title: Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies.
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.
authors: Wyeth Vaccines Research, Pearl River, New York, USA. siberg@wyeth.com
authors: George R
authors: GR
authors: Siber
authors: Ih
authors: I
authors: Chang
authors: Sherryl
authors: S
authors: Baker
authors: Philip
authors: P
authors: Fernsten
authors: Katherine L
authors: KL
authors: O'Brien
authors: Mathuram
authors: M
authors: Santosham
authors: Keith P
authors: KP
authors: Klugman
authors: Shabir A
authors: SA
authors: Madhi
authors: Peter
authors: P
authors: Paradiso
authors: Robert
authors: R
authors: Kohberger
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D000918:Antibody Specificity; D016667:Bacterial Capsules / Q000276:immunology*; D002140:California; D004311:Double-Blind Method; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007198:Indians, North American; D007223:Infant; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D013019:South Africa; D013296:Streptococcus pneumoniae / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate