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

Our findings confirm previous reports that PspC is the major, if not the only, protein that binds to FH. PspC-FH interaction allows pneumococci to protect themselves from the complement system 36 as well as facilitate pneumococcal adherence and uptake by human epithelial cells. 37 Increased adherence to lung epithelial cells was also reported when pneumococci were preincubated with FH 38 and could explain the associated high burden of pneumonia following influenza infections. 39 Polymorphisms in the FH gene have been associated with increased susceptibility to Staphylococcus aureus colonization in humans. 40 Binding to human FH has also been described as an important host-pathogen interaction for Neisseria meningitidis 41 and a FH binding protein is a component in the first licensed vaccine against N. meningitidis serogroup B. [42] [43] [44] Point mutations that eliminate FH binding have been shown to enhance protective antibody responses to vaccination using this meningococcal FH binding protein. 45 Our results support the use of PspC as a mucosal vaccine candidate and highlight that mutations in the FH binding site that allow antibody generation against this region should be considered for any vaccine based on PspC. Blocking PspC-FH interaction with specific PspC antibodies at the mucosa has the potential to reduce viral-associated pneumococcal colonization and burden of pneumonia associated with viral infections. METHODS EHPC study and pneumococcal detection. Healthy adult subjects were enrolled with informed consent to an EHPC trial. 13 All participants were nonsmoking adults aged 18-60 years who had no close contact with at-risk individuals, including young children (under the age of 5 years) and the elderly (over 65 years with comorbidities). Ethical approval was obtained from the National Health Service Research Ethics Committee (11/nasal wash/0592 and 12/nasal wash/0873) and the study was sponsored by the Royal Liverpool and Broadgreen University Hospitals Trust.