Structural characterization of a highly-potent V3-glycan broadly neutralizing antibody bound to natively-glycosylated HIV-1 envelope

Nature Communications

Volumn 9, Issue 1, 2018, Pages

  Barnes, Christopher O ^a   Gristick, Harry B ^a   Freund, Natalia T ^b,d   Escolano, Amelia ^b   Lyubimov, Artem Y ^c   Hartweger, Harald ^b   West, Anthony P ^a   Cohen, Aina E ^c   Nussenzweig, Michel C ^b   Bjorkman, Pamela J ^a  

^a California Institute of Technology   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

^c SLAC NATIONAL ACCELERATOR LABORATORY   (United States)

^d TEL AVIV UNIVERSITY   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

BG18 ANTIBODY; BROADLY NEUTRALIZING ANTIBODY; GLYCAN; MANNOSE OLIGOSACCHARIDE; NEUTRALIZING ANTIBODY; UNCLASSIFIED DRUG; VIRUS ENVELOPE PROTEIN; EPITOPE; GLYCOPROTEIN GP 120; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; POLYSACCHARIDE; PROTEIN BINDING;

ANTIBODY; CRYSTAL STRUCTURE; ENZYME ACTIVITY; GENE EXPRESSION; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNOASSAY; LASER; PEPTIDE; PROTEIN; VACCINE; X-RAY;

ANIMAL CELL; ANTIBODY COMBINING SITE; ANTIGEN BINDING; ARTICLE; CONFORMATION; CRYSTAL STRUCTURE; FEMALE; GLYCOSYLATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PROTEIN CONFORMATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; ANIMAL; CHEMISTRY; CHO CELL LINE; CRICETULUS; HAMSTER; HEK293 CELL LINE; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; PROTEIN DOMAIN; PROTEIN MULTIMERIZATION; X RAY CRYSTALLOGRAPHY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

ANIMALS; ANTIBODIES, NEUTRALIZING; CHO CELLS; CRICETINAE; CRICETULUS; CRYSTALLOGRAPHY, X-RAY; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; EPITOPES; GLYCOSYLATION; HEK293 CELLS; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HUMANS; POLYSACCHARIDES; PROTEIN BINDING; PROTEIN DOMAINS; PROTEIN MULTIMERIZATION;

EID: 85044543312     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-018-03632-y     Document Type: Article

References (74)

1. Klein, F. et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature 492, 118-122 (2012).
2. Horwitz, J. A. et al. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proc. Natl Acad. Sci. USA 110, 16538-16543 (2013).
3. Shingai, M. et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature 503, 277-280 (2013).
4. Barouch, D. H. et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature 503, 224-228 (2013).
5. Bar, K. J. et al. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N. Engl. J. Med. 375, 2037-2050 (2016).
6. Schoofs, T. et al. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science 352, 997-1001 (2016).
7. Caskey, M. et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature 522, 487-491 (2015).
8. Caskey, M. et al. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. Nat. Med. 23, 185-191 (2017).
9. Lynch, R. M. et al. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci. Transl. Med. 7, 319ra206-319ra206 (2015).
10. Klein, F. et al. Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. Cell 153, 126-138 (2013).
11. West, A. P. et al. Structural insights on the role of antibodies in HIV-1 vaccine and therapy. Cell 156, 633-648 (2014).
12. West, A. P. J., Diskin, R., Nussenzweig, M. C. &Bjorkman, P. J. Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1gp120. Proc. Natl Acad. Sci. USA 109, E2083-E2090 (2012).
13. Dingens, A. S., Haddox, H. K., Overbaugh, J. &Bloom, J. D. Comprehensive mapping of HIV-1 escape from a broadly neutralizing antibody. Cell Host Microbe 21, 777-787.e4 (2017).
14. Klein, J. S. &Bjorkman, P. J. Few and far between: how HIV may be evading antibody avidity. PLoS Pathog. 6, e1000908 (2010).
15. Galimidi, R. P. et al. Intra-spike crosslinking overcomes antibody evasion by HIV-1. Cell 160, 433-446 (2015).
16. Wei, X. et al. Antibody neutralization and escape by HIV-1. Nature 422, 307-312 (2003).
17. Zhu, X., Borchers, C., Bienstock, R. J. &Tomer, K. B. Mass spectrometric characterization of the glycosylation pattern of HIV-gp120 expressed in CHOcells. Biochemistry 39, 11194-11204 (2000).
18. Behrens, A.-J. et al. Composition and antigenic effects of individual glycan sites of a trimeric HIV-1 envelope glycoprotein. Cell Rep. 14, 2695-2706 (2016).
19. Binley, J. M. et al. Role of complex carbohydrates in human immunodeficiency virus type 1 infection and resistance to antibody neutralization. J. Virol. 84, 5637-5655 (2010).
20. Sanders, R. W. et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 9, e1003618 (2013).
21. Ward, A. B. &Wilson, I. A. The HIV-1 envelope glycoprotein structure: nailing down a moving target. Immunol. Rev. 275, 21-32 (2017).
22. Scharf, L. et al. Broadly neutralizing antibody 8ANC195 recognizes closed and open states of HIV-1 env. Cell 162, 1379-1390 (2015).
23. Sievers, S. A., Scharf, L., West, A. P. Jr. &Bjorkman, P. J. Antibody engineering for increased potency, breadth and half-life. Curr. Opin. HIV AIDS 10, 151-159 (2015).
24. Diskin, R. et al. Increasing the potency and breadth of an HIV antibody by using structure-based rational design. Science 334, 1289-1293 (2011).
25. Gristick, H. B. et al. Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site. Nat. Struct. Mol. Biol. 23, 906-915 (2016).
26. Pancera, M. et al. Crystal structures of trimeric HIV envelope with entry inhibitors BMS-378806 and BMS-626529. Nat. Chem. Biol. 68, 4031-1122 (2017).
27. Stewart-Jones, G. B. E. et al. Trimeric HIV-1-env structures define glycan shields from clades A, B, and G. Cell 165, 813-826 (2016).
28. Kwon, Y. D. et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat. Struct. 22, 522-531 (2015).
29. Pancera, M. et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514, 455-461 (2014).
30. Kwong, P. D. et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393, 648-659 (1998).
31. Garces, F. et al. Affinity maturation of a potent family of HIV antibodies is primarily focused on accommodating or avoiding glycans. Immunity 43, 1053-1063 (2015).
32. Garces, F. et al. Structural evolution of glycan recognition by a family of potent HIV antibodies. Cell 159, 69-79 (2014).
33. Julien, J.-P. et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342, 1477-1483 (2013).
34. Diskin, R., Marcovecchio, P. M. &Bjorkman, P. J. Structure of a clade C HIV-1 gp120 bound to CD4 and CD4-induced antibody reveals anti-CD4 polyreactivity. Nat. Struct. 17, 1-19 (2010).
35. Kong, R., Xu, K., Zhou, T., Acharya, P. &Lemmin, T. Fusion peptide of HIV-1 a site of vulnerability to neutralizing antibody. Science 352, 828-833 (2016).
36. Zhou, T. et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329, 811-817 (2010).
37. Scharf, L. et al. Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Rep. 7, 785-795 (2014).
38. Lee, J. H., Ozorowski, G. &Ward, A. B. Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer. Science 351, 1043-1048 (2016).
39. Lee, J. H., de Val, N., Lyumkis, D. &Ward, A. B. Model building and refinement of a natively glycosylated HIV-1 env protein by high-resolution cryoelectron microscopy. Structure 23, 1943-1951 (2015).
40. Mouquet, H. et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc. Natl Acad. Sci. USA 109, E3268-E3277 (2012).
41. Walker, L. M. et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477, 466-470 (2011).
42. Sok, D. et al. A prominent site of antibody vulnerability on HIV envelope incorporates a motif associated with CCR5 binding and its camouflaging glycans. Immunity 45, 31-45 (2016).
43. Doores, K. J. et al. Two classes of broadly neutralizing antibodies within a single lineage directed to the high-mannose patch of HIV envelope. J. Virol. 89, 1105-1118 (2015).
44. Kong, L. et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120-803. Nat. Struct. Mol. Biol. 20, 796-803 (2013).
45. Pejchal, R. et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 334, 1097-1103 (2011).
46. Andrabi, R. et al. Glycans function as anchors for antibodies and help drive HIV broadly neutralizing antibody development. Immunity 47, 524-537.e3 (2017).
47. Freund, N. T. et al. Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller. Sci. Transl. Med. 9, eaal2144 (2017).
48. Cohen, A. E. et al. Goniometer-based femtosecond crystallography with X-ray free electron lasers. Proc. Natl Acad. Sci. USA 111, 17122-17127 (2014).
49. Escolano, A. et al. Sequential immunization elicits broadly neutralizing anti-HIV-1 antibodies in Ig knockin mice. Cell 166, 1445-1458.e12 (2016).
50. Steichen, J. M. et al. HIV vaccine design to target germline precursors of glycan-dependent broadly neutralizing antibodies. Immunity 45, 483-496 (2016).
51. Chung, N. P. et al. Stable 293 T and CHO cell lines expressing cleaved, stable HIV-1 envelope glycoprotein trimers for structural and vaccine studies. Retrovirology 11, 33 (2014).
52. Go, E. P. et al. Glycosylation benchmark profile for HIV-1 envelope glycoprotein production based on eleven env trimers. J. Virol. 91, e02428-16-19 (2017).
53. Huang, J. et al. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-120 interface. Nature 515, 138-142 (2014).
54. Zhou, Q. et al. Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis. Nature 525, 62-67 (2015).
55. Liu, C. &Xiong, Y. Electron density sharpening as a general technique in crystallographic studies. J. Mol. Biol. 426, 980-993 (2014).
56. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
57. Cao, L. et al. Global site-specific N-glycosylation analysis of HIV envelope glycoprotein. Nat. Commun. 8, 1-13 (2017).
58. Zhou, T. et al. Quantification of the impact of the HIV-1-glycan shield on antibody elicitation. Cell Rep. 19, 719-732 (2017).
59. Wu, X. et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science 333, 1593-1602 (2011).
60. Zhou, T. et al. Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity 39, 245-258 (2013).
61. Pugach, P. et al. A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene. J. Virol. 89, 3380-3395 (2015).
62. Kabsch, W. XDS. Acta Crystallogr. D Biol. Crystallogr. 66, 125-132 (2010).
63. Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D Biol. Crystallogr. 67, 235-242 (2011).
64. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007).
65. Brunger, A. T. et al. Crystallography &NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr. D Biol. Crystallogr. 54, 905-921 (1998).
66. Emsley, P., Lohkamp, B., Scott, W. G. &Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486-501 (2010).
67. Gristick, H. B., Wang, H. &Bjorkman, P. J. X-ray and EM structures of a natively glycosylated HIV-1 envelope trimer. Acta Crystallogr. D Struct. Biol. 73, 822-828 (2017).
68. Karplus, P. A. &Diederichs, K. Linking crystallographic model and data quality. Science 336, 1030-1033 (2012).
69. Lyubimov, A. Y. et al. IOTA: integration optimization, triage and analysis tool for the processing of XFEL diffraction images. J. Appl. Crystallogr. 49, 1057-1064 (2016).
70. Hattne, J. et al. Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers. Nat. Methods 11, 545-548 (2014).
71. Uervirojnangkoorn, M. et al. Enabling X-ray free electron laser crystallography for challenging biological systems from a limited number of crystals. Elife 4, 213 (2015).
72. Unni, S. et al. Web servers and services for electrostatics calculations with APBS and PDB2PQR. J. Comput. Chem. 32, 1488-1491 (2011).
73. Krissinel, E. &Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797 (2007).
74. West, A. P. et al. Computational analysis of anti-HIV-1 antibody neutralization panel data to identify potential functional epitope residues. Proc. Natl Acad. Sci. USA 110, 10598-10603 (2013).