An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability

Nature Microbiology

Volumn 2, Issue , 2016, Pages

  Van Gils, Marit J ^a,b   Van Den Kerkhof, Tom L G M ^a   Ozorowski, Gabriel ^b   Cottrell, Christopher A ^b   Sok, Devin ^b   Pauthner, Matthias ^b   Pallesen, Jesper ^b   De Val, Natalia ^b   Yasmeen, Anila ^c   De Taeye, Steven W ^a   Schorcht, Anna ^a   Gumbs, Stephanie ^a   Johanna, Inez ^a   Saye Francisco, Karen ^b   Liang, Chi Hui ^b   Landais, Elise ^b   Nie, Xiaoyan ^d   Pritchard, Laura K ^e   Crispin, Max ^e   Kelsoe, Garnett ^d   Wilson, Ian A ^b   Schuitemaker, Hanneke ^a,f   Klasse, Per Johan ^c   Moore, John P ^c   Burton, Dennis R ^b,g   Ward, Andrew B ^b   Sanders, Rogier W ^a,c   more..

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

^d DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f Janssen Research and Development   (Netherlands)

^g HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; GLYCOPROTEIN GP 160; GP160 PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; NEUTRALIZING ANTIBODY;

CRYOELECTRON MICROSCOPY; HIV SURVIVOR; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; ISOLATION AND PURIFICATION; ULTRASTRUCTURE;

ANTIBODIES, NEUTRALIZING; CRYOELECTRON MICROSCOPY; EPITOPES, B-LYMPHOCYTE; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP160; HIV INFECTIONS; HIV LONG-TERM SURVIVORS; HUMANS;

EID: 84995528377     PISSN: None     EISSN: 20585276     Source Type: Journal    
DOI: 10.1038/nmicrobiol.2016.199     Document Type: Article

References (56)

1. Burton, D. R. & Mascola, J. R. Antibody responses to envelope glycoproteins in HIV-1 infection. Nat. Immunol. 16, 571-576 (2015).
2. Doria-Rose, N. A. et al. Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J. Virol. 83, 188-199 (2009).
3. Simek, M. D. et al. HIV-1 elite neutralizers: individuals with broad and potent neutralizing activity identified using a high throughput neutralization assay together with an analytical selection algorithm. J. Virol. 83, 7337-7348 (2009).
4. Euler, Z. & Schuitemaker, H. Cross-reactive broadly neutralizing antibodies: timing is everything. Front. Immunol. 3, 215 (2012).
5. van Gils, M. J. & Sanders, R. W. In vivo protection by broadly neutralizing HIV antibodies. Trends Microbiol. 22, 550-551 (2014).
6. Sather, D. N. et al. Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J. Virol. 83, 757-769 (2009).
7. Moore, P. L., Williamson, C. & Morris, L. Virological features associated with the development of broadly neutralizing antibodies to HIV-1. Trends Microbiol. 23, 204-211 (2015).
8. Wibmer, C. K., Moore, P. L. & Morris, L. HIV broadly neutralizing antibody targets. Curr. Opin. HIV AIDS 10, 135-143 (2015).
9. Sanders, R. W. et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathogens 9, e1003618 (2013).
10. Derking, R. et al. Comprehensive antigenic map of a cleaved soluble HIV-1 envelope trimer. PLoS Pathogens 11, e1004767 (2015).
11. Blattner, C. et al. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity 40, 669-680 (2014).
12. Falkowska, E. et al. Broadly neutralizing HIV antibodies define a glycandependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers. Immunity 40, 657-668 (2014).
13. Huang, J. et al. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature 515, 138-142 (2014).
14. 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).
15. Kong, R. et al. Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science 352, 828-833 (2016).
16. Julien, J.-P. et al. Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens. Proc. Natl Acad. Sci. USA 112, 11947-11952 (2015).
17. 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).
18. Julien, J.-P. et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342, 1477-1483 (2013).
19. Lyumkis, D. et al. Cryo-EMstructure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 342, 1484-1490 (2013).
20. Guenaga, J. et al. Well-ordered trimeric HIV-1 subtype B and C soluble spike mimetics generated by negative selection display native-like properties. PLoS Pathogens 11, e1004570 (2015).
21. Andrabi, R. et al. Identification of common features in prototype broadly neutralizing antibodies to HIV envelope V2 apex to facilitate vaccine design. Immunity 43, 959-973 (2015).
22. de Taeye, S. W. et al. Immunogenicity of stabilized HIV-1 envelope trimers with reduced exposure of non-neutralizing epitopes. Cell 163, 1702-1715 (2015).
23. Sanders, R. W. et al. HIV-1 vaccines. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science 349, aac4223 (2015).
24. van den Kerkhof, T. L. et al. Early development of broadly reactive HIV-1 neutralizing activity in elite neutralizers. AIDS 28, 1237-1240 (2014).
25. Tiller, T. et al. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J. Immunol. Methods 329, 112-124 (2008).
26. Lefranc, M.-P. et al. IMGT, the international ImMunoGeneTics information system. Nucleic Acids Res. 37, D1006-D1012 (2009).
27. Seaman, M. S. et al. Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J. Virol. 84, 1439-1452 (2010).
28. McCoy, L. E. et al. Incomplete neutralization and deviation from sigmoidal neutralization curves for HIV broadly neutralizing monoclonal antibodies. PLoS Pathogens 11, e1005110 (2015).
29. Webb, N. E., Montefiori, D. C. & Lee, B. Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies. Nat. Commun. 6, 8443 (2015).
30. Walker, L. M. et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477, 466-470 (2011).
31. Doria-Rose, N. A. et al. Developmental pathway for potent V1V2-directed HIVneutralizing antibodies. Nature 509, 55-62 (2014).
32. Mascola, J. R. & Haynes, B. F. HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol. Rev. 254, 225-244 (2013).
33. van Esch, W. J. et al. Polyreactivity of human IgG Fc-binding phage antibodies constructed from synovial fluid CD38+ B cells of patients with rheumatoid arthritis. J. Autoimmun. 19, 241-250 (2002).
34. Liu, M. et al. Polyreactivity and autoreactivity among HIV-1 antibodies. J. Virol. 89, 784-798 (2015).
35. Mian, I. S., Bradwell, A. R. & Olson, A. J. Structure, function and properties of antibody binding sites. J. Mol. Biol. 217, 133-151 (1991).
36. Sharma, S. K. et al. Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design. Cell Rep. 11, 539-550 (2015).
37. 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).
38. Wu, X. et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329, 856-861 (2010).
39. Scheid, J. F. et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333, 1633-1637 (2011).
40. Khayat, R. et al. Structural characterization of cleaved, soluble HIV-1 envelope glycoprotein trimers. J. Virol. 87, 9865-9872 (2013).
41. Pritchard, L. K. et al. Structural constraints determine the glycosylation of HIV-1 envelope trimers. Cell Rep. 11, 1604-1613 (2015).
42. Sok, D. et al. Recombinant HIV envelope trimer selects for quaternarydependent antibodies targeting the trimer apex. Proc. Natl Acad. Sci. USA 111, 17624-17629 (2014).
43. 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).
44. 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).
45. Pettersen, E. F. et al. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612 (2004).
46. van 'tWout, A. B., Schuitemaker, H. & Kootstra, N. A. Isolation and propagation of HIV-1 on peripheral blood mononuclear cells. Nat. Protoc. 3, 363-370 (2008).
47. Finzi, A. et al. Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol. Cell 37, 656-667 (2010).
48. Scheres, S. H. W. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519-530 (2012).
49. Scheres, S. H. W. & Chen, S. Prevention of overfitting in cryo-EM structure determination. Nat. Methods 9, 853-854 (2012).
50. Corti, D. et al. Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. PLoS ONE 5, e8805 (2010).
51. Webb, B. & Sali, A. Comparative protein structure modeling using MODELLER. Curr. Protoc. Bioinformatics 47, 1-32 (2014).
52. DiMaio, F. et al. Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density-guided iterative local refinement. Nat. Methods 12, 361-365 (2015).
53. Chen, V. B. et al. Molprobity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12-21 (2010).
54. Yasmeen, A. et al. Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Retrovirology 11, 41 (2014).
55. Yang, G. et al. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. J. Exp. Med. 210, 241-256 (2013).
56. Xu, Y. et al. Addressing polyspecificity of antibodies selected from an in vitro yeast presentation system: a FACS-based, high-throughput selection and analytical tool. Prot. Eng. Des. Sel. 26, 663-670 (2013).