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

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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 IA^9,10.
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Abstract

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