No long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine.

BACKGROUND: A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. OBJECTIVE: This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. METHODS: Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. RESULTS: Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. CONCLUSION: Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group.

Interaction of pneumococcal histidine triad proteins with human complement.

The pneumococcal histidine triad (Pht) proteins PhtA, PhtB, PhtD, and PhtE form a group of conserved pneumococcal surface proteins. Humans produce antibodies to Pht proteins upon exposure to pneumococcus, and immunization of mice has provided protective immunity against sepsis and pneumonia and reduced nasopharyngeal colonization. Pht proteins are candidates for inclusion in multicomponent pneumococcal protein vaccines. Their biological function in pneumococcal infections is not clear, but a role in complement inhibition has been suggested. We measured complement deposition on wild-type and Pht mutant strains in four genetic backgrounds: Streptococcus pneumoniae D39 (serotype 2) and R36A (unencapsulated derivative of D39) and strains of serotypes 3, 4, and 19F. PspA and PspC single and double mutants were compared to the wild-type and Pht-deficient D39 strains. Factor H binding was measured to bacterial cells, lysates, and protein antigens. Deletion of all four Pht proteins (Pht(-)) resulted in increased C3 deposition on the serotype 4 strain but not on the other strains. Pht antigens did not bind factor H, and deletion of Pht proteins did not affect factor H binding by bacterial lysates. The Pht(-) mutant serotype 4 strain bound slightly less factor H than the wild-type strain when binding was measured by flow cytometry. Pht proteins may play a role in immune evasion, but the mechanism of function is unlikely to be mediated by factor H binding. The relative contribution of Pht proteins to the inhibition of complement deposition is likely to be affected by the presence of other pneumococcal proteins and to depend on the genetic background.

Pneumococcal conjugate vaccine administration during therapy for pediatric leukemia.

BACKGROUND: Pediatric leukemia patients are at high risk of invasive pneumococcal disease. The study aim was to determine the antibody response to a 10-valent pneumococcal conjugate vaccine (PCV10) administered during chemotherapy. METHODS: An open-label study in pediatric leukemia patients: Group 1 had completed a primary 7-valent (PCV7) course and received a single PCV10 dose. Group 2 were PCV immunization naïve and received 3 doses of PCV10, administered 2 months apart. Serum samples were taken at baseline and 1 month post each PCV10 dose. Antipneumococcal serotype-specific IgG to 10 serotypes were measured by enzyme-linked immunosorbent assay and the functional response to 4 serotypes (1, 6B, 19F and 23F) was measured using opsonophagocytic assays. RESULTS: Thirty-nine participants were recruited between May 2010 and January 2011; group 1 (n = 27) and group 2 (n = 12). The diagnosis was acute lymphoblastic leukemia (38) and acute myeloid leukemia (1). Median age was 6.2 years (1.7-17.2 years) with 62% male. The median time from diagnosis to baseline serology was 7.4 months (1.6-36.8 months). At baseline, protective geometric mean concentration above the threshold (>0.35 µg/mL) ranged from 5.3% (serotype 4) to 71% (serotype 19F). More than 60% of participants in both groups were above threshold postimmunization for 7 of the 10 PCV serotypes. Opsonophagocytic assay correlated with enzyme-linked immunosorbent assay for 3 of the 4 serotypes and r ranged from 0.51 to 0.84. An injection-site reaction was reported in 73% (27/37). CONCLUSIONS: It is safe to administer PCV10 vaccine during therapy for pediatric leukemia. It provided a satisfactory serum immune response for the majority of vaccine serotypes.