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 virul
ence documented from over 300 million doses administered. We have isol
ated virus in cell culture from sera of six volunteers who received 17
D vaccine and found that very few nucleotide mutations were detected i
n the consensus sequence of the entire genome of each of the serum vir
uses. Moreover, most of these mutations accumulated in the non-structu
ral protein genes, especially the NS5 protein gene. Although no nucleo
tide change was identified in the structural protein genes of any of t
hese six serum viruses, minor sequence heterogeneity existed in the se
rum virus population. Our results indicate that 17D vaccine virus accu
mulates mutations at a very low frequency and may explain in part the
excellent safety record of 17D vaccine. (C) 1998 Elsevier Science B.V.
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