SAFETY AND IMMUNOGENICITY OF HEPTAVALENT PNEUMOCOCCAL VACCINE CONJUGATED TO CRM19(7) IN UNITED-STATES INFANTS

Objective. To determine the safety and immunogenicity of heptavalent p neumococcal saccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F ) individually conjugated to CRM197 (PNCRM7), administered at 2, 4, 6, and 12 to 15 months of age. Design. Two hundred twelve healthy 2-mont h-old infants were equally randomized to receive four consecutive dose s of PNCRM7 or an investigational meningococcal group C conjugate vacc ine, which served as a control. Concomitantly administered routine vac cines were oral polio vaccine and combined diphtheria toroid, tetanus toroid, and whole cell pertussis vaccine/Haemophilus influenzae type b vaccine consisting of capsular oligosaccharides conjugated to CRM197 (DTP/HbOC) at 2, 4, and 6 months, and either measles-mumps-rubella vac cine or HbOC at 12 to 15 months. Active safety surveillance was conduc ted for 3 days after each dose. Antibody concentrations to each of the 7 pneumococcal serotypes were measured by enzyme-linked immunosorbent assay prevaccination, after doses two and three, prebooster, and post booster. Results. Significantly fewer children experienced local react ions at the PNCRM7 injection site than at the DTP/HbOC site. There was no increase in the incidence or severity of local reactions at the PN CRM7 site with increasing doses of vaccine, Mild to moderate postvacci nation fever was common in both the PNCRM7 and control vaccine groups, however DTP/HbOC was administered concurrently. All 7 vaccine serotyp es were immunogenic. The kinetics of the immune responses were serotyp e-specific. After three doses of PNCRM7, between 92% to 100% of childr en had greater than or equal to 0.15 mu g/mL of antibody, and 51% to 9 0% achieved a level of greater than or equal to 1 mu g/mL against spec ific serotypes. A booster dose of PNCRM7 resulted in a brisk anamnesti c response to all 7 vaccine serotypes, demonstrating effective stimula tion of T-cell memory by the primary series of vaccinations. Conclusio n. Primary immunization followed by a booster dose of PNCRM7 seemed to be acceptably safe and resulted in significant rises in antibody to a ll 7 serotypes. Implications. Studies to assess vaccine efficacy of PN CRM7 for prevention of systemic disease, nasopharyngeal colonization, and acute otitis media are in progress. If PNCRM7 proves to be protect ive, there is the potential to prevent up to 85% of invasive pneumococ cal disease occurring in US children.