Elsevier

The Journal of Pediatrics

Volume 157, Issue 5, November 2010, Pages 778-783.e1
The Journal of Pediatrics

Original Article
Serotype-Specific Hyporesponsiveness to Pneumococcal Conjugate Vaccine in Infants Carrying Pneumococcus at the Time of Vaccination

https://doi.org/10.1016/j.jpeds.2010.04.071Get rights and content

Objective

To determine whether pneumococcal carriage at the time of 11-valent pneumococcal conjugate vaccine (PCV-11) administration interferes with immune response in infants.

Study design

A total of 1111 Filipino infants recruited into an immunogenicity and carriage study, nested in an efficacy trial, received PCV-11 or saline solution placebo at 6, 10, and 14 weeks of age. Antibody concentrations to the most frequently carried vaccine serotypes 6B, 19F, and 23F were measured by enzyme immunoassay from sera obtained at 18 weeks and 9 months of age. Serotype-specific antibody concentration was compared between groups of children among PCV-11 recipients stratified according to their carriage status at 6 weeks of age.

Results

Antibody concentrations to 6B, 19F, and 23F were significantly lower at 18 weeks and 9 months of age among children who were carriers of the specific serotype at 6 weeks of age than among non-carriers of the serotype. The hyporesponsiveness was specific to the carried serotype. The specific antibody concentrations induced by PCV-11 among carriers did not differ significantly from those in placebo recipients, whereas the differences were highly significant among noncarriers.

Conclusions

Pneumococcal carriage, prevalent in Filipino infants, interferes with serotype-specific immune response to primary series of PCV and has potential implications for immunization programs.

Section snippets

Methods

The immunogenicity and carriage study was nested within an individually randomized, double-blind, placebo-controlled phase III multicenter trial of 12194 children conducted in the Philippines in 2000–2004 and designed to evaluate the efficacy of the PCV-11 in reducing the incidence of community acquired, radiologically defined childhood pneumonia.17 Enrolled in the nested study were 1111 infants who were randomized to receive intramuscular injections of the study vaccine (n = 555) or saline

Study Cohort

Of the 555 PCV-11 recipients, 532 (96%) and 525 (95%) had carriage measurement available at 6 weeks and serum sample available at 18 weeks or 9 months of age, respectively, and fulfilled the criteria for inclusion in the analyses of this study (Table). The respective numbers among the 556 placebo recipients were 527 (95%) and 523 (94%). All carriers among PCV-11 recipients included in the study had received three doses of PCV-11 as PP. The median ages of children at vaccination and sampling

Discussion

In the present study we show found that carriage in early infancy of serotype 6B, 19F, and 23F pneumococci results in a significantly impaired serotype-specific antibody response to the PCV-11. The hyporesponsiveness is specific to the serotype carried in the nasopharynxgeal and immunization of carriers with the PCV-11 results in concentrations of specific antibodies that are similar to or insignificantly higher than in unvaccinated children. Because pneumococcal carriage, especially in the

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    Supported by grants from European Commission DG Research INCO program (ICA4-CT-2002-10062), PATH (00-GAT.770-790-01115-LPS and 00-GAT.770-790-01115-LPS), and Academy of Finland (111042). The study sponsors had no involvement in study design, the collection, analysis, and interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript. A.S. is a current employee of GlaxoSmithKline (GSK), Finland; H.K., and H.N. have provided consultancies on advisory boards for GSK Biologicals (GSK Bio) and Pfizer (H.N.) and had travels paid by GSK Bio and Pfizer (H.N.) as an invited speaker or expert at symposia. The other authors declare no conflicts of interest.

    List of additional members of the ARIVAC Consortium is available at www.jpeds.com (Appendix).

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