Defining the Immune Response to Nasopharyngeal Colonisation by the Commensal Neisseria Lactamica

The clinical trial is a controlled, volunteer blinded, N. lactamica human challenge study to enable N. lactamica‐specific cellular immune responses to be outlined in detail. In addition, The aim is to determine whether responses directed towards N. lactamica are cross‐reactive with N. meningitidis. Following enrolment onto the study, non‐meningococcal carriers (as determined by microbiological culture of nasopharyngeal wash and retropharyngeal swab) will be challenged intra‐nasally with either 10‐5 cfu of N. lactamica wild‐type strain Y92‐1009 (30,31) suspended in sterile phosphate buffered saline (PBS), as used in previous studies, or PBS alone (control group). Following inoculation on Day 0, biological samples (nasal wash, nasal secretion, throat swabs and blood) will be taken from all volunteers on days +7 (+/‐3), +14(+/‐3) and +28(+/‐5) post‐challenge. On the day of inoculation (Day 0) the biological samples listed will be taken except for the nasal wash. N. lactamica‐specific B‐cell and CD4+ memory T‐cell responses will be measured in blood using a selection of in vitro assays and the results compared longitudinally in N. lactamica challenged (colonised or non‐colonised) vs. control challenged subjects. The experiments will establish the nature of T‐cell and B‐cell memory responses and plasma B‐cell responses induced in response to N. lactamica colonisation and will determine if these responses are cross‐reactive with N. meningitidis. Mucosal immune profiling and microbiome analyses will be performed on nasal secretion and nasal bacterial samples, respectively. Any remaining biological samples (following experiments performed to meet the current study objectives) will be transferred to our registered human tissue bank to enable future studies following additional ethics approval by the relevant bodies.