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.

Inclusion criteria

• Healthy adults aged 18 to 45 years inclusive on the day of enrolment.
• Fully conversant in the English language.
• Able and willing (in the investigator's opinion) to comply with all study requirements.
• Written informed consent to participate in the study.
• For females only, willingness to practice continuous effective contraception (see below) during the study and negative pregnancy test at visit 1 (screening).

Exclusion criteria

• Active smokers.
• N. meningitidis or N. lactamica detected following culture of throat swab or nasal wash taken before the challenge.
• Individuals who have a current infection at the time of inoculation.
• Individuals who have been involved in other clinical studies/trials involving receipt of an investigational product over the last 12 weeks or if there is planned use of an investigational product during the study period.
• Individuals who have previously been involved in clinical studies/trials investigating meningococcal vaccines or experimental challenge with N. lactamica.
• Use of oral or intravenous antibiotics within the period 30 days prior to the challenge.
• Any confirmed or suspected immunosuppressive or immunocompromised state, including HIV infection, asplenia, history of recurrent severe infections or use (more than 14 days) of immunosuppressant medication within the past 6 months (topical/inhaled steroids are allowed).
• Use of immunoglobulins or blood products within 3 months prior to enrolment.
• History of blood donation within the past 12 weeks for male volunteers, or 16 weeks for female volunteers.
• Allergy to yeast extract.
• Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study, or impair interpretation of the study data, for example recent surgery to the nasopharynx.
• Occupational, household or intimate contact with immunosuppressed persons.
• Pregnancy or lactation.