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疫苗接种运动后口服脊髓灰质炎疫苗中与毒力相关突变的迅速出现和传播。

Rapid emergence and transmission of virulence-associated mutations in the oral poliovirus vaccine following vaccination campaigns.

作者信息

Walter Katharine S, Altamirano Jonathan, Huang ChunHong, Carrington Yuan J, Zhou Frank, Andrews Jason R, Maldonado Yvonne

机构信息

Division of Epidemiology, University of Utah, Salt Lake City, UT 84105, USA.

Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94305, USA.

出版信息

medRxiv. 2023 Mar 21:2023.03.16.23287381. doi: 10.1101/2023.03.16.23287381.

Abstract

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 vaccinated children 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. Alarmingly, 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 mutation. Our results suggest that current definitions of cVDPVs may exclude circulating virulent viruses that pose a public health risk and underscore the need for intensive surveillance following OPV use.

摘要

由于口服脊髓灰质炎疫苗(OPV)的持续使用,循环疫苗衍生脊髓灰质炎病毒(cVDPV)的负担日益加重。然而,在对照环境中尚未直接评估常规OPV VP1测序对早期鉴定携带毒力相关回复突变病毒的信息价值。我们前瞻性地收集了15331份粪便样本,以追踪墨西哥韦拉克鲁斯州一次免疫活动后接种疫苗儿童及其接触者10周内OPV的排出情况,并对358份样本的VP1基因进行了测序。我们发现OPV在基因上不稳定,以近似时钟的速率进化,该速率因血清型和疫苗接种状态而异。令人担忧的是,萨宾样病毒中28%(13/47)的OPV-1、12%(14/117)的OPV-2和91%(157/173)的OPV-3有≥1个已知的回复突变。我们的结果表明,目前cVDPV的定义可能排除了对公共卫生构成风险的循环致病病毒,并强调了OPV使用后进行强化监测的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0280/10055580/53cd87f6a38a/nihpp-2023.03.16.23287381v1-f0001.jpg

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