Pertussis Immunization During Pregnancy & HIV Infection

Completed

• Conditions: Pertussis; Immunization; Infection; HIV-1-infection; Pregnancy
• Interventions: Biological: TDaP

• Registration Number: NCT03519373
• Lead Sponsor: Centre Hospitalier Universitaire Saint Pierre

Brief Summary

The impact of chronic HIV infection and pregnancy on different aspects of the humoral response to pertussis immunization with the TDaP vaccine will be studied. The parameters will be measured in 3 groups (HIV-infected pregnant, HIV-uninfected pregnant and HIV-uninfected non pregnant) at different time points before and after immunization (7-10 days, 30 days and at delivery). The transfer ratio and the quality of maternal antibodies will be studied in cord blood.

Detailed Description

Despite the growing importance of maternal immunization in the control of infectious pathogens in early life, the impact of pregnancy on vaccine immunogenicity remains poorly understood. Evidence suggests that pregnancy may influence the quality of the antibody response to vaccines. Pregnancy is associated with modifications in the glycosylation profile of immunoglobulins G (IgG). Different patterns of glycosylation are associated with differential regulation of the effector functions of IgG such as antibody-dependent cell cytotoxicity, complement activation or antibody dependent phagocytosis. Whether similar modifications affect vaccine-induced IgG in pregnant women is unknown.

HIV infection is associated with important alterations in B cells and antibodies. Although antiretroviral therapy partly corrects the proportions of memory B cells (MBC) subsets, it does not restore B cell responses to vaccines, measured as seroconversion rates and antibody persistence. Reduced IgG responses to vaccines have been observed in HIV-infected pregnant women but the impact of HIV on the quality of vaccine-induced IgG has not been reported. On the other hand, HIV infection in pregnancy has a strong impact on the transfer of maternal IgG to the newborn, possibly as a consequence of hypergammaglobulinemia and immune activation.

The investigators will:

1. Assess the respective impact of pregnancy and HIV infection on the magnitude and quality of B cell and antibody responses to pertussis immunization with the TDaP vaccine.

2. Assess the impact of HIV infection and of the timing of maternal immunization on the transplacental transfer and on the quality of pertussis-specific IgG in the newborn.

Study Timeline

• Study Start: 2017-03-01
• Study First Submitted: 2018-04-26
• Study First Submitted QC: 2018-04-26
• Study First Posted: 2018-05-09
• Primary Completion: 2019-06-01
• Study Completion: 2019-06-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-29
• Last Update Posted: 2024-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 135

Inclusion Criteria

• Age over 18
• HIV-infected or uninfected pregnant women in their second/third trimester with an indication of TDaP vaccination
• Non pregnant HIV negative women (having a negative HIV test in the last 6 months or at screening) with an indication of TDaP vaccination

Exclusion Criteria

• Grade III/IV anemia
• Active bacterial infection
• Opportunistic infection (Tuberculosis, 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-TNF, methotrexate, etc)
• Active neoplasia

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PER001	TDaP	HIV 1-infected pregnant women
PER003	TDaP	HIV 1-uninfected non-pregnant women
PER002	TDaP	HIV 1-uninfected pregnant women

Primary Outcome Measures

Name	Time	Method
Pertussis-specific antibodies GMC after immunization	7-10 days, 30 days and at delivery for pregnant women	Anti-Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and pertactin (PRN) specific antibodies levels
Transplacental transfer of pertussis-specific antibodies	Birth	Anti-PT, FHA and PRN specific antibodies levels transfer ratio

Secondary Outcome Measures

Name	Time	Method
Pertussis-specific memory B cells quantification & phenotype	7-10 days, 30 days and at delivery for pregnant women	PT, FHA and PRN-specific memory B cells numbers assessed by ELISPOT assay \& Flow Cytometry
Pertussis-specific antibodies glycosylation profiles	7-10 days, 30 days and at delivery for pregnant women	Anti-PT, FHA and PRN specific antibodies profiles

Trial Locations

Locations (2)

CHU Saint-Pierre; 🇧🇪 Brussels, Belgium

HIS Etterbeek Ixelles; 🇧🇪 Ixelles, Belgium