Antigenic variability in Neuraminidase protein of Influenza A/H3N2 vaccine strains (1968 - 2009).

Pratip Shil,Sarah S Cherian,Sameer S Chavan

doi:10.6026/97320630007076

Abstract

Antigenic drift and shift involving the surface proteins of Influenza virus gave rise to new strains that caused epidemics affecting millions of people worldwide over the last hundred years. Variations in the membrane proteins like Hemagglutinin (HA) and Neuraminidase (NA) necessitates new vaccine strains to be updated frequently and poses challenge to effective vaccine design. Though the HA protein, the primary target of the human immune system, has been well studied, reports on the antigenic variability in the other membrane protein NA are sparse. In this paper we investigate the molecular basis of antigenic drift in the NA protein of the Influenza A/H3N2 vaccine strains between 1968 and 2009 and proceed to establish correlation between antigenic drift and antigen-antibody interactions. Sequence alignments and phylogenetic analyses were carried out and the antigenic variability was evaluated in terms of antigenic distance. To study the effects of antigenic drift on the protein structures, 3D structure of NA from various strains were predicted. Also, rigid body docking protocol has been used to study the interactions between these NA proteins and antibody Mem5, a 1998 antibody.

Highlights

Influenza is a major cause for concern worldwide due to the human suffering and economic burden afflicted by the periodic epidemics
The occurrence of repeated epidemics is attributed to effective evasion of herd immunity in host populations by the Influenza A viruses through antigenic variation in the surface proteins
We studied the antigenic variability of NA proteins of influenza A/H3N2 using bioinformatics tools for sequence and structural analysis

Summary

Introduction

Influenza is a major cause for concern worldwide due to the human suffering and economic burden afflicted by the periodic epidemics. The occurrence of repeated epidemics is attributed to effective evasion of herd immunity in host populations by the Influenza A viruses through antigenic variation in the surface proteins. Though the antigenic variability of the HA protein has been studied [2,3,4,5], reports related to antigenic variability of NA protein are rare This may be due the fact that the NA protein, by the virtue of its positioning on the virus membrane, has somewhat limited interactions with the host immune system [6]. The 2003-2004 epidemic of H3N2 was caused by the proliferation of a new H3N2 subtype strain A/Fujian/411/2002 (an antigenic drift mutant of the A/Panama/2007/99 strain), with the existing vaccine failing to offer any protection [1, 10]. Studies on antigenic variability in the NA protein are necessitated

Methods

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Discussion

Conclusion