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J Glob Infect Dis . Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based

tetano

Editor, Senior Moderator
J Glob Infect Dis


. 2025 Feb 24;17(1):17-23.
doi: 10.4103/jgid.jgid_89_24. eCollection 2025 Jan-Mar. Evaluating Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Influenza: A Sensitivity Analysis Based on Information Theory and Causal Inference

Fenny Ong[SUP] 1 [/SUP], Geert Molenberghs[SUP] 1 2 [/SUP], Andrea Callegaro[SUP] 3 [/SUP], Wim Van Der Elst[SUP] 4 [/SUP], Geert Verbeke[SUP] 2 [/SUP], Florian Stijven[SUP] 2 [/SUP], Ingrid Van Keilegom[SUP] 5 [/SUP], Ariel Alonso Abad[SUP] 2 [/SUP]



Affiliations
Abstract

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.

Keywords: Causal inference; correlate of protection; hemagglutination inhibition antibody titer; information theory; reverse transcription-polymerase chain reaction-confirmed influenza; surrogate.

 
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