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Updated: May 10, 2025

An Optimized Hemagglutination Inhibition HI Assay to Quantify Influenza-specific Antibody Titers
Published on: December 1, 2017
Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity
Fenny Ong1, Geert Molenberghs1,2, Andrea Callegaro3
1I-BioStat, Universiteit Hasselt, Diepenbeek, Belgium.
Introduction:
Identifying hemagglutination inhibition (HI) antibody titers as a key immune correlate of protection (CoP) is crucial for developing, licensing, and monitoring the ongoing effectiveness of new influenza vaccines. Using a new statistical methodology, we explored the link between an inactivated quadrivalent influenza vaccine's impact on HI antibody titers and its effectiveness against A/H1N1-associated influenza illness.
Methods:
We utilized data from a phase 3, observer-blind, randomized, controlled trial in children aged 6-35 months to assess HI antibody titers as an immune CoP. The assessment used a statistical method developed within a causal inference framework and a new information-theoretic metric of surrogacy, the so-called individual causal association (ICA).
Results:
The 75% and 85% uncertainty intervals of the ICA are 0.5511-0.8282 and 0.3632-0.8684, respectively, indicating a substantial reduction in the uncertainty about the vaccine's effect on the absence of infection when its impact on the HI antibody titers is known.
Conclusions:
The evaluation yielded evidence supporting the validity of HI antibody titers as a CoP for influenza infection.

