Despite the use of pneumococcal conjugate vaccines for pediatric immunization, North American Indigenous populations continue to experience high burden of pneumococcal infections. Naturally acquired antibodies, which can protect unvaccinated adults against pneumococcal infections, have not previously been studied in Canadian Indigenous people. We analysed concentrations of natural serum IgG, IgM and IgA antibodies specific to 7 serotype-specific capsular polysaccharides (3, 6B, 9V, 14, 19A, 19F and 23F) in 141 healthy individuals (age between 18 and 80 years), including Indigenous adults living in 2 geographical different areas of Ontario, Canada, and non-Indigenous residing in northwestern Ontario. Regardless of the geographical area, concentrations of IgG specific to serotypes 6B, 9V, and 14, IgM specific to 9V, and all serotype-specific IgA were significantly higher in Indigenous study participants as compared to non-Indigenous. The differences are likely attributed to an increased exposure of Indigenous individuals to
Streptococcus pneumoniaeand/or cross-reactive antigens of other microorganisms or plants present in the environment. Although in non-Indigenous adults concentrations of IgM specific to 9V, 19A, 19F, and 23F significantly decreased with age, this was not observed in Indigenous individuals suggesting that Indigenous people may experience continuous exposure to pneumococci and cross-reactive antigens over the life span. Women had generally higher concentrations of natural IgG and IgM concentrations than men, with more striking differences found in Indigenous adults, potentially associated with larger exposure of women to young children, the major reservoir of pneumococci in communities. Our data suggest that increased rates of pneumococcal infections among Indigenous people are unlikely related to deficiency of naturally acquired antibodies, at least those specific to 7 common serotypes. Determining serological correlates of protection for adults will be essential to identify the groups in need of adult pneumococcal immunizations that may prevent excessive burden of the disease among North American Indigenous people.