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Abstract
Current antigenic targets for influenza vaccine development are either highly immunogenic epitopes of high variability or conserved epitopes of low immunogenicity. This requires continuous update of the variable epitopes in the vaccine formulation or boosting of immunity to invariant epitopes of low natural efficacy. Here we identify a highly immunogenic epitope of limited variability in the head domain of the H1 haemagglutinin protein. We show that a cohort of young children exhibit natural immunity to a set of historical influenza strains which they could not have previously encountered and that this is partially mediated through the epitope. Furthermore, vaccinating mice with these epitope conformations can induce immunity to human H1N1 influenza strains that have circulated since 1918. The identification of epitopes of limited variability offers a mechanism by which a universal influenza vaccine can be created; these vaccines would also have the potential to protect against newly emerging influenza strains.
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Details
; Lourenço, José 2
; Walters, Adam A 3 ; Obolski, Uri 2 ; Edmans, Matthew 1 ; Palmer, Duncan S 2
; Kooblall, Kreepa 4 ; Carnell, George W 5 ; Daniel O’Connor 6
; Bowden, Thomas A 7 ; Pybus, Oliver G 2 ; Pollard, Andrew J 6 ; Temperton, Nigel J 5
; Lambe, Teresa 3 ; Gilbert, Sarah C 3
; Gupta, Sunetra 2 1 Department of Zoology, University of Oxford, Oxford, UK; The Jenner Institute Laboratories, University of Oxford, Oxford, UK
2 Department of Zoology, University of Oxford, Oxford, UK
3 The Jenner Institute Laboratories, University of Oxford, Oxford, UK
4 Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
5 Medway School of Pharmacy, University of Kent, Chatham, UK
6 Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK
7 Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK




