that was derived from 17D-204 strains by NCBI.The second part: Analysising the genetic stability of the YFVBJ-CEF virus. Comparison the nuocleotides sequence of the YFVBJ-CEF virus with YFV that was produced from the whole chicken embryo. The third part: Analysising the history background of the native yellow fever vaccine seed lot. Comparison the nuocleotides sequence of YFV with the given nuocleotides sequence of 17D-204 strain and 17DD strain by NCBI.From our study we concluded that the genes of the passages maybe change during the process of passing the yellow fever vaccine seed by CEF. There are some active nuocleotides changes in the fregent C of the 99/616-CEF virus and the YFVBJ-CEF virus. In the fragment M and E of the 99/616-CEF virus, the active nuocleotides changes also can be observed. But in the fragment M and E of the YFVBJ-CEF virus, the nuocleotides did not change.We also concluded that the yellow fever vaccine seed lot we uasd had something differences in genes with the yellow fever vaccine strain 17D-204 and 17DD, it came from the attenuated yellow fever vaccine strain 17D, and it was another branch of the 17D-204 srain existing beside the former two.