Universal Protection against Influenza Infection by a Multi-Domain Antibody to Influenza Hemagglutinin

• Published in: Science (American Association for the Advancement of Science) 2018-11, Vol.362 (6414), p.598-602
• Main Authors: Laursen, Nick S., Friesen, Robert H. E., Zhu, Xueyong, Jongeneelen, Mandy, Blokland, Sven, Vermond, Jan, van Eijgen, Alida, Tang, Chan, van Diepen, Harry, Oblomova, 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.
• Format: Article
• Language: English
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aaq0620

Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of novel vaccines and therapeutics. Here, we report on diverse camelid single-domain antibodies to influenza hemagglutinin from which we generated multi-domain antibodies with unprecedented breadth and potency. Multi-domain 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 EM structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multi-domain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide a groundbreaking new strategy to prevent infection with influenza virus and other highly variable pathogens. Universal multi-domain influenza antibodies or Multi-domain antibodies provide universal protection against influenza A and B viruses