Abstract
Streptococcus pneumoniae is an invasive mucosal pathogen for which host defense is dependent on capsular polysaccharide-specific antibody. Capsule-specific immunoglobulin G (IgG), IgM, and IgA are produced following pneumococcal vaccination and infection. Serum IgA has two molecular forms, polymeric and monomeric. These forms may modulate the avidity of antigen binding and evolve over time as the immune response matures. Therefore, we sequentially characterized the molecular forms of serum IgA to three serotypes of pneumococcal capsular polysaccharides (types 8, 12F, and 14) after pneumococcal vaccination and after natural infection with type 14 S. pneumoniae. Although typically the form of IgA in antigen-specific systemic responses to protein antigens is predominantly polymeric in sera of patients shortly after exposure and shifts to the monomeric form in sera obtained several weeks later, the form of IgA in response to each pneumococcal capsular polysaccharide remained predominantly polymeric 1 month after natural infection and up to I year following vaccination. In contrast, IgA to pneumococcal cell wall polysaccharide was both polymeric and monomeric. Moreover, the form of IgA in response to polyribosyl-ribitol-phosphate (PRP), the capsular polysaccharide of Haemophilus influenzae type b, was predominantly monomeric in the sera of 8 of 10 subjects tested 1 to 3 months after vaccination with either PRP alone or the diphtheria toxoid conjugate of PRP. We conclude that systemic responses to pneumococcal capsular polysaccharides are distinct in the production of predominantly polymeric IgA over time. The persistence of polymeric IgA may facilitate binding and clearance of pneumococci from the systemic circulation or reflect limited maturation of the immune response to pneumococcal capsular polysaccharides.