Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM197 among infants with sickle cell disease

Objectives. To determine the immunogenicity and safety of heptavalent pneum ococcal polysaccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to CRM197 (7-valent conjugate pneumococcal vaccine [7VPnC]) amo ng infants with sickle cell disease (SCD) and a comparison group of infants without SCD (non-SCD). Design. Two cohorts of infants were enrolled and received open-label doses of 7VPnC vaccine; infants enrolled before 2 months of age received 7VPnC va ccine at 2, 4, and 6 months of age followed by 23-valent pneumococcal polys accharide vaccine (PS-23) at 24 months of age for those infants with SCD (s chedule A), and infants enrolled between 2 and 12 months of age received 7V PnC at 12 months of age followed by PS-23 at 24 months of age for infants w ith SCD (schedule B). Safety data were collected for 3 days after each dose of vaccine. Antibody concentrations were measured to each of the 7VPnC ser otypes by enzyme-linked immunosorbent assay before each vaccine dose and 1 month after the last 7VPnC dose and the PS-23 vaccine dose. Results. Forty-five infants (34 SCD and 11 non-SCD) were vaccinated accordi ng to schedule A and 16 infants (13 SCD and 3 non-SCD) according to schedul e B. The 7VPnC vaccine was highly immunogenic for all serotypes among: infa nts with and without SCD who received 3 doses of vaccine according to sched ule A: depending on serotype, 89% to 100% achieved antibody concentrations above .15 mug/mL and 56% to 100% achieved antibody concentrations above 1.0 mug/mL. Among infants immunized according to schedule B, a single dose of 7VPnC vaccine resulted in antibody concentrations above .15 mug/mL in 53% t o 92% by serotype and above 1.0 mug/mL in 31% to 71% by serotype. A single dose of PS-23 resulted in dramatic increases in the antibody concentrations to all serotypes regardless of 1- or 9-dose priming. There was no differen ce in the reactogenicity of the 7VPnC vaccine between those with and withou t SCD. There were no serious reactions to the 7VPnC or PS-23 vaccines, even among those with high antibody concentrations before immunization. Conclusions. Infants with SCD respond to 7VPnC vaccine with antibody concen trations that are at least as high as infants without SCD. Infants immunize d with 7VPnC vaccine at 2, 4, and 6 months of age developed antibody concen trations in the same range as those achieved among infants without SCD enro lled in a large trial that demonstrated vaccine efficacy against invasive d isease. Significant rises were seen in antibody concentrations to all 7VPnC serotypes after the PS-23 booster in children receiving: schedule A or B.