A Test-Negative Design for Immune Correlates Approximates a Traditional Exposure-Proximal Design but Requires Far Fewer Blood Samples.

Follmann, Dean; Dang, Lauren; Chu, Eric; Fintzi, Jonathan; Janes, Holly; Gilbert, Peter B; Andrews, Leah I B; Serebryannyy, Leonid et al. · J Infect Dis · 2026

retrospective_cohort · Level III

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Abstract

Traditional vaccine clinical trials sample blood from all participants. In contrast, the test-negative immune correlates (TNIC) design only samples blood from participants who develop symptoms. We compared traditional to test-negative immune correlates methods in the mRNA-1273 severe acute respiratory syndrome coronavirus 2 vaccine efficacy clinical trial. Using a neutralizing antibody assay, hazard ratios were 0.48 (95% confidence interval [CI], .29-.73) and 0.55 (95% CI, .28-1.06) for traditional and test-negative methods, respectively. Analogous ratios for binding antibody assay were 0.69 (95% CI, .52-.94) and 0.78 (95% CI, .50-1.20). The results support use of the logistically simpler TNIC design.

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