BACKGROUND: Several Streptococcus pneumoniae proteins play a role in pathogenesis and are being investigated as vaccine targets. It is largely unknown whether naturallyacquired antibodies reduce the risk of colonization with strains expressing a particular antigenic variant. METHODS: Serum IgG titers to 28 pneumococcal protein antigens were measured among 242 individuals, aged < 6 months - 78 years in Native American communities between 2007-2009. Nasopharyngeal swabs were collected at least 30 days after serum collection, and the protein antigen variant in each pneumococcal isolate was determined using genomic data. We assessed the association between preexisting variant-specific antibody titers and subsequent carriage of pneumococcus expressing a particular antigen variant. RESULTS: Antibody titers often increased across pediatric groups before decreasing among adults. PspA and StkP IgG titers decreased from <6 months to 6-12 months (p<0.01). Individuals with low titers against Group 3 PspC variants were more likely to be colonized with pneumococci expressing those variants. For other antigens, variantspecific IgG titers do not predict colonization with pneumococci expressing particular variants CONCLUSION: We observed an inverse association between variant-specific antibody concentration and homologous pneumococcal colonization for only one protein. Further assessment of antibody repertoires may elucidate the nature of anti-pneumococcal antibody-mediated mucosal immunity while informing future vaccine development
