Clinical trial NCT03519373: Pertussis Immunization During Pregnancy & HIV Infection
Official title: Impact of HIV Infection and Pregnancy on Humoral Responses to Pertussis Immunization
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Immunization; Infection
Pertussis
HIV-1-infection
Pregnancy
Lead sponsor: Centre Hospitalier Universitaire Saint Pierre
Sponsor class: OTHER
First posted: 2018-05-09
Enrollment: 135
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pertussis-specific antibodies GMC after immunization
timeFrame: 7-10 days, 30 days and at delivery for pregnant women
measure: Transplacental transfer of pertussis-specific antibodies
timeFrame: Birth
Secondary outcomes:
measure: Pertussis-specific memory B cells quantification & phenotype
timeFrame: 7-10 days, 30 days and at delivery for pregnant women
measure: Pertussis-specific antibodies glycosylation profiles
timeFrame: 7-10 days, 30 days and at delivery for pregnant women
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Saint-Pierre
city: Ixelles
country: Belgium
facility: HIS Etterbeek Ixelles
Study officials:
affiliation: Centre Hospitalier Universitaire Saint Pierre
name: Nicolas Dauby, M.D. Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: