A Human Controlled Infection Study with Neisseria Lactamica in Malian Adults

NCT04665791 | Completed DMC

• 1 other identifier: 62190
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This study is part of a series of projects to improve protection against meningitis. Previously, researchers have given nose drops containing N. lactamica to over 400 volunteers and shown that many of them become colonised with N. lactamica without causing any illness or disease. This has previously been shown to prevent people from becoming colonised with N. meningitidis which can cause meningitis. This study aims to give nose drops containing N. lactamica to healthy adults in Mali, to see if they become safely colonised. In the future the study team would like to find out how N.lactamica helps children resist N.meningitidis, and develop new vaccines that exploit that mechanism.

Conditions

Meningitis, Meningococcal

Keywords

Meningitis; Controlled human infection; Healthy volunteer; Neisseria lactamica; Lyophilization

Outcome Measures

Primary Outcomes (7)

• Establish the impact of nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by assessing nasopharyngeal colonisation with Neisseria species

  Throat swabs will be taken at standardised visits and analysed for nasopharyngeal colonisation with Neisseria species. Standard tests include culture and polymerase chain reaction (PCR)

  6 months

• Establish the effect of the nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by collecting information about symptoms

  Information about symptoms will be collected at standardised visits. Any symptoms will be recorded and assessed by a study doctor. If deemed necessary by the study doctor further tests will be requested.

  6 months

• Analyse the haemoglobin of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

  Blood samples will be taken at specified time points and compared to those collected at baseline. Any change in results will be recorded and, if deemed necessary by the medical team, further tests will be requested. Standard tests - haemoglobin - g/dL

  3 months

• Analyse the white cell count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

  Blood samples will be taken at specified time points and compared to those collected at baseline. Any change in results will be recorded and, if deemed necessary by the medical team, further tests will be requested. Standard tests - white cell count - x 10\^9/L

  3 months

• Analyse the platelet count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

  Blood samples will be taken at specified time points and compared to those collected at baseline. Any change in results will be recorded and, if deemed necessary by the medical team, further tests will be requested. Standard tests - Platelet count x 10\^9/L

  3 months

• Analyse the biochemistry blood results (ALT) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

  Blood samples will be taken at specified time points and compared to those collected at baseline. Any change in results will be recorded and, if deemed necessary by the medical team, further tests will be requested. Standard tests - ALT

  3 months

• Analyse the biochemistry blood results (Creatinine) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica

  Blood samples will be taken at specified time points and compared to those collected at baseline. Any change in results will be recorded and, if deemed necessary by the medical team, further tests will be requested. Standard tests - Creatinine (mg/dL)

  3 months

Secondary Outcomes (2)

• The dose of reconstituted lyophilised Neisseria lactamica required for nasopharyngeal colonisation in at least 70% of inoculees

  6 months

• To measure Neisseria lactamica specific immunity following nasal inoculation with reconstituted lyophilised Neisseria lactamica

  1 year

Study Arms (1)

Challenge

EXPERIMENTAL

Challenge participants will be inoculated intranasally with reconstituted, previously lyophilised Neisseria lactamica (LyoNlac). The initial dose will be 10\^5 colony forming units and will be escalated to a maximum of 10\^7 colony forming units to find the dose which successfully colonises at least 70% of volunteers.

Biological: Intranasal inoculation with Neisseria lactamica

Interventions

Intranasal inoculation with Neisseria lactamica BIOLOGICAL

Lyophilised Neisseria lactamica will be reconstituted and administered to participants intranasally.

Challenge

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 residing outside the demographic surveillance area
• Able and willing (in the investigator's opinion) to understand and comply with all study requirements including availability for all study follow up visits
• Provide written informed consent to participate in the trial
• For females only, all the following:
• willingness to practice continuous effective contraception at least until the Day 28 visit is complete
• negative urine pregnancy test on the screening day
• negative urine pregnancy test on inoculation day

You may not qualify if:

• Eligibility Minimum Age: 18 Years Maximum Age: 45 Years Sex: All Gender Based: No Accepts Healthy Volunteers: Yes
• Healthy adults aged 18 to 45 years inclusive on the day of enrolment residing outside the demographic surveillance area
• Able and willing (in the investigator's opinion) to understand and comply with all study requirements including availability for all study follow up visits
• Provide written informed consent to participate in the trial
• For females only, all the following:
• willingness to practice continuous effective contraception at least until the Day 28 visit is complete
• negative urine pregnancy test on the screening day
• negative urine pregnancy test on inoculation day
• N. lactamica detected on throat swab taken at the screening visit
• Individuals who have an ongoing acute illness 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
• Use of systemic antibiotics within the period 30 days prior to the challenge
• Any confirmed or suspected immunosuppressive or immune-deficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication (including oral steroids) 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 to soya.

Sponsors & Collaborators

• Center for Vaccine Development - Mali: lead
• University of Southampton: collaborator
• University of Maryland: collaborator
• University College, London: collaborator
• University of Oxford: collaborator
• Public Health England: collaborator

Study Sites (1)

CVD Mali

Bamako, Mali

Location

Related Publications (1)

• Gbesemete DF, Haidara F, Laver JR, Ibrahim M, MacLennan J, Dale AP, Gorringe AR, Traore Y, Diallo F, Badji H, Traore A, Onwuchekwa U, Jones E, Webb C, Guy J, Theodosiou AA, Faust SN, Sow SO, Heyderman RS, Tapia MD, Read RC. Controlled Human Infection of Healthy Adults With Lyophilized Neisseria lactamica Induces Asymptomatic, Immunogenic Nasopharyngeal Carriage in the United Kingdom and Mali. Open Forum Infect Dis. 2026 Jan 7;13(1):ofaf809. doi: 10.1093/ofid/ofaf809. eCollection 2026 Jan.

  PMID: 41574175 DERIVED

MeSH Terms

Conditions

Meningitis, Meningococcal; Meningitis

Condition Hierarchy (Ancestors)

Meningitis, Bacterial; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Meningococcal Infections; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Study Officials

• Robert C Read, MD FRCP

  University of Southampton

  PRINCIPAL INVESTIGATOR

• Samba Sow, MD

  Center for Vaccine Development - Mali

  PRINCIPAL INVESTIGATOR

• Milagritos Tapia, MD

  University of Maryland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A prospective dose-ranging human challenge study. Nasal inoculation with reconstituted, previously lyophilised Neisseria lactamica with dose escalation.

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 14, 2020
• Study Start: March 2, 2021
• Primary Completion: October 10, 2021
• Study Completion: June 6, 2023
• Last Updated: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)