© 2018 Geno et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Among 98 serotypes of Streptococcus pneumoniae, only a small subset regularly causes invasive pneumococcal diseases (IPD). We previously demonstrated that serotype 11A binds to ficolin-2 and has low invasiveness in children. Epidemiologic data suggested, however, that serotype 11A IPD afflicts older adults, possibly indicating reduced ficolin-2-mediated immune protection. Therefore, we studied the epidemiology of ficolin-2-bound serotypes. We obtained IPD case data from the United States Centers for Disease Control and Prevention. We studied three prominent ficolin-2-bound serotypes and their acetyltrans-ferase-deficient variants for ficolin-2 binding and ficolin-2-mediated complement deposition with flow-cytometry. We determined the age distributions of these serotypes from the obtained epidemiologic data. We discovered that the serotype 35B capsule is a novel ficolin-2 ligand due to O-acetylation via WciG. Ficolin-2-mediated complement deposition was observed on serotypes 11A and 35B but not serotype 31 or any O-acetyl transferase deficient derivatives of these serotypes. Serotypes 11A, 35B, and 31 cause more IPD among older adults than children. Studies of the three serotypes provide additional evidence for ficolin-2 providing innate immunity against IPD. The skewed age distribution of the three serotypes suggests that older adults have reduced ficolin-2-mediated immunity and are more susceptible to these serotypes.