Pertussis Vaccination Among HIV-infected and HIV-uninfected Pregnant Women

Pertussis (also known as whooping cough) is a highly contagious, vaccine-preventable respiratory tract disease, caused by the bacteria Bordetella pertussis. It can affect people of all ages, however young unimmunised or partially immunised infants are the most vulnerable group with the highest rates of complications and death. Recent surveillance data and an increase in the number of pertussis outbreaks being reported nationally, indicate an increase in the incidence of pertussis disease in South Africa.To date there is no data on the effect of vaccinating HIV-infected pregnant women with pertussis-containing vaccines, although there is no reason to think that vaccinating these women would be harmful for them or their foetus. The knowledge gaps on the immunogenicity, safety and VE of pertussis vaccination of HIV-infected pregnant women should be addressed. Adacel which is a registered and licensed vaccine manufactured by Sanofi Pasteur, will be tested in this study.

Study Overview

• Status: Not yet recruiting
• Conditions: dTap Vaccine
• Intervention / Treatment: Drug: Adacel (Tdap)

• Study Type: Interventional
• Enrollment (Anticipated): 225
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marta Nunes, PhD; Phone Number: +27119834283; Email: marta.nunes@wits-vida.org

Study Locations

• South Africa
  • GP
    • Johannesburg, GP, South Africa, 2192
      • Chris Hani Baragwanath Academic hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women age ≥18 years to <39 years (vaccinated group only).
• Gestational age 20-36 weeks documented by the approximate date of the last menstrual period and corroborated by physical or sonargraphic exam (vaccinated group only).
• Documented to be HIV-infected or HIV-uninfected.
• Good general maternal health.
• Able to understand and comply with planned study procedures.
• Able and willing to provide written informed consent for themselves and infant

Exclusion Criteria:

• Receipt of any live licensed vaccine ≤14 days prior to study initiation.
• Any significant (in the opinion of the site investigator) acute illness.
• Use of anti-cancer systemic chemotherapy or radiation therapy ≤48 weeks of study enrolment or has immunosuppression as a result of an underlying illness or treatment.
• Long term use of glucocorticoids, including oral or parenteral prednisone ≥20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) ≤12 weeks of study entry, or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) ≤12 weeks before study entry (nasal and topical steroids are allowed).
• Receipt of corticosteroids for preterm labour ≤14 days before study entry.
• Receipt of immunoglobulin or other blood products (with exception of Rho D immune globulin) ≤12 weeks prior to enrolment in this study or is scheduled to receive immunoglobulin or other blood products (with the exception of Rho D immune globulin) during pregnancy or for the first 24 weeks after delivery.
• Receipt of IL2, IFN, GMCSF or other immune mediators ≤12 weeks before enrolment.
• Uncontrolled major psychiatric disorder.
• History of a severe adverse reaction to previous vaccines (vaccinated group only).
• Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
• Pregnancy complications (in the current pregnancy) such as pre-term labour, hypertension (BP >140/90 in the presence of proteinuria or BP >150/100, with or without proteinuria or currently on antihypertensive medication) and pre-eclampsia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Open label Adacel; Tdap (Adacel) ADACEL (0,5 ml) should be administered as an injection by the intramuscular route. Re-dosing with ADACEL can be used to boost immunity to diphtheria, tetanus and pertussis at 5- to 10-year intervals. ADACEL may be administered to pregnant women during the second and third trimester to provide passive protection to infants against pertussis.	Drug: Adacel (Tdap); Administer Adacel to hiv infected and hiv uninfected pregnant mothers
No Intervention: control; Infants born to unvaccinated mothers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of antibodies in pregnant women 1 month after vaccination with Tdap.	To measure antibody responses to all Tdap-IPV antigens (diphtheria, tetanus, PT, FHA, PRN, FIM and polioviruses 1, 2 and 3) in HIV-infected compared with HIV-uninfected pregnant women before and one month after Adacel vaccination.	24 months
Concentration of antibodies to all Tdap-IPV and Hexavalent antigens in infants.	To measure antibody responses to all Tdap-IPV and Hexavalent antigens (diphtheria, tetanus, PT, FHA, PRN, FIM, Haemophilus influenzae type-b polyribosyl ribitol phosphate [PRP], polioviruses 1, 2 and 3, and hepatitis B) testing in infants born to mothers who received Adacel during pregnancy and those born to mothers not vaccinated, stratified by maternal HIV status.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transplacental antibody transfer.	To compare the transplacental antibody transfer ratio of all Tdap-IPV antigens to newborns from HIV-infected mothers and those born to HIV-uninfected mothers vaccinated with Adacel during pregnancy.	24 months
Vaccination safety	Number of HIV-infected and HIV-uninfected pregnant women with treatment-related adverse events.	24 months

Collaborators and Investigators

• Sponsor: Shabir Madhi

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: March 2, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Pertussis; Antibodies
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Whooping Cough
• Other Study ID Numbers: Maternal Pertussis

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
• product manufactured in and exported from the U.S.: No