Quality control and the identification of vaccine responders using ELISA-derived antibody data

First vaccines are traditionally licensed after showing favourable results from phase III efficacy trials. Subsequent competing vaccines, however, have been licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Focusing on pneumococcal vaccines where optical densities are measured and serum antibody concentrations are 'estimated' (from a statistical model) using an immunoglobulin (IgG) enzyme-linked immunosorbent assay (ELISA), the focus of this paper will centre on two highly related issues: the determination of an upper limit for quality control used in the assay methodology (let us call it the maximum tolerated limit or MTL) and the identification of vaccine responders. The goal is to show that these two issues are inter-related, so that investigators could reduce misclassification which would interfere with the eventual comparison of immunogenicity results.