An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study

Pneumococcal conjugate vaccines will eventually be licensed after favorable results from phase III efficacy trials. After licensure of a conjugate vac cine for invasive pneumococcal disease in infants, new conjugate vaccines w ill likely be licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Analytical methods must therefore be developed, ev aluated, and validated to compare immunogenicity results accurately within and between laboratories for different vaccines. At present no analytical t echnique is uniformly accepted and used in vaccine evaluation studies to de termine the acceptable level of agreement between a laboratory result and t he assigned value for a given serum sample. This multicenter study describe s the magnitude of agreement among 12 laboratories quantifying an identical series of 48 pneumococcal serum specimens from 24 individuals (quality-con trol sera) by a consensus immunoglobulin G (IgG) enzyme-linked immunosorben t assay (ELISA) developed For this study. After provisional or trial antibo dy concentrations were assigned to the quality-control serum samples for th is study, four methods for comparison of a series of laboratory-determined values with the assigned concentrations were evaluated. The percent error b etween assigned values and laboratory-determined concentrations proved to b e the most informative of the four methods. We present guidelines that a la boratory may follow to analyze a series of quality-control sera to determin e if it can reproduce the assigned antibody concentrations within an accept able level of tolerance. While this study focused on a pneumococcal IgG ELI SA, the methods that we describe are easily generalizable to other immunolo gical assays.