Predicting how pathogen populations will change over time is challenging. Such has been the case with Streptococcus pneumoniae, an important human pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use the frequencies of accessory genes to predict changes in the pneumococcal population after vaccination, hypothesizing that these frequencies reflect negative frequency-dependent selection (NFDS) on the gene products. We find that the standardized predicted fitness of a strain, estimated by an NFDS-based model at the time the vaccine is introduced, enables us to predict whether the strain increases or decreases in prevalence following vaccination. Further, we are able to forecast the equilibrium post-vaccine population composition and assess the invasion capacity of emerging lineages. Overall, we provide a method for predicting the impact of an intervention on pneumococcal populations with potential application to other bacterial pathogens in which NFDS is a driving force.

预测病原体种群将如何随时间变化是具有挑战性的。肺炎链球菌（一种重要的人类病原体）和肺炎球菌结合疫苗（PCV）就是这种情况，该疫苗仅针对人群中的一小部分菌株。在这里，我们使用辅助基因的频率来预测疫苗接种后肺炎球菌种群的变化，假设这些频率反映了基因产物的负频率依赖选择（NFDS）。我们发现，在引入疫苗时，通过基于 NFDS 的模型估计出菌株的标准化预测适合度，使我们能够预测疫苗接种后该菌株的流行率是否会增加或减少。此外，我们能够预测疫苗接种后的平衡种群组成并评估新兴谱系的入侵能力。总的来说，我们提供了一种预测干预措施对肺炎球菌种群影响的方法，并有可能应用于以 NFDS 为驱动力的其他细菌病原体。