Chris Stockmann, Krow Ampofo, Andrew T. Pavia, Anne J. Blaschke, Edward O. Mason, Angela P. Presson, Larry J. Forney, Carrie L. Byington

 The Red Queen hypothesis is an evolutionary theory that describes the reciprocal co-evolution of competing species. We sought to study whether introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) altered pneumococcal serotype dynamics among children with invasive pneumococcal disease (IPD) as predicted by the Red Queen hypothesis.  This study examined pneumococcal isolates (n=641) obtained from children <18 years of age hospitalized with IPD from 1997-2014 in Utah. A review of the literature also identified several additional studies conducted in the United States and Europe that were used to test the external generalizability of our Utah findings. Simpson's Index was used to quantify pneumococcal serotype diversity.  In Utah, the introduction of PCV7 and PCV13 was associated with rapid increases in serotype diversity (P<0.001). Serotypes rarely present before vaccine introduction emerged as common causes of IPD. Diversity then decreased (P<0.001) as competition selected for the fittest serotypes and new evolutionary equilibriums were established. This pattern was also observed more broadly in the United States, the United Kingdom, Norway, and Spain.  This vaccine-driven example of human/bacterial co-evolution appears to confirm the Red Queen hypothesis, which reveals a limitation of serotype-specific vaccines and offers insights that may facilitate alternative strategies for the elimination of IPD.