Influenza evolution and H3N2 vaccine effectiveness, with application to the 2014/2015 season

Abstract

Influenza A is a serious disease that causes significant morbidity and mortality, and vaccines against the seasonal influenza disease are of variable effectiveness. In this article, we discuss the use of the pepitope method to predict the dominant influenza strain and the expected vaccine effectiveness in the coming flu season. We illustrate how the effectiveness of the 2014/2015 A/Texas/50/2012 [clade 3C.1] vaccine against the A/California/02/2014 [clade 3C.3a] strain that emerged in the population can be estimated via pepitope In addition, we show by a multidimensional scaling analysis of data collected through 2014, the emergence of a new A/New Mexico/11/2014-like cluster [clade 3C.2a] that is immunologically distinct from the A/California/02/2014-like strains.

Keywords: dominant strains; influenza evolution; pepitope; phylogeny; vaccine effectiveness.

Fig. 1

Shown is the structure of hemagglutinin in H3N2 (accession number 4O5N). The five epitope regions (Gupta et al., 2006) are color coded: epitope A is red (19 amino acids), B is yellow (21 aa), C is orange (27 aa), D is blue (41 aa), and E is green (22 aa). Note epitope B was dominant in 2013/2014 and 2014/2015.

Fig. 2

Vaccine effectiveness in humans as a function of the p_epitope antigenic distance. Vaccine effectiveness values from epidemiological studies of healthy adults, aged approximately 18–65, are shown (triangles). Also shown is a linear fit to the data (solid, R₂ = 0.75). Vaccine effectiveness declines to zero at p_epitope = 0.19 on average. The error bars show the standard estimate of the mean of each sample point, as discussed in the text.

Fig. 3

Dimensional reduction of all H3N2 influenza sequences collected from humans in 2013 and 2014 and deposited in GenBank. Distances are normalized by the length of the HA1 sequence, 327 aa. Dimensional reduction identifies the principal observed substitutions, i.e. those correlated with fitness of the virus, which we expect to be in the epitope regions. A value of p_epitope = 0.19 corresponds to a distance of 0.012 here. Sequences from Table 2 are labeled. While the A/Texas/50/2012 sequence was collected in 2012, substantially similar strains were collected in 2013 and downloaded from GenBank.

Fig. 4

Gaussian density estimation of sequences in reduced two dimensions for (a) all 2013 H3N2 influenza sequences in humans, (b) those 2014 H3N2 influenza sequences in humans near the A/Texas/50/2012 sequence, and (c) all 2014 H3N2 influenza sequences in humans. The consensus strain of the cluster to which A/Nebraska/4/2014 belongs is A/New Mexico/11/2014.