Maternal Determinants of Immunity to Influenza (MADI-01)

Maternal Determinants of Immunity to Influenza (MADI-01)

The overall objective of the project is to determine the impact of pregnancy on the response to influenza immunization.

Study Overview

• Status: Completed
• Conditions: Influenza; Maternal-Fetal Relations; Vaccination; Infection; Immunoglobulins
• Intervention / Treatment: Biological: Influenza vaccine

Detailed Description

The study compares immune responses to influenza vaccination between a group of pregnant women and a group of non-pregnant controls women. Specifically, the study has three aims:

1. To compare the quality of antibodies induced by influenza immunization in pregnant and non-pregnant women;
2. To identify immune predictors of vaccine responses in pregnant women and compare them to the determinants of vaccine responses in non-pregnant women;
3. To identify immune predictors of the transfer of maternal antibodies to the newborn following influenza immunization during pregnancy;

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • CHU Saint-Pierre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age over 18 and under 40 years.

Exclusion Criteria:

• Grade III/IV anemia
• Human Immunodeficiency Virus (HIV) infection
• Active bacterial infection
• Opportunistic infection (Tuberculosis, cytomegalovirus (CMV), toxoplasmosis, etc)
• Inability to understand the nature and extent of the study and the procedures required
• Current or recent use of immunosuppressive drugs (corticosteroids, anti-tumor necrosis factors (anti-TNF), methotrexate, etc)
• Active neoplasia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pregnant women; Pregnant women receive one dose of influenza-containing vaccine during pregnancy.	Biological: Influenza vaccine; Alpharix-Tetra®, Vaxigrip Tetra® and Influvac Tetra® were used as influenza vaccines in the 2020-2021, 2021-2022, and 2022-2023 seasons respectively.
Active Comparator: Non-pregnant women; Non-pregnant women receive one dose of influenza-containing vaccine.	Biological: Influenza vaccine; Alpharix-Tetra®, Vaxigrip Tetra® and Influvac Tetra® were used as influenza vaccines in the 2020-2021, 2021-2022, and 2022-2023 seasons respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemagglutination Inhibition Assay titre	Haemagglutination Inhibition Assay (HAI) titres are used to measure responses to relevant influenza strains. The HAI method exploits the property of the influenza virus to haemagglutinate red blood cells. HAI titres are determined as the highest serum dilution inhibiting haemagglutination. An HAI titre of >=40 is considered protective in adults. HAI titres will be measured in : Pregnant women; Non-pregnant women	28 days post vaccination
Haemagglutination Inhibition Assay titre	Haemagglutination Inhibition Assay (HAI) titres are used to measure responses to relevant influenza strains. The HAI method exploits the property of the influenza virus to haemagglutinate red blood cells. HAI titres are determined as the highest serum dilution inhibiting haemagglutination. An HAI titre of >=40 is considered protective in adults. HAI titres will be measured in : Pregnant women; In umbilical cord blood	At delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemagglutination inhibition assay titre	Haemagglutination Inhibition Assay (HAI) titres are used to measure responses to relevant influenza strains. The HAI method exploits the property of the influenza virus to haemagglutinate red blood cells. HAI titres are determined as the highest serum dilution inhibiting haemagglutination. An HAI titre of >=40 is considered protective in adults. HAI titres will be measured in : Pregnant women: at day of vaccination, day 7 post-vaccination, day 28 post-vaccination, at delivery, week 6 and 12 post-delivery; Non-pregnant women: at day of vaccination, day 7, day 28, and Month 6 post-vaccination	up to 11 months after vaccination
Micro neutralization assay titre	Micro neutralization assay (MNA) titres are measured on serum samples with detectable HAI titres to determine cross reactivity to related virus strains. This method assesses the ability of serum antibodies to prevent virus from infecting a single layer of cells in a micro titre plate. MNA titres will be measured in : Pregnant women: at day of vaccination, day 7 post-vaccination, day 28 post-vaccination, at delivery, week 6 and 12 post-delivery; Non-pregnant women: at day of vaccination, day 7, day 28, and Month 6 post-vaccination	up to 11 months after vaccination
Influenza virus specific IgG titre	IgG titres specific to influenza virus Hemagglutinin (HA) and Neuraminidase (NA) are measured using conventional Enzyme-linked immunosorbent assay (ELISA) methods. The Enzyme-Linked Lectin Assay (ELLA) is used for detection of NA-specific antibodies only, using reverse genetics viruses with irrelevant HA to ensure only NA antibodies are measured. ELLA is an ELISA variant but adapted to measure the concentration of antibody to NA, determining the amount of sialic acid cleaved from fetuin. IgG titres specific to Influenza Antigens will be assessed by ELISA and ELLA in: Pregnant women: at day of vaccination, day 7 post-vaccination, day 28 post-vaccination, at delivery, week 6 and 12 post-delivery; Non-pregnant women: at day of vaccination, day 7, day 28, and Month 6 post-vaccination	up to 11 month after vaccination
Influenza virus specific IgG antibody avidity	IgG avidity will be measured using chaotropic salts. IgG avidity will be assessed in : Pregnant women: at day of vaccination, day 7 post-vaccination, day 28 post-vaccination, at delivery, week 6 and 12 post-delivery; Non-pregnant women: at day of vaccination, day 7, day 28, and Month 6 post-vaccination	up to 11 months after vaccination

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Saint Pierre
• Collaborators: Institute for Medical Immunology, Université libre de Bruxelles

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2020
• Primary Completion (Actual): November 10, 2023
• Study Completion (Actual): November 10, 2023

Study Registration Dates

• First Submitted: November 29, 2024
• First Submitted That Met QC Criteria: November 29, 2024
• First Posted (Actual): December 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human
• Other Study ID Numbers: B762020201013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No