ArticleThe Journal of infectious diseases2026
Evaluating the Breadth and Reliability of Influenza Vaccine Protection Indicators: A Secondary Analysis of an Animal Challenge Trial.
Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHemagglutination inhibition (HAI) titers are key correlates of influenza vaccine protection, yet a systematic comparison of HAI-based immunogenicity indicators is lacking for guiding vaccine development. This study aimed to compare these indicators by evaluating their correlation with influenza disease outcomes.
methodWe performed a secondary analysis of a mouse challenge study, in which 14 groups of mice were first challenged and received different H3N2 vaccines and were subsequently infected with H3N2 (A/Kansas/14/2017). Disease outcomes were measured by weight loss and lung viral load. HAI titers were assessed against 9 H3N2 strains, including the infecting strain, vaccine strains, and others, generating 11 HAI-based indicators considering that the HAI titer was against the vaccine strains, the infecting strain, and the similarity between strains based on 2 antigenic distance algorithms. Correlations with disease outcomes were evaluated using linear regression models, with R2 values and bootstrap resampling estimating variance.
resultsHAI titers against vaccine strains showed the weakest correlation with disease outcomes due to strain mismatch. The proportion of seroprotection among the 9 strains demonstrated the strongest correlation, with R2 values of approximately 0.4 (weight loss) and approximately 0.6 (lung viral load). Indicators based on antigenic distance were also predictive but not superior.
conclusionsRelying solely on HAI titers against a single virus is insufficient for assessing influenza vaccine effectiveness. Calculating the proportion of seroprotection, a computationally efficient metric, offers robust predictive power and may be superior to traditional single-strain titer even when it matches the infecting strain.
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