Using Sequence Data To Infer the Antigenicity of Influenza Virus

Abstract

The efficacy of current influenza vaccines requires a close antigenic match between circulating and vaccine strains. As such, timely identification of emerging influenza virus antigenic variants is central to the success of influenza vaccination programs. Empirical methods to determine influenza virus antigenic properties are time-consuming and mid-throughput and require live viruses. Here, we present a novel, experimentally validated, computational method for determining influenza virus antigenicity on the basis of hemagglutinin (HA) sequence. This method integrates a bootstrapped ridge regression with antigenic mapping to quantify antigenic distances by using influenza HA1 sequences. Our method was applied to H3N2 seasonal influenza viruses and identified the 13 previously recognized H3N2 antigenic clusters and the antigenic drift event of 2009 that led to a change of the H3N2 vaccine strain.

Molecular Characterization on the Basis of Ha, Na and M Gene Revealed Changes in Critical Amino Acid Positions of Influenza a (H3n2) Virus Circulating in India During 2011-2013

“…All sites are conserved in samples except for the loss of glycosylation observed at position 126 in 7 samples and another at position 45 in a single sample. All positions except 483 have been reported in previous studies (Sun et al, 2013). The study shows a gain of the glycosylation sites in the antigenic region since 2004.…”

“…All sites were seen to be conserved in the samples except for the loss of glycosylation seen at position 126 in 7 samples and another at position 45 in a single sample. All positions except 483 have been reported in previous studies (Sun et al, 2013). Among these sites residues 45,63,122,126,133,144,165 and 246 were found to occur on antigenic sites and these changes may alter the ability of antibodies to bind antigenic site and may thus contribute to the generation of escape mutants.…”

“…Influenza viruses can efficiently escape from host antibodies by means of accumulation of mutations in their surface glycoproteins HA and NA (antigenic drift) or by the introduction of new subtypes of these glycoproteins through gene segment reassortment (antigenic shift) and it has been observed that antigenic drift occurs more frequently in H3N2 viruses than any other seasonal virus, which is reflected by the number of times H3N2 vaccine strain has been updated in comparison to H1N1 and influenza B virus (Sun et al, 2013).…”

“…It has been suggested that amino acid changes occurring in epitopes of high neutralization efficiencies (i.e., epitope A, B and D) are associated with antigenic drift, rather than those in epitope of low neutralization efficiencies (i.e., C and E) (Sun et al, 2013;Ndifon et al, 2009). It has been also been proposed that a minimum of four substitutions in two or more antigenic sites of HA protein were required for an epidemically important strain (Huang et al, 2011).…”

“…HA1 forms the globular head domain which contains the receptor binding site for sialic acid receptor present on host cells, along with 5 antigenic sites (A-E) (Bush et al, 1999). HA1 mutates more frequently than HA2 and plays a major role in natural selection and antibody escape (Sun et al, 2013).…”