The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication. Understanding the early genetic changes that occur as OPV evolves and transmits is important for preventing future outbreaks. Here, we use deep sequencing to define the evolutionary trajectories of type 2 OPV in a vaccine trial. By sequencing 497 longitudinal stool samples from 271 OPV2 recipients and household contacts, we were able to examine the extent of convergent evolution in vaccinated individuals and the amount of viral diversity that is transmitted. In addition to rapid reversion of key attenuating mutations, we identify strong selection at 19 sites across the genome. We find that a tight transmission bottleneck limits the onward transmission of these early adaptive mutations. Our results highlight the distinct evolutionary dynamics of live attenuated virus vaccines and have important implications for the success of next-generation OPV.

通过口服脊髓灰质炎疫苗 (OPV) 的进化而出现的循环疫苗衍生脊髓灰质炎病毒对根除脊髓灰质炎构成了重大障碍。了解随着 OPV 进化和传播而发生的早期基因变化对于预防未来的爆发很重要。在这里，我们使用深度测序来定义疫苗试验中 2 型 OPV 的进化轨迹。通过对来自 271 名 OPV2 接受者和家庭接触者的 497 个纵向粪便样本进行测序，我们能够检查接种疫苗个体的趋同进化程度和传播的病毒多样性数量。除了关键减毒突变的快速回复外，我们还在基因组的 19 个位点确定了强选择。我们发现紧密的传输瓶颈限制了这些早期适应性突变的向前传输。