Neisseria meningitidis, meningococcal meningitis, Neisseria lactamica Infections and Infestations
Conditions
Interventions
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 challeng
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 i
Sponsors
University of Southampton
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 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 contraception during the study 9. Agreement to take antibiotic eradication therapy according to the study protocol 10. TOPS registration completed and no conflict found
Exclusion criteria
Exclusion criteria: 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 5 years or an older child with a tendency to co-sleep with the participant 14. Any abnormal finding on clinical examination or screening investigations assessed by the investigator to be clinically significant. In the event of abnormal test results, confirmatory repeat tests may be requested. 15. Pregnancy, lactation or intention to become pregnant during the study 16. Any other significant disease, disorder, or finding which may significantly increase the risk to the participant, affect their participation in the study or impair interpretation of the study data, for example recent surgery to the nasopharynx. The contact participant may not enter the study if any of the following criteria apply: 1. 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 2. Contraindications to the use of ceftriaxone, specifically known hypersensitivity to cephalosporins or severe penicillin allergies (e.g. anaphylaxis or Stevens Johnson Syndrome) 3. 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) 4. Use of immu
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| 1. The proportion of previously colonised challenge or contact participants who have colonisation cleared by a single dose of ciprofloxacin, assessed by culture of N. lactamica from nasal wash and throat swab samples taken 24-48 hours following antibiotic administration 2. The proportion of contact participants of colonised challenge participants who become colonised with any of the GM-Nlac strains, assessed by culture of throat swab samples at the day 28 visit or any additional visits prior to the day 28 visit | — |
Countries
England, United Kingdom
Contacts
Public ContactAndrew Procter
Outcome results
None listed