[Source: Science, full page: (LINK). Abstract, edited.]
Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin
Nick S. Laursen1,*, Robert H. E. Friesen2,†, Xueyong Zhu1, Mandy Jongeneelen3, Sven Blokland3, Jan Vermond4, Alida van Eijgen4, Chan Tang3, Harry van Diepen4, Galina Obmolova2, Marijn van der Neut Kolfschoten3, David Zuijdgeest3, Roel Straetemans5, Ryan M. B. Hoffman1, Travis Nieusma1, Jesper Pallesen1, Hannah L. Turner1, Steffen M. Bernard1, Andrew B. Ward1, Jinquan Luo2, Leo L. M. Poon6, Anna P. Tretiakova7,‡, James M. Wilson7, Maria P. Limberis7, Ronald Vogels3, Boerries Brandenburg3, Joost A. Kolkman8,§, Ian A. Wilson1,9,§
1 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 2 Janssen Research and Development, Spring House, PA 19002, USA. 3 Janssen Vaccines and Prevention, Archimedesweg 4-6, 2333 CN, Leiden, Netherlands. 4 Janssen Prevention Center, Archimedesweg 6, 2333 CN, Leiden, Netherlands. 5 Quantitative Sciences, Janssen Pharmaceutical Companies of Johnson and Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium. 6 Center of Influenza Research and School of Public Health, The University of Hong Kong, Hong Kong SAR, China. 7 Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 8 Janssen Infectious Diseases, Turnhoutseweg 30, 2340, Beerse, Belgium. 9 Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
§Corresponding author. Email: email@example.com (I.A.W.); firstname.lastname@example.org (J.A.K.)
* Present address: Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark.
† Present address: Ablynx, a Sanofi company, Technologiepark 21, 9052 Zwijnaarde, Belgium.
‡ Present address: Pfizer, Rare Disease Research Unit, 610 Main Street, Cambridge, MA 02139, USA.
Science 02 Nov 2018: Vol. 362, Issue 6414, pp. 598-602 / DOI: 10.1126/science.aaq0620
Durable influenza protection
Vaccines are indispensable for the control and prevention of influenza, but there are several challenges to efficacy. Some individuals respond poorly to vaccination, and virus variation makes targeting optimal antigens difficult. Broadly neutralizing antibodies are one solution, but they have their own pitfalls, including limited cross-reactivity to both influenza A and B strains and the need for repeated injections. Now, Laursen et al. have developed multidomain antibodies with breadth and potency. Administered intranasally to mice with an adenovirus vector, the antibodies provided durable and continuous protection from a panoply of influenza strains.
Science, this issue p. 598
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.
Keywords: Influenza A; Influenza B; Monoclonal Antibodies; Animal Models.