Abstract
BackgroundPersistent carriage of pneumococcal vaccine serotypes has occurred after introduction of PCV13 vaccination in Africa but the mechanisms are unclear. We tested the feasibility of using a human pneumococcal challenge model in Malawi to understand immune correlates of protection against carriage and to trial alternative vaccine candidates. We aimed to identify a dose of Streptococcus pneumoniae serotype 6B sufficient to establish nasopharyngeal carriage in 40% of those nasally inoculated and evaluate nasal mucosal immunity before and after experimental inoculation.MethodsHealthy student volunteers were recruited and inoculated with saline, 20,000 CFU/naris or 80,000 CFU/naris of Streptococcus pneumoniae serotype 6B Post inoculation carriage was determined by nasal sampling for bacterial culture and lytA PCR. Immunological responses were measured in serum and nasal mucosal biopsies before and after bacterial inoculation.FindingsTwenty-four subjects completed the feasibility protocol with minimal side effects. pneumococcal carriage was established in 0/6, 3/9 and 4/9 subjects in the saline, 20,000 CFU/naris and 80,000 CFU/naris groups, respectively. Incidental (natural) serotype carriage was common (7/24 participants carried non-6B strains, 29.2%. Experimentally induced type 6B pneumococcal carriage was associated with pro-inflammatory nasal mucosal responses prior to inoculation and altered mucosal recruitment of immune cells post bacterial challenge. There was no association with serum anti-capsular antibody.InterpretationThe serotype 6B experimental human pneumococcal carriage model is feasible in Malawi and can now be used to determine the immunological correlates of protection against carriage and vaccine efficacy in this population.
Highlights
Research in contextEvidence before this studyExperimental human pneumococcal carriage has been used to measure humoral and cellular responses in mucosal and systemic compartments and as a method to test new vaccines in high income settings
We report the establishment of a controlled human infection model of Streptococcus pneumoniae in Malawi, a low-resourced setting with high burden of invasive pneumococcal disease
Neutrophils and T cells were the predominant immune cells in nasal mucosal samples (Supplementary Fig. 1), we focused our analysis on these major immune cells
Summary
Research in contextEvidence before this studyExperimental human pneumococcal carriage has been used to measure humoral and cellular responses in mucosal and systemic compartments and as a method to test new vaccines in high income settings. Despite the roll out of pneumococcal conjugate vaccines in Malawi, vaccine serotype carriage remains high, leading to persistent population transmission and constraining herd effects. We tested the feasibility of using a human pneumococcal challenge model in Malawi to understand immune correlates of protection against carriage and to trial alternative vaccine candidates. Induced type 6B pneumococcal carriage was associated with pro-inflammatory nasal mucosal responses prior to inoculation and altered mucosal recruitment of immune cells post bacterial challenge. Interpretation: The serotype 6B experimental human pneumococcal carriage model is feasible in Malawi and can be used to determine the immunological correlates of protection against carriage and vaccine efficacy in this population.
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