title: Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM(197) among infants with sickle cell disease. Pneumococcal Conjugate Vaccine Study Group.
abstract: OBJECTIVE
  To determine the immunogenicity and safety of heptavalent pneumococcal polysaccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to CRM(197) (7-valent conjugate pneumococcal vaccine [7VPnC]) among infants with sickle cell disease (SCD) and a comparison group of infants without SCD (non-SCD).
  
  
  METHODS
  Two cohorts of infants were enrolled and received open-label doses of 7VPnC vaccine; infants enrolled before 2 months of age received 7VPnC vaccine at 2, 4, and 6 months of age followed by 23-valent pneumococcal polysaccharide vaccine (PS-23) at 24 months of age for those infants with SCD (schedule A), and infants enrolled between 2 and 12 months of age received 7VPnC at 12 months of age followed by PS-23 at 24 months of age for infants with SCD (schedule B). Safety data were collected for 3 days after each dose of vaccine. Antibody concentrations were measured to each of the 7VPnC serotypes 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 according to schedule A and 16 infants (13 SCD and 3 non-SCD) according to schedule B. The 7VPnC vaccine was highly immunogenic for all serotypes among infants with and without SCD who received 3 doses of vaccine according to schedule A: depending on serotype, 89% to 100% achieved antibody concentrations above.15 microg/mL and 56% to 100% achieved antibody concentrations above 1.0 microg/mL. Among infants immunized according to schedule B, a single dose of 7VPnC vaccine resulted in antibody concentrations above.15 microg/mL in 53% to 92% by serotype and above 1.0 microg/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 3-dose priming. There was no difference in the reactogenicity of the 7VPnC vaccine between those with and without 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 concentrations that are at least as high as infants without SCD. Infants immunized with 7VPnC vaccine at 2, 4, and 6 months of age developed antibody concentrations in the same range as those achieved among infants without SCD enrolled in a large trial that demonstrated vaccine efficacy against invasive disease. Significant rises were seen in antibody concentrations to all 7VPnC serotypes after the PS-23 booster in children receiving schedule A or B.
authors.affiliation: Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland, 21205, USA. klobrien@jhsph.edu
authors.forename: K L
authors.initials: KL
authors.lastname: O'Brien
authors.forename: A J
authors.initials: AJ
authors.lastname: Swift
authors.forename: J A
authors.initials: JA
authors.lastname: Winkelstein
authors.forename: M
authors.initials: M
authors.lastname: Santosham
authors.forename: B
authors.initials: B
authors.lastname: Stover
authors.forename: R
authors.initials: R
authors.lastname: Luddy
authors.forename: J E
authors.initials: JE
authors.lastname: Gootenberg
authors.forename: J T
authors.initials: JT
authors.lastname: Nold
authors.forename: A
authors.initials: A
authors.lastname: Eskenazi
authors.forename: S J
authors.initials: SJ
authors.lastname: Snader
authors.forename: H M
authors.initials: HM
authors.lastname: Lederman
mesh_terms: D000755:Anemia, Sickle Cell / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D002675:Child, Preschool; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods; D007223:Infant; D008297:Male; D015337:Multicenter Studies as Topic; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000517:prevention & control*; D012805:Sickle Cell Trait / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: C058384:CRM 107; D004167:Diphtheria Toxin; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate