Carmona Martinez, AlfonsoPrymula, RomanMiranda Valdivieso, MarianoOtero Reigada, Maria Del CarmenMerino Arribas, Jose ManuelBrzostek, JerzySzenborn, LeszekRuzkova, RenataHorn, Michael RJackowska, TeresaCenteno-Malfaz, FernandoTraskine, MagaliDobbelaere, KurtBorys, Dorota2023-01-252023-01-252018-07-24http://hdl.handle.net/10668/12767We assessed 2 investigational 11- and 12-valent vaccines, containing capsular polysaccharides of 10 serotypes as in the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and CRM197-conjugated capsular polysaccharides of serotypes 19A (11-valent) or 19A and 6A (12-valent). In this phase II, partially-blind, multicentre study (NCT01204658), healthy infants were randomised (1:1:1:1) to receive 11vPHiD-CV, 12vPHiD-CV, PHiD-CV, or 13-valent CRM197-conjugate pneumococcal vaccine (PCV13), at 2, 3, and 4 (primary series), and 12-15 months of age (booster dose), co-administered with DTPa-HBV-IPV/Hib. Confirmatory objectives assessed non-inferiority of investigational vaccines to comparators (PHiD-CV for common serotypes; PCV13 for 19A and 6A), in terms of percentage of infants with pneumococcal antibody concentrations ≥0.2 μg/mL and antibody geometric mean concentrations, post-primary vaccination. Reactogenicity and safety were assessed. 951 children received ≥1 primary dose, 919 a booster dose. Pre-defined immunological non-inferiority criteria were met simultaneously for 9/11 11vPHiD-CV serotypes (all except 23F and 19A) and 10/12 12vPHiD-CV serotypes (all except 19A and 6A); thus, non-inferiority objectives were reached. For each PHiD-CV serotype, percentages of children with antibody concentrations ≥0.2 µg/mL were ≥96.7% post-primary (except 6B [≥75.2%] and 23F [≥81.1%]), and ≥98.1% post-booster vaccination. For each PHiD-CV serotype except serotype 1, ≥81.0% and ≥93.9% of children had opsonophagocytic activity titres ≥8, post-primary and booster vaccination. AEs incidence was similar across all groups. SAEs were reported for 117 children (29 in the 11vPHiD-CV group, 26 in the 12vPHiD-CV group, 38 in the PHiD-CV group and 24 in the PCV13 group); 4 SAEs were considered vaccination-related. No fatal events were recorded. Addition of 19A and 6A CRM197-conjugates did not alter immunogenicity of the PHiD-CV conjugates; for both investigational vaccines post-booster immune responses to 10 common serotypes appeared similar to those elicited by PHiD-CV. Safety and reactogenicity profiles of the investigational vaccines were comparable to PHiD-CV. Clinical trial registry: NCT01204658.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/ImmunogenicityInfants/childrenNon-inferiorityPHiD-CVPneumococcal conjugate vaccineSafetyAntibodies, BacterialBacterial ProteinsCarrier ProteinsDiphtheria-Tetanus-Pertussis VaccineFemaleHaemophilus influenzaeHepatitis B VaccinesHumansImmunization, SecondaryImmunogenicity, VaccineImmunoglobulin DInfantLipoproteinsMalePneumococcal InfectionsPneumococcal VaccinesPoliovirus Vaccine, InactivatedSerogroupStreptococcus pneumoniaeVaccines, CombinedVaccines, Conjugateresearch article30054160open access10.1016/j.vaccine.2018.07.0231873-2518https://doi.org/10.1016/j.vaccine.2018.07.023