What is driving the resurgence and persistence of vaccine-targeted pneumococcal serotypes?-Serotype 19F as the paradigm.

Over the past 25 years, pneumococcal conjugate vaccines (PCVs) have markedly reduced both pneumococcal disease and nasopharyngeal carriage caused by vaccine serotypes among the more than 100 known pneumococcal serotypes. In the United States, the transition from the original 7-valent formulation (PCV7) to the 13-valent vaccine (PCV13) occurred approximately a decade after the initial introduction of PCVs, whereas several other countries implemented higher-valency formulations over shorter time intervals. More recently, next-generation PCVs targeting 15 (PCV15) or 20 (PCV20) serotypes have been introduced into pediatric immunization programmes, along with a novel 10-valent PCV designed for use in low- and middle-income countries. These vaccines are also now available for use in older adults, including a 21-valent formulation (V116) that targets a distinct set of serotypes. Since the introduction of PCVs, the composition of pneumococcal serotypes responsible for severe disease has changed substantially. In many settings, several vaccine-targeted serotypes have been nearly eliminated as causes of disease; however, the incidence of disease caused by certain non-vaccine serotypes has increased. In some settings, like the United States, serotypes that were initially suppressed following PCV7 introduction have subsequently re-emerged and again constitute major causes of disease, despite the continued use of PCVs that include those serotypes. The mechanisms underlying this resurgence of vaccine-targeted serotypes remain poorly understood. Elucidating the processes that drive these patterns is critical for assessing whether additional serotypes may re-emerge in the future and for identifying strategies to mitigate such increases. Here, we outline several hypotheses regarding potential mechanisms contributing to serotype resurgence and discuss how vaccine characteristics and serotype-specific traits may shape future pneumococcal population dynamics. We also identify key data gaps and priority research questions that must be addressed to improve understanding of serotype resurgence.