Neisseria meningitidis, meningococcal meningitis, Neisseria lactamica
This is a prospective, single-arm, open-label, controlled human infection model experiment in which 10 healthy adult volunteers will be nasally inoculated with 4xrNlac. This is a multi-strain challenge agent containing approximately equal doses of four genetically modified (GM) strains of Neisseria lactamica (Nlac), each expressing the meningococcal antigen Neisseria adhesin A (NadA) and one of four variants of the meningococcal antigen Factor H binding protein (FHbP) on its surface. Following inoculation, participants will be followed up over 28 days to review safety, nasopharyngeal colonisation with the GM-Nlac strains and immunogenicity. A single dose of oral ciprofloxacin will be administered at day 28 with a final visit at day 30 to confirm clearance of colonisation. Bedroom contacts will be enrolled to look for transmission of the GM-Nlac strains. Volunteers who receive an intranasal inoculum of 4xrNlac will be enrolled as "challenge participants”. Challenge participants will attend a screening visit to complete informed consent and medical screening; a pre-challenge visit approximately 5 days prior to inoculation; and a challenge visit at which they will receive the intranasal inoculum of 4xrNlac. Following inoculation, they will attend regular outpatient visits over 30 days to assess safety, colonisation and immunogenicity, with antibiotic administration to clear colonisation at day 28 post-inoculation, regardless of colonisation status. To assess for any onward transmission of the GM strains, individuals who share a bedroom with challenge participants will be enrolled as "contact participants”. Contact participants will be screened and consented prior to inoculation of the challenge participant, with a maximum of one contact participant per challenge participant. Contact participants will attend for a single visit at day 28 post-inoculation of the challenge participant, at which a throat swab will be taken to assess for colonisation with the GM-Nlac stra
The challenge participant must satisfy all the following inclusion criteria to be eligible for the study: 1. Healthy adults aged 18 to 45 years inclusive on the day of enrolment 2. Fully conversant in the English language 3. Able and willing (in the investigator’s opinion) to comply with all study requirements 4. Able to correctly answer all questions in the pre-consent questionnaire 5. Provide written informed consent to participate in the study including agreement to abide by infection control guidelines during the study period 6. Provide written consent to allow the study team to discuss the participant’s medical history with the General Practitioner and access electronic medical records 7. Written informed consent provided by any bedroom sharer who is eligible to be enrolled as a contact participant (if applicable) 8. For females of child-bearing potential, a negative pregnancy test on the days of screening and challenge 9. Use of continuous effective contraception during the study 10. Agreement to take antibiotic eradication therapy according to the study protocol 11. TOPS registration completed and no conflict found The contact participant must satisfy all the following inclusion criteria to be eligible for the study: 1. Healthy adults aged 18 to 55 years inclusive on the day of enrolment 2. Fully conversant in the English language 3. Able and willing (in the investigator’s opinion) to comply with all study requirements 4. Able to correctly answer all questions in the pre-consent questionnaire 5. Provide written informed consent to participate in the study including agreement to abide by infection control guidelines during the study period 6. Provide written consent to allow the study team to discuss the participant’s medical history with the General Practitioner and access electronic medical records 7. For females of child-bearing potential, a negative pregnancy test on the days of screening and challenge 8. Use of continuous effective contraceptio
The challenge participant may not enter the study if any of the following criteria apply: 1. Individuals who have a current infection at the time of inoculation 2. Use of systemic antibiotics within the period 30 days prior to inoculation 3. Current active smokers defined as having smoked or vaped in the week prior to inoculation 4. N. lactamica or N. meningitidis detected on throat swab or nasal wash taken at screening or at the pre-challenge visit 5. Individuals who have been challenged with wild-type or GM-Nlac in a previous controlled human infection study 6. Individuals who have received one or more doses of a meningococcus B vaccine (Bexsero or Trumenba) 7. History of allergy or intolerance to any component of the inoculum 8. Contraindications to the use of ciprofloxacin, specifically hypersensitivity to quinolones, a history of tendon disorders related to quinolone use, epilepsy, a personal or family history of aneurysm or congenital heart valve disease, and prolonged QT interval 9. Contraindications to the use of ceftriaxone, specifically known hypersensitivity to cephalosporins or severe penicillin allergies (e.g. anaphylaxis or Stevens Johnson Syndrome) 10. Any confirmed or suspected immunosuppressive or immune-deficient state, specifically terminal complement component deficiencies, eculizumab use, known HIV infection, malignancy, asplenia, recurrent severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed) 11. Use of immunoglobulins or blood products within 3 months prior to enrolment 12. Household, close social or regular occupational contact with persons known to be immunosuppressed, specifically HIV infection with a CD4 count < 200 cells/mm³, asplenia; any malignancy, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed) 13. Household or regular occupational contact with children under