Defining the Immune Response to Nasopharyngeal Colonisation by the Commensal Neisseria Lactamica

NCT03633474 | Completed Early Phase 1

• 1 other identifier: Lactamica-7
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Neisseria meningitidis is a 'bad bacteria' which lives harmlessly in the nose and throat of many young adults (a process called colonisation). However, it can occasionally cause serious disease including meningitis. Vaccines have proven effective in preventing disease associated with a number of strains of this bacterium, however some disease-causing strains are not covered by currently available vaccines. This research is focused on exploring new approaches to preventing colonisation and disease caused by this bacterium. Neisseria lactamica is a 'good bacteria' that colonises the nose and throat of young children. It does not cause disease in healthy people. In a previous study it has been demonstrated that the introduction of Neisseria lactamica into the noses of healthy adult volunteers resulted in a significant decrease in Neisseria meningitidis colonisation. However, it is not yet understood why this effect occurs. One theory is that the immune response the body mounts in response to colonisation with the 'good bacteria' cross-reacts with the 'bad bacteria' and in so doing eradicates the bad bacteria from the nose and throat. This study aims to outline the nature of the immune responses mounted in response to colonisation with the good bacteria, N. lactamica, after introducing it into the noses of healthy adult volunteers. In addition, the study aims to establish how the introduction of the good bacteria changes the other bacterial populations that live in the nose and throat.

Conditions

Meningitis, Bacterial

Keywords

Healthy volunteer; Human Challenge study

Outcome Measures

Primary Outcomes (1)

• To measure host T-cell and B-cell memory responses and plasma B-cell responses in blood to experimentally-induced nasopharyngeal colonisation with N. lactamica.

  Measurements from baseline will compare the host T and B-cell memory response (ug/mL) to samples taken post inoculation.

  Up to Day 33

Secondary Outcomes (1)

• Determine if N. lactamica-specific CD4+ T-cell memory responses detected in blood cross-react with N. meningitidis.

  Up to Day 33

Study Arms (2)

N. Lactamica in PBS

EXPERIMENTAL

Wild-type Neisseria lactamica (strain Y92-1009, sequence type 3493, clonal complex 613) will be used for this human challenge experiment. This strain is identical to that utilised in our previous challenge experiments (\>350 volunteers to date).

Biological: N. lactamica

PBS Control

PLACEBO COMPARATOR

PBS only control. Volunteers randomized to this arm will receive a PBS only solution which contains no bacteria.

Other: PBS only

Interventions

N. lactamica BIOLOGICAL

Stocks of N. lactamica (strain Y92-1009, sequence type 3493, clonal complex 613) in Frantz medium containing 30% (v/v) glycerol have been previously prepared using the Good Manufacturing Practices pharmaceutical manufacturing facilities at Public Health England (Porton Down, United Kingdom).

N. Lactamica in PBS

PBS only OTHER

Sterile PBS only containing no bacteria

PBS Control

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Southampton: lead
• University Hospital Southampton NHS Foundation Trust: collaborator

Study Sites (1)

NIHR Southampton Clinical Research Facility

Southampton, United Kingdom

Location

Related Publications (1)

• Dale 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.

  PMID: 36462524 DERIVED

MeSH Terms

Conditions

Meningitis, Bacterial

Condition Hierarchy (Ancestors)

Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases

Study Officials

• Adam P Dale

  University of Southampton

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Non-Neisseria spp. carriers will randomised in a ratio of 2:1 to receive either 10-5 cfu N. lactamica or PBS control using randomisation software, e.g. Sealed envelope (TM) available online.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Volunteers will be blinded to the inoculum type received (i.e. N. lactamica or PBS control) throughout the study duration. Nasal secretion and throat swabs will be taken to enable mucosal immune profiling and microbiome analyses to be performed. Subjects will be screened for nasopharyngeal N. meningitidis carriage -28 to -7 days (visit 1) and non-Neisseria spp. carriers will be challenged with either 105 cfu N. lactamica suspended in PBS or PBS only control (day 0, visit 2). Volunteers identified as carriers of N. meningitidis at visit 1 will be excluded from the study and will not progress to experimental human challenge. Biological samples (nasal secretion, microbiome swab and blood) will be collected from volunteers who progress to the challenge (visit 2, Day 0) and on days +7 (+/-3), +14 (+/-3) and +28 (+/-5) post-challenge. Nasal wash sampling will not be taken at the challenge visit (Day 0) but will be taken on days +7(+/-3), +14 (+/-3) and +28 (+/-5) post-challenge.

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 16, 2018
• Study Start: September 1, 2018
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: October 22, 2019

Record last verified: 2019-10

Locations

GB (1)