학술논문
Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin
Document Type
Report
Author
Laursen, Nick S.; Friesen, Robert H. E.; Zhu, Xueyong; Jongeneelen, Mandy; Blokland, Sven; Vermond, Jan; Eygen, Alida van; Tang, Chan; Diepen, Harry van; Obmolova, Galina; Neut Kolfschoten, Marijn van der; 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.
Source
Science. Nov 2, 2018, Vol. 362 Issue 6414, p598, 5 p.
Subject
Language
English
ISSN
0036-8075
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.