Lactamica 9: Neisseria Lactamica Inoculation in Late Pregnancy

NCT04784845 | Completed DMC

• 1 other identifier: 61640
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Bacteria living in the nose and throat are generally harmless, but in some circumstances cause infections of the lungs (pneumonia) and brain (meningitis), which are among the commonest causes of death worldwide in young children (especially newborns). Babies with certain 'good' bacteria in the nose and throat are less likely to have infections by such 'bad' bacteria. Scientists have tried giving probiotics ('good' bacteria swallowed or sprayed into the nose) to pregnant women, new mothers and babies. These studies show that many probiotics are safe, but the amount of bacteria given is often unknown, and it is unclear if they work. A more precise option is to use controlled inoculation, by inserting a specific amount of particular 'good' bacteria into the nose under carefully controlled conditions. Our team have previously shown that inoculation with Neisseria lactamica ('good' bacteria) safely and reliably decreases Neisseria meningitidis ('bad' bacteria) in healthy adults' noses. N. lactamica is a type of harmless bacteria found in over 40% of children aged 1-2 years, but is uncommon in newborns and adults. We plan to inoculate 20 healthy pregnant women with N. lactamica nose drops, to find out if it is transferred to their babies after birth. Newborns become rapidly covered (colonised) with bacteria from their mothers, other people, and the environment, so this method mimics a natural way that babies receive bacteria. We will take saliva and nose swabs one day, one week, one month and four months after birth, and will use microbiological and genetic methods to study how the bacteria changes in babies compared with their mothers.

Conditions

Microbial Colonization

Keywords

Human challenge study; Controlled human infection; Neonatal microbiome; Pregnancy; Respiratory Tract Infections; Meningitis; Respiratory microbiome

Outcome Measures

Primary Outcomes (1)

• Neonatal N. lactamica colonisation

  Confirmation of neonatal (aged 0-30 days) N. lactamica colonisation by selective culture of biological (nasopharyngeal and/or saliva) samples

  Up to 4 weeks post-partum

Secondary Outcomes (5)

• Adverse reactions or serious adverse events

  Enrolment (34+0 to 36+6 weeks gestation) to 4 weeks post-partum

• Neonatal N. lactamica Y92-1009 colonisation

  Birth (0-24 hours post-partum), 7+/-3 days post-partum, 28+/-3 days post-partum

• N. lactamica colonisation kinetics

  Birth (0-24 hours post-partum), 7+/-3 days post-partum, 28+/-3 days post-partum

• Upper respiratory microbiome

  Birth (0-24 hours post-partum), 7+/-3 days post-partum, 28+/-3 days post-partum

• N. lactamica Y92-1009 microevolution

  Birth (0-24 hours post-partum), 7+/-3 days post-partum, 28+/-3 days post-partum

Study Arms (1)

N. lactamica Y92-1009

EXPERIMENTAL

Nasal inoculation with 10\^5 CFU N. lactamica in 1ml phosphate-buffered saline via pipette to both nostrils; single inoculation at 36+0 to 37+6 weeks gestation

Biological: N. lactamica Y92-1009

Interventions

N. lactamica Y92-1009 BIOLOGICAL

Lyophilised N. lactamica reconstituted in phosphate-buffered saline

N. lactamica Y92-1009

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Only healthy pregnant women will be recruited. Neonates of any gender will be included.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adult aged 18 years or over on the day of enrolment.
• Singleton pregnancy, 34+0 to 36+6 weeks gestation on the day of enrolment.
• Documentation of a 20-week ultrasound scan with no life-limiting congenital anomalies, and no maxillofacial / otorhinolaryngological / neuroanatomical anomalies.
• Able and willing (in the Investigator's opinion) to comply with all study requirements.
• Able and willing to give written informed consent to participate in the study.
• Booked to receive antenatal care at University Hospital Southampton NHS Foundation Trust.

You may not qualify if:

• Any confirmed or suspected immunosuppressive or immunocompromised state, including: HIV infection; asplenia; recurrent severe infections; or use of immunosuppressant medication (for more than 14 days within the past 6 months, excluding topical and inhaled steroids).
• Planned use of immunosuppressant medication in later pregnancy or post-partum.
• Occupational, household or intimate contact with any immunosuppressed persons.
• Participation within the last 12 weeks in a clinical trial involving receipt of an investigational product, or planned use of an investigational product during the study period.
• Prior participation at any time in research studies involving inoculation with N. lactamica.
• Use of oral or intravenous antibiotics within 30 days prior to the N. lactamica inoculation visit.
• Planned use of oral or intravenous antibiotics at any time during the study period (e.g. for planned elective caesarean section or group B streptococcus colonisation).
• Allergy to soya or yeast.
• Previous stillbirth or neonatal death.
• Pre-pregnancy diabetes mellitus.
• Any other finding that may (in the Investigator's opinion): increase the risk to the volunteer (or their fetus/infant or close contacts) of participating in the study; affect the volunteer's ability to participate in the study and complete follow-up; or impair interpretation of study data.

Sponsors & Collaborators

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

Study Sites (1)

University Hospital Southampton NHS Foundation Trust

Southampton, SO166YD, United Kingdom

Location

Related Publications (3)

• Theodosiou AA, Bogaert D, Cleary DW, Dale AP, Gbesemete DF, Guy JM, Laver JR, Raud L, Jones CE, Read RC. Controlled human infection model of Neisseria lactamica in late pregnancy investigating mother-to-infant transmission in the UK: a single-arm pilot trial. Lancet Microbe. 2025 Apr;6(4):100986. doi: 10.1016/j.lanmic.2024.100986. Epub 2025 Feb 19.

  PMID: 39986292 DERIVED

• Bevan JHJ, Theodosiou AA, Corner J, Dorey RB, Read RC, Jones CE. A Questionnaire-based Study Exploring Participant Perspectives in a Perinatal Human Challenge Trial. Pediatr Infect Dis J. 2023 Nov 1;42(11):935-941. doi: 10.1097/INF.0000000000004036. Epub 2023 Jul 18.

  PMID: 37463362 DERIVED

• Theodosiou AA, Laver JR, Dale AP, Cleary DW, Jones CE, Read RC. Controlled human infection with Neisseria lactamica in late pregnancy to measure horizontal transmission and microbiome changes in mother-neonate pairs: a single-arm interventional pilot study protocol. BMJ Open. 2022 May 18;12(5):e056081. doi: 10.1136/bmjopen-2021-056081.

  PMID: 35584870 DERIVED

MeSH Terms

Conditions

Communicable Diseases; Respiratory Tract Infections; Meningitis

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Diseases; Neuroinflammatory Diseases; Nervous System Diseases

Study Officials

• Christine E Jones

  University of Southampton

  PRINCIPAL INVESTIGATOR

• Robert C Read

  University of Southampton

  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 single intervention cohort will receive one open label intervention (nasal inoculation with 10\^5 CFU N. lactamica). If any naturally-occurring N. lactamica carriers are identified at screening, they will not attend for inoculation with N. lactamica, but will be invited to remain in the study. They (and their neonates) will undergo the same follow-up visits and sampling as inoculated volunteers. This observational cohort is not considered a separate study arm, and there is no recruitment target for this cohort.

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 5, 2021
• Study Start: October 1, 2021
• Primary Completion: July 12, 2022
• Study Completion: July 12, 2022
• Last Updated: September 6, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)