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''' | ==Crystal structure of a monomeric influenza hemagglutinin stem in complex with an broadly neutralizing antibody CR9114== | ||
<StructureSection load='5cjs' size='340' side='right' caption='[[5cjs]], [[Resolution|resolution]] 4.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5cjs]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CJS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CJS FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cjq|5cjq]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5cjs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cjs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5cjs RCSB], [http://www.ebi.ac.uk/pdbsum/5cjs PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The identification of human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem revitalized hopes of developing a universal influenza vaccine. Using a rational design and library approach, we engineered stable HA stem antigens ('mini-HAs') based on an H1 subtype sequence. Our most advanced candidate exhibits structural and bnAb binding properties comparable to full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever following sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bind a wide range of HAs, compete with human bnAbs for HA stem binding, neutralize H5N1 viruses, and mediate antibody-dependent effector activity. These results provide proof-of-concept for design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses. | |||
A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen.,Impagliazzo A, Milder F, Kuipers H, Wagner M, Zhu X, Hoffman RM, van Meersbergen R, Huizingh J, Wanningen P, Verspuij J, de Man M, Ding Z, Apetri A, Kukrer B, Sneekes-Vriese E, Tomkiewicz D, Laursen NS, Lee PS, Zakrzewska A, Dekking L, Tolboom J, Tettero L, van Meerten S, Yu W, Koudstaal W, Goudsmit J, Ward AB, Meijberg W, Wilson IA, Radosevic K Science. 2015 Aug 24. pii: aac7263. PMID:26303961<ref>PMID:26303961</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
[[Category: Wilson, I | __TOC__ | ||
</StructureSection> | |||
[[Category: Wilson, I A]] | |||
[[Category: Zhu, X]] | [[Category: Zhu, X]] | ||
[[Category: Antibody]] | |||
[[Category: Glycoprotein]] | |||
[[Category: Hemagglutinin]] | |||
[[Category: Immunogen]] | |||
[[Category: Influenza]] | |||
[[Category: Influenza vaccine]] | |||
[[Category: Monoclonal]] | |||
[[Category: Neutralizing]] | |||
[[Category: Trimer]] | |||
[[Category: Viral protein-immune system complex]] | |||
Revision as of 14:14, 9 September 2015
Crystal structure of a monomeric influenza hemagglutinin stem in complex with an broadly neutralizing antibody CR9114Crystal structure of a monomeric influenza hemagglutinin stem in complex with an broadly neutralizing antibody CR9114
Structural highlights
Publication Abstract from PubMedThe identification of human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem revitalized hopes of developing a universal influenza vaccine. Using a rational design and library approach, we engineered stable HA stem antigens ('mini-HAs') based on an H1 subtype sequence. Our most advanced candidate exhibits structural and bnAb binding properties comparable to full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever following sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bind a wide range of HAs, compete with human bnAbs for HA stem binding, neutralize H5N1 viruses, and mediate antibody-dependent effector activity. These results provide proof-of-concept for design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen.,Impagliazzo A, Milder F, Kuipers H, Wagner M, Zhu X, Hoffman RM, van Meersbergen R, Huizingh J, Wanningen P, Verspuij J, de Man M, Ding Z, Apetri A, Kukrer B, Sneekes-Vriese E, Tomkiewicz D, Laursen NS, Lee PS, Zakrzewska A, Dekking L, Tolboom J, Tettero L, van Meerten S, Yu W, Koudstaal W, Goudsmit J, Ward AB, Meijberg W, Wilson IA, Radosevic K Science. 2015 Aug 24. pii: aac7263. PMID:26303961[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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