TY - JOUR
T1 - Rapid emergence and transmission of virulence-associated mutations in the oral poliovirus vaccine following vaccination campaigns
AU - Walter, Katharine S.
AU - Altamirano, Jonathan
AU - Huang, ChunHong
AU - Carrington, Yuan J.
AU - Zhou, Frank
AU - Andrews, Jason R.
AU - Maldonado, Yvonne
N1 - Funding Information: This project was funded by the National Institutes of Health 5R21AI148810 to Y.M; K.S.W. was funded by a Thrasher Early Career Award and a Stanford Child Health Research Institute postdoctoral fellowship. Publisher Copyright: © 2023, Springer Nature Limited.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - There is an increasing burden of circulating vaccine-derived polioviruses (cVDPVs) due to the continued use of oral poliovirus vaccine (OPV). However, the informativeness of routine OPV VP1 sequencing for the early identification of viruses carrying virulence-associated reversion mutations has not been directly evaluated in a controlled setting. We prospectively collected 15,331 stool samples to track OPV shedding from children receiving OPV and their contacts for ten weeks following an immunization campaign in Veracruz State, Mexico and sequenced VP1 genes from 358 samples. We found that OPV was genetically unstable and evolves at an approximately clocklike rate that varies across serotypes and by vaccination status. Overall, 61% (11/18) of OPV-1, 71% (34/48) OPV-2, and 96% (54/56) OPV-3 samples with available data had evidence of a reversion at the key 5’ UTR attenuating position and 28% (13/47) of OPV-1, 12% (14/117) OPV-2, and 91% (157/173) OPV-3 of Sabin-like viruses had ≥1 known reversion mutations in the VP1 gene. Our results are consistent with previous work documenting rapid reversion to virulence of OPV and underscores the need for intensive surveillance following OPV use.
AB - There is an increasing burden of circulating vaccine-derived polioviruses (cVDPVs) due to the continued use of oral poliovirus vaccine (OPV). However, the informativeness of routine OPV VP1 sequencing for the early identification of viruses carrying virulence-associated reversion mutations has not been directly evaluated in a controlled setting. We prospectively collected 15,331 stool samples to track OPV shedding from children receiving OPV and their contacts for ten weeks following an immunization campaign in Veracruz State, Mexico and sequenced VP1 genes from 358 samples. We found that OPV was genetically unstable and evolves at an approximately clocklike rate that varies across serotypes and by vaccination status. Overall, 61% (11/18) of OPV-1, 71% (34/48) OPV-2, and 96% (54/56) OPV-3 samples with available data had evidence of a reversion at the key 5’ UTR attenuating position and 28% (13/47) of OPV-1, 12% (14/117) OPV-2, and 91% (157/173) OPV-3 of Sabin-like viruses had ≥1 known reversion mutations in the VP1 gene. Our results are consistent with previous work documenting rapid reversion to virulence of OPV and underscores the need for intensive surveillance following OPV use.
UR - http://www.scopus.com/inward/record.url?scp=85172374136&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41541-023-00740-9
DO - https://doi.org/10.1038/s41541-023-00740-9
M3 - Article
C2 - 37749086
SN - 1476-0584
VL - 8
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 137
ER -