3-year Follow-up After a Single Dose Acellular Pertussis Vaccination

Mahidol University181 enrolled

Overview

In July 2015-November 2016, a phase II/III randomized, observer-blind,controlled study of two acellular Pertussis vaccines (aP standalone and TdaP combined vaccined) manufactured by BioNet-Asia Co., Ltd. (Bionet) and chemically-detoxified Adacel Tdap vaccine was conducted in Bangkok, Thailand in healthy subjects aged 12-17 years (Protocol No. TDA202; http://clinicaltrials.in.th;Study ID:TCTR20150703002). A total of 450 subjects were enrolled into the study at 2 study sites (Site No.1:Faculty of Medicine Siriraj Hospital; Site No.2:Vaccine Trial Centre (VTC), Faculty of Tropical Medicine, Mahidol University) with equal number of 225 subjects enrolled at each study site. During the study, the subjects had been randomized in a 1:1:1 ratio to received intramuscularly a booster dose (0.5 mL) of the study vaccines. This is further follow-up from TDA202 clinical trial, which was completed on 29 November 2016. Target population for this study is the group of subjects who had received one dose of one of the three study vaccines in the TDA202 trial at site VTC and who had completed the study follow-up at 1-year after vaccination (223 subjects). In this current study, the long-term persistence of pertussis antibodies induced by a booster dose of recombinant acellular Pertussis based vaccines (Pertagen and Boostagen) manufactured by Bionet will be evaluated and compared to the conventional chemically-detoxified Tdap vaccine (Adacel) at 3 years after previously immunized in the TDA202 study.

The study population will included all subjects who participated in the TDA202 study at the Vaccine Trial Centre (VTC), Faculty of Tropical Medicine, Mahidol University, Bangkok. The subjects who had received a single dose of one of the 3 study vaccines and completed 1-year follow-up visit at Day 336±28 during the TDA202 study will be called in for consent process at 3 years after vaccination based on Vaccination Date in TDA202 study within ±1 month window period. Subjects aged ≥ 18 years who have signed the written informed consent form or subjects aged \< 18 years who have signed the assent form with their parent/legal guardian's given written informed consent will be screened for general health status and those who fulfill all inclusion and exclusion criteria will be enrolled into the study. Once enrolled, blood sample (approximately 5 mL) will be taken from all subjects. After blood collection, vaccination with a licensed influenza vaccine will be offered to all subjects.Blood samples will be processed for serum separation and shipped to Bionet Human Serology Laboratory where immunogenicity testing (ELISA antibodies against tetanus (TT), diphtheria(DT), Pertussis Toxin (PT) and Filamentous hemagglutinin (FHA) and PT neutralizing antibody by Chinese Hamster Ovary (CHO cell assay) will be performed . ELISA testing to detect antibodies against tetanus, diphtheria, and pertussis antigens (PT and FHA) will be performed for all enrolled subjects while CHO cell assay to detect PT neutralizing antibody will be performed only in the same subset of 75 subjects (25 subjects in each vaccine group) who had been selected for PT neutralizing antibody assessment in the previous TDA202 study. The knowledge from this long-term 3-year antibody persistence study will provide supportive data to identify the best alternative acellular pertussis vaccines to conventional chemically-detoxified vaccines for controlling the resurgence of pertussis disease. Data management and statistical analysis will be performed by Center of Excellence for Biomedical and Public Health Informatics (BIOPHICS), Bangkok, Thailand.

Interventions

Pertagen (aP BioNet)BIOLOGICAL

Pertagen (aP BioNet) was produced with a recombinant B pertussis strain that was genetically inactivated by the introduction of mutations (Arg9Lys and Glu129Gly) in the ptx operon of the S1 gene. Each 0.5 mL dose of Pertagen (aP BioNet) contained 5 µg PTgen, 5 µg FHA, and 0.3 mg as aluminium cation. The study vaccine will be presented in a single-dose prefilled syringe. Each subject will be received one intramuscular injection in the non-dominant deltoid region.

Boostagen (TDaP BioNet)BIOLOGICAL

Boostagen (TDaP BioNet) was produced with a recombinant B pertussis strain that was genetically inactivated by the introduction of mutations (Arg9Lys and Glu129Gly) in the ptx operon of the S1 gene. Each 0.5 mL dose of Boostagen (TDaP BioNet) contained 5 µg PTgen, 5 µg FHA, and 0.3 mg as aluminium cation. TDaP dose additional contained at least 7.5 Lf tetanus toxoid and at least 2.0 Lf diphtheria toxoid. The study vaccine will be presented in a single-dose prefilled syringe. Each subject will be received one intramuscular injection in the non-dominant deltoid region.

AdacelBIOLOGICAL

Comparator vaccine, Adacel (Sanofi-Pasteur, North York, ON, Canada) was produced chemically inactivated pertussis toxin. Each 0.5 mL dose of Adacel (as comparator vaccine) contained 2.5 µg PTchem, 5 µg FHA, 3 µg pertactin, 5 µg fimbriae types 2 and 3, 5.0 Lf tetanus toxoid, 2.0 Lf diphtheria toxoid and 0.33 mg as aluminium cation. The study vaccine will be presented in a single-dose prefilled syringe. Each subject will be received one intramuscular injection in the non-dominant deltoid region.