A glycoconjugate antigen based on the recognition motif of a broadly neutralizing human immunodeficiency virus antibody, 2G12, is immunogenic but elicits antibodies unable to bind to the self glycans of gp120

Journal of Virology

Volumn 82, Issue 13, 2008, Pages 6359-6368

  Astronomo, Rena D ^a   Lee, Hing Ken ^a,d   Scanlan, Christopher N ^a,b   Pantophlet, Ralph ^a   Huang, Cheng Yuan ^a,c   Wilson, Ian A ^a   Blixt, Ola ^a,e   Dwek, Raymond A ^b   Wong, Chi Huey ^a   Burton, Dennis R ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c NAGOYA UNIVERSITY   (Japan)

^d Intertek Testing Services Shenzhen Ltd   (China)

^e UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

2G12 ANTIBODY; BOVINE SERUM ALBUMIN; CHITOBIOSE; GLYCAN; GLYCOPROTEIN GP 120; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; LYSINE; MANNOSIDE; NEUTRALIZING ANTIBODY;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY TITER; ANTIGEN BINDING; ANTIGEN RECOGNITION; ARTICLE; CONJUGATION; CONTROLLED STUDY; CROSS REACTION; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMORAL IMMUNITY; IMMUNIZATION; IMMUNOGENICITY; NONHUMAN; PRIORITY JOURNAL; RABBIT;

AMINO ACID MOTIFS; ANTIBODIES, MONOCLONAL; ANTIGENS; ENZYME-LINKED IMMUNOSORBENT ASSAY; GLYCOCONJUGATES; HIV ENVELOPE PROTEIN GP120; HIV-1; MICROARRAY ANALYSIS; OLIGOSACCHARIDES; POLYSACCHARIDES;

BOVINAE; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; ORYCTOLAGUS CUNICULUS;

EID: 45749138808     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.00293-08     Document Type: Article

References (82)

1. Baba, T. W., V. Liska, R. Hofmann-Lehmann, J. Vlasak, W. Xu, S. Ayehunie, L. A. Cavacini, M. R. Posner, H. Katinger, G. Stiegler, B. J. Bernacky, T. A. Rizvi, R. Schmidt, L. R. Hill, M. E. Keeling, Y. Lu, J. E. Wright, T. C. Chou, and R. M. Ruprecht. 2000. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat. Med. 6:200-206.
2. Barbas, C. F., III, T. A. Collet, W. Amberg, P. Roben, J. M. Binley, D. Hoekstra, D. Cababa, T. M. Jones, R. A. Williamson, G. R. Pilkington, et al. 1993. Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries. J. Mol. Biol. 230:812-823.
3. Beirnaert, E., S. De Zutter, W. Janssens, and G. van der Groen. 2001. Potent broad cross-neutralizing sera inhibit attachment of primary HIV-1 isolates (groups M and O) to peripheral blood mononuclear cells. Virology 281:305-314.
4. Binley, J. M., T. Wrin, B. Korber, M. B. Zwick, M. Wang, C. Chappey, G. Stiegler, R. Kunert, S. Zolla-Pazner, H. Katinger, C. J. Petropoulos, and D. R. Burton. 2004. Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J. Virol. 78:13232-13252.
5. Blixt, O., S. Head, T. Mondala, C. Scanlan, M. E. Huflejt, R. Alvarez, M. C. Bryan, F. Fazio, D. Calarese, J. Stevens, N. Razi, D. J. Stevens, J. J. Skehel, I. van Die, D. R. Burton, I. A. Wilson, R. Cummings, N. Bovin, C. H. Wong, and J. C. Paulson. 2004. Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc. Natl. Acad. Sci. USA 101:17033-17038.
6. Bolmstedt, A., S. Sjolander, J. E. Hansen, L. Akerblom, A. Hemming, S. L. Hu, B. Morein, and S. Olofsson. 1996. Influence of N-linked glycans in V4-V5 region of human immunodeficiency virus type 1 glycoprotein gp160 on induction of a virus-neutralizing humoral response. J. Acquir. Immune Defic. Syndr. Hum. Retrovir. 12:213-220.
7. Bryan, M. C., F. Fazio, H. K. Lee, C. Y. Huang, A. Chang, M. D. Best, D. A. Calarese, O. Blixt, J. C. Paulson, D. Burton, I. A. Wilson, and C. H. Wong. 2004. Covalent display of oligosaccharide arrays in microtiter plates. J. Am. Chem. Soc. 126:8640-8641.
8. Buchacher, A., R. Predl, K. Strutzenberger, W. Steinfellner, A. Trkola, M. Purtscher, G. Gruber, C. Tauer, F. Steindl, A. Jungbauer, 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. Retrovir. 10:359-369.
9. Burton, D. R. 2002. Antibodies, viruses and vaccines. Nat. Rev. Immunol. 2:706-713.
10. Burton, D. R. 1997. A vaccine for HIV type 1: the antibody perspective. Proc. Natl. Acad. Sci. USA 94:10018-10023.
11. Burton, D. R., C. F. Barbas III, M. A. Persson, S. Koenig, R. M. Chanock, and R. A. Lerner. 1991. A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc. Natl. Acad. Sci. USA 88:10134-10137.
12. Burton, D. R., R. C. Desrosiers, R. W. Doms, W. C. Koff, P. D. Kwong, J. P. Moore, G. J. Nabel, J. Sodroski, I. A. Wilson, and R. T. Wyatt. 2004. HIV vaccine design and the neutralizing antibody problem. Nat. Immunol. 5:233-236.
13. Burton, D. R., J. Pyati, R. Koduri, S. J. Sharp, G. B. Thornton, P. W. Parren, L. S. Sawyer, R. M. Hendry, N. Dunlop, P. L. Nara, et al. 1994. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 266:1024-1027.
14. Burton, D. R., R. L. Stanfield, and I. A. Wilson. 2005. Antibody vs. HIV in a clash of evolutionary titans. Proc. Natl. Acad. Sci. USA 102:14943-14948.
15. Calarese, D. A., H. K. Lee, C. Y. Huang, M. D. Best, R. D. Astronomo, R. L. Stanfield, H. Katinger, D. R. Burton, C. H. Wong, and I. A. Wilson. 2005. Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12. Proc. Natl. Acad. Sci. USA 102:13372-13377.
16. Calarese, D. A., C. N. Scanlan, M. B. Zwick, S. Deechongkit, Y. Mimura, R. Kunert, P. Zhu, M. R. Wormald, R. L. Stanfield, K. H. Roux, J. W. Kelly, P. M. Rudd, R. A. Dwek, H. Katinger, D. R. Burton, and I. A. Wilson. 2003. Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science 300:2065-2071.
17. Chen, B., E. M. Vogan, H. Gong, J. J. Skehel, D. C. Wiley, and S. C. Harrison. 2005. Structure of an unliganded simian immunodeficiency virus gp120 core. Nature 433:834-841.
18. Conley, A. J., M. K. Gorny, J. A. Kessler II, L. J. Boots, M. Ossorio-Castro, S. Koenig, D. W. Lineberger, E. A. Emini, C. Williams, and S. Zolla-Pazner. 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.
19. Conley, A. J., J. A. Kessler II, L. J. Boots, J. S. Tung, B. A. Arnold, P. M. Keller, A. R. Shaw, and E. A. Emini. 1994. Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody. Proc. Natl. Acad. Sci. USA 91:3348-3352.
20. Cutalo, J. M., L. J. Deterding, and K. B. Tomer. 2004. Characterization of glycopeptides from HIV-I(SF2) gp120 by liquid chromatography mass spectrometry. J. Am. Soc. Mass Spectrom. 15:1545-1555.
21. Donners, H., B. Willems, E. Beirnaert, R. Colebunders, D. Davis, and G. van der Groen. 2002. Cross-neutralizing antibodies against primary isolates in African women infected with HIV-1. AIDS 16:501-503.
22. Douek, D. C., P. D. Kwong, and G. J. Nabel. 2006. The rational design of an AIDS vaccine. Cell 124:677-681.
23. D'Souza, M. P., D. Livnat, J. A. Bradac, S. H. Bridges, et al. 1997. Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. J. Infect. Dis. 175:1056-1062.
24. Dudkin, V. Y., M. Orlova, X. Geng, M. Mandal, W. C. Olson, and S. J. Danishefsky. 2004. Toward fully synthetic carbohydrate-based HIV antigen design: on the critical role of bivalency. J. Am. Chem. Soc. 126:9560-9562.
25. Ferrantelli, F., R. A. Rasmussen, K. A. Buckley, P. L. Li, T. Wang, D. C. Montefiori, H. Katinger, G. Stiegler, D. C. Anderson, H. M. McClure, and R. M. Ruprecht. 2004. Complete protection of neonatal rhesus macaques against oral exposure to pathogenic simian-human immunodeficiency virus by human anti-HIV monoclonal antibodies. J. Infect. Dis. 189:2167-2173.
26. Fromme, R., Z. Katiliene, B. Giomarelli, F. Bogani, J. Mc Mahon, T. Mori, P. Fromme, and G. Ghirlanda. 2007. A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity. Biochemistry 46:9199-9207.
27. Gauduin, M. C., P. W. Parren, R. Weir, C. F. Barbas, D. R. Burton, and R. A. Koup. 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.
28. Geng, X., V. Y. Dudkin, M. Mandal, and S. J. Danishefsky. 2004. In pursuit of carbohydrate-based HIV vaccines, part 2: the total synthesis of high-mannose-type gp120 fragments - evaluation of strategies directed to maximal convergence. Angew. Chem. Int. Ed. Engl. 43:2562-2565.
29. Harlow, E., and D. Lane. 1988. Antibodies: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
30. Hofmann-Lehmann, R., J. Vlasak, R. A. Rasmussen, B. A. Smith, T. W. Baba, V. Liska, F. Ferrantelli, D. C. Montefiori, H. M. McClure, D. C. Anderson, B. J. Bernacky, T. A. Rizvi, R. Schmidt, L. R. Hill, M. E. Keeling, H. Katinger, G. Stiegler, L. A. Cavacini, M. R. Posner, T. C. Chou, J. Andersen, and R. M. Ruprecht. 2001. Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge. J. Virol. 75:7470-7480.
31. Huang, B. X., H. Y. Kim, and C. Dass. 2004. Probing three-dimensional structure of bovine serum albumin by chemical cross-linking and mass spectrometry. J. Am. Soc. Mass Spectrom. 15:1237-1247.
32. Johnston, M. I., and A. S. Fauci. 2007. An HIV vaccine - evolving concepts. N. Engl. J. Med. 356:2073-2081.
33. Krauss, I. J., J. G. Joyce, A. C. Finnefrock, H. C. Song, V. Y. Dudkin, X. Geng, J. D. Warren, M. Chastain, J. W. Shiver, and S. J. Danishefsky. 2007. Fully synthetic carbohydrate HIV antigens designed on the logic of the 2G12 antibody. J. Am. Chem. Soc. 129:11042-11044.
34. Kunert, R., F. Ruker, and H. Katinger. 1998. Molecular characterization of five neutralizing anti-HIV type 1 antibodies: identification of nonconventional D segments in the human monoclonal antibodies 2G12 and 2F5. AIDS Res. Hum. Retrovir. 14:1115-1128.
35. Kwong, P. D., R. Wyatt, J. Robinson, R. W. Sweet, J. Sodroski, and W. A. Hendrickson. 1998. Structure of an H1V gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393:648-659.
36. Kwong, P. D., R. Wyatt, Q. J. Sattentau, J. Sodroski, and W. A. Hendrickson. 2000. Oligomeric modeling and electrostatic analysis of the gp120 envelope glycoprotein of human immunodeficiency virus. J. Virol. 74:1961-1972.
37. Lee, H. K., C. N. Scanlan, C. Y. Huang, A. Y. Chang, D. A. Calarese, R. A. Dwek, P. M. Rudd, D. R. Burton, I. A. Wilson, and C. H. Wong. 2004. Reactivity-based one-pot synthesis of oligomannoses: defining antigens recognized by 2G12, a broadly neutralizing anti-HIV-1 antibody. Angew. Chem. Int. Ed. Engl. 43:1000-1003.
38. Letvin, N. L. 2006. Progress and obstacles in the development of an AIDS vaccine. Nat. Rev. Immunol. 6:930-939.
39. Li, H., and L. X. Wang. 2004. Design and synthesis of a template-assembled oligomannose cluster as an epitope mimic for human HIV-neutralizing antibody 2G12. Org. Biomol. Chem. 2:483-48.
40. Li, Y., S. A. Migueles, B. Welcher, K. Svehla, A. Phogat, M. K. Louder, X. Wu, G. M. Shaw, M. Connors, R. T. Wyatt, and J. R. Mascola. 2007. Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat. Med. 13:1032-1034.
41. Mandal, M., V. Y. Dudkin, X. Geng, and S. J. Danishefsky. 2004. In pursuit of carbohydrate-based HIV vaccines, part 1: the total synthesis of hybrid-type gp120 fragments. Angew. Chem. Int. Ed. Engl. 43:2557-2561.
42. Mascola, J. R., M. G. Lewis, G. Stiegler, D. Harris, T. C. VanCott, D. Hayes, M. K. Louder, C. R. Brown, C. V. Sapan, S. S. Frankel, Y. Lu, M. L. Robb, H. Katinger, and D. L. Birx. 1999. Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J. Virol. 73:4009-4018.
43. Mascola, J. R., G. Stiegler, T. C. VanCott, H. Katinger, C. B. Carpenter, C. E. Hanson, H. Beary, D. Hayes, S. S. Frankel, D. L. Birx, and M. G. Lewis. 2000. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat. Med. 6:207-210.
44. McCaffrey, R. A., C. Saunders, M. Hensel, and L. Stamatatos. 2004. N-linked glycosylation of the V3 loop and the immunologically silent face of gp120 protects human immunodeficiency virus type 1 SF162 from neutralization by anti-gp120 and anti-gp41 antibodies. J. Virol. 78:3279-3295.
45. McMichael, A. J. 2006. HIV vaccines. Annu. Rev. Immunol. 24:227-255.
46. Mehandru, S., B. Vcelar, T. Wrin, G. Stiegler, B. Joos, H. Mohri, D. Boden, J. Galovich, K. Tenner-Racz, P. Racz, M. Carrington, C. Petropoulos, H. Katinger, and M. Markowitz. 2007. Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection. J. Virol. 81:11016-11031.
47. Muster, T., F. Steindl, M. Purtscher, A. Trkola, A. Klima, G. Himmler, F. Ruker, and H. Katinger. 1993. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J. Virol. 67:6642-6647.
48. Ni, J., H. Song, Y. Wang, N. M. Stamatos, and L. X. Wang. 2006. Toward a carbohydrate-based HIV-1 vaccine: synthesis and immunological studies of oligomannose-containing glycoconjugates. Bioconjug. Chem. 17:493-500.
49. Nishimura, Y., T. Igarashi, N. Haigwood, R. Sadjadpour, R. J. Plishka, A. Buckler-White, R. Shibata, and M. A. Martin. 2002. Determination of a statistically valid neutralization titer in plasma that confers protection against simian-human immunodeficiency virus challenge following passive transfer of high-titered neutralizing antibodies. J. Virol. 76:2123-2130.
50. Pantophlet, R., and D. R. Burton. 2006. gp120: target for neutralizing HIV-1 antibodies. Annu. Rev. Immunol. 24:739-769.
51. Parren, P. W., H. J. Ditzel, R. J. Gulizia, J. M. Binley, C. F. Barbas III, D. R. Burton, and D. E. Mosier. 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-F6.
52. Parren, P. W., P. A. Marx, A. J. Hessell, A. Luckay, J. Harouse, C. Cheng-Mayer, J. P. Moore, and D. R. Burton. 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.
53. Ratner, D. M., and P. H. Seeberger. 2007. Carbohydrate microarrays as tools in HIV glycobiology. Curr. Pharm. Des. 13:173-183.
54. Richman, D. D., T. Wrin, S. J. Little, and C. J. Petropoulos. 2003. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc. Natl. Acad. Sci. USA 100:4144-4149.
55. Roben, P., J. P. Moore, M. Thali, J. Sodroski, C. F. Barbas III, and D. R. Burton. 1994. Recognition properties of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1. J. Virol. 68:4821-4828.
56. Rudd, P. M., and R. A. Dwek. 1997. Glycosylation: heterogeneity and the 3D structure of proteins. Crit. Rev. Biochem. Mol. Biol. 32:1-100.
57. Sanders, R. W., M. Venturi, L. Schiffner, R. Kalyanaraman, H. Katinger, K. O. Lloyd, P. D. Kwong, and J. P. Moore. 2002. The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J. Virol. 76:7293-7305.
58. Sattentau, Q. J., and J. P. Moore. 1995. Human immunodeficiency virus type 1 neutralization is determined by epitope exposure on the gp120 oligomer. J. Exp. Med. 182:185-196.
59. Scanlan, C. N., J. Offer, N. Zitzmann, and R. A. Dwek. 2007. Exploiting the defensive sugars of HIV-1 for drug and vaccine design. Nature 446:1038-1045.
60. Scanlan, C. N., R. Pantophlet, M. R. Wormald, E. Ollmann Saphire, R. Stanfield, I. A. Wilson, H. Katinger, R. A. Dwek, P. M. Rudd, and D. R. Burton. 2002. The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of α1→2 mannose residues on the outer face of gp120.1. Virol. 76:7306-7321.
61. Shibata, R., T. Igarashi, N. Haigwood, A. Buckler-White, R. Ogert, W. Ross, R. Willey, M. W. Cho, and M. A. Martin. 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.
62. Thomas, R., S. I. Patenaude, C. R. MacKenzie, R. To, T. Hirama, N. M. Young, and S. V. Evans. 2002. Structure of an anti-blood group A Fv and improvement of its binding affinity without loss of specificity. J. Biol. Chem. 277:2059-2064.
63. Trkola, A., H. Kuster, P. Rusert, B. Joos, M. Fischer, C. Leemann, A. Manrique, M. Huber, M. Rehr, A. Oxenius, R. Weber, G. Stiegler, B. Vcelar, H. Katinger, L. Aceto, and H. F. Gunthard. 2005. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat. Med. 11:615-622.
64. Trkola, A., A. B. Pomales, H. Yuan, B. Korber, P. J. Maddon, G. P. Allaway, H. Katinger, C. F. Barbas III, D. R. Burton, and D. D. Ho. 1995. Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG. J. Virol. 69:6609-6617.
65. Trkola, A., M. Purtscher, T. Muster, C. Ballaun, A. Buchacher, N. Sullivan, K. Srinivasan, J. Sodroski, J. P. Moore, and H. Katinger. 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.
66. Vliegenthart, J. F. 2006. Carbohydrate based vaccines. FEBS Lett. 580:2945-2950.
67. Wang, J., H. Li, G. Zou, and L. X. Wang. 2007. Novel template-assembled oligosaccharide clusters as epitope mimics for HIV-neutralizing antibody 2G12. Design, synthesis, and antibody binding study. Org. Biomol. Chem. 5:1529-1540.
68. Wang, L. X. 2006. Toward oligosaccharide- and glycopeptide-based HIV vaccines. Curr. Opin. Drug Discov. Devel. 9:194-206.
69. Wang, L. X., J. Ni, S. Singh, and H. Li. 2004. Binding of high-mannose-type oligosaccharides and synthetic oligomannose clusters to human antibody 2G12: implications for HIV-1 vaccine design. Chem. Biol. 11:127-134.
70. Wei, X., J. M. Decker, S. Wang, H. Hui, J. C. Kappes, X. Wu, J. F. Salazar-Gonzalez, M. G. Salazar, J. M. Kilby, M. S. Saag, N. L. Komarova, M. A. Nowak, B. H. Hahn, P. D. Kwong, and G. M. Shaw. 2003. Antibody neutralization and escape by HIV-1. Nature 422:307-312.
71. Weis, W. I., and K. Drickamer. 1996. Structural basis of lectin-carbohydrate recognition. Annu. Rev. Biochem. 65:441-473.
72. Wilson, I. A., and R. L. Stanfield. 1995. A Trojan horse with a sweet tooth. Nat. Struct. Biol. 2:433-436.
73. Woods, R. J., C. J. Edge, and R. A. Dwek. 1994. Protein surface oligosaccharides and protein function. Nat. Struct. Biol. 1:499-501.
74. Woods, R. J., A. Pathiaseril, M. R. Wormald, C. J. Edge, and R. A. Dwek. 1998. The high degree of internal flexibility observed for an oligomannose oligosaccharide does not alter the overall topology of the molecule. Eur. J. Biochem. 258:372-386.
75. World Health Organization. 2007. AIDS epidemic update: December 2007. Ioint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization, Geneva, Switzerland.
76. Wyatt, R., P. D. Kwong, E. Desjardins, R. W. Sweet, J. Robinson, W. A. Hendrickson, and J. G. Sodroski. 1998. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 393:705-711.
77. Wyatt, R., and J. Sodroski. 1998. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280:1884-1888.
78. Zanetti, G., J. A. Briggs, K. Grunewald, Q. J. Sattentau, and S. D. Fuller. 2006. Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ. PLoS Pathog. 2:e83.
79. Zhang, P. F., F. Cham, M. Dong, A. Choudhary, P. Bouma, Z. Zhang, Y. Shao, Y. R. Feng, L. Wang, N. Mathy, G. Voss, C. C. Broder, and G. V. Quinnan, Jr. 2007. Extensively cross-reactive anti-HIV-1 neutralizing antibodies induced by gp140 immunization. Proc. Natl. Acad. Sci. USA 104: 10193-10198.
80. Zhu, P., J. Liu, J. Bess, Jr., E. Chertova, J. D. Lifson, H. Grise, G. A. Ofek, K. A. Taylor, and K. H. Roux. 2006. Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441:847-852.
81. Zhu, X., C. Borchers, R. J. Bienstock, and K. B. Tomer. 2000. Mass spectrometric characterization of the glycosylation pattern of HIV-gp120 expressed in CHO cells. Biochemistry 39:11194-11204.
82. Zwick, M. B., A. F. Labrijn, M. Wang, C. Spenlehauer, E. O. Saphire, J. M. Binley, J. P. Moore, G. Stiegler, H. Katinger, D. R. Burton, and P. W. Parren. 2001. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol. 75:10892-10905.