Mechanisms in the serotype-independent pneumococcal immunity induced in mice by intranasal vaccination with the cell wall polysaccharide

We previously reported that cell wall polysaccharide (CWPS) given to mice intranasally with adjuvant induces serotype-independent immunity to pneumococci. Some strains make CWPS with one phosphocholine group (CWPS/1), but most express two per tetrasaccharide repeat unit (CWPS/2). Here, CWPS/1 and CWPS/2 were equally protective against colonization by CWPS/2-type pneumococci, but the related Streptococcus mitis polymer lacking phosphocholine was non-protective. Previously the protection was shown to be CD4 + T cell-dependent, abrogated by antiserum to interleukin (IL)-17A, and demonstrable in antibody-defective mice. Here, CWPS failed to protect IL-17A receptor knockout mice, further indicating IL-17A-dependence. When commercial CWPS/1 was size-fractionated preparatively, the larger exceeded the smaller molecules in their capacity to prime for IL-17A responses, and only the larger protected against pneumococcal colonization. However, a CWPS-tetanus toxoid conjugate – despite raising high titers of phosphocholine antibody – was non-protective, confirming the irrelevance of humoral immunity in this model. The results strengthen the concept that IL-17A-mediated T cell immunity is inducible by zwitterionic polysaccharides with sufficient chain length to provide coiled secondary structure. Coupling CWPS to protein, which paradoxically prevents protection, may occlude this regular linear conformation. We suggest that mucosal immunization with CWPS primes TH17 cells, which – upon contact with the phosphocholine of colonizing pneumococci – elaborate IL-17A, enhancing phagocytosis.