Cross-comparison study of three ELISA methodologies to measure Shigella Sonnei O-antigen serum IgG

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ABSTRACT Measurement of serum immunoglobulin G (IgG) to Shigella lipopolysaccharide (LPS) has been proposed as a correlate of protection against shigellosis, the confirmation of which in the target population of infants in low- and middle-income countries will facilitate vaccine development and licensure. Data obtained from Shigella sonnei vaccine clinical studies have identified a protective serum LPS IgG threshold value that is assay-specific. In the interim period before an International Standard serum was available, a retrospective bridging study using a panel of human serum samples had been conducted to estimate the anti- S . sonnei LPS IgG levels in two ELISA methods, employed in several ongoing or recently completed age-descending Shigella vaccine clinical studies that correspond to the threshold titer of 1,600 established using the Tel Aviv University ELISA method. Each lab performed its own in-house ELISA protocol and tested a panel of 32 human serum samples, covering a range of anti- S . sonnei LPS IgG levels. We observed excellent correlation of the ELISA data between the laboratories and used the fitted equations from regression analysis to determine the values that correspond to an endpoint titer of 1,600 in the Tel Aviv University ELISA method. Our analysis provides a way to meaningfully compare results obtained with clinical samples across the ELISA methods used by the three participating laboratories. IMPORTANCE To support large-scale efficacy trials, especially where efficacy trials are not feasible, the ability to compare immune response data across candidate Shigella vaccines can be very valuable for identifying the most promising vaccine platform and immunobridging to other populations, vaccine formulations, or additional platforms in the future. However, international standards for antibody assays are not yet available for Shigella vaccines currently in clinical development. Lack of standardization of Shigella immunoassays means that the results of antibody measurement in clinical samples from different vaccine trials or those from seroepidemiology studies cannot be easily compared. The results from this study will facilitate the comparison of immunological titers obtained across different Shigella vaccine studies as an interim measure until such time that immunoassays can be better harmonized through the use of an International Standard Serum.

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