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Initial attempts to develop monoclonal antibodies as therapeutics to resolve influenza infections focused mainly on searching for antibodies with the potential to neutralise the virus in vitro with classical haemagglutination inhibition and microneutralisation assays. This led to the identification of many antibodies that bind to the head domain of haemagglutinin (HA), which generally have potent neutralisation capabilities that block viral entry or viral membrane fusion. However, this class of antibodies has a narrow breadth of protection in that they are usually strain-specific. This led to the emphasis on stalk-targeting antibodies, which are able to bind a broad range of viral targets that span across different influenza subtypes. Recently, a third class of antibodies targeting the vestigial esterase (VE) domain have been characterised. In this review, we describe the key features of neutralising VE-targeting antibodies and compare them with head- and stalk-class antibodies.

The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis