Immunogenicity and safety of a 2 + 1 schedule of the DTaP-IPV-HB-Hib hexavalent combination vaccine in preterm infants in Spain.

Preterm infants are at higher risk of mortality, disabilities, and infections. Hexavalent DTaP-IPV-HB-Hib vaccines against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type b are standards of care in pediatric immunization. Evidence on the use of these vaccines in preterm infants remains limited, particularly in extreme preterms. This open-label, multicenter, non-randomized phase IV trial conducted in Spain evaluated the immunogenicity and safety of a 2 + 1 schedule of the DTaP-IPV-HB-Hib vaccine in preterm infants (stratified by gestational age: 24-27, 28-30, 31-33, 34-36 weeks). Immunogenicity was described using seroprotection/vaccine response (VR) rates. Safety was described using solicited and unsolicited adverse events (AEs). A total of 143 infants received at least one vaccination (22 born at 24-27 weeks of gestation, 29 at 28-30 weeks, 38 at 31-33 weeks, and 54 at 34-36 weeks), 135 received three doses, and 132 completed the study. Post-dose 3 seroprotection rates were 100% against diphtheria (≥0.1 UI/mL), tetanus (≥0.1 UI/mL), and polio type 1/2/3 (≥8/dil), 94.5% against hepatitis B (≥10 mIU/mL), and 92.3% against polyribosylribitol phosphate (≥1 µg/mL). VR rates against pertussis toxoid and filamentous hemagglutinin were 94.1% and 76.5%, respectively. Within 7 days post-vaccination, 51.0% of participants experienced solicited AE related to vaccination, 0.7% reporting Grade 3 AEs. Within 30 days post-vaccination, 9.8% of infants had unsolicited related AEs (none of Grade 3). No serious AEs considered related were reported. This study demonstrated that a 2 + 1 schedule of the hexavalent DTaP-IPV-HB-Hib vaccine is immunogenic and well tolerated in preterm infants.Trial registration: EudraCT Number: 2018-004581-34.