Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites

Winarski, Katie L.; Thornburg, Natalie J.; Yu, Yingchun; Sapparapu, Gopal; Crowe, James. E.; Spiller, Benjamin W.

doi:10.1073/pnas.1502762112

Title: Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites

Journal Article · Mon Jul 13 00:00:00 EDT 2015 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1502762112· OSTI ID:1214868

Winarski, Katie L. ^[1]; Thornburg, Natalie J. ^[2]; Yu, Yingchun ^[2]; Sapparapu, Gopal ^[2]; Crowe, James. E. ^[3]; Spiller, Benjamin W. ^[4]

Vanderbilt Univ. School of Medicine, Nashville, TN (United States). Dept. of Pathology, Microbiology and Immunology
Vanderbilt Univ. School of Medicine, Nashville, TN (United States). Vanderbilt Vaccine Center
Vanderbilt Univ. School of Medicine, Nashville, TN (United States). Dept. of Pathology, Microbiology and Immunology. Vanderbilt Vaccine Center
Vanderbilt Univ. School of Medicine, Nashville, TN (United States). Dept. of Pathology, Microbiology and Immunology. Dept. of Pharmacology. Center for Structural Biology

Antigenic drift of circulating seasonal influenza viruses necessitates an international vaccine effort to reduce the impact on human health. A critical feature of the seasonal vaccine is that it stimulates an already primed immune system to diversify memory B cells to recognize closely related, but antigenically distinct, influenza glycoproteins (hemagglutinins). Influenza pandemics arise when hemagglutinins to which no preexisting adaptive immunity exists acquire the capacity to infect humans. Hemagglutinin 5 is one subtype to which little preexisting immunity exists and is only a few acquired mutations away from the ability to transmit efficiently between ferrets, and possibly humans. In this paper, we describe the structure and molecular mechanism of neutralization by H5.3, a vaccine-elicited antibody that neutralizes hemagglutinin 5 viruses and variants with expanded host range. H5.3 binds in the receptor-binding site, forming contacts that recapitulate many of the sialic acid interactions, as well as multiple peripheral interactions, yet is not sensitive to mutations that alter sialic acid binding. H5.3 is highly specific for a subset of H5 strains, and this specificity arises from interactions to the periphery of the receptor-binding site. Finally, H5.3 is also extremely potent, despite retaining germ line-like conformational flexibility.

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Research Organization:: Vanderbilt Univ. School of Medicine, Nashville, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States); Defense Threat Reduction Agency (DTRA) (United States); Michigan Economic Development Corporation (United States); Michigan Technology Tri-Corridor (United States)

Grant/Contract Number:: AC02-06CH11357; R01 AI106002; R21 AI092268; HHSN272200900047C; HDTRA1-10-1-0067; 085P1000817; T32 GM008320; RR026915

OSTI ID:: 1214868

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 30; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 22 works

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References (56)

Principles of protein-protein interactions. Jones, S.; Thornton, J. M. Proceedings of the National Academy of Sciences, Vol. 93, Issue 1 https://doi.org/10.1073/pnas.93.1.13	journal	January 1996
Influenza virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium; the role of the host cell in selection of hemagglutinin receptor specificity Couceiro, J. Nelson S. S.; Paulson, James C.; Baum, Linda G. Virus Research, Vol. 29, Issue 2 https://doi.org/10.1016/0168-1702(93)90056-S	journal	August 1993
Expanding the Options for Confronting Pandemic Influenza Treanor, John J. JAMA, Vol. 312, Issue 14 https://doi.org/10.1001/jama.2014.12558	journal	October 2014
Safety and Immunogenicity of an Inactivated Subvirion Influenza A (H5N1) Vaccine Treanor, John J.; Campbell, James D.; Zangwill, Kenneth M. New England Journal of Medicine, Vol. 354, Issue 13 https://doi.org/10.1056/NEJMoa055778	journal	March 2006
Structure of influenza virus haemagglutinin complexed with a neutralizing antibody Bizebard, Thierry; Gigant, BenoÃ®t; Rigolet, Pascal Nature, Vol. 376, Issue 6535 https://doi.org/10.1038/376092a0	journal	July 1995
Influenza Pandemics of the 20th Century Kilbourne, Edwin D. Emerging Infectious Diseases, Vol. 12, Issue 1 https://doi.org/10.3201/eid1201.051254	journal	January 2006
Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity Rogers, G. N.; Paulson, J. C.; Daniels, R. S. Nature, Vol. 304, Issue 5921 https://doi.org/10.1038/304076a0	journal	July 1983
An Airborne Transmissible Avian Influenza H5 Hemagglutinin Seen at the Atomic Level Zhang, W.; Shi, Y.; Lu, X. Science, Vol. 340, Issue 6139 https://doi.org/10.1126/science.1236787	journal	May 2013
Molecular evolution of affinity and flexibility in the immune system Thorpe, I. F.; Brooks, C. L. Proceedings of the National Academy of Sciences, Vol. 104, Issue 21 https://doi.org/10.1073/pnas.0610064104	journal	May 2007
T Follicular Helper Cell Differentiation, Function, and Roles in Disease Crotty, Shane Immunity, Vol. 41, Issue 4 https://doi.org/10.1016/j.immuni.2014.10.004	journal	October 2014
Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin Skehel, John J.; Wiley, Don C. Annual Review of Biochemistry, Vol. 69, Issue 1 https://doi.org/10.1146/annurev.biochem.69.1.531	journal	June 2000
Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans Garten, R. J.; Davis, C. T.; Russell, C. A. Science, Vol. 325, Issue 5937 https://doi.org/10.1126/science.1176225	journal	May 2009
Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine Pallikkuth, Suresh; Parmigiani, Anita; Silva, Sandra Y. Blood, Vol. 120, Issue 5 https://doi.org/10.1182/blood-2011-12-396648	journal	August 2012
Enhanced human receptor binding by H5 haemagglutinins Xiong, Xiaoli; Xiao, Haixia; Martin, Stephen R. Virology, Vol. 456-457 https://doi.org/10.1016/j.virol.2014.03.008	journal	May 2014
Induction of ICOS+CXCR3+CXCR5+ TH Cells Correlates with Antibody Responses to Influenza Vaccination Bentebibel, S. -E.; Lopez, S.; Obermoser, G. Science Translational Medicine, Vol. 5, Issue 176 https://doi.org/10.1126/scitranslmed.3005191	journal	March 2013
Safety and Immunogenicity of Influenza A H5 Subunit Vaccines: Effect of Vaccine Schedule and Antigenic Variant Belshe, Robert B.; Frey, Sharon E.; Graham, Irene The Journal of Infectious Diseases, Vol. 203, Issue 5 https://doi.org/10.1093/infdis/jiq093	journal	March 2011
PHENIX : building new software for automated crystallographic structure determination Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11 https://doi.org/10.1107/S0907444902016657	journal	October 2002
New World Bats Harbor Diverse Influenza A Viruses Tong, Suxiang; Zhu, Xueyong; Li, Yan PLoS Pathogens, Vol. 9, Issue 10 https://doi.org/10.1371/journal.ppat.1003657	journal	October 2013
Immunoglobulin Gene Insertions and Deletions in the Affinity Maturation of HIV-1 Broadly Reactive Neutralizing Antibodies Kepler, Thomas B.; Liao, Hua-Xin; Alam, S. Munir Cell Host & Microbe, Vol. 16, Issue 3 https://doi.org/10.1016/j.chom.2014.08.006	journal	September 2014
Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid Weis, W.; Brown, J. H.; Cusack, S. Nature, Vol. 333, Issue 6172 https://doi.org/10.1038/333426a0	journal	June 1988
Integration, scaling, space-group assignment and post-refinement Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 133-144 https://doi.org/10.1107/S0907444909047374	journal	January 2010
Robust indexing for automatic data collection Sauter, Nicholas K.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 37, Issue 3 https://doi.org/10.1107/S0021889804005874	journal	May 2004
Imaging proteins in live mammalian cells with biotin ligase and monovalent streptavidin Howarth, Mark; Ting, Alice Y. Nature Protocols, Vol. 3, Issue 3 https://doi.org/10.1038/nprot.2008.20	journal	March 2008
Likelihood-enhanced fast translation functions McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Storoni, Laurent C. Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 4 https://doi.org/10.1107/S0907444905001617	journal	March 2005
Influenza virus receptors in the human airway Shinya, Kyoko; Ebina, Masahito; Yamada, Shinya Nature, Vol. 440, Issue 7083 https://doi.org/10.1038/440435a	journal	March 2006
Human antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses Thornburg, Natalie J.; Nannemann, David P.; Blum, David L. Journal of Clinical Investigation, Vol. 123, Issue 10 https://doi.org/10.1172/JCI69377	journal	September 2013
Human Germline Antibody Gene Segments Encode Polyspecific Antibodies Willis, Jordan R.; Briney, Bryan S.; DeLuca, Samuel L. PLoS Computational Biology, Vol. 9, Issue 4 https://doi.org/10.1371/journal.pcbi.1003045	journal	April 2013
Variation and infectivity neutralization in influenza Knossow, Marcel; Skehel, John J. Immunology, Vol. 119, Issue 1 https://doi.org/10.1111/j.1365-2567.2006.02421.x	journal	September 2006
Influenza Vaccines for the Future Lambert, Linda C.; Fauci, Anthony S. New England Journal of Medicine, Vol. 363, Issue 21 https://doi.org/10.1056/NEJMra1002842	journal	November 2010
A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin Xu, Rui; Krause, Jens C.; McBride, Ryan Nature Structural & Molecular Biology, Vol. 20, Issue 3 https://doi.org/10.1038/nsmb.2500	journal	February 2013
Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets Imai, Masaki; Watanabe, Tokiko; Hatta, Masato Nature, Vol. 486, Issue 7403 https://doi.org/10.1038/nature10831	journal	May 2012
xia2 : an expert system for macromolecular crystallography data reduction Winter, G. Journal of Applied Crystallography, Vol. 43, Issue 1 https://doi.org/10.1107/S0021889809045701	journal	December 2009
Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets Herfst, S.; Schrauwen, E. J. A.; Linster, M. Science, Vol. 336, Issue 6088 https://doi.org/10.1126/science.1213362	journal	June 2012
Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza A viruses Nobusawa, E.; Aoyama, T.; Kato, H. Virology, Vol. 182, Issue 2 https://doi.org/10.1016/0042-6822(91)90588-3	journal	June 1991
Broadly neutralizing antibodies against influenza viruses Laursen, Nick S.; Wilson, Ian A. Antiviral Research, Vol. 98, Issue 3 https://doi.org/10.1016/j.antiviral.2013.03.021	journal	June 2013
New applications of simulated annealing in X-ray crystallography and solution NMR Brünger, Axel T.; Adams, Paul D.; Rice, Luke M. Structure, Vol. 5, Issue 3 https://doi.org/10.1016/S0969-2126(97)00190-1	journal	March 1997
Influenza H5 Hemagglutinin DNA Primes the Antibody Response Elicited by the Live Attenuated Influenza A/Vietnam/1203/2004 Vaccine in Ferrets Suguitan, Amorsolo L.; Cheng, Xing; Wang, Weijia PLoS ONE, Vol. 6, Issue 7 https://doi.org/10.1371/journal.pone.0021942	journal	July 2011
An Antibody That Prevents the Hemagglutinin Low pH Fusogenic Transition Barbey-Martin, C.; Gigant, B.; Bizebard, T. Virology, Vol. 294, Issue 1 https://doi.org/10.1006/viro.2001.1320	journal	March 2002
Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans Treanor, John J.; Wilkinson, Bethanie E.; Masseoud, Feda Vaccine, Vol. 19, Issue 13-14 https://doi.org/10.1016/S0264-410X(00)00395-9	journal	February 2001
Antibody Recognition of the Pandemic H1N1 Influenza Virus Hemagglutinin Receptor Binding Site Hong, M.; Lee, P. S.; Hoffman, R. M. B. Journal of Virology, Vol. 87, Issue 22 https://doi.org/10.1128/JVI.01388-13	journal	September 2013
Multiple layers of B cell memory with different effector functions Dogan, Ismail; Bertocci, Barbara; Vilmont, Valérie Nature Immunology, Vol. 10, Issue 12 https://doi.org/10.1038/ni.1814	journal	October 2009
Immunogenicity of Avian Influenza A/Anhui/01/2005(H5N1) Vaccine With MF59 Adjuvant: A Randomized Clinical Trial Belshe, Robert B.; Frey, Sharon E.; Graham, Irene L. JAMA, Vol. 312, Issue 14 https://doi.org/10.1001/jama.2014.12609	journal	October 2014
Receptor Specificity in Human, Avian, and Equine H2 and H3 Influenza Virus Isolates Connor, Robert J.; Kawaoka, Yoshihiro; Webster, Robert G. Virology, Vol. 205, Issue 1 https://doi.org/10.1006/viro.1994.1615	journal	November 1994
Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody Schmidt, A. G.; Xu, H.; Khan, A. R. Proceedings of the National Academy of Sciences, Vol. 110, Issue 1 https://doi.org/10.1073/pnas.1218256109	journal	November 2012
NMRPipe: A multidimensional spectral processing system based on UNIX pipes Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW. Journal of Biomolecular NMR, Vol. 6, Issue 3 https://doi.org/10.1007/BF00197809	journal	November 1995
Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza Nicholson, Karl G.; Colegate, Anthony E.; Podda, Audino The Lancet, Vol. 357, Issue 9272 https://doi.org/10.1016/S0140-6736(00)05066-2	journal	June 2001
Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization Klein, Florian; Diskin, Ron; Scheid, Johannes F. Cell, Vol. 153, Issue 1 https://doi.org/10.1016/j.cell.2013.03.018	journal	March 2013
Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus Stevens, J.; Blixt, O.; Tumpey, T. M. Science, Vol. 312, Issue 5772 https://doi.org/10.1126/science.1124513	journal	March 2006
Receptor binding by a ferret-transmissible H5 avian influenza virus Xiong, Xiaoli; Coombs, Peter J.; Martin, Stephen R. Nature, Vol. 497, Issue 7449 https://doi.org/10.1038/nature12144	journal	April 2013
MOLREP an Automated Program for Molecular Replacement Vagin, A.; Teplyakov, A. Journal of Applied Crystallography, Vol. 30, Issue 6, p. 1022-1025 https://doi.org/10.1107/S0021889897006766	journal	December 1997
Receptor mimicry by antibody F045–092 facilitates universal binding to the H3 subtype of influenza virus Lee, Peter S.; Ohshima, Nobuko; Stanfield, Robyn L. Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4614	journal	April 2014
Structural Insights into the Evolution of an Antibody Combining Site Wedemayer, G. J. Science, Vol. 276, Issue 5319 https://doi.org/10.1126/science.276.5319.1665	journal	June 1997
Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors Yamada, Shinya; Suzuki, Yasuo; Suzuki, Takashi Nature, Vol. 444, Issue 7117 https://doi.org/10.1038/nature05264	journal	November 2006
Serological Responses to an Avian Influenza A/H7N9 Vaccine Mixed at the Point-of-Use With MF59 Adjuvant: A Randomized Clinical Trial Mulligan, Mark J.; Bernstein, David I.; Winokur, Patricia JAMA, Vol. 312, Issue 14 https://doi.org/10.1001/jama.2014.12854	journal	October 2014
Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin Whittle, J. R. R.; Zhang, R.; Khurana, S. Proceedings of the National Academy of Sciences, Vol. 108, Issue 34 https://doi.org/10.1073/pnas.1111497108	journal	August 2011
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997

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Title: Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites

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