Pediatrics · Medical Literature
Immunogenicity and safety of primary three-dose series with diphtheria, tetanus and pertussis (acellular, three components) combined vaccine, adsorbed in 3 months infants.
Abstract
This study aimed to evaluate the safety and immunogenicity of a novel diphtheria, tetanus, and pertussis (acellular, three components) combined vaccine, adsorbed (DTcP) vaccine compared to the existing co-purified DTaP vaccine in China. In this partially randomized, blinded, controlled Phase III trial, we assessed a DTcP vaccine against two controls: a licensed co-purified DTaP and a DTaP-IPV-Hib vaccine. A total of 1,140 infants (3 months old) received a 3-dose primary series at 3, 4, and 5 months. Both of DTcP and co-purified DTaP had lower incidences of overall adverse reactions than the DTaP-IPV-Hib vaccine (17.99%/18.08% vs. 21.96%). The DTcP vaccine demonstrated non-inferiority and superiority over the co-purified DTaP for anti-PT and anti-FHA immunogenicity. In addition, the DTcP achieved a 98.16% seroconversion rate for anti-FHA, versus only 14.29% for the co-purified DTaP. Besides, DTcP vaccine also induced high antibody level in GMC results. Specifically, the anti-PT GMC was 85.10 in the DTcP group versus 49.86 in the DTaP group (P < 0.001) and 74.25 in the DTaP-IPV-Hib (P = 0.001). For anti-FHA, the GMC was 108.28 in the DTcP group compared to only 10.69 in the DTaP group. In conclusion, DTcP vaccine induces a significantly more robust immune response to key pertussis antigens --compared to the co-purified DTaP, with a comparable safety profile. These data support the potential optimization of China's immunization strategy by transitioning from co-purified to component-based acellular pertussis vaccines to address waning immunity and the ongoing pertussis resurgence. ClinicalTrial.gov, identifier NCT05951725.
Clinical relevance
Pertussis resurgence remains a critical public health concern, particularly in infants under 6 months who bear the highest morbidity and mortality burden. China's immunization program currently relies on co-purified DTaP vaccines, which may offer suboptimal antigen-specific immunogenicity compared to component-based acellular formulations. This Phase III trial directly addresses whether transitioning to a three-component acellular DTcP vaccine could meaningfully improve humoral immune responses to key pertussis antigens (PT and FHA) in the primary series schedule.
Key findings
1. In a partially randomized, blinded, controlled Phase III trial (NCT05951725), 1,140 three-month-old infants received a 3-dose primary series (at 3, 4, and 5 months) of either DTcP, co-purified DTaP, or DTaP-IPV-Hib. 2. The DTcP vaccine demonstrated non-inferiority AND superiority over the co-purified DTaP for both anti-PT and anti-FHA immunogenicity endpoints. 3. Anti-PT geometric mean concentration (GMC) was 85.10 in the DTcP group versus 49.86 in the co-purified DTaP group (P < 0.001) and 74.25 in the DTaP-IPV-Hib group (P = 0.001), indicating significantly stronger pertussis toxin-specific responses with DTcP. 4. Anti-FHA GMC was 108.28 in the DTcP group compared to only 10.69 in the co-purified DTaP group, representing an approximately 10-fold superiority in filamentous hemagglutinin-specific antibody levels. 5. Seroconversion rate for anti-FHA was 98.16% in the DTcP group versus only 14.29% in the co-purified DTaP group, a clinically striking difference in antigen-specific immunogenicity. 6. Overall adverse reaction incidences were lower for both DTcP (17.99%) and co-purified DTaP (18.08%) compared to DTaP-IPV-Hib (21.96%), supporting a comparable and favorable safety profile for the novel DTcP formulation.
Practice implications
Pediatric immunization programs in China and comparable settings should consider transitioning from co-purified DTaP to component-based acellular DTcP vaccines for the primary infant series (3–5 months), given the dramatically superior anti-PT and anti-FHA immunogenicity — particularly the near-universal anti-FHA seroconversion rate of 98.16% versus 14.29% — without an increase in adverse reactions. Clinicians and policymakers should recognize that the existing co-purified DTaP formulation may leave the majority of infants immunologically underprotected against FHA-mediated pertussis pathogenesis, which is especially consequential given ongoing global pertussis resurgence and waning immunity concerns. These Phase III data support regulatory and programmatic prioritization of the DTcP vaccine as a platform upgrade, pending longer-term follow-up data on durability of immune response and effectiveness against clinical pertussis disease.