Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage

Glennie, S; Gritzfeld, J F; Pennington, S H; Garner-Jones, M; Coombes, N; Hopkins, M J; Vadesilho, C F; Miyaji, E N; Wang, D; Wright, A D; Collins, A M; Gordon, S B; Ferreira, D M

Anti-PspC epitope mapping revealed lack of human antibodies recognizing the binding site for FH after intranasal exposure to pneumococcus To explore reasons for the inefficient blocking of the FHpneumococcus interaction by anti-PspC IgG, we used peptide arrays to define the epitopes of PspC recognized by human antibodies. We used serum from 18 healthy adults challenged with pneumococcus to probe peptide arrays containing the entire sequence of PspC group 3 (PspC3, 491/00 strain). We observed that despite high levels of anti-PspC antibodies, only 1 out of the 29 samples had antibodies recognizing the binding sites for FH ( Figure 5 ) that supports the partial inhibition of FH binding to pneumococcus observed in vitro (Figure 4b) . Secretory IgA binding sites were recognized by all samples ( Figure 5 ). PspC-FH binding is specific to humans and does not occur in mice. 25, 26 We repeated the peptide arrays using sera from mice immunized with PspC3 to test the hypothesis that PspC would not be masked by binding of FH and therefore mice would produce antibodies against this region. We found that sera from immunized mice recognized the binding site for FH as well as all the other peptides already identified by human sera (Supplementary Figure S2) . These findings support our previous results and suggest that PspC-FH is an important interaction that occurs in the nasopharynx during pneumococcal colonization.