Pertussis Immunization During Pregnancy & HIV Infection

Impact of HIV Infection and Pregnancy on Humoral Responses to Pertussis Immunization

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.

Study Overview

• Status: Completed
• Conditions: Pertussis; Pregnancy; HIV-1-infection; Immunization; Infection
• Intervention / Treatment: Biological: TDaP

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 Type: Observational
• Enrollment (Actual): 135

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • CHU Saint-Pierre
  • Ixelles, Belgium, 1050
    • HIS Etterbeek Ixelles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Recruitment at the Pre-natal clinic for pregnant women (HIV-infected or uninfected) on voluntary basis Recruitment at the Travel & Vaccine Clinic for HIV-uninfected non-pregnant women

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PER001; HIV 1-infected pregnant women	Biological: TDaP; Tetanus, Diphteria and Acellular Pertussis vaccine (Boostrix)
PER002; HIV 1-uninfected pregnant women	Biological: TDaP; Tetanus, Diphteria and Acellular Pertussis vaccine (Boostrix)
PER003; HIV 1-uninfected non-pregnant women	Biological: TDaP; Tetanus, Diphteria and Acellular Pertussis vaccine (Boostrix)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Saint Pierre
• Investigators: Principal Investigator: Nicolas Dauby, M.D. Ph.D., Centre Hospitalier Universitaire Saint Pierre

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: April 26, 2018
• First Posted (Actual): May 9, 2018

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; HIV Infections; Infections; Communicable Diseases; Whooping Cough
• Other Study ID Numbers: Pertussis

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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