Erratum: Functional characterization of two scFv-Fc antibodies from an HIV controller selected on soluble HIV-1 Env complexes: A neutralizing V3- and a trimer-specific gp41 antibody (PLoS ONE (2014) 9:5 (e97478) (DOI:10.1371/journal.pone.0097478));Functional characterization of two scFv-Fc antibodies from an HIV controller selected on soluble HIV-1 Env complexes: A neutralizing V3- and a trimer-specific gp41 antibody

PLoS ONE

Volumn 9, Issue 5, 2014, Pages

  Trott, Maria ^a   Weiß, Svenja ^a   Antoni, Sascha ^a,d   Koch, Joachim ^a   Von Briesen, Hagen ^b   Hust, Michael ^c   Dietrich, Ursula ^a  

^a INSTITUTE FOR TUMOR BIOLOGY AND EXPERIMENTAL THERAPY   (Germany)

^b FRAUNHOFER INSTITUTE FOR BIOMEDICAL ENGINEERING   (Germany)

^c TECHNICAL UNIVERSITY OF BRAUNSCHWEIG   (Germany)

^d ROCHE DIAGNOSTICS GMBH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; GLYCOPROTEIN GP 41; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY A2; MONOCLONAL ANTIBODY A7; NEUTRALIZING ANTIBODY; SCFC ANTIBODY; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; UNCLASSIFIED DRUG; VIRUS ENVELOPE PROTEIN; GLYCOPROTEIN GP 120; GP140 ENVELOPE PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1; HIV ENVELOPE PROTEIN GP120 (305-321); HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; IMMUNOGLOBULIN FC FRAGMENT; PEPTIDE FRAGMENT;

ARTICLE; CHO CELL LINE; CONTROLLED STUDY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; PHAGE DISPLAY; VIRUS ENVELOPE; HEK293 CELL LINE; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; PROCEDURES; SERODIAGNOSIS;

ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; EPITOPES; HEK293 CELLS; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP120; HIV ENVELOPE PROTEIN GP41; HIV INFECTIONS; HIV-1; HUMANS; IMMUNOGLOBULIN FC FRAGMENTS; NEUTRALIZATION TESTS; PEPTIDE FRAGMENTS; SINGLE-CHAIN ANTIBODIES;

EID: 84901348882     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0107089     Document Type: Erratum

References (87)

1. Baba TW, Liska V, Hofmann-Lehmann R, Vlasak J, Xu W, et al. (2000) Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat Med 6: 200-206. (Pubitemid 30082366)
2. Ferrantelli F, Hofmann-Lehmann R, Rasmussen RA, Wang T, Xu W, et al. (2003) Post-exposure prophylaxis with human monoclonal antibodies prevented SHIV89.6P infection or disease in neonatal macaques. AIDS 17: 301-309. (Pubitemid 36223254)
3. Hessell AJ, Poignard P, Hunter M, Hangartner L, Tehrani DM, et al. (2009) Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat Med 15: 951-954.
4. Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, et al. (2010) Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. J Virol 84: 1302-1313.
5. Jaworski JP, Kobie J, Brower Z, Malherbe DC, Landucci G, et al. (2013) Neutralizing polyclonal IgG present during acute infection prevents rapid disease onset in simian-human immunodeficiency virus SHIVSF162P3-infected infant rhesus macaques. J Virol 87: 10447-10459.
6. Mascola JR, Lewis MG, Stiegler G, Harris D, VanCott TC, et al. (1999) Protection of Macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J Virol 73: 4009-4018. (Pubitemid 29189846)
7. Parren PW, Marx PA, Hessell AJ, Luckay A, Harouse J, et al. (2001) Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J Virol 75: 8340-8347. (Pubitemid 32743706)
8. Ruprecht RM (2009) Passive immunization with human neutralizing monoclonal antibodies against HIV-1 in macaque models: experimental approaches. Methods Mol Biol 525: 559-566, xiv.
9. Shibata R, Igarashi T, Haigwood N, Buckler-White A, Ogert R, et al. (1999) Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys. Nat Med 5: 204-210. (Pubitemid 29068528)
10. Balazs AB, Chen J, Hong CM, Rao DS, Yang L, et al. (2012) Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 481: 81-84.
11. Gauduin MC, Parren PW, Weir R, Barbas CF, Burton DR, et al. (1997) Passive immunization with a human monoclonal antibody protects hu-PBL-SCID mice against challenge by primary isolates of HIV-1. Nat Med 3: 1389-1393. (Pubitemid 28011040)
12. Parren PW, Ditzel HJ, Gulizia RJ, Binley JM, Barbas CF III, et al. (1995) Protection against HIV-1 infection in hu-PBL-SCID mice by passive immunization with a neutralizing human monoclonal antibody against the gp120 CD4-binding site. AIDS 9: F1-6.
13. Pietzsch J, Gruell H, Bournazos S, Donovan BM, Klein F, et al. (2012) A mouse model for HIV-1 entry. Proc Natl Acad Sci U S A 109: 15859-15864.
14. Veselinovic M, Neff CP, Mulder LR, Akkina R (2012) Topical gel formulation of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 confers protection against HIV-1 vaginal challenge in a humanized mouse model. Virology 432: 505-510.
15. Barouch DH, Whitney JB, Moldt B, Klein F, Oliveira TY, et al. (2013) Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature 503: 224-228.
16. Shingai M, Nishimura Y, Klein F, Mouquet H, Donau OK, et al. (2013) Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature 503: 277-280.
17. Corti D, Lanzavecchia A (2013) Broadly neutralizing antiviral antibodies. Annu Rev Immunol 31: 705-742.
18. Burton DR, Pyati J, Koduri R, Sharp SJ, Thornton GB, et al. (1994) Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 266: 1024-1027. (Pubitemid 24373715)
19. Buchacher A, Predl R, Strutzenberger K, Steinfellner W, Trkola A, et al. (1994) Generation of human monoclonal antibodies against HIV-1 proteins; electrofusion and Epstein-Barr virus transformation for peripheral blood lymphocyte immortalization. AIDS Res Hum Retroviruses 10: 359-369. (Pubitemid 24141210)
20. Zwick MB, Labrijn AF, Wang M, Spenlehauer C, Saphire EO, et al. (2001) Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol 75: 10892-10905. (Pubitemid 33034579)
21. Scanlan CN, Pantophlet R, Wormald MR, Ollmann Saphire E, Stanfield R, et al. (2002) The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1-.2 mannose residues on the outer face of gp120. J Virol 76: 7306-7321.
22. Trkola A, Purtscher M, Muster T, Ballaun C, Buchacher A, et al. (1996) Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol 70: 1100-1108. (Pubitemid 26029030)
23. Burton DR, Weiss RA (2010) AIDS/HIV. A boost for HIV vaccine design. Science 329: 770-773.
24. Corti D, Langedijk JP, Hinz A, Seaman MS, Vanzetta F, et al. (2010) Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. PLoS One 5: e8805.
25. Moore PL, Gray ES, Sheward D, Madiga M, Ranchobe N, et al. (2011) Potent and broad neutralization of HIV-1 subtype C by plasma antibodies targeting a quaternary epitope including residues in the V2 loop. J Virol 85: 3128-3141.
26. Morris L, Chen X, Alam M, Tomaras G, Zhang R, et al. (2011) Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting. PLoS One 6: e23532.
27. Scheid JF, Mouquet H, Feldhahn N, Seaman MS, Velinzon K, et al. (2009) Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458: 636-640.
28. Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, et al. (2011) Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477: 466-470.
29. Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, et al. (2010) Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329: 856-861.
30. Kwong PD, Mascola JR (2012) Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies. Immunity 37: 412-425.
31. Mikell I, Sather DN, Kalams SA, Altfeld M, Alter G, et al. (2011) Characteristics of the earliest cross-neutralizing antibody response to HIV-1. PLoS Pathog 7: e1001251.
32. Humbert M, Antoni S, Brill B, Landersz M, Rodes B, et al. (2007) Mimotopes selected with antibodies from HIV-1-neutralizing long-term non-progressor plasma. Eur J Immunol 37: 501-515. (Pubitemid 46915589)
33. Zhou M, Meyer T, Koch S, Koch J, von Briesen H, et al. (2013) Identification of a new epitope for HIV-neutralizing antibodies in the gp41 membrane proximal external region by an Env-tailored phage display library. Eur J Immunol 43: 499-509.
34. Schreiber A, Humbert M, Benz A, Dietrich U (2005) 3D-Epitope-Explorer (3DEX): localization of conformational epitopes within three-dimensional structures of proteins. J Comput Chem 26: 879-887. (Pubitemid 40860391)
35. Zhou M, Kostoula I, Brill B, Panou E, Sakarellos-Daitsiotis M, et al. (2012) Prime boost vaccination approaches with different conjugates of a new HIV-1 gp41 epitope encompassing the membrane proximal external region induce neutralizing antibodies in mice. Vaccine 30: 1911-1916.
36. Beddows S, Franti M, Dey AK, Kirschner M, Iyer SP, et al. (2007) A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120. Virology 360: 329-340. (Pubitemid 46482615)
37. Binley JM, Sanders RW, Clas B, Schuelke N, Master A, et al. (2000) A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J Virol 74: 627-643. (Pubitemid 30036198)
38. Earl PL, Broder CC, Long D, Lee SA, Peterson J, et al. (1994) Native oligomeric human immunodeficiency virus type 1 envelope glycoprotein elicits diverse monoclonal antibody reactivities. J Virol 68: 3015-3026. (Pubitemid 24129751)
39. Earl PL, Sugiura W, Montefiori DC, Broder CC, Lee SA, et al. (2001) Immunogenicity and protective efficacy of oligomeric human immunodeficiency virus type 1 gp140. J Virol 75: 645-653. (Pubitemid 32037268)
40. Harris A, Borgnia MJ, Shi D, Bartesaghi A, He H, et al. (2011) Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope glycoproteins display the same closed and open quaternary molecular architectures. Proc Natl Acad Sci U S A 108: 11440-11445.
41. Hoorelbeke B, van Montfort T, Xue J, LiWang PJ, Tanaka H, et al. (2013) HIV-1 envelope trimer has similar binding characteristics for carbohydrate-binding agents as monomeric gp120. FEBS Lett 587: 860-866.
42. Kim M, Qiao ZS, Montefiori DC, Haynes BF, Reinherz EL, et al. (2005) Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies. AIDS Res Hum Retroviruses 21: 58-67. (Pubitemid 40179802)
43. Nkolola JP, Peng H, Settembre EC, Freeman M, Grandpre LE, et al. (2010) Breadth of neutralizing antibodies elicited by stable, homogeneous clade A and clade C HIV-1 gp140 envelope trimers in guinea pigs. J Virol 84: 3270-3279.
44. Sundling C, Forsell MN, O'Dell S, Feng Y, Chakrabarti B, et al. (2010) Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates. J Exp Med 207: 2003-2017.
45. Yang X, Wyatt R, Sodroski J (2001) Improved elicitation of neutralizing antibodies against primary human immunodeficiency viruses by soluble stabilized envelope glycoprotein trimers. J Virol 75: 1165-1171. (Pubitemid 32094675)
46. Antoni S, Walz N, Landersz M, Humbert M, Seidl C, et al. (2007) Genetic and biological characterization of recombinant HIV type 1 with Env derived from long-term nonprogressor (LTNP) viruses. AIDS Res Hum Retroviruses 23: 1377-1386.
47. Migueles SA, Sabbaghian MS, Shupert WL, Bettinotti MP, Marincola FM, et al. (2000) HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc Natl Acad Sci U S A 97: 2709-2714. (Pubitemid 30159236)
48. Hust M, Meyer T, Voedisch B, Rulker T, Thie H, et al. (2011) A human scFv antibody generation pipeline for proteome research. J Biotechnol 152: 159-170.
49. Rondot S, Koch J, Breitling F, Dubel S (2001) A helper phage to improve single-chain antibody presentation in phage display. Nat Biotechnol 19: 75-78. (Pubitemid 32051961)
50. Soltes G, Hust M, Ng KK, Bansal A, Field J, et al. (2007) On the influence of vector design on antibody phage display. J Biotechnol 127: 626-637. (Pubitemid 44959123)
51. Hust M, Dubel S, Schirrmann T (2007) Selection of recombinant antibodies from antibody gene libraries. Methods Mol Biol 408: 243-255.
52. Miethe S, Rasetti-Escargueil C, Liu Y, Chahboun S, Pelat T, et al. (2014) Development of neutralizing scFv-Fc against botulinum neurotoxin A light chain from a macaque immune library. MAbs 6: 446-459.
53. Jager V, Bussow K, Wagner A, Weber S, Hust M, et al. (2013) High level transient production of recombinant antibodies and antibody fusion proteins in HEK293 cells. BMC Biotechnol 13: 52.
54. Zhang CW, Chishti Y, Hussey RE, Reinherz EL (2001) Expression, purification, and characterization of recombinant HIV gp140. The gp41 ectodomain of HIV or simian immunodeficiency virus is sufficient to maintain the retroviral envelope glycoprotein as a trimer. J Biol Chem 276: 39577-39585.
55. Zahn RC, Hermann FG, Kim EY, Rett MD, Wolinsky SM, et al. (2008) Efficient entry inhibition of human and nonhuman primate immunodeficiency virus by cell surface-expressed gp41-derived peptides. Gene Ther 15: 1210-1222.
56. Plewnia G, Schulze K, Hunte C, Tampe R, Koch J (2007) Modulation of the antigenic peptide transporter TAP by recombinant antibodies binding to the last five residues of TAP1. J Mol Biol 369: 95-107. (Pubitemid 46635432)
57. Montefiori DC (2009) Measuring HIV neutralization in a luciferase reporter gene assay. Methods Mol Biol 485: 395-405.
58. Schultz A, Koch S, Fuss M, Mazzotta AS, Sarzotti-Kelsoe M, et al. (2012) An automated HIV-1 Env-pseudotyped virus production for global HIV vaccine trials. PLoS One 7: e51715.
59. Davenport TM, Friend D, Ellingson K, Xu H, Caldwell Z, et al. (2011) Binding interactions between soluble HIV envelope glycoproteins and quaternary-structure-specific monoclonal antibodies PG9 and PG16. J Virol 85: 7095-7107.
60. Retter I, Althaus HH, Munch R, Muller W (2005) VBASE2, an integrative V gene database. Nucleic Acids Res 33: D671-674. (Pubitemid 40207959)
61. Yu X, Lu L, Cai L, Tong P, Tan S, et al. (2012) Mutations of Gln64 in the HIV-1 gp41 N-terminal heptad repeat render viruses resistant to peptide HIV fusion inhibitors targeting the gp41 pocket. J Virol 86: 589-593.
62. Eckert DM, Kim PS (2001) Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem 70: 777-810. (Pubitemid 32662225)
63. Izumi K, Watanabe K, Oishi S, Fujii N, Matsuoka M, et al. (2011) Potent anti-HIV-1 activity of N-HR-derived peptides including a deep pocket-forming region without antagonistic effects on T-20. Antivir Chem Chemother 22: 51-55.
64. Chan DC, Fass D, Berger JM, Kim PS (1997) Core structure of gp41 from the HIV envelope glycoprotein. Cell 89: 263-273. (Pubitemid 27199898)
65. Mascola JR, Montefiori DC (2010) The role of antibodies in HIV vaccines. Annu Rev Immunol 28: 413-444.
66. Klein F, Halper-Stromberg A, Horwitz JA, Gruell H, Scheid JF, et al. (2012) HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature 492: 118-122.
67. Huang KH, Bonsall D, Katzourakis A, Thomson EC, Fidler SJ, et al. (2010) B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection. Nat Commun 1: 102.
68. Schmitz JE, Kuroda MJ, Santra S, Simon MA, Lifton MA, et al. (2003) Effect of humoral immune responses on controlling viremia during primary infection of rhesus monkeys with simian immunodeficiency virus. J Virol 77: 2165-2173. (Pubitemid 36110029)
69. Derby NR, Gray S, Wayner E, Campogan D, Vlahogiannis G, et al. (2007) Isolation and characterization of monoclonal antibodies elicited by trimeric HIV-1 Env gp140 protein immunogens. Virology 366: 433-445. (Pubitemid 47398914)
70. Gorny MK, Zolla-Pazner S (2000) Recognition by human monoclonal antibodies of free and complexed peptides representing the prefusogenic and fusogenic forms of human immunodeficiency virus type 1 gp41. J Virol 74: 6186-6192. (Pubitemid 30412992)
71. Yuan W, Li X, Kasterka M, Gorny MK, Zolla-Pazner S, et al. (2009) Oligomer-specific conformations of the human immunodeficiency virus (HIV-1) gp41 envelope glycoprotein ectodomain recognized by human monoclonal antibodies. AIDS Res Hum Retroviruses 25: 319-328.
72. Almond D, Kimura T, Kong X, Swetnam J, Zolla-Pazner S, et al. (2010) Structural conservation predominates over sequence variability in the crown of HIV type 19s V3 loop. AIDS Res Hum Retroviruses 26: 717-723.
73. Sharon M, Kessler N, Levy R, Zolla-Pazner S, Gorlach M, et al. (2003) Alternative conformations of HIV-1 V3 loops mimic beta hairpins in chemokines, suggesting a mechanism for coreceptor selectivity. Structure 11: 225-236. (Pubitemid 36183646)
74. Zolla-Pazner S (2005) Improving on nature: focusing the immune response on the V3 loop. Hum Antibodies 14: 69-72.
75. Zolla-Pazner S, Cardozo T (2010) Structure-function relationships of HIV-1 envelope sequence-variable regions refocus vaccine design. Nat Rev Immunol 10: 527-535.
76. Andrabi R, Williams C, Wang XH, Li L, Choudhary AK, et al. (2013) Cross-neutralizing activity of human anti-V3 monoclonal antibodies derived from non-B clade HIV-1 infected individuals. Virology 439: 81-88.
77. Binley JM, Wrin T, Korber B, Zwick MB, Wang M, et al. (2004) Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol 78: 13232-13252. (Pubitemid 39507829)
78. Conley AJ, Gorny MK, Kessler JA Jr, Boots LJ, Ossorio-Castro M, et al. (1994) Neutralization of primary human immunodeficiency virus type 1 isolates by the broadly reactive anti-V3 monoclonal antibody, 447-52D. J Virol 68: 6994-7000. (Pubitemid 24328749)
79. Gorny MK, Williams C, Volsky B, Revesz K, Cohen S, et al. (2002) Human monoclonal antibodies specific for conformation-sensitive epitopes of V3 neutralize human immunodeficiency virus type 1 primary isolates from various clades. J Virol 76: 9035-9045. (Pubitemid 34919862)
80. Stanfield RL, Gorny MK, Williams C, Zolla-Pazner S, Wilson IA (2004) Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D. Structure 12: 193-204. (Pubitemid 38224543)
81. Gorny MK, Sampson J, Li H, Jiang X, Totrov M, et al. (2011) Human anti-V3 HIV-1 monoclonal antibodies encoded by the VH5-51/VL lambda genes define a conserved antigenic structure. PLoS One 6: e27780.
82. Gorny MK, Revesz K, Williams C, Volsky B, Louder MK, et al. (2004) The v3 loop is accessible on the surface of most human immunodeficiency virus type 1 primary isolates and serves as a neutralization epitope. J Virol 78: 2394-2404. (Pubitemid 38228932)
83. Gorny MK, Xu JY, Karwowska S, Buchbinder A, Zolla-Pazner S (1993) Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120. J Immunol 150: 635-643. (Pubitemid 23133641)
84. Tilley SA, Honnen WJ, Racho ME, Chou TC, Pinter A (1992) Synergistic neutralization of HIV-1 by human monoclonal antibodies against the V3 loop and the CD4-binding site of gp120. AIDS Res Hum Retroviruses 8: 461-467.
85. Ringe RP, Sanders RW, Yasmeen A, Kim HJ, Lee JH, et al. (2013) Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation. Proc Natl Acad Sci U S A 110: 18256-18261.
86. Julien JP, Cupo A, Sok D, Stanfield RL, Lyumkis D, et al. (2013) Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342: 1477-1483.
87. Lyumkis D, Julien JP, de Val N, Cupo A, Potter CS, et al. (2013) Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 342: 1484-1490.