Science. 2018 Nov 2;362(6414):598-602. doi: 10.1126/science.aaq0620.
Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin.

Laursen NS1, Friesen RHE2, Zhu X1, Jongeneelen M3, Blokland S3, Vermond J4, van Eijgen A4, Tang C3, van Diepen H4, Obmolova G2, van der Neut Kolfschoten M3, Zuijdgeest D3, Straetemans R5, Hoffman RMB1, Nieusma T1, Pallesen J1, Turner HL1, Bernard SM1, Ward AB1, Luo J2, Poon LLM6, Tretiakova AP7, Wilson JM7, Limberis MP7, Vogels R3, Brandenburg B3, Kolkman JA8, Wilson IA9,10.
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Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.

PMID: 30385580 DOI: 10.1126/science.aaq0620