High Genetic Stability of the Region Coding for the Structural Proteins of Yellow Fever Virus Strain 17D

Researchers cloned and sequenced approximately 3,680 bases of the yellow fever virus (YFV) Pasteur 17D-204 vaccine strain genome, specifically the 5' region encoding the structural proteins C, prM, M, and E, plus the non-structural protein NS1. The viral RNA was extracted from purified virus, reverse-transcribed into cDNA, and cloned into plasmid vectors. Ten overlapping clones covering the complete genome were isolated and analyzed by restriction mapping. The sequencing revealed that the Pasteur substrain (IP/F2, passage 235) showed identical nucleotide sequence to a previously published 17D strain from the American Type Culture Collection (passage 234), with only one apparent sequencing artifact. This extraordinary genetic stability between two independently maintained vaccine substrains, despite sharing a common seed from only 2-3 passages ago, suggests strong selective pressure during egg passage propagation. The findings demonstrate remarkable conservation of the structural protein-coding regions in 17D YFV vaccines currently manufactured worldwide.

Key findings

• The 3,680-base 5' region coding for structural proteins (C, prM, M, E) and NS1 is identical between two independently maintained 17D vaccine substrains (Pasteur and American), indicating high genetic stability
• Only one nucleotide difference (U to C substitution) was detected, which was determined to be a sequencing artifact rather than genuine viral variation
• The two vaccine substrains had undergone independent passages for only 2-3 generations in separate laboratories before sequencing, yet maintained complete sequence homology in the structural protein region
• The genetic stability observed contradicts the known high variability of RNA virus genomes, suggesting selective pressure constrains genetic changes during vaccine production