Three Shigella ELISA Labs Align on Antibody Thresholds for Vaccine Trials

Shigellosis remains a major cause of diarrheal disease burden globally, particularly in young children in low- and middle-income countries. Multiple Shigella sonnei vaccine candidates are in clinical development, and serum IgG against S. sonnei lipopolysaccharide (LPS) O-antigen has been proposed as a correlate of protection. A protective threshold titer of 1,600 was previously established using the Tel Aviv University (TAU) ELISA method, but different research groups conducting age-descending vaccine trials have developed their own in-house ELISA protocols, making cross-study immune response comparisons difficult in the absence of an internationally recognized reference serum standard.

To address this gap, researchers from four institutions — MHRA (UK), GSK Vaccines Institute for Global Health (Italy), Tel Aviv University (Israel), and Walter Reed Army Institute of Research (USA) — conducted a retrospective bridging study. A panel of 32 characterized human serum samples covering a broad dynamic range of anti-S. sonnei LPS IgG levels was tested independently by each laboratory using their respective in-house ELISA protocols. The three ELISA methods differed in coating antigen preparation, assay format, reference standards, and data expression units, representing the real-world variation present across active clinical trial programs.

Despite these methodological differences, the study found excellent inter-laboratory correlation across all pairwise comparisons. Regression analysis was applied to the data sets to derive fitted equations that mathematically relate the antibody values measured by each lab's method. Using these equations, the team calculated the equivalent antibody values in the MHRA and Walter Reed ELISA systems that correspond to the TAU threshold titer of 1,600. This provides actionable conversion factors that investigators can apply to interpret and compare immunogenicity data from trials using different assay platforms.

The practical implication is significant: ongoing and recently completed age-descending Shigella vaccine trials — which test vaccines in progressively younger age groups including the target infant population — can now cross-reference their immunogenicity data in a quantitatively meaningful way. This is particularly important for immunobridging strategies, where immune responses in populations where efficacy trials are impractical must be inferred from correlates established in populations where efficacy data exist.

The authors acknowledge that this bridging approach is an interim solution. True harmonization of Shigella immunoassays awaits the development and availability of an International Standard Serum, which would allow all laboratories to calibrate their assays to a common reference, eliminating the need for pairwise conversion studies. The panel size of 32 samples, while sufficient for robust regression, may not capture the full biological variability in target populations, and the conversion equations are specific to the assay configurations tested.