Heterogeneous nature of the genome of the ARILVAX yellow fever 17D vaccine revealed by consensus sequencing

Abstract

Consensus sequencing of the genome of the ARILVAX live attenuated yellow fever (YF) 17D vaccine was performed directly on reconstituted virus from a vial of the vaccine secondary seed (without plaque-purification or cloning of cDNA). The genome of ARILVAX was identical in organization and size (10,862 nucleotides (nt)) to other published YF 17D sequences. A total of 12 nt heterogeneities were detected indicating that the vaccine is a heterogeneous population. Some of these indicated the presence of quasispecies with residues not reported previously for other sequenced YF 17D strains. A number of nts clearly differed from some YF vaccine strain sequences but coincided with the others, which could be due to the use of consensus sequencing approach in this study. Most (but not all) of the heterogeneities and nt differences were silent (i.e. did not result in an amino acid change). The differences are inconsequential to safety and effectiveness of ARILVAX. Other YF 17D vaccines are undoubtedly also heterogeneous and need to be re-examined using the consensus approach.