Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant acellular Pertussis vaccine (TdaP) in healthy Thai adults.
An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP).



A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18-35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay.



A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (P< 0.05). The anti-PRN IgG, anti-tetanus and anti-diphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline.



In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed a similar tolerability and safety profile to Adacel® and elicited significantly higher immune responses to PT and FHA.
a Department of Tropical Pediatrics , Faculty of Tropical Medicine, Mahidol University , Bangkok , Thailand.
Chukiat
C
Sirivichayakul
a Department of Tropical Pediatrics , Faculty of Tropical Medicine, Mahidol University , Bangkok , Thailand.
Pornthep
P
Chanthavanich
a Department of Tropical Pediatrics , Faculty of Tropical Medicine, Mahidol University , Bangkok , Thailand.
Kriengsak
K
Limkittikul
b WHO Collaborating Center for Vaccine Immunology, Faculty of Medicine, University of Geneva , Geneva , Switzerland.
Claire-Anne
CA
Siegrist
c BioNet-Asia Co., Ltd., Prakanong , Bangkok , Thailand.
Wassana
W
Wijagkanalan
c BioNet-Asia Co., Ltd., Prakanong , Bangkok , Thailand.
Pailinrut
P
Chinwangso
c BioNet-Asia Co., Ltd., Prakanong , Bangkok , Thailand.
Jean
J
Petre
c BioNet-Asia Co., Ltd., Prakanong , Bangkok , Thailand.
Pham
P
Hong Thai
c BioNet-Asia Co., Ltd., Prakanong , Bangkok , Thailand.
Mukesh
M
Chauhan
c BioNet-Asia Co., Ltd., Prakanong , Bangkok , Thailand.
Simonetta
S
Viviani
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D002470:Cell Survival / Q000187:drug effects; D004165:Diphtheria / Q000517:prevention & control*; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D008297:Male; D009500:Neutralization Tests; D013742:Tetanus / Q000517:prevention & control*; D013785:Thailand; D014917:Whooping Cough / Q000517:prevention & control*; D055815:Young Adult
D000907:Antibodies, Bacterial; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D007074:Immunoglobulin G
TdaP; Thailand; clinical trial; phase I/II; recombinant acellular pertussis vaccine
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