Serological profiling of pneumococcal proteins reveals unique patterns of acquisition, maintenance and waning of antibodies throughout life

Streptococcus pneumoniae is a leading cause of morbidity and mortality in children and older adults. However, knowledge on the development of pneumococcal protein-specific antibody responses throughout life is limited. To investigate this, we measured serum immunoglobulin G (IgG) levels to 55 pneumococcal proteins in 11-month-old infants (n = 73), 24-month-old children (n = 101), parents (n = 99), adults without children <6 years of age (n = 99), and older adults aged >60 years (n = 100). Our findings revealed low IgG levels in infancy, with distinct development patterns peaking in adults. A decrease in levels was observed for 27 antigens towards older age. Adults and older adults had increased IgG levels during pneumococcal carriage and at increased exposure risk to S. pneumoniae. Carriage was a stronger predictor than exposure or age for antibody responses. These findings highlight the dynamic nature of naturally acquired humoral immunity to pneumococcal proteins throughout life, offering insights for age-Targeted interventions. Clinical Trials Registration: Participants were selected from three clinical studies (NTR3462, NTR5405 and NTR3386) conducted in the Netherlands by the National Institute for Public Health and the Environment (RIVM).