Association of mucosal neutrophil inflammation and cytokine responses with natural and experimental pneumococcal carriage in a randomised vaccine trial using experimental human pneumococcal carriage

Background: Mucosal inflammation is associated with increased nasal pneumococcal colonisation, but the specific mechanisms are not fully understood. We aimed to find innate immune factors associated with pneumococcal carriage using a controlled human infection model. Methods: Healthy Malawian adults participating in a randomised trial of pneumococcal conjugate vaccine (PCV13) were inoculated with one of three doses of Streptococcus pneumoniae 6B. We categorised the participants into 4 pneumococcal carriage outcome groups - no carriage; natural carriage; experimental carriage; and dual carriage. We then measured neutrophil to lymphocyte ratio (NLR) in nasal mucosa and cytokine levels in nasal lining fluid at 7 days before and 2, 7 and 14 days after inoculation. Findings: We found that 45 % of participants had no carriage, 35 % had natural carriage, 12 % experimental carriage and 8 % dual carriage. At 2- and 7-days post inoculation, all groups showed an increase in NLR compared to 7 days before inoculation, accompanied by small changes in cytokine levels. An early increase in NLR was associated with protection against experimental carriage while cytokines did not associate with carriage pattern. Conclusion: Nasal inoculation with S. pneumoniae 6B induced mild, mucosal inflammation but established carriage was not pro-inflammatory. This suggests that nasal inoculation as a vaccine strategy could be asymptomatic.