ORIGINAL RESEARCH Pneumococcal Conjugate Vaccine Impact on Serotype 3: A Review of Surveillance Data Heather L. Sings . Bradford D. Gessner . Matt D. Wasserman . Luis Jodar Received: November 5, 2020 / Accepted: January 20, 2021 / Published online: February 15, 2021 Ó The Author(s) 2021 ABSTRACT Introduction: Limited changes in serotype 3 invasive pneumococcal disease (IPD) incidence rates after a decade of 13-valent pneumococcal conjugate vaccine (PCV13) introduction into several national immunization programs (NIP) have raised questions about PCV13’s effective- ness against this serotype. Methods: We analyzed the impact of pediatric PCV programs on serotype 3 IPD with two approaches. First, we reviewed the publicly available surveillance data from countries identified in two recently published reviews to describe the population impact of pediatric PCV13 or PCV10 vaccination programs on ser- otype 3 IPD. We then compared the observed trends in PCV10 and PCV13 countries to a previously described dynamic transmission model that simulates the spread of pneumo- coccal carriage and development of IPD in a population over time. Results: When serotype 3 disease rates are compared from countries that have introduced either a 10-valent (PCV10) vaccine that does not contain serotype 3 in its formulation or PCV13 in their pediatric NIP, over time, ser- otype 3 incidence rate trends are markedly dif- ferent. Countries with a PCV10 NIP showed a substantial linear increase in serotype 3 pneu- mococcal disease among all age groups since the time of PCV10 introduction, whereas countries with a PCV13 NIP experienced a modest decline during the 3–4 years after vaccine introduction followed by an inflection upward in subsequent years. Conclusion: These data suggest that PCV13 provides a certain degree of direct and indirect protection against serotype 3 at the population level and direct adult vaccination with a ser- otype 3-containing vaccine is likely to provide substantial benefit in the context of a pediatric PCV NIP. Further research around serotype 3 transmission patterns and epidemiology is nonetheless warranted. Keywords: Pneumococcal conjugate vaccine; Serotype 3; Surveillance data; Vaccine effectiveness Supplementary Information The online version contains supplementary material available at https:// doi.org/10.1007/s40121-021-00406-w. H. L. Sings (&) Á B. D. Gessner Á L. Jodar Vaccines Medical Development and Scientific and Clinical Affairs, Pfizer Inc, Collegeville, PA, USA e-mail: heather.sings@pfizer.com M. D. Wasserman Health Economics and Outcomes Research, Pfizer Inc, New York, NY, USA Infect Dis Ther (2021) 10:521–539 https://doi.org/10.1007/s40121-021-00406-w