Safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers

Objectives, The objectives of this study were (1) to determine the safety a nd immunogenicity of heptavalent pneumococcal CRM197 conjugate (PNCRM7) vac cine in infants and (2) to determine the effect of concurrent hepatitis B i mmunization during the primary series and the effect of concurrent diphther ia and tetanus toroid and acellular pertussis [DTaP (ACEL-IMUNE)] and conju gate CRM197 Haemophilus influenzae type b [HbOC (HibTITER) immunization at time of the booster dose on the safety and immunogenicity of PNCRM7 and the se other concurrently administered vaccines. Methods. This was a randomized double-blinded study in 302 healthy infants in the Northern California Kaiser Permanente (NCKP) Health Plan. Infants re ceived either PNCRM7 vaccine or meningococcal group C conjugate vaccine as a control at 2, 4 and 6 months of age and a booster at 12 to 15 months of a ge. Study design permitted the evaluation of immunology and safety of concu rrent administration of routine vaccines. Antibody titers were determined o n blood samples drawn before and 1 month after the primary series and the b ooster dose. Results. After the third dose of PNCRM7 geometric mean concentrations (GMCs ) ranged from 1.01 for serotype 9V to 3.72 mu g/ml for serotype 14. More th an 90% of all subjects had a post-third dose titer of greater than or equal to 0.15 mu g/ml for all serotypes, and the percentage of infants with a po st-third dose titer of greater than or equal to 1.0 mu g/ml ranged from 51% for type 9V to 89% for type 14. After the PNCRM7 booster dose, the GMCs of all seven serotypes increased significantly over both post-Dose 3 and pre- Dose 4 antibody levels. In the primary series there were no significant dif ferences in GMCs of pneumococcal antibodies between the subjects given PNCR M7 alone or concurrently with hepatitis B vaccine. At the toddler dose conc urrent administration of PNCRM7 and DTaP and HbOC resulted in a near conven tional threshold for statistical significance of a post-Dose 4 GMC for sero type 23F [alone 6.75 mu g/ml us. concurrent 4.11 mu g/ml (P = 0.057)] as we ll as significantly lower antibody GMCs for H. influenzae polyribosylribito l phosphate, diphtheria toroid, pertussis toxin and filamentous hemagglutin in. For all antigens there were no differences between study groups in defi ned antibody titers that are considered protective. Conclusion. We conclude that PNCRM7 vaccine was safe and immunogenic. When this vaccine was administered concurrently at the booster dose with DTaP an d HbOC vaccines, lower antibody titers were noted for some of the antigens when compared with the antibody response when PNCRM7 was given separately. Because the GMCs of the booster responses were all generally high and all s ubjects achieved similar percentages above predefined antibody titers, thes e differences are probably not clinically significant.