Safety and immunogenicity of SIIPL Tdap, a new tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, in healthy subjects 4–65 years of age: A Phase II/III randomized, observer-blinded, active controlled, multicenter clinical study in Germany

• Published in: Vaccine Vol. 41; no. 46; pp. 6810 - 6819
• Main Authors: Aydin, Inci, May, Marcus, Pisano, Fabio, Mpofu-Maetzig, Nontsikelelo, Grode, Leander, Parekh, Sameer, Pujari, Pramod, Shewale, Sunil, Desai, Shivani, Sharma, Hitt, Rao, Harish, Gautam, Manish, Gairola, Sunil, Shaligram, Umesh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 02.11.2023; Elsevier Limited
• Subjects: Acellular pertussis; Active control; Adolescent; Adult; Age; Aged; Allergy and Immunology; Antibodies; Antibodies, Bacterial - blood; Antigens; blood serum; Booster; Child; Child, Preschool; Comparators; Diphtheria; Diphtheria - immunology; Diphtheria - prevention & control; Diphtheria Toxoid - administration & dosage; Diphtheria Toxoid - adverse effects; Diphtheria Toxoid - immunology; Diphtheria-Tetanus-acellular Pertussis Vaccines - administration & dosage; Diphtheria-Tetanus-acellular Pertussis Vaccines - adverse effects; Diphtheria-Tetanus-acellular Pertussis Vaccines - immunology; Diphtheria-Tetanus-Pertussis Vaccine; Female; Germany; Guardians; Healthy Volunteers; Hemagglutinins; Humans; Immunization, Secondary - methods; Immunogenicity; Immunogenicity, Vaccine; India; Informed consent; Laboratories; Male; Middle Aged; Pertussis; pertussis toxin; Safety; secondary immunization; seroprevalence; Teenagers; Tetanus; Tetanus - immunology; Tetanus - prevention & control; Tetanus Toxoid - administration & dosage; Tetanus Toxoid - adverse effects; Tetanus Toxoid - immunology; Vaccination - methods; Vaccine; Vaccines; Whooping cough; Whooping Cough - immunology; Whooping Cough - prevention & control; Young Adult; Young adults; Germany; Belgium; United States > US; India; TT; DTP; LLOQ; DSMB; PT; SAS; IWRS; NALB; PRN; aP; COVID-19; DT; Td; ANCOVA; SARS-CoV-2; EMA; Tdap; GMC; SIIPL; Acellular pertussis; WHO; EEA; AE; MIA; CI; Booster; Vaccine; WMA; Diphtheria; IU; US FDA; IMP; ICH; EU; SAE; ICP; FAS; wP; Tetanus; FHA; DTaP; full analysis set; geometric mean concentration; Interactive Vice/Web Response System; tetanus and diphtheria; diphtheria toxoid; diphtheria tetanus pertussis; immune correlate of protection; Serum Institute of India Pvt. Ltd; multiplex immunoassay; International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use; lower limit of quantification; National Accreditation Board for Testing and Calibration Laboratories; tetanus, diphtheria and pertussis; tetanus toxoid; United States Food and Drug Administration; serious adverse events; international units; World Health Organization; World Medical Association; pertussis toxoid; coronavirus disease 2019; filamentous hemagglutinin; investigational medicinal product; analysis of covariance; tetanus, diphtheria, acellular pertussis; safety analysis set; Data Safety Monitoring Board; pertactin; adverse events; European Economic Area; European Union; confidence interval; severe Acute respiratory syndrome coronavirus 2; whole cell pertussis; European Medicines Agency
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2023.09.060

•To avoid a global pertussis resurgence, booster Tdap immunization is recommended.•Global shortages of acellular pertussis vaccines have been reported.•Safety and immunogenicity of SIIPL Tdap was compared to an approved Tdap vaccine.•SIIPL Tdap immune responses were non-inferior to comparator Tdap vaccine.•SIIPL Tdap was safe and well tolerated. This study assessed the safety and immunogenicity of a new booster vaccine against tetanus, diphtheria, and pertussis manufactured by Serum Institute of India Pvt. Ltd (SIIPL Tdap). The Phase II/III trial was randomized (2:1), observer blinded and active controlled. Healthy subjects aged 4–65 years received a single dose of either SIIPL Tdap or comparator Tdap vaccine (Boostrix®, GlaxoSmithKline, Belgium), and were followed-up for 30 days. Blood samples for safety and immunogenicity assessments were collected pre-vaccination and on day 30 post-vaccination. The study assessed safety and reactogenicity of SIIPL Tdap compared to the comparator Tdap as well as the co-primary immunogenicity outcomes: (i) seroprotection rates against diphtheria toxoid (DT) and tetanus toxoid (TT) and (ii) the booster response rates against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) 30 days post-vaccination in all study subjects. A margin of −10 % was used for non-inferiority testing. Secondary outcomes included the booster response rates against DT and TT, seropositivity rates against pertussis antigens, and antibody geometric mean concentrations (GMCs) for all vaccine components. At Day 30 post-vaccination, SIIPL Tdap was assessed as non-inferior to the comparator Tdap in terms of: i) seroprotection rates against DT (94.4 % vs. 94.9 %) and TT (99.9 % vs. 100 %) and ii) pertussis booster response rates (93.8 % vs. 88.4 % anti-PT, 89.7 % vs. 90.9 % anti-FHA and 86.3 % vs. 84.4 % anti-PRN), for SIIPL Tdap versus comparator Tdap, respectively. GMCs for anti-PT and anti-PRN were higher in subjects vaccinated with SIIPL Tdap compared to comparator Tdap. All other secondary outcomes were comparable. The overall frequency of local and systemic solicited AEs was comparable; no treatment related SAEs were reported. Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to the immunogenicity of the vaccine components and was equally well tolerated. EudraCT number: 2019-002706-46.