6orq: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab275MUR== | |||
<StructureSection load='6orq' size='340' side='right'caption='[[6orq]], [[Resolution|resolution]] 4.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6orq]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ORQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ORQ FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></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=6orq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6orq OCA], [http://pdbe.org/6orq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6orq RCSB], [http://www.ebi.ac.uk/pdbsum/6orq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6orq ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires. | |||
Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.,Escolano A, Gristick HB, Abernathy ME, Merkenschlager J, Gautam R, Oliveira TY, Pai J, West AP Jr, Barnes CO, Cohen AA, Wang H, Golijanin J, Yost D, Keeffe JR, Wang Z, Zhao P, Yao KH, Bauer J, Nogueira L, Gao H, Voll AV, Montefiori DC, Seaman MS, Gazumyan A, Silva M, McGuire AT, Stamatatos L, Irvine DJ, Wells L, Martin MA, Bjorkman PJ, Nussenzweig MC Nature. 2019 May 29. pii: 10.1038/s41586-019-1250-z. doi:, 10.1038/s41586-019-1250-z. PMID:31142836<ref>PMID:31142836</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6orq" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Abernathy, M E]] | |||
[[Category: Bjorkman, P J]] | |||
[[Category: Gristick, H B]] | |||
[[Category: Antiviral protein]] | |||
[[Category: Cryo-em]] | |||
[[Category: Env trimer structure]] | |||
[[Category: Hiv-1 broadly-neutralizing antibody]] | |||
[[Category: Immunogen design]] | |||
[[Category: Rc1]] | |||
[[Category: V3-glycan patch]] | |||
[[Category: Viral protein-immune system complex]] | |||
Revision as of 08:44, 12 June 2019
Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab275MURModified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab275MUR
Structural highlights
Publication Abstract from PubMedBroadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires. Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.,Escolano A, Gristick HB, Abernathy ME, Merkenschlager J, Gautam R, Oliveira TY, Pai J, West AP Jr, Barnes CO, Cohen AA, Wang H, Golijanin J, Yost D, Keeffe JR, Wang Z, Zhao P, Yao KH, Bauer J, Nogueira L, Gao H, Voll AV, Montefiori DC, Seaman MS, Gazumyan A, Silva M, McGuire AT, Stamatatos L, Irvine DJ, Wells L, Martin MA, Bjorkman PJ, Nussenzweig MC Nature. 2019 May 29. pii: 10.1038/s41586-019-1250-z. doi:, 10.1038/s41586-019-1250-z. PMID:31142836[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||