Sources of COmplement in Meningococcal and Pertussis Serum Bactericidal Antibody Assays (COMPAre)

This study is designed to allow cord blood sample collection from the cords of babies born in three gestational age windows: ≥37 gestational weeks, 32-36+6 gestational weeks and less than 32 gestational weeks to investigate whether the result obtained using a standard hSBA assay is comparable to that achieved using complement from a gestation matched population for meningococcal B and pertussis.

Study Overview

• Status: Unknown
• Conditions: Pertussis; Prematurity; Meningococcal Disease
• Intervention / Treatment: Procedure: Cord blood sampling

Detailed Description

Newborn infants, particularly those who are born preterm, are vulnerable to infection because of their immature immune systems. Invasive meningococcal disease (IMD) and pertussis both represent significant risks to the newborn infant.

Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, is a devastating illness with a case fatality rate of 10-20% even with intensive treatment. Even infants who survive IMD experience significant disability in 10-20% of cases. Serogroups A, B, C, Y, W and X cause almost all cases of IMD, and in Europe, North America and parts of Latin America serogroup B is responsible for the majority of cases. In the UK there were 747 cases of IMD in 2016/17 and Men B was responsible for 396 (53%) of these. The major burden of disease is in infants under the age of 1 year. Pertussis is a highly infectious respiratory illness caused by Bordetella pertussis which can cause significant morbidity and mortality in young infants. There has been an increase in the incidence of pertussis in the UK, along with other high income countries in recent years which has disproportionately affected young infants.

Infants in the UK are vaccinated against meningococcal group B disease at 2, 4 and 12 months with Bexsero® and against pertussis at 2,3 and 4 months as part of the 6-in-1 vaccine Infanrix hexa®. Additionally, since 2012 pregnant women in the UK have been routinely offered pertussis vaccination during pregnancy to protect the infant in the first few months of life prior to them receiving their own vaccinations.

Serum bactericidal antibody (SBA) assays are important in the assessment of immunity following vaccination and are used in the production, release and licensure of some vaccines and the evaluation of the function of others. SBA assays for pertussis and meningococcal B typically use adult complement from a healthy adult donor pool. There is some concern that using adult complement may not allow an adequate assessment of neonatal immunity. The concentration of most complement components in the neonate is around 10-80% of that in the adult and circulating regulator levels are also reduced. Differences in complement function are more pronounced in preterm infants and the differences in the quality and activation of complement in neonates raises questions about whether an SBA assay using adult complement sources allows an accurate assessment of neonatal immunity.

In this study the investigators will create a pooled complement source for three different gestational ages, ≥37 gestational weeks, 32-36+6 gestational weeks and less than 32 gestational weeks, which will allow the investigators to compare the results of the pertussis and meningococcal SBA assays when using both standard adult complement and a gestational age appropriate complement source. To do this the investigators will collect cord blood samples from deliveries within the three gestational age groups.

• Study Type: Observational
• Enrollment (Anticipated): 45

Contacts and Locations

• Study Contact: Name: Kirsty Le Doare, PhD; Phone Number: 02087253887; Email: kiledoar@sgul.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SW17 0RE
    • Recruiting
    • St George's, University of London
    • Contact: Vanessa Greening; Phone Number: 02087253887; Email: vgreenin@sgul.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women

Description

Inclusion Criteria:

• Pregnant and planning to deliver at St George's University Hospitals NHS Foundation Trust

Exclusion Criteria:

• Aged less than 16 years
• Known complement deficiency

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Term babies; Babies who are born at or after 37 gestational weeks.	Procedure: Cord blood sampling; A cord blood sample will be obtained after the baby has been delivered and the cord has been clamped and cut.
Preterm babies; Babies who are born between 32 and 36+6 gestational weeks.	Procedure: Cord blood sampling; A cord blood sample will be obtained after the baby has been delivered and the cord has been clamped and cut.
Very preterm babies; Babies who are born before 32 gestational weeks.	Procedure: Cord blood sampling; A cord blood sample will be obtained after the baby has been delivered and the cord has been clamped and cut.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SBA assay results	Comparison of the SBA assay results obtained when using adult human complement compared with a gestationally matched complement source	Cord blood sampling will be performed at the time of delivery

Collaborators and Investigators

• Sponsor: St George's, University of London
• Investigators: Principal Investigator: Anna Calvert, MBChB, St George's, Univeristy of London

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2020
• Primary Completion (Anticipated): September 21, 2021
• Study Completion (Anticipated): September 21, 2021

Study Registration Dates

• First Submitted: July 15, 2019
• First Submitted That Met QC Criteria: July 15, 2019
• First Posted (Actual): July 18, 2019

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 8, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Whooping Cough; Meningococcal Infections
• Other Study ID Numbers: 2019.0116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No