Yellow fever 17D vaccine virus isolated from healthy vaccinees accumulates very few mutations

The live attenuated yellow fever (YF) vaccine strain 17D is one of the safest vaccines in use today with only 22 cases of reversion to virulence documented from over 300 million doses administered. We have isolated virus in cell culture from sera of six volunteers who received 17D vaccine and found that very few nucleotide mutations were detected in the consensus sequence of the entire genome of each of the serum viruses. Moreover, most of these mutations accumulated in the non-structural protein genes, especially the NS5 protein gene. Although no nucleotide change was identified in the structural protein genes of any of these six serum viruses, minor sequence heterogeneity existed in the serum virus population. Our results indicate that 17D vaccine virus accumulates mutations at a very low frequency and may explain in part the excellent safety record of 17D vaccine.