Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin

Laursen, Nick S.; Friesen, Robert H.  E.; Zhu, Xueyong; Jongeneelen, Mandy; Blokland, Sven; Vermond, Jan; van Eijgen, Alida; Tang, Chan; van Diepen, Harry; Obmolova, Galina; van der Neut Kolfschoten, Marijn; Zuijdgeest, David; Straetemans, Roel; Hoffman, Ryan M.  B.; Nieusma, Travis; Pallesen, Jesper; Turner, Hannah L.; Bernard, Steffen M.; Ward, Andrew B.; Luo, Jinquan; Poon, Leo L.  M.; Tretiakova, Anna P.; Wilson, James M.; Limberis, Maria P.; Vogels, Ronald; Brandenburg, Boerries; Kolkman, Joost A.; Wilson, Ian A.

doi:10.1126/science.aaq0620

Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin

Journal Article · Thu Nov 01 00:00:00 EDT 2018 · Science

DOI:https://doi.org/10.1126/science.aaq0620· OSTI ID:1481297

; Friesen, Robert H. E.; Zhu, Xueyong; Jongeneelen, Mandy; Blokland, Sven; ; van Eijgen, Alida; ; ; ; ; ; Straetemans, Roel; Hoffman, Ryan M. B.; Nieusma, Travis; ; Turner, Hannah L.; Bernard, Steffen M.; ; Luo, Jinquan more »

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.

Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: INDUSTRYNIH

OSTI ID:: 1481297

Journal Information:: Science, Journal Name: Science Journal Issue: 6414 Vol. 362; ISSN 0036-8075

Publisher:: AAAS

Country of Publication:: United States

Language:: ENGLISH

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