Antibody epitope exposure and neutralization of HIV-1

Current Pharmaceutical Design

Volumn 16, Issue 33, 2010, Pages 3729-3743

  Pantophlet, Ralph A ^a  

^a SIMON FRASER UNIVERSITY   (Canada)

Author keywords

Epitope accessibility; HIV envelope glycoprotein; Neutralizing antibodies; Non neutralizing antibodies

Indexed keywords

EPITOPE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; NEUTRALIZING ANTIBODY; VIRUS ENVELOPE PROTEIN; VIRUS PROTEIN; GLYCOPROTEIN GP 120; GLYCOPROTEIN GP 41;

ANTIBODY RESPONSE; ANTIGEN ANTIBODY COMPLEX; ARTICLE; B LYMPHOCYTE; CRYSTAL STRUCTURE; DRUG DESIGN; GENETIC VARIABILITY; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNOGENICITY; MOLECULAR MODEL; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; VIRUS ISOLATION; VIRUS NEUTRALIZATION; VIRUS STRAIN; ANIMAL; CHEMISTRY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; METABOLISM; PROTEIN CONFORMATION; REVIEW;

AIDS VACCINES; ANIMALS; ANTIBODIES, NEUTRALIZING; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; EPITOPES; HIV ENVELOPE PROTEIN GP120; HIV ENVELOPE PROTEIN GP41; HIV INFECTIONS; HIV-1; HUMANS; PROTEIN CONFORMATION;

EID: 79955688993     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161210794079182     Document Type: Article

References (256)

1. Plotkin SA. Immunologic correlates of protection induced by vaccination. Pediatr Infect Dis J 2001; 20: 63-75.
2. Zinkernagel RM, LaMarre A, Ciurea A, et al. Neutralizing antiviral antibody responses. Adv Immunol 2001; 79: 1-53.
3. Lambert PH, Liu M, Siegrist CA. Can successful vaccines teach us how to induce efficient protective immune responses? Nat Med 2005; 11: S54-62.
4. Parren PW, Burton DR. The antiviral activity of antibodies in vitro and in vivo. Adv Immunol 2001; 77: 195-262.
5. Klasse PJ, Sattentau QJ. Occupancy and mechanism in antibodymediated neutralization of animal viruses. J Gen Virol 2002; 83: 2091-108.
6. Burton DR. Antibodies, viruses and vaccines. Nat Rev Immunol 2002; 2: 706-13.
7. Forthal DN, Moog C. Fc receptor-mediated antiviral antibodies. Curr Opin HIV AIDS 2009; 4: 388-93.
8. Fauci AS, Johnston MI, Dieffenbach CW, et al. HIV vaccine research: the way forward. Science 2008; 321: 530-2.
9. Burton DR, Desrosiers RC, Doms RW, et al. HIV vaccine design and the neutralizing antibody problem. Nat Immunol 2004; 5: 233-6.
10. Fast PE, Walker MC. Human trials of experimental AIDS vaccines. Aids 1993; 7: S147-S60.
11. Graham BS, Wright PF. Candidate AIDS vaccines. N Engl J Med 1995; 333: 1331-9.
12. Weiss CD, Levy JA, White JM. Oligomeric organization of gp120 on infectious human immunodeficiency virus type 1 particles. J Virol 1990; 64: 5674-7.
13. Allan JS, Coligan JE, Barin F, et al. Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science 1985; 228: 1091-4.
14. Veronese FD, DeVico AL, Copeland TD, Oroszlan S, Gallo RC, Sarngadharan MG. Characterization of gp41 as the transmembrane protein coded by the HTLV-III/LAV envelope gene. Science 1985; 229: 1402-5.
15. Weissenhorn W, Dessen A, Calder LJ, Harrison SC, Skehel JJ, Wiley DC. Structural basis for membrane fusion by enveloped viruses. Mol Membr Biol 1999; 16: 3-9.
16. Robey WG, Arthur LO, Matthews TJ, et al. Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody. Proc Natl Acad Sci U S A 1986; 83: 7023-7.
17. Montefiori DC, Graham BS, Kliks S, Wright PF. Serum antibodies to HIV-1 in recombinant vaccinia virus recipients boosted with purified recombinant gp160. NIAID AIDS Vaccine Clinical Trials Network. J Clin Immunol 1992; 12: 429-39.
18. Kahn JO, Steimer KS, Baenziger J, et al. Clinical, immunologic, and virologic observations related to human immunodeficiency virus (HIV) type 1 infection in a volunteer in an HIV-1 vaccine clinical trial. J Infect Dis 1995; 171: 1343-7.
19. Mascola JR, Snyder SW, Weislow OS, et al. Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. J Infect Dis 1996; 173: 340-8.
20. Berman PW, Gray AM, Wrin T, et al. Genetic and immunologic characterization of viruses infecting MN-rgp120-vaccinated volunteers. J Infect Dis 1997; 176: 384-97.
21. Connor RI, Korber BT, Graham BS, et al. Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J Virol 1998; 72: 1552-76.
22. Beddows S, Lister S, Cheingsong R, Bruck C, Weber J. Comparison of the antibody repertoire generated in healthy volunteers following immunization with a monomeric recombinant gp120 construct derived from a CCR5/CXCR4-using human immunodeficiency virus type 1 isolate with sera from naturally infected individuals. J Virol 1999; 73: 1740-5.
23. Kumar A, Lifson JD, Silverstein PS, et al. Evaluation of immune responses induced by HIV-1 gp120 in rhesus macaques: effect of vaccination on challenge with pathogenic strains of homologous and heterologous simian human immunodeficiency viruses. Virology 2000; 274: 149-64.
24. Earl PL, Sugiura W, Montefiori DC, et al. Immunogenicity and protective efficacy of oligomeric human immunodeficiency virus type 1 gp140. J Virol 2001; 75: 645-53.
25. Graham BS. Clinical trials of HIV vaccines. Annu Rev Med 2002; 53: 207-21.
26. Li M, Gao F, Mascola JR, et al. Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J Virol 2005; 79: 10108-25.
27. Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 2005; 191: 654-65.
28. Gilbert P, Wang M, Wrin T, et al. Magnitude and Breadth of a Nonprotective Neutralizing Antibody Response in an Efficacy Trial of a Candidate HIV-1 gp120 Vaccine. J Infect Dis 2010; 202: 595-605.
29. Phogat S, Wyatt R. Rational modifications of HIV-1 envelope glycoproteins for immunogen design. Curr Pharm Des 2007; 13: 213-27.
30. Dormitzer PR, Ulmer JB, Rappuoli R. Structure-based antigen design: a strategy for next generation vaccines. Trends Biotechnol 2008; 26: 659-67.
31. Haynes BF, Montefiori DC. Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates. Expert Rev Vaccines 2006; 5: 579-95.
32. Hu SL, Stamatatos L. Prospects of HIV Env modification as an approach to HIV vaccine design. Curr HIV Res 2007; 5: 507-13.
33. Parren PW, Mondor I, Naniche D, et al. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J Virol 1998; 72: 3512-9.
34. Schonning K, Lund O, Lund OS, Hansen JE. Stoichiometry of monoclonal antibody neutralization of T-cell line-adapted human immunodeficiency virus type 1. J Virol 1999; 73: 8364-70.
35. Yang X, Kurteva S, Lee S, Sodroski J. Stoichiometry of antibody neutralization of human immunodeficiency virus type 1. J Virol 2005; 79: 3500-8.
36. Ren X, Sodroski J, Yang X. An unrelated monoclonal antibody neutralizes human immunodeficiency virus type 1 by binding to an artificial epitope engineered in a functionally neutral region of the viral envelope glycoproteins. J Virol 2005; 79: 5616-24.
37. Pantophlet R, Wang M, Aguilar-Sino RO, Burton DR. The human immunodeficiency virus type 1 envelope spike of primary viruses can suppress antibody access to variable regions. J. Virol. 2009; 83: 1649-59.
38. Wallace A, Stamatatos L. Introduction of exogenous epitopes in the variable regions of the human immunodeficiency virus type 1 envelope glycoprotein: effect on viral infectivity and the neutralization phenotype. J Virol 2009; 83: 7883-93.
39. Fouts TR, Binley JM, Trkola A, Robinson JE, Moore JP. Neutralization of the human immunodeficiency virus type 1 primary isolate JR-FL by human monoclonal antibodies correlates with antibody binding to the oligomeric form of the envelope glycoprotein complex. J Virol 1997; 71: 2779-85.
40. Roben P, Moore JP, Thali M, Sodroski J, Barbas CF, 3rd, Burton DR. 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 1994; 68: 4821-8.
41. Parren PW, Fisicaro P, Labrijn AF, et al. In vitro antigen challenge of human antibody libraries for vaccine evaluation: the human immunodeficiency virus type 1 envelope. J Virol 1996; 70: 9046-50.
42. Sattentau QJ, Zolla-Pazner S, Poignard P. Epitope exposure on functional, oligomeric HIV-1 gp41 molecules. Virology 1995; 206: 713-7.
43. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 1998; 393: 648-59.
44. Kwong PD, Wyatt R, Majeed S, et al. Structures of HIV-1 gp120 envelope glycoproteins from laboratory-adapted and primary isolates. Struct Fold Des 2000; 8: 1329-39.
45. Huang CC, Venturi M, Majeed S, et al. Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120. Proc Natl Acad Sci U S A2004; 101: 2706-11.
46. Ofek G, Tang M, Sambor A, et al. Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J Virol 2004; 78: 10724-37.
47. Huang CC, Tang M, Zhang MY, et al. Structure of a V3-containing HIV-1 gp120 core. Science 2005; 310: 1025-8.
48. Huang CC, Lam SN, Acharya P, et al. Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science 2007; 317: 1930-4.
49. Zhou T, Xu L, Dey B, et al. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 2007; 445: 732-7.
50. Chen L, Do Kwon Y, Zhou T, et al. Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120. Science 2009; 326: 1123-7.
51. Pancera M, Majeed S, Ban Y-EA, et al. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility. Proc Natl Acad Sci U S A 2010; 107: 1166-71.
52. Zhou T, Georgiev I, Wu X, et al. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science 2010; 29: 811-7.
53. Rini JM, Stanfield RL, Stura EA, Salinas PA, Profy AT, Wilson IA. Crystal structure of a human immunodeficiency virus type 1 neutralizing antibody, 50.1, in complex with its V3 loop peptide antigen. Proc Natl Acad Sci U S A 1993; 90: 6325-9.
54. Ghiara JB, Stura EA, Stanfield RL, Profy AT, Wilson IA. Crystal structure of the principal neutralization site of HIV-1. Science 1994; 264: 82-5.
55. Stanfield R, Cabezas E, Satterthwait A, Stura E, Profy A, Wilson I. Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing fabs. Struct Fold Des 1999; 7: 131-42.
56. Calarese DA, Scanlan CN, Zwick MB, et al. Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science 2003; 300: 2065-71.
57. Stanfield RL, Ghiara JB, Ollmann Saphire E, Profy AT, Wilson IA. Recurring conformation of the human immunodeficiency virus type 1 gp120 V3 loop. Virology 2003; 315: 159-73.
58. Stanfield RL, Gorny MK, Williams C, Zolla-Pazner S, Wilson IA. Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D. Structure (Camb) 2004; 12: 193-204.
59. Cardoso RM, Zwick MB, Stanfield RL, et al. Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41. Immunity 2005; 22: 163-73.
60. Stanfield RL, Gorny MK, Zolla-Pazner S, Wilson IA. Crystal structures of human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 2219 in complex with three different V3 peptides reveal a new binding mode for HIV-1 cross-reactivity. J Virol 2006; 80: 6093-105.
61. Bell CH, Pantophlet R, Schiefner A, et al. Structure of antibody F425-B4e8 in complex with a V3 peptide reveals a new binding mode for HIV-1 neutralization. J Mol Biol 2008; 375: 969-78.
62. Pejchal R, Gach JS, Brunel FM, et al. A conformational switch in human immunodeficiency virus gp41 revealed by the structures of overlapping epitopes recognized by neutralizing antibodies. J Virol 2009; 83: 8451-62.
63. Burke V, Williams C, Sukumaran M, et al. Structural basis of the cross-reactivity of genetically related human anti-HIV-1 mAbs: implications for design of V3-based immunogens. Structure 2009; 17: 1538-46.
64. Julien J-P, Bryson S, Nieva JL, Pai EF. Structural details of HIV-1 recognition by the broadly neutralizing monoclonal antibody 2F5: epitope conformation, antigen-recognition loop mobility, and anion-binding site. J Mol Biol 2008; 384: 377-92.
65. Bryson S, Julien J-P, Hynes RC, Pai EF. Crystallographic definition of the epitope promiscuity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5: vaccine design implications. J Virol 2009; 83: 11862-75.
66. Zwick MB, Burton DR. HIV-1 neutralization: mechanisms and relevance to vaccine design. Curr HIV Res 2007; 5: 608-24.
67. Mascola JR, Montefiori DC. The role of antibodies in HIV vaccines. Annu Rev Immunol 2010; 28: 413-44.
68. Stamatatos L, Morris L, Burton DR, Mascola JR. Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? Nat Med 2009; 15: 866-70.
69. Robey WG, Safai B, Oroszlan S, et al. Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients. Science 1985; 228: 593-5.
70. Earl PL, Moss B, Doms RW. Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein. J Virol 1991; 65: 2047-55.
71. Center RJ, Leapman RD, Lebowitz J, Arthur LO, Earl PL, Moss B. Oligomeric structure of the human immunodeficiency virus type 1 envelope protein on the virion surface. J Virol 2002; 76: 7863-7.
72. Hallenberger S, Moulard M, Sordel M, Klenk H, Garten W. The role of eukaryotic subtilisin-like endoproteases for the activation of human immunodeficiency virus glycoproteins in natural host cells. J Virol 1997; 71: 1036-45.
73. Moulard M, Hallenberger S, Garten W, Klenk H-D. Processing and routage of HIV glycoproteins by furin to the cell surface. Virus Res 1999; 60: 55-65.
74. Kowalski M, Potz J, Basiripour L, et al. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science 1987; 237: 1351-5.
75. Wiley DC, Skehel JJ. The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem 1987; 56: 365-94.
76. Leung K, Kim J-O, Ganesh L, Kabat J, Schwartz O, Nabel GJ. HIV-1 assembly: viral glycoproteins segregate quantally to lipid rafts that associate individually with HIV-1 capsids and virions. Cell Host Microbe 2008; 3: 285-92.
77. Chertova E, Bess Jr JW, Jr., Crise BJ, et al. Envelope glycoprotein incorporation, not shedding of surface envelope glycoprotein (gp120/SU), Is the primary determinant of SU content of purified human immunodeficiency virus type 1 and simian immunodeficiency virus. J Virol 2002; 76: 5315-25.
78. Zhu P, Chertova E, Bess J, Jr., et al. Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Proc Natl Acad Sci U S A 2003; 100: 15812-7.
79. Louder MK, Sambor A, Chertova E, et al. HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity. Virology 2005; 339: 226-38.
80. Liu J, Bartesaghi A, Borgnia MJ, Sapiro G, Subramaniam S. Molecular architecture of native HIV-1 gp120 trimers. Nature 2008; 455: 109-13.
81. Beniac DR, Andonov A, Grudeski E, Booth TF. Architecture of the SARS coronavirus prefusion spike. Nat Struct Mol Biol 2006; 13: 751-2.
82. Harris A, Cardone G, Winkler DC, et al. Influenza virus pleiomorphy characterized by cryoelectron tomography. Proc Natl Acad Sci U S A 2006; 103: 19123-7.
83. Yamaguchi M, Danev R, Nishiyama K, Sugawara K, Nagayama K. Zernike phase contrast electron microscopy of ice-embedded influenza A virus. J Struct Biol 2008; 162: 271-6.
84. Loney C, Mottet-Osman G, Roux L, Bhella D. Paramyxovirus ultrastructure and genome packaging: cryo-electron tomography of sendai virus. J Virol 2009; 83: 8191-7.
85. Moore JP, Ho DD. HIV-1 neutralization: the consequences of viral adaptation to growth on transformed T cells. Aids 1995; 9 (Suppl A): S117-36.
86. Wrin T, Loh TP, Vennari JC, Schuitemaker H, Nunberg JH. Adaptation to persistent growth in the H9 cell line renders a primary isolate of human immunodeficiency virus type 1 sensitive to neutralization by vaccine sera. J Virol 1995; 69: 39-48.
87. Pugach P, Kuhmann SE, Taylor J, et al. The prolonged culture of human immunodeficiency virus type 1 in primary lymphocytes increases its sensitivity to neutralization by soluble CD4. Virology 2004; 321: 8-22.
88. Moore JP, Cao Y, Qing L, et al. Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120. J Virol 1995; 69: 101-9.
89. Wu X, Zhou T, O'Dell S, Wyatt RT, Kwong PD, Mascola JR. Mechanism of human immunodeficiency virus type 1 resistance to monoclonal antibody b12 that effectively targets the site of CD4 attachment. J Virol 2009; 83: 10892-907.
90. Brown BK, Darden JM, Tovanabutra S, et al. Biologic and genetic characterization of a panel of 60 human immunodeficiency virus type 1 isolates, representing clades A, B, C, D, CRF01_AE, and CRF02_AG, for the development and assessment of candidate vaccines. J Virol 2005; 79: 6089-101.
91. Li M, Salazar-Gonzalez JF, Derdeyn CA, Morris L, et al. Genetic and neutralization properties of acute and early subtype C human immunodeficiency virus type 1 molecular env clones from heterosexually acquired infections in Southern Africa. J Virol 2006; 80: 11776-90.
92. Brown BK, Wieczorek L, Sanders-Buell E, et al. Cross-clade neutralization patterns among HIV-1 strains from the six major clades of the pandemic evaluated and compared in two different models. Virology 2008; 375: 529-38.
93. Seaman MS, Janes H, Hawkins N, et al. Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J Virol 2010; 84: 1439-52.
94. Willey RL, Rutledge RA, Dias S, et al. Identification of conserved and divergent domains within the envelope gene of the acquired immunodeficiency syndrome retrovirus. Proc Natl Acad Sci USA 1986; 83: 5038-42.
95. Modrow S, Hahn BH, Shaw GM, Gallo RC, Wong-Staal F, Wolf H. Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions. J Virol 1987; 61: 570-8.
96. Helseth E, Olshevsky U, Furman C, Sodroski J. Human immunodeficiency virus type 1 gp120 envelope glycoprotein regions important for association with the gp41 transmembrane glycoprotein. J Virol 1991; 65: 2119-23.
97. Wyatt R, Desjardin E, Olshevsky U, et al. Analysis of the interaction of the human immunodeficiency virus type 1 gp120 envelope glycoprotein with the gp41 transmembrane glycoprotein. J Virol 1997; 71: 9722-31.
98. Moore JP, Sattentau QJ, Wyatt R, Sodroski J. Probing the structure of the human immunodeficiency virus surface glycoprotein gp120 with a panel of monoclonal antibodies. J Virol 1994; 68: 469-84.
99. Moore JP, Sodroski J. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J Virol 1996; 70: 1863-72.
100. Wyatt R, Sodroski J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 1998; 280: 1884-8.
101. Pollard SR, Rosa MD, Rosa JJ, Wiley DC. Truncated variants of gp120 bind CD4 with high affinity and suggest a minimum CD4 binding region. EMBO J 1992; 11: 585-91.
102. Rizzuto CD, Wyatt R, Hernandez-Ramos N, et al. A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 1998; 280: 1949-53.
103. Olshevsky U, Helseth E, Furman C, Li J, Haseltine W, Sodroski J. Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding. J Virol 1990; 64: 5701-7.
104. Wu L, Gerard NP, Wyatt R, et al. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature 1996; 384: 179-83.
105. Wu L, LaRosa G, Kassam N, et al. Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding. J Exp Med 1997; 186: 1373-81.
106. Poss M, Rodrigo AG, Gosink JJ, et al. Evolution of envelope sequences from the genital tract and peripheral blood of women infected with clade A human immunodeficiency virus type 1. J Virol 1998; 72: 8240-51.
107. Wei X, Decker JM, Wang S, et al. Antibody neutralization and escape by HIV-1. Nature 2003; 422: 307-12.
108. Sagar M, Wu X, Lee S, Overbaugh J. Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection, and these modifications affect antibody neutralization sensitivity. J Virol 2006; 80: 9586-98.
109. Gray ES, Moore PL, Choge IA, et al. Neutralizing antibody responses in acute human immunodeficiency virus type 1 subtype C infection. J Virol 2007; 81: 6187-96.
110. van Gils MJ, Bunnik EM, Burger JA, et al. Rapid escape from preserved cross-reactive neutralizing humoral immunity without loss of viral fitness in HIV-1-infected progressors and long-term nonprogressors. J Virol 2010; 84: 3576-85.
111. Leonard CK, Spellman MW, Riddle L, Harris RJ, Thomas JN, Gregory TJ. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese Hamster Ovary cells. J Biol Chem 1990; 265: 10373-82.
112. Doores KJ, Bonomelli C, Harvey DJ, et al. Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Proc Natl Acad Sci U S A 2010; 107: 13800-5.
113. Gabuzda DH, Lever A, Terwilliger E, Sodroski J. Effects of deletions in the cytoplasmic domain on biological functions of human immunodeficiency virus type 1 envelope glycoproteins. J Virol 1992; 66: 3306-15.
114. Chan DC, Fass D, Berger JM, Kim PS. Core structure of gp41 from the HIV envelope glycoprotein. Cell 1997; 89: 263-73.
115. Zwick MB, Saphire EO, Burton DR. gp41: HIV's shy protein. Nat Med 2004; 10: 133-4.
116. Sattentau QJ, Moore JP. Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding. J Exp Med 1991; 174: 407-15.
117. Sattentau QJ. CD4 activation of HIV fusion. Int J Cell Cloning 1992; 10: 323-32.
118. Furuta RA, Wild CT, Weng Y, Weiss CD. Capture of an early fusion-active conformation of HIV-1 gp41. Nat Struct Biol 1998; 5: 276-9.
119. Tan K, Liu J, Wang J, Shen S, Lu M. Atomic structure of a thermostable subdomain of HIV-1 gp41. Proc Natl Acad Sci U S A 1997; 94: 12303-8.
120. Weissenhorn W, Dessen A, Harrison SC, Skehel JJ, Wiley DC. Atomic structure of the ectodomain from HIV-1 gp41. Nature 1997; 387: 426-30.
121. Zolla-Pazner S. Identifying epitopes of HIV-1 that induce protective antibodies. Nat Rev Immunol 2004; 4: 199-210.
122. Burton DR, Stanfield RL, Wilson IA. Antibody vs. HIV in a clash of evolutionary titans. Proc Natl Acad Sci U S A 2005; 102: 14943-8.
123. Wrin T, Crawford L, Sawyer L, Weber P, Sheppard HW, Hanson CV. Neutralizing antibody responses to autologous and heterologous isolates of human immunodeficiency virus. J Acquir Immune Defic Syndr 1994; 7: 211-9.
124. Moog C, Fleury HJ, Pellegrin I, Kirn A, Aubertin AM. Autologous and heterologous neutralizing antibody responses following initial seroconversion in human immunodeficiency virus type 1-infected individuals. J Virol 1997; 71: 3734-41.
125. Pilgrim AK, Pantaleo G, Cohen OJ, et al. Neutralizing antibody responses to human immunodeficiency virus type 1 in primary infection and long-term-nonprogressive infection. J Infect Dis 1997; 176: 924-32.
126. Quinnan GV, Jr., Zhang PF, Fu DW, Dong M, Margolick JB. Evolution of neutralizing antibody response against HIV type 1 virions and pseudovirions in multicenter AIDS cohort study participants. AIDS Res Hum Retroviruses 1998; 14: 939-49.
127. Zhang PF, Chen X, Fu DW, Margolick JB, Quinnan GV, Jr. Primary virus envelope cross-reactivity of the broadening neutralizing antibody response during early chronic human immunodeficiency virus type 1 infection. J Virol 1999; 73: 5225-30.
128. Richman DD, Wrin T, Little SJ, Petropoulos CJ. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A 2003; 100: 4144-9.
129. Geffin R, Hutto C, Andrew C, Scott GB. A longitudinal assessment of autologous neutralizing antibodies in children perinatally infected with human immunodeficiency virus type 1. Virology 2003; 310: 207-15.
130. Deeks SG, Schweighardt B, Wrin T, et al. Neutralizing antibody responses against autologous and heterologous viruses in acute versus chronic human immunodeficiency virus (HIV) infection: evidence for a constraint on the ability of HIV to completely evade neutralizing antibody responses. J Virol 2006; 80: 6155-64.
131. Klein JS, Bjorkman PJ. Few and Far Between: How HIV May Be Evading Antibody Avidity. PLoS Pathog 2010; 6: e1000908.
132. Wyatt R, Kwong PD, Desjardins E, Sweet RW, Robinson J, Hendrickson WA, et al. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 1998; 393: 705-11.
133. Wyatt R, Sullivan N, Thali M, et al. Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions. J Virol 1993; 67: 4557-65.
134. Jeffs SA, McKeating J, Lewis S, et al. Antigenicity of truncated forms of the human immunodeficiency virus type 1 envelope glycoprotein. J Gen Virol 1996; 77 (Pt 7): 1403-10.
135. Sullivan N, Sun Y, Li J, Hofmann W, Sodroski J. Replicative function and neutralization sensitivity of envelope glycoproteins from primary and T-cell line-passaged human immunodeficiency virus type 1 isolates. J Virol 1995; 69: 4413-22.
136. D'Souza MP, Livnat D, Bradac JA, Bridges SH. Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. AIDS Clinical Trials Group Antibody Selection Working Group. J Infect Dis 1997; 175: 1056-62.
137. Sattentau QJ, Moore JP. Human immunodeficiency virus type 1 neutralization is determined by epitope exposure on the gp120 oligomer. J Exp Med 1995; 182: 185-96.
138. Barbas CF, 3rd, Bjorling E, Chiodi F, et al. Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro. Proc Natl Acad Sci U S A 1992; 89: 9339-43.
139. Binley JM, Wrin T, Korber B, et al. Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol 2004; 78: 13232-52.
140. Parren PW, Marx PA, Hessell AJ, et al. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J Virol 2001; 75: 8340-7.
141. Veazey RS, Shattock RJ, Pope M, et al. Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120. Nat Med 2003; 9: 343-6.
142. Hessell AJ, Hangartner L, Hunter M, et al. Fc receptor but not complement binding is important in antibody protection against HIV. Nature 2007; 449: 101-4.
143. Walker BD, Burton DR. Toward an AIDS vaccine. Science 2008; 320: 760-4.
144. Li Y, Migueles SA, Welcher B, et al. Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat Med 2007; 13: 1032-4.
145. Dhillon AK, Donners H, Pantophlet R, et al. Dissecting the neutralizing antibody specificities of broadly neutralizing sera from human immunodeficiency virus type 1-infected donors. J Virol 2007; 81: 6548-62.
146. Binley JM, Lybarger EA, Crooks ET, et al. Profiling the specificity of neutralizing antibodies in a large panel of plasmas from patients chronically infected with human immunodeficiency virus type 1 subtypes B and C. J Virol 2008; 82: 11651-68.
147. Li Y, Svehla K, Louder MK, et al. Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals. J Virol 2009; 83: 1045-59.
148. Sather DN, Armann J, Ching LK, et al. Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J Virol 2009; 83: 757-69.
149. Nandi A, Lavine CL, Wang P, et al. Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1. Virology 2010; 396: 339-48.
150. Corti D, Langedijk JPM, Hinz A, et al. Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals. PLoS One 2010; 5: e8805.
151. Wu X, Yang Z-Y, Li Y, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010; 329: 856-61.
152. Sanders R, van Anken E, Nabatov A, et al. The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion. Retrovirology 2008; 5: 10.
153. Duenas-Decamp MJ, Peters P, Burton D, Clapham PR. Natural resistance of human immunodeficiency virus type 1 to the CD4bs antibody b12 conferred by a glycan and an arginine residue close to the CD4 binding loop. J Virol 2008; 82: 5807-14.
154. Kwong PD, Doyle ML, Casper DJ, et al. HIV-1 evades antibodymediated neutralization through conformational masking of receptor-binding sites. Nature 2002; 420: 678-82.
155. Duenas-Decamp MJ, Peters PJ, Burton D, Clapham PR. Determinants flanking the CD4 binding loop modulate macrophage tropism of human immunodeficiency virus type 1 R5 envelopes. J Virol 2009; 83: 2575-83.
156. Trkola A, Purtscher M, Muster T, et al. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol 1996; 70: 1100-8.
157. Sanders RW, Venturi M, Schiffner L, et al. The mannosedependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J Virol 2002; 76: 7293-305.
158. Scanlan CN, Pantophlet R, Wormald MR, et al. 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. J Virol 2002; 76: 7306-21.
159. Bures R, Morris L, Williamson C, et al. Regional clustering of shared neutralization determinants on primary isolates of clade C human immunodeficiency virus type 1 from South Africa. J Virol 2002; 76: 2233-44.
160. Gray ES, Moore PL, Pantophlet RA, Morris L. N-linked glycan modifications in gp120 of human immunodeficiency virus type 1 subtype C render partial sensitivity to 2G12 antibody neutralization. J Virol 2007; 81: 10769-76.
161. Mascola JR, Lewis MG, Stiegler G, et al. Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J Virol 1999; 73: 4009-18.
162. Hessell AJ, Rakasz EG, Poignard P, et al. Broadly neutralizing human Anti-HIV antibody 2G12 is effective in protection against mucosal SHIV challenge even at low serum neutralizing titers. PLoS Pathog 2009; 5: e1000433.
163. Trkola A, Kuster H, Rusert P, et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat Med 2005; 11: 615-22.
164. Muller-Loennies S, MacKenzie CR, Patenaude SI, et al. Characterization of high affinity monoclonal antibodies specific for chlamydial lipopolysaccharide. Glycobiology 2000; 10: 121-30.
165. MacKenzie CR, Hirama T, Deng S-j, Bundle DR, Narang SA, Young NM. Analysis by surface plasmon resonance of the influence of valence on the ligand binding affinity and kinetics of an anti-carbohydrate antibody. J Biol Chem 1996; 271: 1527-33.
166. Deng SJ, MacKenzie CR, Sadowska J, et al. Selection of antibody single-chain variable fragments with improved carbohydrate binding by phage display. J Biol Chem 1994; 269: 9533-8.
167. Astronomo RD, Burton DR. Carbohydrate vaccines: developing sweet solutions to sticky situations? Nat Rev Drug Discov 2010; 9: 308-24.
168. Walker LM, Simek MD, Priddy F, et al. A limited number of antibody specificities mediate broad and potent serum neutralization in selected HIV-1 infected individuals. PLoS Pathog 2010; 6: e1001028.
169. Sather DN, Stamatatos L. Epitope specificities of broadly neutralizing plasmas from HIV-1 infected subjects. Vaccine 2010; 28: B8-B12.
170. Scheid JF, Mouquet H, Feldhahn N, et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIVinfected individuals. Nature 2009.
171. Braibant MA, Brunet SA, Costagliola DB, et al. Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non-progressors: prevalence and association with neutralizing activity. AIDS 2006; 20: 1923-30.
172. Müller WE, Schröder HC, Reuter P, Maidhof A, Uhlenbruck G, Winkler I. Polyclonal antibodies to mannan from yeast also recognize the carbohydrate structure of gp120 of the AIDS virus: an approach to raise neutralizing antibodies to HIV-1 infection in vitro. AIDS 1990; 4: 159-62.
173. Astronomo RD, Lee H-K, Scanlan CN, et al. 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. J Virol 2008; 82: 6359-68.
174. Luallen RJ, Lin J, Fu H, et al. An engineered Saccharomyces cerevisiae strain binds the broadly neutralizing human immunodeficiency virus type 1 antibody 2G12 and elicits mannosespecific gp120-binding antibodies. J Virol 2008; 82: 6447-57.
175. [Menendez A, Calarese DA, Stanfield RL, et al. A peptide inhibitor of HIV-1 neutralizing antibody 2G12 is not a structural mimic of the natural carbohydrate epitope on gp120. FASEB J. 2008: fj.07-8983com.
176. Joyce JG, Krauss IJ, Song HC, et al. An oligosaccharide-based HIV-1 2G12 mimotope vaccine induces carbohydrate-specific antibodies that fail to neutralize HIV-1 virions. Proc Natl Acad Sci U S A 2008; 105: 15684-9.
177. Dunlop DC, Bonomelli C, Mansab F, et al. Polysaccharide mimicry of the epitope of the broadly neutralising anti-HIV antibody, 2G12, induces enhanced antibody responses to self oligomannose glycans. Glycobiology 2010.
178. Luallen RJ, Agrawal-Gamse C, Fu H, Smith DF, Doms RW, Geng Y. Antibodies against Man??1,2-Man??1,2-Man oligosaccharide structures recognize envelope glycoproteins from HIV-1 and SIV strains. Glycobiology 2010; 20: 280-6.
179. Astronomo RD, Kaltgrad E, Udit AK, et al. Defining criteria for oligomannose immunogens for HIV using icosahedral virus capsid scaffolds. Chem Biol 2010; 17: 357-70.
180. [Doores KJ, Fulton Z, Huber M, Wilson IA, Burton DR. Antibody 2G12 recognizes Di-mannose equivalently in domain- and nondomain- exchanged forms, but only binds the HIV-1 glycan shield if domain-exchanged. J Virol 2010: JVI.01110-10.
181. Gerstenbruch S, Brooks CL, Kosma P, et al. Analysis of crossreactive and specific anti-carbohydrate antibodies against lipopolysaccharide from Chlamydophila psittaci. Glycobiology 2010; 20: 461-72.
182. Pinter A, Honnen WJ, He Y, Gorny MK, Zolla-Pazner S, Kayman SC. The V1/V2 domain of gp120 is a global regulator of the sensitivity of primary human immunodeficiency virus type 1 isolates to neutralization by antibodies commonly induced upon infection. J Virol 2004; 78: 5205-15.
183. Krachmarov CP, Honnen WJ, Kayman SC, Gorny MK, Zolla-Pazner S, Pinter A. Factors determining the breadth and potency of neutralization by V3-specific human monoclonal antibodies derived from subjects infected with clade A or clade B strains of human immunodeficiency virus type 1. J Virol 2006; 80: 7127-35.
184. LaRosa GJ, Weinhold K, Profy AT, et al. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant: further clarifications. Science 1991; 253: 1146.
185. LaRosa GJ, Davide JP, Weinhold K, et al. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science 1990; 249: 932-5.
186. Korber BT, MacInnes K, Smith RF, Myers G. Mutational trends in V3 loop protein sequences observed in different genetic lineages of human immunodeficiency virus type 1. J Virol 1994; 68: 6730-44.
187. Catasti P, Fontenot JD, Bradbury EM, Gupta G. Local and global structural properties of the HIV-MN V3 loop. J Biol Chem 1995; 270: 2224-32.
188. Cormier EG, Dragic T. The crown and stem of the V3 loop play distinct roles in human immunodeficiency virus type 1 envelope glycoprotein interactions with the CCR5 coreceptor. J Virol 2002; 76: 8953-7.
189. Suphaphiphat P, Essex M, Lee TH. Mutations in the V3 stem versus the V3 crown and C4 region have different effects on the binding and fusion steps of human immunodeficiency virus type 1 gp120 interaction with the CCR5 coreceptor. Virology 2007; 360: 182-90.
190. Cardozo T, Kimura T, Philpott S, Weiser B, Burger H, Zolla-Pazner S. Structural basis for coreceptor selectivity by the HIV type 1 V3 loop. AIDS Res Hum Retroviruses 2007; 23: 415-26.
191. Xiang S-H, Finzi A, Pacheco B, et al. A V3 loop-dependent gp120 element disrupted by CD4 binding stabilizes the human immunodeficiency virus envelope glycoprotein trimer. J Virol 2010; 84: 3147-61.
192. Rosen O, Sharon M, Quadt-Akabayov SR, Anglister J. Molecular switch for alternative conformations of the HIV-1 V3 region: Implications for phenotype conversion. Proc Natl Acad Sci U S A 2006; 103: 13950-5.
193. Pantophlet R, Wrin T, Cavacini LA, Robinson JE, Burton DR. Neutralizing activity of antibodies to the V3 loop region of HIV-1 gp120 relative to their epitope fine specificity. Virology 2008.
194. Zolla-Pazner S, Zhong P, Revesz K, et al. The cross-clade neutralizing activity of a human monoclonal antibody is determined by the GPGR V3 motif of HIV type 1. AIDS Res Hum Retroviruses 2004; 20: 1254-8.
195. Keller PM, Arnold BA, Shaw AR, et al. Identification of HIV vaccine candidate peptides by screening random phage epitope libraries. Virology 1993; 193: 709-16.
196. Rosen O, Chill J, Sharon M, et al. Induced fit in HIV-neutralizing antibody complexes: evidence for alternative conformations of the gp120 V3 loop and the molecular basis for broad neutralization. Biochemistry 2005; 44: 7250-8.
197. Gorny MK, Conley AJ, Karwowska S, et al. Neutralization of diverse human immunodeficiency virus type 1 variants by an anti- V3 human monoclonal antibody. J Virol 1992; 66: 7538-42.
198. Gorny MK, Xu JY, Karwowska S, Buchbinder A, Zolla-Pazner S. Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120. J Immunol 1993; 150: 635-43.
199. Pantophlet R, Aguilar-Sino RO, Wrin T, Cavacini LA, Burton DR. Analysis of the neutralization breadth of the anti-V3 antibody F425-B4e8 and re-assessment of its epitope fine specificity by scanning mutagenesis. Virology 2007; 364: 441-53.
200. Gupta G, Anantharamaiah GM, Scott DR, Eldridge JH, Myers G. Solution structure of the V3 loop of a Thailand HIV isolate. J Biomol Struct Dyn 1993; 11: 345-66.
201. Hartley O, Klasse PJ, Sattentau QJ, Moore JP. V3: HIV's switchhitter. AIDS Res Hum Retroviruses 2005; 21: 171-89.
202. Burton DR, Montefiori DC. The antibody response in HIV-1 infection. AIDS 1997; 11 (Suppl A): S87-98.
203. Rappuoli R. Bridging the knowledge gaps in vaccine design. Nat Biotech 2007; 25: 1361-6.
204. Delves PJ, Lund T, Roitt IM. Can epitope-focused vaccines select advantageous immune responses? Mol Med Today 1997; 3: 55-60.
205. Parren PW, Burton DR, Sattentau QJ. HIV-1 antibody-debris or virion? Nat Med 1997; 3: 366-7.
206. Gorny MK, Stamatatos L, Volsky B, et al. Identification of a new quaternary neutralizing epitope on human immunodeficiency virus type 1 virus particles. J Virol 2005; 79: 5232-7.
207. Pinter A. Roles of HIV-1 Env variable regions in viral neutralization and vaccine development. Curr HIV Res 2007; 5: 542-53.
208. Ditzel HJ, Binley JM, Moore JP, et al. Neutralizing recombinant human antibodies to a conformational V2- and CD4-binding sitesensitive epitope of HIV-1 gp120 isolated by using an epitopemasking procedure. J Immunol 1995; 154: 893-906.
209. He Y, Honnen WJ, Krachmarov CP, et al. Efficient isolation of novel human monoclonal antibodies with neutralizing activity against HIV-1 from transgenic mice expressing human Ig loci. J Immunol 2002; 169: 595-605.
210. Ho DD, Fung MS, Cao YZ, et al. Another discontinuous epitope on glycoprotein gp120 that is important in human immunodeficiency virus type 1 neutralization is identified by a monoclonal antibody. Proc Natl Acad Sci U S A 1991; 88: 8949-52.
211. McKeating JA, Shotton C, Cordell J, et al. Characterization of neutralizing monoclonal antibodies to linear and conformationdependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120. J Virol 1993; 67: 4932-44.
212. Shotton C, Arnold C, Sattentau Q, Sodroski J, McKeating JA. Identification and characterization of monoclonal antibodies specific for polymorphic antigenic determinants within the V2 region of the human immunodeficiency virus type 1 envelope glycoprotein. J Virol 1995; 69: 222-30.
213. Gorny MK, Moore JP, Conley AJ, et al. Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory isolates of human immunodeficiency virus type 1. J Virol 1994; 68: 8312-20.
214. Honnen WJ, Krachmarov C, Kayman SC, Gorny MK, Zolla-Pazner S, Pinter A. Type-specific epitopes targeted by monoclonal antibodies with exceptionally potent neutralizing activities for selected strains of human immunodeficiency virus type 1 map to a common region of the V2 domain of gp120 and differ only at single positions from the clade B consensus sequence. J Virol 2007; 81: 1424-32.
215. Walker LM, Phogat SK, Chan-Hui PY, et al. Broad and potent neutralizing antibodies from an african donor reveal a new HIV-1 vaccine target. Science 2009.
216. Simek MD, Rida W, Priddy FH, et al. Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol 2009; 83: 7337-48.
217. [Doores KJ, Burton DR. Variable loop glycan dependency of the broad and potent HIV-1 neutralizing antibodies PG9 and PG16. J Virol 2010: JVI.00552-10.
218. Pejchal R, Walker LM, Stanfield RL, et al. Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1. Proc Natl Acad Sci U S A 2010; 107: 11483-8.
219. Pancera M, McLellan JS, Wu X, et al. Crystal structure of PG16 and chimeric dissection with somatically related PG9: structurefunction analysis of two quaternary-specific antibodies that effectively neutralize HIV-1. J Virol 2010; 84: 8098-110.
220. Robinson JE, Franco K, Elliott DH, et al. Quaternary Epitope Specificities of Anti-HIV-1 Neutralizing Antibodies Generated in Rhesus Macaques Infected by the Simian/Human Immunodeficiency Virus SHIVSF162P4. J Virol 2010; 84: 3443-53.
221. Zolla-Pazner S, Cardozo T. Structure-function relationships of HIV-1 envelope sequence-variable regions refocus vaccine design. Nat Rev Immunol 2010; 10: 527-35.
222. Rizzuto C, Sodroski J. Fine definition of a conserved CCR5- binding region on the human immunodeficiency virus type 1 glycoprotein 120. AIDS Res Hum Retroviruses 2000; 16: 741-9.
223. Decker JM, Bibollet-Ruche F, Wei X, et al. Antigenic conservation and immunogenicity of the HIV coreceptor binding site. J Exp Med 2005; 201: 1407-19.
224. Salzwedel K, Smith ED, Dey B, Berger EA. Sequential CD4- coreceptor interactions in human immunodeficiency virus type 1 Env function: soluble CD4 activates Env for coreceptor-dependent fusion and reveals blocking activities of antibodies against cryptic conserved epitopes on gp120. J Virol 2000; 74: 326-33.
225. Xiang SH, Doka N, Choudhary RK, Sodroski J, Robinson JE. Characterization of CD4-induced epitopes on the HIV type 1 gp120 envelope glycoprotein recognized by neutralizing human monoclonal antibodies. AIDS Res Hum Retroviruses 2002; 18: 1207-17.
226. Sullivan N, Sun Y, Sattentau Q, et al. CD4-Induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: consequences for virus entry and neutralization. J Virol 1998; 72: 4694-703.
227. Labrijn AF, Poignard P, Raja A, et al. Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary human immunodeficiency virus type 1. J Virol 2003; 77: 10557-65.
228. [Jiang SB, Lin K, Strick N, Neurath AR. HIV-1 inhibition by a peptide. Nature 1993; 365: 113
229. Wild CT, Shugars DC, Greenwell TK, McDanal CB, Matthews TJ. Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc Natl Acad Sci U S A 1994; 91: 9770-4.
230. Eron Joseph J, Gulick Roy M, Bartlett John A, et al. Short-Term Safety and Antiretroviral Activity of T-1249, a Second-Generation Fusion Inhibitor of HIV. J Infect Dis 2004; 189: 1075-83.
231. Naito T, Izumi K, Kodama E, et al. SC29EK, a peptide fusion inhibitor with enhanced α-helicity, inhibits replication of human immunodeficiency virus type 1 mutants resistant to enfuvirtide. Antimicrob Agents Chemother 2009; 53: 1013-8.
232. Deng Y, Zheng Q, Ketas TJ, Moore JP, Lu M. Protein design of a bacterially expressed HIV-1 gp41 fusion inhibitor. Biochemistry 2007; 46: 4360-9.
233. Hamburger AE, Kim S, Welch BD, Kay MS. Steric accessibility of the HIV-1 gp41 N-trimer region. J Biol Chem 2005; 280: 12567-72.
234. Louis JM, Nesheiwat I, Chang L, Clore GM, Bewley CA. Covalent trimers of the internal N-terminal trimeric coiled-coil of gp41 and antibodies directed against them are potent inhibitors of HIV envelope-mediated cell fusion. J Biol Chem 2003; 278: 20278-85.
235. Miller MD, Geleziunas R, Bianchi E, et al. A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope. Proc Natl Acad Sci U S A 2005; 102: 14759-64.
236. Luftig MA, Mattu M, Di Giovine P, et al. Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody. Nat Struct Mol Biol 2006; 13: 740-7.
237. Gustchina E, Louis JM, Lam SN, Bewley CA, Clore GM. A monoclonal Fab derived from a human nonimmune phage library reveals a new epitope on gp41 and neutralizes diverse human immunodeficiency virus type 1 strains. J Virol 2007; 81: 12946-53.
238. Nelson JD, Kinkead H, Brunel FM, et al. Antibody elicited against the gp41 N-heptad repeat (NHR) coiled-coil can neutralize HIV-1 with modest potency but non-neutralizing antibodies also bind to NHR mimetics. Virology 2008; 377: 170-83.
239. Gustchina E, Louis JM, Frisch C, et al. Affinity maturation by targeted diversification of the CDR-H2 loop of a monoclonal Fab derived from a synthetic naïve human antibody library and directed against the internal trimeric coiled-coil of gp41 yields a set of Fabs with improved HIV-1 neutralization potency and breadth. Virology 2009; 393: 112-9.
240. Zwick MB. The membrane-proximal external region of HIV-1 gp41: a vaccine target worth exploring. AIDS 2005; 19: 1725-37.
241. Buchacher A, Predl R, Strutzenberger K, et al. Generation of human monoclonal antibodies against HIV-1 proteins; electrofusion and Epstein-Barr virus transformation for peripheral blood lymphocyte immortalization. AIDS Res Hum Retroviruses 1994; 10: 359-69.
242. Purtscher M, Trkola A, Gruber G, et al. A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses 1994; 10: 1651-8.
243. Zwick MB, Labrijn AF, Wang M, et al. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol 2001; 75: 10892-905.
244. Nelson JD, Brunel FM, Jensen R, et al. An affinity-enhanced neutralizing antibody against the membrane-proximal external region of human immunodeficiency virus type 1 gp41 recognizes an epitope between those of 2F5 and 4E10. J Virol 2007; 81: 4033-43.
245. Muster T, Steindl F, Purtscher M, et al. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol 1993; 67: 6642-7.
246. Conley AJ, Kessler JA, 2nd, Boots LJ, et al. 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 U S A 1994; 91: 3348-52.
247. Hessell AJ, Rakasz EG, Tehrani DM, et al. 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 2010; 84: 1302-13.
248. Shen X, Parks RJ, Montefiori DC, et al. In Vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth. J Virol 2009; 83: 3617-25.
249. Gray ES, Madiga MC, Moore PL, et al. Broad neutralization of human immunodeficiency virus type 1 mediated by plasma antibodies against the gp41 membrane proximal external region. J Virol 2009; 83: 11265-74.
250. Haynes BF, Fleming J, St Clair EW, et al. Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science 2005; 308: 1906-8.
251. Haynes BF, Moody MA, Verkoczy L, Kelsoe G, Alam SM. Antibody polyspecificity and neutralization of HIV-1: a hypothesis. Hum Antibodies 2005; 14: 59-67.
252. Li Y, Svehla K, Mathy NL, Voss G, Mascola JR, Wyatt R. Characterization of antibody responses elicited by human immunodeficiency virus type 1 primary isolate trimeric and monomeric envelope glycoproteins in selected adjuvants. J Virol 2006; 80: 1414-26.
253. Hoxie JA. Toward an antibody-based HIV-1 vaccine. Annu Rev Med 2010; 61: 135-52.
254. Messer RJ, Dittmer U, Peterson KE, Hasenkrug KJ. Essential role for virus-neutralizing antibodies in sterilizing immunity against Friend retrovirus infection. Proc Natl Acad Sci U S A 2004; 101: 12260-5.
255. Hangartner L, Zellweger RM, Giobbi M, et al. Nonneutralizing antibodies binding to the surface glycoprotein of lymphocytic choriomeningitis virus reduce early virus spread. J Exp Med 2006; 203: 2033-42.
256. Hessell AJ, Poignard P, Hunter M, et al. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat Med 2009; 15: 951-4.