Influenza hemagglutinin antigenic distance measures capture trends in HAI differences and infection outcomes, but are not suitable predictive tools

Abstract

Vaccination is the most effective method to combat influenza. Vaccine effectiveness is influenced by the antigenic distance between the vaccine strain and the actual circulating virus. Amino acid sequence based methods of quantifying the antigenic distance were designed to predict influenza vaccine effectiveness in humans. The use of these antigenic distance measures has been proposed as an additive method for seasonal vaccine selection. In this report, several antigenic distance measures were evaluated as predictors of hemagglutination inhibition titer differences and clinical outcomes following influenza vaccination or infection in mice or ferrets. The antigenic distance measures described the increasing trend in the change of HAI titer, lung viral titer and percent weight loss in mice and ferrets. However, the variability of outcome variables produced wide prediction intervals for any given antigenic distance value. The amino acid substitution based antigenic distance measures were no better predictors of viral load and weight loss than HAI titer differences, the current predictive measure of immunological correlate of protection for clinical signs after challenge.