A statistical analysis of antigenic similarity among influenza A (H3N2) viruses

An accurate assessment of antigenic similarity between influenza viruses is important for vaccine strain recommendations and influenza surveillance. Due to the mechanisms that result in frequent changes in the antigenicities of strains, it is desirable to obtain an antigenic similarity measure that accounts for specific changes in strains that are of epidemiological importance in influenza. Empirically grounded statistical models best achieve this. In this study, an interpretable machine-learning model was developed using distinguishing features of antigenic variants to analyze antigenic similarity. The features comprised of cluster information, amino acid sequences located in known antigenic and receptor-binding sites of influenza A (H3N2). In order to assess validity of parameters, accuracy and relevance of model to vaccine effectiveness, the model was applied to influenza A (H3N2) viruses due to their abundant genetic data and epidemiological relevance to influenza surveillance. An application of the model revealed that all model parameters were statistically significant to determining antigenic similarity between strains. Furthermore, upon evaluating the model for predicting antigenic similarity between strains, it achieved 95% area under Receiver Operating Characteristic curve (AUC), 94% accuracy, 76% precision, 97% specificity, 68% sensitivity and a diagnostic odds ratio (DOR) of 83.19. Above all, the model was found to be strongly related to influenza vaccine effectiveness to indicate the correlation between vaccine effectiveness and antigenic similarity between vaccine and circulating strains in an epidemic. The study predicts probabilities of antigenic similarity and estimates changes in strains that lead to antigenic variants. A successful application of the methods presented in this study would complement the global efforts in influenza surveillance.