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  • 1
    Publication Date: 2012-08-11
    Description: 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538841/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538841/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dreyfus, Cyrille -- Laursen, Nick S -- Kwaks, Ted -- Zuijdgeest, David -- Khayat, Reza -- Ekiert, Damian C -- Lee, Jeong Hyun -- Metlagel, Zoltan -- Bujny, Miriam V -- Jongeneelen, Mandy -- van der Vlugt, Remko -- Lamrani, Mohammed -- Korse, Hans J W M -- Geelen, Eric -- Sahin, Ozcan -- Sieuwerts, Martijn -- Brakenhoff, Just P J -- Vogels, Ronald -- Li, Olive T W -- Poon, Leo L M -- Peiris, Malik -- Koudstaal, Wouter -- Ward, Andrew B -- Wilson, Ian A -- Goudsmit, Jaap -- Friesen, Robert H E -- GM080209/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- RR017573/RR/NCRR NIH HHS/ -- T32 GM080209/GM/NIGMS NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 14;337(6100):1343-8. doi: 10.1126/science.1222908. Epub 2012 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22878502" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/chemistry/*immunology ; Antibodies, Neutralizing/chemistry/immunology ; Conserved Sequence ; Hemagglutinin Glycoproteins, Influenza Virus/*immunology ; Humans ; Immunodominant Epitopes/chemistry/*immunology ; Influenza B virus/*immunology ; Influenza Vaccines/*immunology ; Mice ; Molecular Sequence Data ; Neutralization Tests ; Orthomyxoviridae Infections/*prevention & control ; Protein Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2018-11-02
    Description: 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: Biochemistry, Immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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