dc.contributor.author | de Taeye, Steven W. | |
dc.contributor.author | Go, Eden P. | |
dc.contributor.author | Sliepen, Kwinten | |
dc.contributor.author | de la Peña, Alba Torrents | |
dc.contributor.author | Badal, Kimberly | |
dc.contributor.author | Medina-Ramírez, Max | |
dc.contributor.author | Lee, Wen-Hsin | |
dc.contributor.author | Desaire, Heather | |
dc.contributor.author | Wilson, Ian A. | |
dc.contributor.author | Moore, John P. | |
dc.contributor.author | Ward, Andrew B. | |
dc.contributor.author | Sanders, Rogier W. | |
dc.date.accessioned | 2020-11-24T16:31:03Z | |
dc.date.available | 2020-11-24T16:31:03Z | |
dc.date.issued | 2019-02-06 | |
dc.identifier.citation | de Taeye, S. W., Go, E. P., Sliepen, K., de la Peña, A. T., Badal, K., Medina-Ramírez, M., Lee, W. H., Desaire, H., Wilson, I. A., Moore, J. P., Ward, A. B., & Sanders, R. W. (2019). Stabilization of the V2 loop improves the presentation of V2 loop-associated broadly neutralizing antibody epitopes on HIV-1 envelope trimers. The Journal of biological chemistry, 294(14), 5616–5631. https://doi.org/10.1074/jbc.RA118.005396 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/30913 | |
dc.description | This research was originally published in the Journal of Biological Chemistry. de Taeye, S. W., Go, E. P., Sliepen, K., de la Peña, A. T., Badal, K., Medina-Ramírez, M., Lee, W. H., Desaire, H., Wilson, I. A., Moore, J. P., Ward, A. B., & Sanders, R. W. (2019). Stabilization of the V2 loop improves the presentation of V2 loop-associated broadly neutralizing antibody epitopes on HIV-1 envelope trimers. The Journal of biological chemistry, 294(14), 5616–5631. https://doi.org/10.1074/jbc.RA118.005396 © the Author(s).
This work is licensed under a Creative Commons Attribution 4.0 International License. | en_US |
dc.description.abstract | A successful HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs) that target the envelope glycoprotein (Env) spike on the virus. Native-like recombinant Env trimers of the SOSIP design now serve as a platform for achieving this challenging goal. However, SOSIP trimers usually do not bind efficiently to the inferred germline precursors of bNAbs (gl-bNAbs). We hypothesized that the inherent flexibilities of the V1 and V2 variable loops in the Env trimer contribute to the poor recognition of gl-bNAb epitopes at the trimer apex that extensively involve V2 residues. To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and gl-bNAbs, we designed BG505 SOSIP.664 trimer variants containing newly created disulfide bonds intended to stabilize the V2 loop in an optimally antigenic configuration. The first variant, I184C/E190C, contained a new disulfide bond within the V2 loop, whereas the second variant, E153C/R178C, had a new disulfide bond that cross-linked V2 and V1. The resulting engineered native-like trimer variants were both more reactive with and were neutralized by V2 bNAbs and gl-bNAbs, a finding that may be valuable in the design of germline targeting and boosting trimer immunogens to create an antigenic conformation optimal for HIV vaccine development. | en_US |
dc.publisher | American Society for Biochemistry and Molecular Biology | en_US |
dc.rights | © 2019 de Taeye et al. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Human immunodeficiency virus (HIV) | en_US |
dc.subject | Glycoprotein structure | en_US |
dc.subject | Structure-function | en_US |
dc.subject | Protein design | en_US |
dc.subject | Antibody | en_US |
dc.subject | Vaccine development | en_US |
dc.subject | HIV-1 envelope glycoprotein trimer | en_US |
dc.title | Stabilization of the V2 loop improves the presentation of V2 loop–associated broadly neutralizing antibody epitopes on HIV-1 envelope trimers | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Go, Eden P. | |
kusw.kuauthor | Desaire, Heather | |
kusw.kudepartment | Chemistry | en_US |
dc.identifier.doi | 10.1074/jbc.RA118.005396 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-9445-6671 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC6462529 | en_US |
dc.rights.accessrights | openAccess | en_US |