Phase III Infant Trial Supports DTcP Immunogenicity

Key Takeaways

• In a 3-arm, Phase III comparison, 1,140 healthy infants aged 90 to 119 days were enrolled; DTcP and co-purified DTaP were randomized 1:1, the DTaP-IPV-Hib comparator arm was open-label and nonrandomized, and all vaccines were given at 3, 4, and 5 months.
• DTcP was reported to meet non-inferiority across evaluated antigens versus co-purified DTaP and to show superiority for anti-PT and anti-FHA, with the clearest separation seen in anti-FHA seroconversion at 98.16% versus 14.29%.
• Short-term safety appeared similar between DTcP and co-purified DTaP, with overall adverse reaction rates of 17.99% and 18.08%, respectively, compared with 21.96% for DTaP-IPV-Hib; no vaccine-related serious adverse events were reported within 30 days after primary vaccination.

After a 3-dose primary series in 1,140 infants, DTcP produced a much stronger anti-FHA response than co-purified DTaP, with seroconversion rates of 98.16% versus 14.29%, while overall adverse reaction rates were similar between those 2 vaccines. In the Phase III DTcP infant trial, healthy infants aged 90 to 119 days in Henan Province, China, received DTcP, co-purified DTaP, or DTaP-IPV-Hib on a 3-, 4-, and 5-month schedule in a partially randomized, partially blinded, controlled design with a nonrandomized open-label DTaP-IPV-Hib arm. DTcP was reported to be non-inferior overall and superior to co-purified DTaP for anti-PT and anti-FHA, while PT and FHA comparisons with DTaP-IPV-Hib met non-inferiority but not superiority.

Healthy infants aged 90 to 119 days received vaccinations at 3, 4, and 5 months; DTcP and co-purified DTaP were randomized 1:1 by block randomization, and the DTaP-IPV-Hib arm was open-label and nonrandomized. The primary immunogenicity endpoints were seroconversion rates and geometric mean concentrations for PT, FHA, PRN, DT, and TT antibodies 30 days after the primary series, with adverse reactions assessed over the same 30-day window. Prespecified non-inferiority margins were -10% for seroconversion-rate difference and 0.67 for geometric mean concentration ratio. Near-universal postvaccination responses to diphtheria and tetanus antigens were reported across groups.

The main immunogenicity pattern favored DTcP over co-purified DTaP, with stronger PT, FHA, and PRN responses across seroconversion, geometric mean concentration, and geometric mean increase measures. For superiority versus co-purified DTaP, the anti-PT seroconversion-rate difference was 2.94% (95% CI 0.49 to 5.39) with a GMC ratio of 1.71 (1.57 to 1.86), and the anti-FHA seroconversion-rate difference was 83.87% (95% CI 79.86 to 87.89) with a GMC ratio of 10.13 (9.23 to 11.12). Anti-PT GMCs were 85.10 with DTcP, 49.86 with co-purified DTaP, and 74.25 with DTaP-IPV-Hib; PRN was not part of the DTaP-IPV-Hib comparison because that vaccine did not contain PRN antigen. These findings reflected immunogenicity readouts 30 days after the primary series rather than direct measures of pertussis prevention or durability.

Within the same 30-day postvaccination window, fever was reported more often with DTaP-IPV-Hib than with DTcP, cough was less common with DTcP than with co-purified DTaP, swelling was more common with DTcP than with co-purified DTaP, and erythema was less common with DTcP than with co-purified DTaP. No vaccine-related serious adverse events were reported. The trial was conducted in a single province and did not assess longer-term antibody persistence, booster responses, or clinical effectiveness against pertussis disease.

Clinician Questions

How did DTcP compare with co-purified DTaP for anti-FHA responses in 3-month-old infants?

Thirty days after a 3-dose primary series in healthy infants aged 90 to 119 days, anti-FHA seroconversion was 98.16% with DTcP versus 14.29% with co-purified DTaP. The reported superiority metrics were a seroconversion-rate difference of 83.87% with 95% CI 79.86 to 87.89 and a GMC ratio of 10.13 with 95% CI 9.23 to 11.12.

What was the trial design for the Phase III DTcP infant vaccine comparison in Henan Province?

The trial was partially randomized, partially blinded, and controlled; 1,140 healthy infants aged 90 to 119 days were enrolled; DTcP and co-purified DTaP were randomized 1:1 by block randomization; the DTaP-IPV-Hib arm was nonrandomized and open-label; and vaccines were given at 3, 4, and 5 months with immunogenicity and adverse reactions assessed 30 days after the primary series.

Were short-term adverse reactions with DTcP similar to co-purified DTaP and DTaP-IPV-Hib in infants?

Overall adverse reaction rates were 17.99% with DTcP, 18.08% with co-purified DTaP, and 21.96% with DTaP-IPV-Hib. Fever was more common with DTaP-IPV-Hib than DTcP, cough was lower with DTcP than co-purified DTaP, swelling was higher with DTcP than co-purified DTaP, erythema was lower with DTcP than co-purified DTaP, and no vaccine-related serious adverse events were reported within 30 days after primary vaccination.

Did DTcP outperform DTaP-IPV-Hib on pertussis antibody endpoints after the primary series?

DTcP met non-inferiority for PT and FHA versus DTaP-IPV-Hib but did not demonstrate superiority on those comparisons. Anti-PT GMC was 85.10 with DTcP versus 74.25 with DTaP-IPV-Hib, anti-FHA GMCs were 108.28 and 121.04 respectively, and PRN was not compared because the DTaP-IPV-Hib vaccine did not contain PRN antigen.