Abstract
BackgroundIn circulating influenza viruses, gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition is highly correlated to the conformation change on the antigenic sites (epitopes), which locate on HA surface. To quantify a changed epitope for escaping from neutralizing antibodies is the basis for the antigenic drift and vaccine development.ResultsWe have developed an epitope-based method to identify the antigenic drift of influenza A utilizing the conformation changes on epitopes. A changed epitope, an antigenic site on HA with an accumulated conformation change to escape from neutralizing antibody, can be considered as a "key feature" for representing the antigenic drift. According to hemagglutination inhibition (HI) assays and HA/antibody complex structures, we statistically measured the conformation change of an epitope by considering the number of critical position mutations with high genetic diversity and antigenic scores. Experimental results show that two critical position mutations can induce the conformation change of an epitope to escape from the antibody recognition. Among five epitopes of HA, epitopes A and B, which are near to the receptor binding site, play a key role for neutralizing antibodies. In addition, two changed epitopes often drive the antigenic drift and can explain the selections of 24 WHO vaccine strains.ConclusionsOur method is able to quantify the changed epitopes on HA for predicting the antigenic variants and providing biological insights to the vaccine updates. We believe that our method is robust and useful for studying influenza virus evolution and vaccine development.
Highlights
In circulating influenza viruses, gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system
Models for antigenic variants based on changed epitopes To address the issue of measuring accumulated mutations on an epitope to escape from neutralizing antibody, we proposed 4 models considering the number of amino acid mutations on 329 amino acids and 64 selected critical positions of HA (Table 1)
Epitopes A and B, which are near to the receptor binding site, often play the key role for escaping from neutralizing antibody
Summary
Gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition is highly correlated to the conformation change on the antigenic sites (epitopes), which locate on HA surface. To quantify a changed epitope for escaping from neutralizing antibodies is the basis for the antigenic drift and vaccine development. Gradually accumulated mutations on the HA, which interacts with infectivityneutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition of HA is highly correlated to the conformation changes on the antigenic sites (epitopes). The HA consists of five epitopes and each epitope has ~20 structural neighbour amino acids locating on the protein surface [8]. Few studies discussed the relationships between the epitopes and vaccine efficiency [9]
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