Abstract

Cross-Neutralising Single Domain Antibodies to Influenza – Preparing for the Next Pandemic

Simon Hufton, Section Head Molecular Immunology, National Institute for Biological Standard and Control (NIBSC)

The response to the 2009 A(H1N1) influenza pandemic has highlighted the need for additional strategies of intervention which are independent of the prior availability of the influenza strain. We have isolated panels of single domain antibodies (nanobodies) specific for important influenza subtypes including ‘swine flu’ A(H1N1), highly pathogenic avian influenza A(H5N1), avian influenza A(H7N9), A(H3N2) and B lineage influenza viruses. Nanobodies with cross-subtype neutralisation activity are of particular interest and by using yeast display in combination with deep mutational scanning we have mapped positions within the antibody-antigen interface crucial for binding. In addition, we have been able to identify residues which have a minimal effect on binding if mutated, so predicting the relative genetic barrier each nanobody might present to a rapidly evolving influenza virus. The unique properties and advantages of nanobodies as alternatives to conventional monoclonal antibodies are well documented. These advantages will be discussed in the context of preparing for the next influenza pandemic specifically in relation to influenza vaccine potency testing and immunotherapy.