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O040 - IDENTIFYING SEROTYPE-INDEPENDENT CORRELATES OF PROTECTION AGAINST PNEUMOCOCCAL COLONISATION IN A HUMAN CHALLENGE MODEL (ID 231)
Abstract
Background
Identification of serotype-independent correlates of protection against S. pneumoniae (Spn) infection will accelerate development of vaccines with broad coverage. In mice, nasopharyngeal-resident memory IL-17A-secreting CD4+ T-cells mediate pneumococcal clearance and systemic IL-17A responses predict resistance to colonisation. We evaluated whether humoral and cellular responses to conserved pneumococcal proteins predict resistance to experimental colonisation.
Methods
A multiplex Luminex assay was used to measure serum IgG to 75 conserved pneumococcal antigens pre- and post-intranasal inoculation with Spn6B in 39 healthy adults. Baseline PBMCs from 60 volunteers were stimulated with killed pneumococcus or 70 antigens. Secreted concentrations of 4 cytokines/chemokines were correlated with subsequent pneumococcal carriage acquisition or density. PBMCs taken pre- and post-challenge were used to evaluate B-cell responses to five selected proteins by ELISpot.
Results
Baseline IgG or B-cell responses did not correlate with protection against colonisation. Successful colonisation associated with significantly increased antibody levels to five antigens and B-cell responses to two antigens increased 29 days post-challenge, whereas there were no significant increases in IgG or B-cell responses in non-colonised volunteers. PBMC-elicited protein-specific IL-17A responses were detected at baseline but did not correlate with carriage acquisition or density. Protein-specific MCP-1 levels at baseline were higher in non-colonised volunteers.
Conclusions
Baseline IgG, B-cell or PBMC-elicited IL-17A responses to single protein antigens did not predict resistance to experimental colonisation in this study. The association between MCP-1, a key chemokine for monocyte recruitment, and colonisation may suggest a possible correlate of protection. Further work is needed to assess whether protein-specific immune responses post-colonisation protect against re-colonisation.