title: Human nasal challenge with Streptococcus pneumoniae is immunising in the absence of carriage.
abstract: Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans.
authors.affiliation: Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Adam K A
authors.initials: AK
authors.lastname: Wright
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Ferreira
authors.forename: Jenna F
authors.initials: JF
authors.lastname: Gritzfeld
authors.forename: Angela D
authors.initials: AD
authors.lastname: Wright
authors.forename: Kathryn
authors.initials: K
authors.lastname: Armitage
authors.forename: Kondwani C
authors.initials: KC
authors.lastname: Jambo
authors.forename: Emily
authors.initials: E
authors.lastname: Bate
authors.forename: Sherouk
authors.initials: S
authors.lastname: El Batrawy
authors.forename: Andrea
authors.initials: A
authors.lastname: Collins
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G