Safety, colonisation and immunogenicity following nasal inoculation with genetically modified Neisseria lactamica expressing Factor H binding protein and Neisseria adhesin A - a pilot controlled human infection study
| ISRCTN | ISRCTN10930766 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10930766 |
| Integrated Research Application System (IRAS) | 364569 |
| Central Portfolio Management System (CPMS) | 73046 |
| Grant Code | MR/X019284/1 |
| Sponsor | University of Southampton |
| Funder | Medical Research Council |
- Submission date
- 23/04/2026
- Registration date
- 08/05/2026
- Last edited
- 08/05/2026
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
This study is part of a research programme that aims to improve ways of protecting people from meningitis and sepsis caused by a bacterium called Neisseria meningitidis (Nmen). These are serious illnesses which mainly affect young children and adolescents both in the UK and globally, particularly in areas of Sub-Saharan Africa. Nmen meningitis and sepsis can rapidly cause death or serious disability, and improving strategies to prevent these illnesses is one pillar of the World Health Organisation vision “Defeating meningitis by 2030”.
Who can participate?
1. Challenge participants: Healthy adult volunteers aged 18-45 years
2. Contact participants: Bedroom sharers of challenge participants – healthy adult volunteers aged 18-55 years
What does the study involve?
This study involves a screening visit and then 7 study visits over 5 weeks. This is a controlled human infection study, which means that participants will be given a small dose of live bacteria, which are expected to be harmless. Participants (and contact participants, if applicable) will be required to follow infection control rules throughout the study and will be given a dose of antibiotic treatment at the end of the study.
What are the possible benefits and risks of participating?
It is unlikely that participants will benefit directly from this study. We hope that the information gained from this study will help inform the development of strategies to prevent meningitis and the associated serious illnesses in the future. Participants may gain some general information about their health as part of this study. Anticipated risks are bruising and tenderness at the site where the blood samples are taken from; inoculation may cause some irritation of the nose that will disappear within a few seconds, and the antibiotic treatment (ciprofloxacin) may cause some side effects such as abdominal ache, diarrhoea, nausea, tiredness and headaches.
Where is the study run from?
The NIHR Clinical Research Facility at Southampton General Hospital (UK)
When is the study starting and how long is it expected to run for?
May 2025 to April 2036
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Andrew Procter, andrew.procter@uhs.nhs.uk
Contact information
Scientific, Public, Principal investigator
NIHR Clinical Research Facility
University Hospital Southampton NHS Foundation Trust
Mailpoint 218
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
| Phone | +44 (0)23 8120 4479 |
|---|---|
| andrew.procter@uhs.nhs.uk |
Principal investigator
University of Southampton
C Level South Lab & Pathology Block
University Hospital Southampton
Tremona Road
Southampton
SO16 6YD
United Kingdom
| d.gbesemete@soton.ac.uk |
Scientific
University of Southampton
C Level South Lab & Pathology Block
University Hospital Southampton
Tremona Road
Southampton
SO16 6YD
United Kingdom
| j.r.laver@soton.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | N/A: single arm study |
| Masking | Open (masking not used) |
| Control | Uncontrolled |
| Assignment | Single |
| Purpose | Basic science |
| Scientific title | Safety, colonisation and immunogenicity following nasal inoculation with genetically modified Neisseria lactamica expressing Factor H binding protein and Neisseria adhesin A - a pilot controlled human infection study |
| Study acronym | GM-Nlac Study - Pilot |
| Study objectives | The co-primary objectives are: 1. To establish the safety of nasal inoculation of healthy adult participants with four strains of genetically modified Neisseria lactamica expressing FHbp and NadA 2. To demonstrate successful induction of nasopharyngeal colonisation following nasal inoculation with genetically modified Neisseria lactamica expressing FHbp and NadA |
| Ethics approval(s) |
Approved 15/04/2026, South Central - Oxford A Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; -; oxforda.rec@hra.nhs.uk), ref: 26/SC/0072 |
| Health condition(s) or problem(s) studied | Neisseria meningitidis, meningococcal meningitis, Neisseria lactamica |
| Intervention | 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 strains. Contact participants will also be screened for GM-Nlac colonisation at an additional visit if symptoms suggestive of respiratory or systemic infection occur during the study period or if they, or their corresponding challenge participant, withdraw prior to the end of the study. A single dose of ciprofloxacin will be administered for the contact participant to take home, and if the throat swab is positive for GM-Nlac then the contact participant will be instructed to take the ciprofloxacin and invited to a further visit to confirm clearance of colonisation. The duration of involvement of challenge and contact participants in the study will be from the screening visit (up to 90 days prior to inoculation) until 30 days after inoculation. |
| Intervention type | Biological/Vaccine |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Genetically modified Neisseria lactamica expressing Factor H binding protein and Neisseria adhesin A |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) |
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 |
| Completion date | 30/04/2036 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 55 Years |
| Sex | All |
| Target sample size at registration | 20 |
| Key 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 |
| Key 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 immunoglobulins or blood products within 3 months prior to enrolment 5. 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) 6. Household or regular occupational contact with children under 5 years or an older child with a tendency to co-sleep with the participant 7. 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. 8. Pregnancy, lactation or intention to become pregnant during the study 9. 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 |
| Date of first enrolment | 18/05/2026 |
| Date of final enrolment | 01/10/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Tremona Road
Southampton
SO16 6YD
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.2 | 29/03/2026 | 01/05/2026 | No | No |
Additional files
- 49412_PROTOCOL_29Mar2026_V1.2.pdf
- Protocol file
Editorial Notes
23/04/2026: Study's existence confirmed by the NIHR.
