A randomized study comparing the safety and immunogenicity of a conjugate vaccine combination containing meningococcal group C and pneumococcal capsular polysaccharide--CRM197 with a meningococcal group C conjugate vaccine in healthy infants: challenge phase.

BACKGROUND: A combination nonavalent pneumococcal-group C meningococcal conjugate vaccine (Pnc9-MenC) was previously found to be safe and immunogenic when administered to infants at 2, 3 and 4 months. This study describes the persistence of immunity at 12 months of age and the immunologic response to a challenge dose of either meningococcal polysaccharide vaccine (Meningivac A+C; MnA+C), or MenC. METHODS: A phase II, randomized, controlled trial of healthy infants. Subjects were given Pnc9-MenC or MenC vaccine at 2, 3 and 4 months of age and then challenged with either MenC or MnA+C. Group C meningococcal immunogenicity was measured by serum bactericidal assay (SBA) and an enzyme-linked immunosorbent assay (ELISA) adapted to measure antibody avidity pre- and post-challenge. RESULTS: The MenC vaccine was more immunogenic than the Pnc9-MenC vaccine in persistence of serogroup C meningococcal polysaccharide antibodies at 12 months of age. Post-challenge at 13 months there were significant differences between the four groups in the induction of serogroup C meningococcal polysaccharide antibodies. The responses to MenC/MenC were significantly higher than in the other groups (p<0.001) and the responses to Pnc9-MenC/MnA+C were significantly lower than in the other groups (p<0.001). There was no difference between the four groups in the proportions with geometric mean concentrations (GMC) greater than 2 microg/ml (p=0.18) or with SBA titres greater than or equal to the protective level of 1:8 (p=0.89). The SBA geometric mean ratio (GMR) between pre- and post-challenge was higher in the groups challenged with MenC than those challenged with MnA+C. Antibody avidity increased over time. CONCLUSION: We have shown that Pnc9-MenC primes effectively for immunological memory. At 13 months of age the highest immune responses were seen in the subjects primed and challenged with MenC alone. However, all groups achieved the threshold levels required for protection.