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.