Vaccine escape in 2013-4 and the hydropathic evolution of glycoproteins of A/H3N2 viruses

TL;DR

This study uses hydropathic force analysis of influenza neuraminidase to understand vaccine escape and virulence evolution, providing a rapid, sequence-based method for predicting vaccine targets and viral changes.

Contribution

It introduces a hydropathic force analysis approach to quantify neuraminidase evolution and predict vaccine escape, offering a faster alternative to traditional antigenic drift methods.

Findings

Hydropathic analysis correlates with increased virulence in H3N2 strains.

The method predicts vaccine escape and suggests improved vaccine targets.

Sequence-based analysis can be completed in days, unlike traditional methods.

Abstract

More virulent strains of influenza virus subtypes H1N1 appeared widely in 2007 and H3N2 in 2011, and especially 2013-4, when the effectiveness of the H3N2 vaccine decreased nearly to zero. The amino acid differences of neuraminidase from prior less virulent strains appear to be small (<1%) when tabulated through sequence alignments and counting site identities and similarities. Here we show how analyzing fractal hydropathic forces responsible for neuraminidase globular compaction and modularity quantifies the mutational origins of increased virulence. It also predicts vaccine escape and specifies optimized targets for the 2015 H3N2 vaccine different from the WHO target. Unlike some earlier methods based on measuring hemagglutinin antigenic drift and ferret sera, which take several years, cover only a few candidate strains, and are ambiguous, the new methods are timely and can be completed, using NCBI and GISAID amino acid sequences only, in a few days.