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Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies
George R Siber1, Ih Chang, Sherryl Baker
1Wyeth Vaccines Research, Pearl River, New York, USA. siberg@wyeth.com
Insights
A minimum protective antibody concentration of 0.35 microg/ml was established for pneumococcal conjugate vaccines. This threshold helps assess new vaccines against invasive pneumococcal disease (IPD) in infants globally.
Area of Science:
- Immunology
- Vaccinology
- Pediatrics
Background:
- Assessing vaccine efficacy relies on minimum protective antibody concentrations.
- Pneumococcal conjugate vaccines (PnC) require validated antibody correlates for efficacy evaluation.
Purpose of the Study:
- To establish a minimum protective antibody concentration for pneumococcal anticapsular antibodies.
- To validate this concentration for use in assessing PnC vaccine efficacy in infants globally.
- To outline principles for adjusting this concentration based on assay modifications.
Main Methods:
- A meta-analysis of data from three double-blind controlled trials in diverse infant populations.
- Correlation of pneumococcal anticapsular antibody responses with protection against invasive pneumococcal disease (IPD).
- Application of assay modification principles using 22F absorption ELISA.
Main Results:
- A protective concentration of 0.35 microg/ml for anticapsular antibodies against 7 serotypes in Prevenar was derived.
- This 0.35 microg/ml threshold was recommended by a WHO Working Group for global use.
- Improved ELISA with 22F absorption minimally impacted antibody levels in immunized infants, supporting the 0.35 microg/ml threshold.
Conclusions:
- The established 0.35 microg/ml minimum protective antibody concentration is robust and suitable for global assessment of PnC vaccine efficacy.
- The principles for assay modification validation ensure continued reliability of the protective concentration.
- This standardized approach aids in the development and approval of future pneumococcal vaccines.
Abstract:
Estimates of minimum protective antibody concentrations for vaccine preventable diseases are of critical importance in assessing whether new vaccines will be as effective as those for which clinical efficacy was shown directly. We describe a method for correlating pneumococcal anticapsular antibody responses of infants immunized with pneumococcal conjugate (PnC) vaccine (Prevenar) with clinical protection from invasive pneumococcal disease (IPD). Data from three double blind controlled trials in Northern Californian, American Indian and South African infants were pooled in a meta-analysis to derive a protective concentration of 0.35 microg/ml for anticapsular antibodies to the 7 serotypes in Prevenar. This concentration has been recommended by a WHO Working Group as applicable on a global basis for assessing the efficacy of future pneumococcal conjugate vaccines. The WHO Working Groups anticipated that modifications in antibody assays for pneumococcal anticapsular antibodies would occur. The principles for determining whether such assay modifications should change the protective concentration are outlined. These principles were applied to an improvement in the ELISA for anticapsular antibodies, i.e. absorption with 22F pneumococcal polysaccharide, which increases the specificity of the assay for vaccine serotype anticapsular antibodies by removing non-specific antibodies. Using sera from infants in the pivotal efficacy trial in Northern California Kaiser Permanente (NCKP), 22F absorption resulted in minimal declines in pneumococcal antibody in Prevenar immunized infants but significant declines in unimmunized controls. Recalculation of the protective concentration after 22F absorption resulted in only a small decline from 0.35 microg/ml to 0.32 microg/ml. These data support retaining the 0.35 microg/ml minimum protective concentration recommended by WHO for assessing the efficacy of pneumococcal conjugate vaccines in infants.
