BACKGROUND: We 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Department of Paediatric Infectious Diseases Wroclaw Medical University 2 2A Chalubinskiego 50 368 Wroclaw Poland

Department of Pediatrics Centre of Postgraduate Medical Education ul Marymoncka 99 103 01 813 Warsaw Poland

Department of Pediatrics Rio Hortega University Hospital Calle Dulzaina 2 47012 Valladolid Spain

Department of Social Medicine Faculty of Medicine in Hradec Králové Charles University Prague Šimkova 870 500 38 Hradec Králové Czech Republic

GSK Av Fleming 20 1300 Wavre Belgium

Health Care Establishment in Debica Infectious Diseases Outpatient Clinic ul Krakowska 91 39 200 Debica Poland

Hospital de Antequera Avenida Poeta Muñoz Rojas s n 29200 Antequera Málaga Spain

Instituto Hispalense de Pediatría C Manuel Siurot 45 41013 Sevilla Spain

La Fe Hospital Avinguda de Fernando Abril Martorell 106 46026 Valencia Spain

Pediatric Department Burgos Universitary Hospital Avenida Islas Baleares s n 09006 Burgos Spain

Pediatric Office Dr Med Michael Horn Achenweg 1 83471 Schönau am Königssee Germany

Pediatric Office Dr Renata Ruzkova Kladenska 53 Medicentrum 6 s r o 160 00 Prague Czech Republic

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