Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal Inference

Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal Inference

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 inac...

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Bibliographic Details
Main Authors: Fenny Ong, Geert Molenberghs, Andrea Callegaro, Wim Van Der Elst, Geert Verbeke, Florian Stijven, Ingrid Van Keilegom, Ariel Alonso Abad
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2025-01-01
Series:Journal of Global Infectious Diseases
Subjects:
causal inference
correlate of protection
hemagglutination inhibition antibody titer
information theory
reverse transcription-polymerase chain reaction-confirmed influenza
surrogate
Online Access:https://journals.lww.com/10.4103/jgid.jgid_89_24
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Summary: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.
ISSN:0974-777X
0974-8245

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