Prediction of post-PCV13 pneumococcal evolution using invasive disease data enhanced by inverse-invasiveness weighting.

, a common colonizer in the human nasopharynx, can cause invasive diseases including pneumonia, bacteremia, and meningitis mostly in children under 5 years or older adults. The PCV7 was introduced in 2000 in the United States within the pediatric population to prevent disease and reduce deaths, followed by PCV13 in 2010, PCV15 in 2022, and PCV20 in 2023. After the removal of vaccine serotypes, the prevalence of carriage remained stable as the vacated pediatric ecological niche was filled with certain non-vaccine serotypes. Predicting which pneumococcal clones, and which serotypes, will be most successful in colonization after vaccination can enhance vaccine design and public health interventions, while also improving our understanding of pneumococcal evolution. While carriage data, which are collected from the pneumococcal population that is competing to colonize and transmit, are most directly relevant to evolutionary studies, invasive disease data are often more plentiful. Previously, evolutionary models based on negative frequency-dependent selection (NFDS) on the accessory genome were shown to predict which non-vaccine strains and serotypes were most successful in colonization following the introduction of PCV7. Here, we show that an inverse-invasiveness weighting system applied to invasive disease surveillance data allows the NFDS model to predict strain proportions in the projected carriage population in the post-PCV13/pre-PCV15 and -PCV20 epoch. The significance of our research lies in using a sample of invasive disease surveillance data to extend the use of NFDS as an evolutionary mechanism to predict post-PCV13 population dynamics. This has shown that we can correct for biased sampling that arises from differences in virulence and can enrich the value of genomic data from disease surveillance and advances our understanding of how NFDS impacts carriage population dynamics after both PCV7 and PCV13 vaccination.