Wild type N. lactamica challenge and eradication pilot study
Research type
Research Study
Full title
A human controlled infection study to assess colonisation and immunogenicity following nasal inoculation with Neisseria lactamica with eradication on Day 4 or 14
IRAS ID
207453
Contact name
Robert C. Read
Contact email
Sponsor organisation
Southampton University Hospital
Duration of Study in the UK
0 years, 5 months, 31 days
Research summary
Research Summary:
Neisseria lactamica are bacteria frequently found in the noses of infants which don't cause disease and can be considered `friendly bacteria`. In a previous study we showed that if you put N. lactamica in the nose of healthy adults, this causes no harm to the volunteers, the bacteria can colonise their noses and cause an immune response, measured two weeks after giving it. Furthermore the bacteria seem to prevent the colonisation of the nose by potentially harmful bacteria (ones that can cause meningitis). In order to design further studies looking at this we need to shorten the period of experimental colonisation, so in this study we will find out if a short period of colonisation (4 days) results in the same level of immune response as if a volunteers has a longer period of colonisation (14 days). This study will also test how effective antibiotic treatment is in eradicating colonisation. To accomplish this, healthy adult volunteers will receive a nasal inoculation of N. lactamica and antibiotic therapy will be given on day 4 or 14. A wild-type strain of N. lactamica will be used for this study, selected because we have previously used it safely in experimental challenge of over 340 human volunteers.
Summary of Results:
Summary of study results A human controlled infection study to assess colonisation and immunogenicity following nasal inoculation with Neisseria lactamica with eradication on Day 4 or 14: Lactamica 3
Neisseria lactamica research programme
The Neisseria lactamica controlled human infection research programme looking at the relationship between the harmless bacterium Neisseria lactamica (Nlac) and the bacterium Neisseria meningitidis (Nmen) which can cause meningitis and sepsis. This research programme aims to use that relationship to find better ways of protecting people from the diseases caused by Nmen. From our previous studies we know that giving people nose drops containing Nlac – this is known as “challenge” - causes Nlac bacteria to live silently in the nose and throat without causing symptoms – this is known as “colonisation”. This colonisation produces an immune response targeting Nlac and Nmen and reduces the chances of becoming colonised with Nmen, which we hope can be developed into a way of protecting against Nmen. Lactamica 3 was designed to look at how long Nlac colonisation takes to produce this immune response, in order to help us plan the best way to further develop Nlac challenge.Lactamica 3 overview
Lactamica 3 is In Lactamica 3 we challenged participants with Nlac and then gave antibiotics to clear colonisation after either 4 or 14 days. The main aim of the study was to compare the immune response to Nlac colonisation in those participants colonised for a short time (those who received antibiotics after 4 days, Group 1) with participants colonised for a longer time (those who received antibiotics after 14 days, Group 2). We also aimed to look at the proportion of participants who became colonised in each group, to confirm that a single dose of antibiotic cleared colonisation quickly and effectively, and to assess shedding (breathing out) of the bacteria and any symptoms that occurred during colonisation.Lactamica 3 results
Recruitment
32 volunteers were screened as potential participants, of whom 21 were enrolled to the study and challenged (received nose drops containing Nlac). 13 of these were enrolled to Group 1 who received antibiotics after 4 days, and 8 were enrolled to Group 2 who received antibiotics after 14 days. One participant from each group did not complete the study.Colonisation
By Day 4 following challenge, 7 of 13 participants in Group 1 (54%) and 3 of 7 participants in Group 2 (43%) were colonised with Nlac. Those in Group 1 were given antibiotics on Day 4 and no further colonisation was seen in this group. In Group 2, who had not yet received antibiotics, colonisation increased to 6 of 7 participants (86%) by Day 7 following challenge. Antibiotics were given to all participants in Group 2 on Day 14 following challenge. A single dose of antibiotics was effective in clearing colonisation within 24 hours in all colonised participants.Symptoms
Mild upper respiratory tract symptoms (sore throat, blocked nose) occurred in a small number of participants but resolved on their own. Such symptoms are often seen as a result of viral infections and may not have been related to colonisation with Nlac. There were no significant symptoms or safety concerns during the study.Shedding
Shedding (breathing out) of the Nlac bacteria was assessed by looking at air samples and mask samples from participants who were colonised. No shedding was detected in any of these samples.Immune response
Antibodies (part of the immune response) targeting Nlac were measured before challenge and at two visits following challenge, in both groups. As in our previous studies, immune responses targeting both Nlac and Nmen were seen among colonised participants, but only in Group 2 who were colonised for a longer period of time. No immune response was detected in Group 1 where participants were only colonised for four days.Next steps
The results of Lactamica 3 have confirmed that Nlac challenge results in safe Nlac colonisation in a high proportion of participants, causing an immune response targeting both Nlac and Nmen, and that this colonisation can be quickly and effectively cleared with a single dose of antibiotics. Importantly, this study has shown that a shortened period from challenge to antibiotics is not sufficient to allow colonisation or the associated immune response to fully develop, and that a longer period of colonisation is required in order to be fully effective. This crucial information has already been used in the development of further studies within this research programme, in which Nlac has been modified to strengthen the immune response and therefore protection from Nmen. We hope that over the coming years this will be developed into a strategy to improve protection against Nmen disease in the real world.
Further information:For any further information, please email the study team: CRFstudyteam@uhs.nhs.uk The published study report is available at:
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.thelancet.com%252Fjournals%252Flanmic%252Farticle%252FPIIS2666-5247&data=05%7C02%7Champshirea.rec%40hra.nhs.uk%7C66d41251fcf44da04f3f08de5a62d393%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639047577669133707%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=%2BNgnL9BjB%2FoUrmdu7prqj%2FXXRYzLppz2X7nltW87pAI%3D&reserved=0(22)00283-X%2Ffulltext/NBTI/4OjCAQ/AQ/0854840d-3a2b-401c-9c57-7f33b2254039/2/ZlckLElKBf.REC name
South Central - Hampshire A Research Ethics Committee
REC reference
16/SC/0425
Date of REC Opinion
25 Oct 2016
REC opinion
Further Information Favourable Opinion