Meningitis, MeningococcalLac-3NCT03549325
A Study Assessing Colonisation & Immunogenicity After Nasal Inoculation With N. Lactamica and Eradication on Day 4 or 14
A study testing Neisseria lactamica in people with Meningitis, Meningococcal, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This study is part of a project that aims to develop a vaccine with N. lactamica that prevents meningitis. The investigators have previously given nose drops containing N. lactamica to over 340 volunteers, and shown that many of the volunteers (35-60%) become colonised without causing any illness or disease. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Meningitis, Meningococcal
- What is being tested?
- Neisseria lactamica
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 Mar 2017to 2 Dec 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 trial
- Willingness to take an antibiotic regimen after inoculation according to the study protocol
- For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and inoculation
Who cannot join
- Current active smokers
- N. lactamica or N. meningitidis detected on 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 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 trials investigating meningococcal vaccines or experimental challenge with N. lactamica
- Use of systemic antibiotics within the period 30 days prior to the challenge
Show all 14Show fewer
- Any confirmed or suspected immunosuppressive or immune-deficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed)
- Use of immunoglobulins or blood products within 3 months prior to enrolment.
- History of allergic disease or reactions likely to be exacerbated by any component of the inoculum
- Contraindications to the use of ciprofloxacin, specifically a history of epilepsy, prolonged QT interval, hypersensitivity to quinolones or a history of tendon disorders related to quinolone use
- Any clinically significant abnormal finding on clinical examination
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Southampton NIHR Clinical Research Facility
Southampton, Hampshire, SO166YD
About this study
Official title: A Human Controlled Infection Study to Assess Colonisation and Immunogenicity Following Nasal Inoculation With Neisseria Lactamica With Eradication on Day 4 or 14
This study is part of a project that aims to develop a vaccine with N. lactamica that prevents meningitis. The investigators have previously given nose drops containing N. lactamica to over 340 volunteers, and shown that many of the volunteers (35-60%) become colonised without causing any illness or disease. In the future the investigators would like to modify N. lactamica so that it can carry vaccine molecules into the nose of children. To do this the investigators need to know more about the immune response generated against N. lactamica. Previously the investigators have shown that inoculation resulted in an immune (antibody) response in volunteers who were colonised. Taking an antibiotic called ciprofloxacin will treat N.lactamica in the nose and throat of the volunteers. The investigators need to know if the immune response to N. lactamica is the same when colonised volunteers are treated with the antibiotic after 4 days, is the same if the investigators treat volunteers after 14 days of carriage. This information will inform future studies.
Read the detailed description
- lactamica (Nlac) has been shown to be safe to use in human challenge experiments. Even at a very low dose of 10,000 colony forming units (cfu) long lasting colonisation with Nlac is easily induced in 35-65% of volunteers. The investigators have previously showed that increasing the inoculum to 100,000 cfu increased the subsequent carriage of Nlac to 50%. In 80-90% of those volunteers successfully colonised, this is detectable by 1-2 weeks.
Data regarding earlier detection of colonisation is currently lacking.
Colonisation has a clear effect on the volunteers nasal mucosal microbiome, in that meningococcal acquisition is effectively inhibited in volunteers who carry the organism. Colonisation is immunogenic, with an increase in specific serum IgG by 2 weeks and specific salivary IgA by 4 weeks.
No antibiotic eradication therapy has previously been given following experimental inoculation but Ciprofloxacin has been shown to be effective in the eradication of N. meningitidis.
To design future planned studies using Nlac nasal inoculation and colonisation in order to prevent invasive N. meningitidis disease, it is necessary to further evaluate the colonisation kinetics and efficacy of the eradication following antibiotic treatment. In previous challenges the investigators inoculated volunteers with Nlac and followed those volunteers for prolonged periods of time (over 6 months).
This study will compare the effect of short (4 days) versus longer (14 days) periods of nasal carriage of Nlac in volunteers on immunogenicity, and confirm the efficacy of antibiotic eradication therapy with ciprofloxacin.
Healthy adult volunteers will receive a nasal inoculation of Nlac with an antibiotic given on day 4 or 14. This information will be used to inform the design of future research into the colonisation and immunogenicity of related organisms.
Before designing future protocols the study investigators need to know whether a short containment of the volunteers will be sufficient for immunogenicity, and how quickly the volunteers can be discharged after antibiotic treatment.
A wild-type strain of Nlac (Y92-100) will be used for this study, selected because the investigators have previously used it safely in experimental challenge of over 340 human volunteers.
The same strain will be the parent strain for any future GMO work.
- Conditions
- Meningitis, Meningococcal
- Being tested
- Neisseria lactamica
- Keywords
- Neisseria lactamica, healthy volunteers, nasal inoculation, colonisation
- Medical subject headings
- Meningitis, Meningococcal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neisseria lactamicaBiological
Colonisation by bacteria is an immunising event; we proved this in humans by inoculating university students intranasally with the harmless commensal N. lactamica and we observed both specific systemic and mucosal antibody responses by 4 weeks. Experimental challenge with defined bacteria could tease out the Th17-mediated response mechanisms, which include waning of immunity over time, the induction of an incorrectly polarised T cell response, lack of cross-reactivity between strains or active immune evasion mechanisms employed by bacteria to subvert host immune effector mechanisms.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Nasal drops containing Neisseria lactamica are administered at Day 0 by the study doctor.
Eradication therapy with the antibiotic Ciprofloxacin given on Day 4, unless required sooner.
Follow up visits occur on Days 5, 14 and 32. Receives: Biological: Neisseria lactamica |
| Group 2 | Experimental | Nasal drops containing Neisseria lactamica are administered at Day 0 by the study doctor.
Follow up visits on Day 4 and 7 to check for N. lactamica carriage. Eradication therapy with the antibiotic Ciprofloxacin given on Day 14, unless required sooner.
Follow up visits occur on Days 15, 24 and 42. Receives: Biological: Neisseria lactamica |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure the Antibodies, by Serological Antibody Titration, of Short Term Colonisation and Longer Colonisation
Measure any rise in serological specific antibodies from samples taken at the start of the study (Day 0) and samples taken on Day 14 post inoculation and Day 28 post antibiotic eradication (Group 1 = Day 32 or Group 2 = Day 42)
Measured: Up to 42 Days
Secondary outcomes (2)
Measure the Colonisation of Neisseria Lactamica
Measure if Neisseria lactamica is able to colonise at or before Day 4 (for group 1) or Day 14 (for group 2) from cultured throat swabs.
Measured: Up to 14 Days
Measure the Eradication of Neisseria Lactamica
Record how successful eradication is up to Day 42, using throat swab samples.
Measured: Up to 42 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2018
- Study start13 Mar 2017
- Primary completion2 Dec 2021
- Study completion2 Dec 2021
Why it stopped: Recruitment was paused in March 2020 due to the COVID pandemic. An interim data analysis was conducted in 2021 which confirmed that sufficient data had been collected to meet the primary objective, therefore the study was terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Meningitis, MeningococcalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Group 1: Nasal inoculation with Neisseria lactamica with eradication on day 4 - up to 22 volunteers or until 11 colonised on day 4 Group 2: Nasal inoculation with Neisseria lactamica with eradication on day 14 - up to 22 volunteers or until 11 colonised on day 4
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Southampton NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southampton
- Responsible party
- Sponsor
- Investigators
- Robert Read, Principal investigator, University of Southampton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03549325
- Sponsor's protocol ID
- MED1354
- Acronym
- Lac-3
- Status last verified
- Jan 2026
- First submitted
- 23 Oct 2017
- Last updated
- 12 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Evans CM, Pratt CB, Matheson M, Vaughan TE, Findlow J, Borrow R, Gorringe AR, Read RC. Nasopharyngeal colonization by Neisseria lactamica and induction of protective immunity against Neisseria meningitidis. Clin Infect Dis. 2011 Jan 1;52(1):70-7. doi: 10.1093/cid/ciq065.
PubMed 21148522Dale AP, Theodosiou AA, Gbesemete DF, Guy JM, Jones EF, Hill AR, Ibrahim MM, de Graaf H, Ahmed M, Faust SN, Gorringe AR, Polak ME, Laver JR, Read RC. Effect of colonisation with Neisseria lactamica on cross-reactive anti-meningococcal B-cell responses: a randomised, controlled, human infection trial. Lancet Microbe. 2022 Dec;3(12):e931-e943. doi: 10.1016/S2666-5247(22)00283-X.
PubMed 36462524
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Human Controlled Infection Study to Assess Colonisation and Immunogenicity Following Nasal Inoculation With Neisseria Lactamica With Eradication on Day 4 or 14
- ClinicalTrials.gov ID
- NCT03549325
- Acronym / sponsor ID
- Lac-3 / MED1354
- Conditions
- Meningitis, Meningococcal
- Keywords
- Neisseria lactamica, healthy volunteers, nasal inoculation, colonisation
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment was paused in March 2020 due to the COVID pandemic. An interim data analysis was conducted in 2021 which confirmed that sufficient data had been collected to meet the primary objective, therefore the study was terminated.
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University Hospital Southampton NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Southampton
- Study start
- 13 Mar 2017 (actual)
- Primary completion
- 2 Dec 2021 (actual)
- Study completion
- 2 Dec 2021 (actual)
- First posted
- 8 Jun 2018 (actual)
- Results
- Posted 12 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is part of a project that aims to develop a vaccine with N. lactamica that prevents meningitis. The investigators have previously given nose drops containing N. lactamica to over 340 volunteers, and shown that many of the volunteers (35-60%) become colonised without causing any illness or disease. In the future the investigators would like to modify N. lactamica so that it can carry vaccine molecules into the nose of children. To do this the investigators need to know more about the immune response generated against N. lactamica. Previously the investigators have shown that inoculation resulted in an immune (antibody) response in volunteers who were colonised. Taking an antibiotic called ciprofloxacin will treat N.lactamica in the nose and throat of the volunteers. The investigators need to know if the immune response to N. lactamica is the same when colonised volunteers are treated with the antibiotic after 4 days, is the same if the investigators treat volunteers after 14 days of carriage. This information will inform future studies.
Detailed description
- lactamica (Nlac) has been shown to be safe to use in human challenge experiments. Even at a very low dose of 10,000 colony forming units (cfu) long lasting colonisation with Nlac is easily induced in 35-65% of volunteers. The investigators have previously showed that increasing the inoculum to 100,000 cfu increased the subsequent carriage of Nlac to 50%. In 80-90% of those volunteers successfully colonised, this is detectable by 1-2 weeks.
Data regarding earlier detection of colonisation is currently lacking.
Colonisation has a clear effect on the volunteers nasal mucosal microbiome, in that meningococcal acquisition is effectively inhibited in volunteers who carry the organism. Colonisation is immunogenic, with an increase in specific serum IgG by 2 weeks and specific salivary IgA by 4 weeks.
No antibiotic eradication therapy has previously been given following experimental inoculation but Ciprofloxacin has been shown to be effective in the eradication of N. meningitidis.
To design future planned studies using Nlac nasal inoculation and colonisation in order to prevent invasive N. meningitidis disease, it is necessary to further evaluate the colonisation kinetics and efficacy of the eradication following antibiotic treatment. In previous challenges the investigators inoculated volunteers with Nlac and followed those volunteers for prolonged periods of time (over 6 months).
This study will compare the effect of short (4 days) versus longer (14 days) periods of nasal carriage of Nlac in volunteers on immunogenicity, and confirm the efficacy of antibiotic eradication therapy with ciprofloxacin.
Healthy adult volunteers will receive a nasal inoculation of Nlac with an antibiotic given on day 4 or 14. This information will be used to inform the design of future research into the colonisation and immunogenicity of related organisms.
Before designing future protocols the study investigators need to know whether a short containment of the volunteers will be sufficient for immunogenicity, and how quickly the volunteers can be discharged after antibiotic treatment.
A wild-type strain of Nlac (Y92-100) will be used for this study, selected because the investigators have previously used it safely in experimental challenge of over 340 human volunteers.
The same strain will be the parent strain for any future GMO work.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Group 1: Nasal inoculation with Neisseria lactamica with eradication on day 4 - up to 22 volunteers or until 11 colonised on day 4 Group 2: Nasal inoculation with Neisseria lactamica with eradication on day 14 - up to 22 volunteers or until 11 colonised on day 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: Neisseria lactamicaNasal drops containing Neisseria lactamica are administered at Day 0 by the study doctor. Eradication therapy with the antibiotic Ciprofloxacin given on Day 4, unless required sooner. Follow up visits occur on Days 5, 14 and 32. |
| Group 2 | Experimental | Biological: Neisseria lactamicaNasal drops containing Neisseria lactamica are administered at Day 0 by the study doctor. Follow up visits on Day 4 and 7 to check for N. lactamica carriage. Eradication therapy with the antibiotic Ciprofloxacin given on Day 14, unless required sooner. Follow up visits occur on Days 15, 24 and 42. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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 trial
- Willingness to take an antibiotic regimen after inoculation according to the study protocol
Key exclusion criteria (14 listed)
- Current active smokers
- N. lactamica or N. meningitidis detected on 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 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 trials investigating meningococcal vaccines or experimental challenge with N. lactamica
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neisseria lactamicaColonisation by bacteria is an immunising event; we proved this in humans by inoculating university students intranasally with the harmless commensal N. lactamica and we observed both specific systemic and mucosal antibody responses by 4 weeks. Experimental challenge with defined bacteria could tease out the Th17-mediated response mechanisms, which include waning of immunity over time, the induction of an incorrectly polarised T cell response, lack of cross-reactivity between strains or active immune evasion mechanisms employed by bacteria to subvert host immune effector mechanisms. | Biological | Group 1, Group 2 |
Primary outcome
Measure the Antibodies, by Serological Antibody Titration, of Short Term Colonisation and Longer Colonisation
Time frame: Up to 42 Days
Measure any rise in serological specific antibodies from samples taken at the start of the study (Day 0) and samples taken on Day 14 post inoculation and Day 28 post antibiotic eradication (Group 1 = Day 32 or Group 2 = Day 42)
2 secondary outcomes
Measure the Colonisation of Neisseria Lactamica
Time frame: Up to 14 Days
Measure the Eradication of Neisseria Lactamica
Time frame: Up to 42 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21148522Evans CM, Pratt CB, Matheson M, Vaughan TE, Findlow J, Borrow R, Gorringe AR, Read RC. Nasopharyngeal colonization by Neisseria lactamica and induction of protective immunity against Neisseria meningitidis. Clin Infect Dis. 2011 Jan 1;52(1):70-7. doi: 10.1093/cid/ciq065.
- Derived from this study: PubMed 36462524Dale AP, Theodosiou AA, Gbesemete DF, Guy JM, Jones EF, Hill AR, Ibrahim MM, de Graaf H, Ahmed M, Faust SN, Gorringe AR, Polak ME, Laver JR, Read RC. Effect of colonisation with Neisseria lactamica on cross-reactive anti-meningococcal B-cell responses: a randomised, controlled, human infection trial. Lancet Microbe. 2022 Dec;3(12):e931-e943. doi: 10.1016/S2666-5247(22)00283-X.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Read principal investigator
University of Southampton
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neisseria lactamica in people with Meningitis, Meningococcal, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure the Antibodies, by Serological Antibody Titration, of Short Term Colonisation and Longer Colonisation (time frame: Up to 42 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03549325, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2026; AzTrials last refreshed its copy on 30 Oct 2026.