WHO/BS/2017.2307 A WHO collaborative study to evaluate a candidate IS for anti-Typhoid capsular Vi polysaccharide IgG (Human)

Overview

Candidate International Standard (IS) 16/138 is a serum pool of 9 volunteers vaccinated with Vi polysaccharide Tetanus Toxoid (Vi-TT) conjugate and 7 volunteers vaccinated with plain Vi, which contains IgG directed against the Vi capsular polysaccharide of Salmonella enterica subspecies enterica serovar Typhi. At the National Institute for Biological Standards and Control (NIBSC), 2551 ampoules were filled with 1 mL of candidate IS 16/138, freeze dried and stored at -20oC. As part of a collaborative study, 7 laboratories from 6 countries assessed the suitability of candidate IS 16/138 as a reference for anti-Vi IgG serum (human), alongside U.S. reference reagent Vi-IgGR1, 2011 (Center for Biologics Evaluation and Research, Food & Drug Administration, USA), NIBSC 10/126 (the previous candidate IS), 3 post-vaccination sera and one pre-vaccination serum in several Vi ELISA formats. Datasets of the VaccZyme ELISA (Binding Site, n=7), a biotinylated Vi ELISA developed at NIBSC (NIBSC ELISA, n=7) and in-house ELISAs based on locally prepared or modified Vi (n=7) were used to calculate the potency of test samples relative to candidate IS 16/138 and U.S. reference reagent Vi-IgGR1, 2011. In the majority of cases, valid estimates were obtained for the potency of coded samples relative to candidate IS 16/138 or U.S. reference reagent Vi-IgGR1, 2011, and for the relative potency of the two standards to each other. Six datasets (NIBSC ELISA, n=2; Vacczyme ELISA, n=1; and in-house ELISAs, n=3) were not included in the final analysis, because data did not meet criteria for parallelism and repeatability, or did not allow estimates of relative potency to be calculated. The outcomes of the study were the same for both candidate IS NIBSC 16/138 and U.S. reference Vi-IgGR1, 2011. Candidate IS 16/138 is suitable as a reference standard for anti-Vi IgG serum (human) in the VaccZyme ELISA and in in-house ELISAs where the commutability of 16/138 with the coded samples and U.S. reference reagent Vi-IgGR1, 2011 was evident. Assuming an arbitrary unitage of 100 IU is assigned per ampoule or 100 IU mL-1 to NIBSC 16/138, based on the VaccZyme ELISA, then the potency of U.S. reference reagent Vi-IgGR1, 2011 is 163 IU per vial and the potency of NIBSC 10/126 is 54 IU per ampoule.