title: Differential reactivity of anti-primate and anti-human secondary antibodies against human and monkey immunoglobulins: implications for determining the sensitivity of immunogenicity assays.
abstract: Development of immunogenicity assays for assessment of human antibodies to therapeutic proteins requires a quantitative determination of assay sensitivity. In the absence of true human positive controls, this is usually accomplished by utilizing affinity-purified antibodies from non-human primates or monoclonal antibodies. In the former case, it is generally considered that non-human primate antibodies will be recognized equally to human antibodies by secondary anti-human immunoglobulin reagents used in immunogenicity assays. We present results here demonstrating that this is not the case. In reality, anti-human immunoglobulin secondary antibodies do not recognize primate immunoglobulins as well as human immunoglobulins. As a result, the use of affinity purified primate antibodies to determine the sensitivity of an immunogenicity assay will likely result in the true sensitivity of the assay being underestimated.
authors: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States. bourdageja@lilly.com
authors: James S
authors: JS
authors: Bourdage
authors: John T
authors: JT
authors: Brandt
authors: Thomas N
authors: TN
authors: Lee
authors: Robert J
authors: RJ
authors: Konrad
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data*; D005188:False Negative Reactions; D006041:Goats; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D011817:Rabbits; D012680:Sensitivity and Specificity
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007136:Immunoglobulins