Highly Conserved Protective Epitopes on Influenza B Viruses

Cyrille Dreyfus,^1,* Nick S. Laursen,^1,2,* Ted Kwaks,³ David Zuijdgeest,³ Reza Khayat,¹ Damian C. Ekiert,^1, Jeong Hyun Lee,¹ Zoltan Metlagel,^1, Miriam V. Bujny,³ Mandy Jongeneelen,³ Remko van der Vlugt,³ Mohammed Lamrani,³ Hans J. W. M. Korse,³ Eric Geelen,³ Özcan Sahin,³ Martijn Sieuwerts,³ Just P. J. Brakenhoff,³ Ronald Vogels,³ Olive T. W. Li,⁴ Leo L. M. Poon,⁴ Malik Peiris,⁴ Wouter Koudstaal,³ Andrew B. Ward,¹ Ian A. Wilson,^1,5, Jaap Goudsmit,^3, Robert H. E. Friesen³

Abstract: Identification of broadly neutralizing antibodies against influenza A viruses has raised hopes for the development of monoclonal antibody–based immunotherapy and "universal" vaccines for influenza. However, a substantial part of the annual flu burden is caused by two cocirculating, antigenically distinct lineages of influenza B viruses. Here, we report human monoclonal antibodies, CR8033, CR8071, and CR9114, that protect mice against lethal challenge from both lineages. Antibodies CR8033 and CR8071 recognize distinct conserved epitopes in the head region of the influenza B hemagglutinin (HA), whereas CR9114 binds a conserved epitope in the HA stem and protects against lethal challenge with influenza A and B viruses. These antibodies may inform on development of monoclonal antibody–based treatments and a universal flu vaccine for all influenza A and B viruses.

¹ Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
² Department of Molecular Biology, Gustav Wieds Vej 10C, Aarhus 8000, Denmark.
³ Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, 2301 CA Leiden, Netherlands.
⁴ State Key Laboratory of Emerging Infectious Diseases and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China.
⁵ Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Present address: Department of Microbiology and Immunology, University of California—San Francisco, 600 16th Street, San Francisco, CA 94143, USA.

Present address: Lawrence Berkeley National Laboratory, Department of Bioenergy/GTL and Structural Biology, Berkeley, CA 94720, USA.

To whom correspondence should be addressed. E-mail: wilson{at}scripps.edu (I.A.W.); jaap.goudsmit{at}crucell.com (J.G.)

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