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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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
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Online Access:https://journals.lww.com/10.4103/jgid.jgid_89_24
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author Fenny Ong
Geert Molenberghs
Andrea Callegaro
Wim Van Der Elst
Geert Verbeke
Florian Stijven
Ingrid Van Keilegom
Ariel Alonso Abad
author_facet Fenny Ong
Geert Molenberghs
Andrea Callegaro
Wim Van Der Elst
Geert Verbeke
Florian Stijven
Ingrid Van Keilegom
Ariel Alonso Abad
author_sort Fenny Ong
collection DOAJ
description 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.
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language English
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spelling doaj-art-00db97b73fd24e9da84c903d0d545bc22025-08-20T02:10:39ZengWolters Kluwer Medknow PublicationsJournal of Global Infectious Diseases0974-777X0974-82452025-01-01171172310.4103/jgid.jgid_89_24Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal InferenceFenny OngGeert MolenberghsAndrea CallegaroWim Van Der ElstGeert VerbekeFlorian StijvenIngrid Van KeilegomAriel Alonso AbadIntroduction: 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.https://journals.lww.com/10.4103/jgid.jgid_89_24causal inferencecorrelate of protectionhemagglutination inhibition antibody titerinformation theoryreverse transcription-polymerase chain reaction-confirmed influenzasurrogate
spellingShingle Fenny Ong
Geert Molenberghs
Andrea Callegaro
Wim Van Der Elst
Geert Verbeke
Florian Stijven
Ingrid Van Keilegom
Ariel Alonso Abad
Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal Inference
Journal of Global Infectious Diseases
causal inference
correlate of protection
hemagglutination inhibition antibody titer
information theory
reverse transcription-polymerase chain reaction-confirmed influenza
surrogate
title Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal Inference
title_full Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal Inference
title_fullStr Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal Inference
title_full_unstemmed Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal Inference
title_short Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal Inference
title_sort evaluating hemagglutination inhibition antibody titers as a correlate of protection for influenza a sensitivity analysis based on information theory and causal inference
topic causal inference
correlate of protection
hemagglutination inhibition antibody titer
information theory
reverse transcription-polymerase chain reaction-confirmed influenza
surrogate
url https://journals.lww.com/10.4103/jgid.jgid_89_24
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