Immunogenicity and safety of 11-and 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccines (11vPHiD-CV, 12vPHiD-CV) in infants: Results from a phase II, randomised, multicentre study
Abstrakt
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 CRIA(197)-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 mu g/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 AgirnL 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. (C) 2018 The Authors. Published by Elsevier Ltd.
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