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

As we observed that the PspC-FH interaction was associated with high rates and densities of carriage in humans coinfected with virus, we tested whether antibodies to the vaccine candidate PspC could block this interaction. PspC-based vaccines are protective against both invasive pulmonary disease and colonization in murine models of infection. 32, 33 We observed a partial blocking of FH binding to pneumococcus by flow cytometry analysis and epithelial adherence assay. Anti-PspC IgG purified from serum blocked bacterial attachment when low levels of FH were present in the assay. These results could be explained by the fact that healthy adults do not have antibodies specific to the PspC region that binds FH. By using sera from mice immunized with PspC in these assays, we found that human carriage induces anti-PspC antibodies to the same epitopes as the ones induced by parenteral immunization with purified protein in mice. Two major differences were that (i) mice did not have antibodies against the proline-rich region of PspC, although this was one of the most recognized regions by human antibodies and (ii) human antibodies did not recognize the binding site for FH on PspC whereas immunized mice did. Crossreactive antibodies against the proline-rich region of the PspA could explain the high levels of recognition of the PspC proline-rich region in humans. 34, 35 We have previously observed that colonization increased mucosal IgG antibodies to the N-terminal region of PspA but not PspC. 17 Most importantly, the fact that humans have an inefficient presentation of the PspC region that binds to FH strongly suggests that FH binding to pneumococcus during colonization covers this site of the PspC antigen.