Coadministered PCV15, DTaP Show No Immunogenicity Interference in Infants

Researchers in Hebei Province, China, conducted a single-center, open-label, active-controlled, randomized phase 3 trial to evaluate the mutual effects on safety and immunogenicity of combined vaccination with 15-valent pneumococcal conjugate vaccine (PCV15) and adsorbed acellular diphtheria-tetanus-pertussis vaccine (DTaP) in healthy 3-month-old infants.¹

The trial enrolled 1110 infants aged 90 to 119 days, randomly assigned in equal numbers to 3 groups: coadministration of PCV15 and DTaP at different injection sites (P+DTP group), PCV15 followed by DTaP after a 7-day interval (P-DTP group), or DTaP alone (DTP group).¹

All 3 groups received vaccination according to a 3-dose schedule at 0, 1, and 2 months. PCV15, manufactured by Beijing Zhifei Lvzhu Biopharmaceutical Co Ltd, was injected in the anterior outer thigh, and DTaP, manufactured by the Wuhan Institute of Biological Products, was injected in the deltoid muscle.¹

Blood samples were collected before the first dose and 30 days after completion of the full immunization series to measure antibody titers for diphtheria (anti-DT), tetanus (anti-TT), pertussis toxin (anti-PT), and pertussis filamentous hemagglutinin (anti-FHA), along with IgG antibodies against all 15 pneumococcal serotypes. Of the 1110 enrolled infants, 1084 completed the study.¹

Coadministration Did Not Compromise DTaP Response, but Interval Dosing Did

The primary study hypothesis required that seroconversion rates for anti-DT, anti-TT, anti-PT, and anti-FHA in the P+DTP and P-DTP groups be noninferior to the DTP-alone group, using a noninferiority margin of −10%. In the P+DTP group, all 4 DTaP component antibodies met noninferiority criteria compared with DTaP given alone.¹

The P-DTP group told a different story. Although seroconversion rates for anti-DT and anti-TT were noninferior to the DTP group, seroconversion rates for anti-PT and anti-FHA did not meet the noninferiority criteria set in the study. The difference in anti-PT seroconversion rates between the P-DTP and DTP groups was −9.89% (95% CI, −16.10% to −4.72%), a statistically significant reduction.¹

The study authors noted this finding contrasted with prior research on PCV13 coadministered with DTP, which found no interference with the immune response to diphtheria, tetanus, pertussis toxin, and filamentous hemagglutinin antigens. They proposed that the longer interval between first blood collection and completion of the P-DTP group's 6-dose vaccination course, along with independent immune induction by the diphtheria toxoid carrier protein in PCV15, may explain the divergent finding.¹

For the pneumococcal antibody response itself, positive rates for 14 of 15 serotypes in both the P+DTP and P-DTP groups exceeded 90%, with the exception of serotype 3 in the P-DTP group (89.88%). Differences in seroconversion rates between the P+DTP and P-DTP groups were not statistically significant except for serotypes 5, 6A, 6B, 9V, 12F, and 23F.¹

Safety Profile Considered Acceptable Despite Higher Adverse Event Rates

Total adverse event (TEAE) incidence was 62.67% in the P+DTP group, 72.16% in the P-DTP group, and 56.91% in the DTP-alone group. The most common systemic and local adverse events were fever and induration. Investigators noted that because the P-DTP group received 6 total doses across its separated schedule, compared with 3 doses in the other groups, it had twice as many safety follow-up time points, which they said made its higher adverse event rate expected.¹

Serious adverse events (SAEs) occurred in 7.63% of the P+DTP group, 4.86% of the P-DTP group, and 8.13% of the DTP group, a difference that was not statistically significant. All SAEs were judged unrelated to vaccination. The study authors concluded that coadministration of PCV15 and DTaP "can be regarded as having a favorable safety profile."¹

Pneumococcal Disease Burden and Prior PCV15 Evidence

The trial's rationale rests on a well-documented disease burden. Pneumococcal infections cause more than 1.2 million deaths annually worldwide, with young children among the most disproportionately affected, particularly in low- and middle-income countries.¹

A retrospective US claims analysis covering 1998 to 2019 similarly found that infants aged 0 to 6 months carried the highest incidence of invasive pneumococcal disease and inpatient all-cause pneumonia among children up to 48 months old, even as overall incidence rates declined substantially following the introduction of conjugate vaccines.²

A separate systematic review and meta-analysis of 20 randomized controlled trials found that PCV15 produced immune responses non-inferior to the 13-valent pneumococcal conjugate vaccine (PCV13) for shared serotypes in both infants and adults, with comparable safety profiles in children and a slightly higher rate of adverse events—driven mainly by local injection-site reactions—in adults. That review did not identify any trials examining PCV15 coadministered specifically with DTaP in infants, underscoring the novelty of the Hebei Province trial's design.³

For older adults, the CDC's Advisory Committee on Immunization Practices GRADE evidence review supporting PCV15 use in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults 65 years and older similarly found immune responses from PCV15 plus PPSV23 that were generally comparable to or higher than PCV13 plus PPSV23, with no vaccine-related serious adverse events reported across the 3 trials reviewed.⁴

For pharmacists administering or counseling on pediatric immunizations, the trial's findings speak directly to a common practical question: whether pneumococcal and DTaP vaccines can be given at the same visit without compromising protection. The study data support coadministration at separate injection sites as the preferred approach over a staggered 7-day interval, since the interval schedule was associated with reduced pertussis antibody responses.¹

The Children's Hospital of Philadelphia's Vaccine Education Center notes that infants are recommended to receive 4 doses of the pneumococcal vaccine and that combination scheduling generally supports treatment adherence and completion of the recommended immunization series.⁵

Limitations

The study authors acknowledged several limitations, including the absence of a PCV15-alone control group, which limits assessment of coadministration's effect on PCV15 immunogenicity independent of the phase 3 immunogenicity data from a related trial of the same vaccine. The trial was also conducted at sites in only 2 counties in Hebei Province, limiting generalizability, and its open-label design—while mitigated through standardized procedures and objective laboratory endpoints—introduced potential for performance, detection, and reporting bias.¹

REFERENCES

1. Lu-Lu P, Hong-Ze M, Zhao G, et al. The mutual effects on safety and immunogenicity of combined vaccination with 15-valent pneumococcal conjugate vaccine and adsorbed acellular DPT in 3-month healthy infants: A randomized, open-label, controlled, phase III clinical trial. Hum Vaccin Immunother. 2026;22(1):2654914. doi:10.1080/21645515.2026.2654914

2. Mohanty S, Done N, Liu Q, et al. Incidence of pneumococcal disease in children ≤48 months old in the United States: 1998-2019. Vaccine. 2024;42(11):2758-2769. doi:10.1016/j.vaccine.2024.03.013

3. Wagner G, Gartlehner G, Thaler K, et al. Immunogenicity and safety of the 15-valent pneumococcal conjugate vaccine, a systematic review and meta-analysis. NPJ Vaccines. 2024;9(1):257. Published 2024 Dec 30. doi:10.1038/s41541-024-01048-y

4. Centers for Disease Control and Prevention. GRADE: 15-valent pneumococcal conjugate vaccine (PCV15) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥65 years. ACIP. Updated September 9, 2024. Accessed August 11, 2026. https://www.cdc.gov/acip/grade/pneumo-PCV15-PPSV23-age-based.html

5. Children's Hospital of Philadelphia. Pneumococcus: the disease & vaccines. Vaccine Education Center. Reviewed November 4, 2025. Accessed August 11, 2026. https://www.chop.edu/vaccine-education-center/vaccine-details/pneumococcal-vaccine