Safety and Immunogenicity of Diphtheria, Tetanus and Pertussis (Acellular, Three Components) Combined Vaccine, Adsorbed after three-dose priming in 2 Months Age Infants: A Randomized, Blinded, Controlled Phase III Clinical Trial in China

Pertussis remains a leading cause of infant mortality globally, with rising cases in China post-COVID-19. Despite vaccination, waning immunity from acellular pertussis vaccines has driven resurgence. We evaluated a novel diphtheria, tetanus and pertussis (acellular, three components) combined vaccine, adsorbed (DTcP), China's first genetically engineered three-component pertussis vaccine, administered under two primary schedules (2/3/4 vs. 2/4/6 months) compared to licensed DTaP-IPV-Hib (Pentaxim). In this randomized, blinded, phase III clinical trial, 1380 healthy 2-month-old infants from Henan, China, received DTcP-1 (2/3/4 months) or DTcP-2 (2/4/6 months) or DTaP-IPV-Hib (2/3/4 months). The primary safety endpoints were the incidence of adverse reactions within 0∼30 days after primary vaccination. The primary immunogenicity endpoints were to evaluate the non-inferiority and superiority of seroconversion rates and geometric mean concentrations (GMCs) of anti-pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), tetanus toxoid (TT), antibodies 30 days after primary vaccination. Immunogenicity was assessed via Luminex-based multiplex immunoassay. Both DTcP-1 and DTcP-2 schedules demonstrated non-inferior safety to DTaP-IPV-Hib (total adverse reactions: 14.52/16.59% vs. 16.91%, P = 0.183), with DTcP-2 (2/4/6 months) showing lower swelling (2.59% vs. 4.83%, P = 0.008) and irritability (0.07% vs. 1.02/1.40%, P < 0.001). DTcP-2 elicited higher GMCs against pertussis antigens (PT: 84.23 vs. 65.35; FHA: 132.16 vs. 102.13, both P < 0.001) and comparable DT/TT responses. DTcP exhibited favorable safety and superior pertussis immunogenicity, particularly with the 2/4/6-month schedule. Its genetically engineered three-component design offers a promising strategy to combat pertussis amid global resurgence.