HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite

作者: Bartek Nogal , Laura E. McCoy , Marit J. van Gils , Christopher A. Cottrell , James E. Voss

DOI: 10.1101/831008

关键词:

摘要: To date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed 241/289 glycan hole as dominant neutralizing antibody epitope. Here, we isolated monoclonal antibodies from a rabbit that did not exhibit hole-dependent autologous serum neutralization. The compete previously hole-specific but N332 supersite broadly antibodies. A high resolution cryoEM structure one in complex trimer demonstrated that, while epitope recognized overlapped by contacting GDIR motif at base V3, primary contacts were located variable V1 loop. These data suggest strain-specific responses to may interfere and vaccine immunogens require engineering minimize these off-target or steer them toward more desirable pathway.

参考文章(54)
John R. Mascola, Gabriela Stiegler, Thomas C. VanCott, Hermann Katinger, Calvin B. Carpenter, Chris E. Hanson, Holly Beary, Deborah Hayes, Sarah S. Frankel, Deborah L. Birx, Mark G. Lewis, Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies Nature Medicine. ,vol. 6, pp. 207- 210 ,(2000) , 10.1038/72318
Jeong Hyun Lee, Natalia de Val, Dmitry Lyumkis, Andrew B. Ward, Model Building and Refinement of a Natively Glycosylated HIV-1 Env Protein by High-Resolution Cryoelectron Microscopy Structure. ,vol. 23, pp. 1943- 1951 ,(2015) , 10.1016/J.STR.2015.07.020
D. W. Kulp, J.-P. Julien, S. Menis, L. Wickramasinghe, M. S. Seaman, W. R. Schief, I. A. Wilson, P. Poignard, D. R. Burton, D. Sok, K. J. Doores, B. Briney, K. M. Le, K. L. Saye-Francisco, A. Ramos, Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV Science Translational Medicine. ,vol. 6, pp. 1- 13 ,(2014) , 10.1126/SCITRANSLMED.3008104
Ann J. Hessell, Eva G. Rakasz, Pascal Poignard, Lars Hangartner, Gary Landucci, Donald N. Forthal, Wayne C. Koff, David I. Watkins, Dennis R. Burton, Broadly neutralizing human anti-HIV antibody 2G12 is effective in protection against mucosal SHIV challenge even at low serum neutralizing titers PLOS Pathogens. ,vol. 5, ,(2009) , 10.1371/JOURNAL.PPAT.1000433
D. Lyumkis, J.-P. Julien, N. de Val, A. Cupo, C. S. Potter, P.-J. Klasse, D. R. Burton, R. W. Sanders, J. P. Moore, B. Carragher, I. A. Wilson, A. B. Ward, Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer Science. ,vol. 342, pp. 1484- 1490 ,(2013) , 10.1126/SCIENCE.1245627
J.-P. Julien, A. Cupo, D. Sok, R. L. Stanfield, D. Lyumkis, M. C. Deller, P.-J. Klasse, D. R. Burton, R. W. Sanders, J. P. Moore, A. B. Ward, I. A. Wilson, Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science. ,vol. 342, pp. 1477- 1483 ,(2013) , 10.1126/SCIENCE.1245625
Leopold Kong, Jeong Hyun Lee, Katie J Doores, Charles D Murin, Jean-Philippe Julien, Ryan McBride, Yan Liu, Andre Marozsan, Albert Cupo, Per-Johan Klasse, Simon Hoffenberg, Michael Caulfield, C Richter King, Yuanzi Hua, Khoa M Le, Reza Khayat, Marc C Deller, Thomas Clayton, Henry Tien, Ten Feizi, Rogier W Sanders, James C Paulson, John P Moore, Robyn L Stanfield, Dennis R Burton, Andrew B Ward, Ian A Wilson, Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120 Nature Structural & Molecular Biology. ,vol. 20, pp. 796- 803 ,(2013) , 10.1038/NSMB.2594
B. Moldt, E. G. Rakasz, N. Schultz, P.-Y. Chan-Hui, K. Swiderek, K. L. Weisgrau, S. M. Piaskowski, Z. Bergman, D. I. Watkins, P. Poignard, D. R. Burton, Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo Proceedings of the National Academy of Sciences of the United States of America. ,vol. 109, pp. 18921- 18925 ,(2012) , 10.1073/PNAS.1214785109
N.R. Voss, C.K. Yoshioka, M. Radermacher, C.S. Potter, B. Carragher, DoG Picker and TiltPicker: software tools to facilitate particle selection in single particle electron microscopy. Journal of Structural Biology. ,vol. 166, pp. 205- 213 ,(2009) , 10.1016/J.JSB.2009.01.004
Jean-Philippe Julien, Devin Sok, Reza Khayat, Jeong Hyun Lee, Katie J. Doores, Laura M. Walker, Alejandra Ramos, Devan C. Diwanji, Robert Pejchal, Albert Cupo, Umesh Katpally, Rafael S. Depetris, Robyn L. Stanfield, Ryan McBride, Andre J. Marozsan, James C. Paulson, Rogier W. Sanders, John P. Moore, Dennis R. Burton, Pascal Poignard, Andrew B. Ward, Ian A. Wilson, Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans PLoS Pathogens. ,vol. 9, pp. e1003342- ,(2013) , 10.1371/JOURNAL.PPAT.1003342