Meningitis, Meningococcal
Conditions
Keywords
Meningitis, Controlled human infection, Healthy volunteer, Neisseria lactamica, Lyophilization
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.
Detailed description
In this pilot research, the study team will use a methodology of nasal inoculation with reconstituted lyophilised N. lactamica (hereafter LyoNlac) developed in a previous, UK-based, human challenge study. This methodology and will be developed further and validated in healthy Malian adults. A dose-ranging strategy will be used, starting with the dose identified as the standard inoculum in healthy adults in the UK, which was the dose required to induce colonisation in approximately 80% of volunteers. The dose will be escalated to a dose able to induce a similar level of colonisation in Malian adults. This study will inform the study team whether intranasal inoculation of reconstituted lyophilised Nlac (hereafter, lyoNlac), can result in immunising colonisation of adult Malian volunteers and the optimal dose to achieve this. This dose and methodology will then be used in future studies looking at the duration and immunogenicity of colonisation induced by LyoNlac in Mali.
Interventions
BIOLOGICALIntranasal inoculation with Neisseria lactamica
Lyophilised Neisseria lactamica will be reconstituted and administered to participants intranasally.
Sponsors
University of Southampton
University of Maryland
University College, London
University of Oxford
Public Health England
Center for Vaccine Development - Mali
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
A prospective dose-ranging human challenge study. Nasal inoculation with reconstituted, previously lyophilised Neisseria lactamica with dose escalation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
Eligibility Minimum Age: 18 Years Maximum Age: 45 Years Sex: All Gender Based: No Accepts Healthy Volunteers: Yes Criteria: Inclusion Criteria: * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Analyse the biochemistry blood results (Creatinine) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica | 3 months | 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) |
| Analyse the platelet count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica | 3 months | 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 |
| Analyse the biochemistry blood results (ALT) of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica | 3 months | 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 |
| Establish the impact of nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by assessing nasopharyngeal colonisation with Neisseria species | 6 months | 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) |
| Establish the effect of the nasal inoculation of healthy Malian volunteers with reconstituted lyophilised Neisseria lactamica by collecting information about symptoms | 6 months | 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. |
| Analyse the haemoglobin of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica | 3 months | 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 |
| Analyse the white cell count of healthy Malian volunteers inoculated with reconstituted lyophilised Neisseria lactamica | 3 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To measure Neisseria lactamica specific immunity following nasal inoculation with reconstituted lyophilised Neisseria lactamica | 1 year | Blood samples will be collected at standardised visits and antibody levels (mg/dL) will be measured to assess if those colonised with Neisseria lactamica show an increase in antibody levels in comparison to baseline |
| The dose of reconstituted lyophilised Neisseria lactamica required for nasopharyngeal colonisation in at least 70% of inoculees | 6 months | The dose will be confirmed by throat swabs taken from participants and analysed for bacteria by culture and polymerase chain reaction. The desired dose will be confirmed when at least 70%o of inoculees are colonised |
Countries
Mali
Outcome results
None listed