Safety and immunogenicity of CRM197-conjugated pneumococcal–meningococcal C combination vaccine (9vPnC–MnCC) whether given in two or three primary doses

Abstract

This randomized trial compares safety and immunogenicity when vaccinating infants with a pneumococcal–meningococcal conjugate vaccine in two doses vs. three doses. Infants ( N = 223) received 9vPnC–MnCC (CRM197-conjugated pneumococcal serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F and meningococcal C polysaccharides) either at 3 and 5 or 3, 4 and 5 months and a booster with either 9vPnC–MnCC or 23-valent pneumococcal-polysaccharide vaccine (23vPPS) and CRM197-MnCC, at 12 months. Safety was monitored and IgG measured at 3, 6, 12 and 13 months in all subjects and serum bactericidal activity (SBA) in half. The 9vPnC–MnCC vaccine was safe and induced significant IgG to all components. Three doses induced higher antibody GMCs (geometric mean concentrations) at 6 months to seven of nine pneumococcal serotypes. This was most significant for 6B and 23F ( p < 0.001), that also showed lower rate of responders >0.35 (6B, 23F) and >0.5 μg/mL (6B). Antibody GMCs remained lower following 9vPnC–MnCC booster in subjects primed with two doses although only significant for serotype 18C. Significant memory responses were observed 1 week after the 23vPPS toddler dose. MnCC–IgG GMC was lower after two doses, however with comparable SBA. This study shows that the 9vPnC–MnCC vaccine is safe and induces successful immunological memory, whether given in two or three primary doses.