Neutralization of Tier-2 Viruses and Epitope Profiling of Plasma Antibodies from Human Immunodeficiency Virus Type 1 Infected Donors from India

PLoS ONE

Volumn 7, Issue 8, 2012, Pages

  Andrabi, Raiees ^a   Bala, Manju ^b   Kumar, Rajesh ^a   Wig, Naveet ^a   Hazarika, Anjali ^a   Luthra, Kalpana ^a  

^a ALL INDIA INSTITUTE OF MEDICAL SCIENCES   (India)

^b SAFDARJUNG HOSPITAL   (India)

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; ANTIBODY SPECIFICITY; ANTIBODY TITER; ANTIGEN SPECIFICITY; ARTICLE; BINDING SITE; CONTROLLED STUDY; EPITOPE MAPPING; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNOGENICITY; INDIA; MAJOR CLINICAL STUDY; MALE; NUCLEOTIDE SEQUENCE; ORGAN DONOR; PROTEIN BINDING; PROTEIN DEPLETION; PROTEIN PURIFICATION; VIRUS ISOLATION; VIRUS LOAD; VIRUS NEUTRALIZATION;

ADULT; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; ANTIGENS, VIRAL; BLOOD DONORS; CROSS REACTIONS; EPITOPE MAPPING; FEMALE; HIV ENVELOPE PROTEIN GP41; HIV INFECTIONS; HIV-1; HUMANS; IMMUNOGLOBULIN G; INDIA; MALE; MIDDLE AGED; YOUNG ADULT;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84865614995     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0043704     Document Type: Article

References (85)

1. Hemelaar J, Gouws E, Ghys PD, Osmanov S, (2006) Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004. AIDS 20: W13-23 doi:10.1097/01.aids.0000247564.73009.bc.
2. Taylor BS, Sobieszczyk ME, McCutchan FE, Hammer SM, (2008) The challenge of HIV-1 subtype diversity. N Engl J Med 358: 1590-1602 doi:10.1056/NEJMra0706737.
3. Lynch RM, Shen T, Gnanakaran S, Derdeyn CA, (2009) Appreciating HIV type 1 diversity: subtype differences in Env. AIDS Res Hum Retroviruses 25: 237-248 doi:10.1089/aid.2008.0219.
4. Liu P, Overman RG, Yates NL, Alam SM, Vandergrift N, et al. (2011) Dynamic antibody specificities and virion concentrations in circulating immune complexes in acute to chronic HIV-1 infection. J Virol 85: 11196-11207 doi:10.1128/JVI.05601-11.
5. Haynes BF, Montefiori DC, (2006) Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates. Expert Rev Vaccines 5: 347-363 doi:10.1586/14760584.5.3.347.
6. Parren PW, Gauduin MC, Koup RA, Poignard P, Fisicaro P, et al. (1997) Relevance of the antibody response against human immunodeficiency virus type 1 envelope to vaccine design. Immunol Lett 57: 105-112.
7. Sather DN, Armann J, Ching LK, Mavrantoni A, Sellhorn G, et al. (2009) Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J Virol 83: 757-769 doi:10.1128/JVI.02036-08.
8. Burton DR, Desrosiers RC, Doms RW, Koff WC, Kwong PD, et al. (2004) HIV vaccine design and the neutralizing antibody problem. Nat Immunol 5: 233-236 doi:10.1038/ni0304-233.
9. McMichael AJ, Hanke T, (2003) HIV vaccines 1983-2003. Nat Med 9: 874-880 doi:10.1038/nm0703-874.
10. Koff WC, (2011) HIV vaccine development: Challenges and opportunities towards solving the HIV vaccine-neutralizing antibody problem. Vaccine Available: http://www.ncbi.nlm.nih.gov/pubmed/22100891. Accessed 2012 January 28.
11. Kim JH, Rerks-Ngarm S, Excler J-L, Michael NL, (2010) HIV vaccines: lessons learned and the way forward. Curr Opin HIV AIDS 5: 428-434 doi:10.1097/COH.0b013e32833d17ac.
12. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, et al. (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361: 2209-2220 doi:10.1056/NEJMoa0908492.
13. Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, et al. (2012) Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med 366: 1275-1286 doi:10.1056/NEJMoa1113425.
14. Corti D, Langedijk JPM, 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 doi:10.1371/journal.pone.0008805.
15. Lynch RM, Tran L, Louder MK, Schmidt SD, Cohen M, et al. (2012) The Development of CD4 Binding Site Antibodies During HIV-1 Infection. Journal of virology Available: http://www.ncbi.nlm.nih.gov/pubmed/22573869. Accessed 2012 May 22.
16. Mascola JR, Montefiori DC, (2010) The role of antibodies in HIV vaccines. Annu Rev Immunol 28: 413-444 doi:10.1146/annurev-immunol-030409-101256.
17. Stamatatos L, Morris L, Burton DR, Mascola JR, (2009) Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? Nat Med 15: 866-870 doi:10.1038/nm.1949.
18. 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 doi:10.1038/nature10373.
19. Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, et al. (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312: 763-767.
20. Wyatt R, Sodroski J, (1998) The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280: 1884-1888.
21. Pantophlet R, Burton DR, (2006) GP120: target for neutralizing HIV-1 antibodies. Annu Rev Immunol 24: 739-769 doi:10.1146/annurev.immunol.24.021605.090557.
22. Montero M, van Houten NE, Wang X, Scott JK, (2008) The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design. Microbiol Mol Biol Rev 72: 54-84 table of contents. doi:10.1128/MMBR.00020-07.
23. Li Y, Migueles SA, Welcher B, Svehla K, Phogat A, et al. (2007) Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat Med 13: 1032-1034 doi:10.1038/nm1624.
24. Zolla-Pazner S, Cohen SS, Krachmarov C, Wang S, Pinter A, et al. (2008) Focusing the immune response on the V3 loop, a neutralizing epitope of the HIV-1 gp120 envelope. Virology 372: 233-246 doi:10.1016/j.virol.2007.09.024.
25. Hioe CE, Wrin T, Seaman MS, Yu X, Wood B, et al. (2010) Anti-V3 monoclonal antibodies display broad neutralizing activities against multiple HIV-1 subtypes. PLoS ONE 5: e10254 doi:10.1371/journal.pone.0010254.
26. Wu X, Yang Z-Y, Li Y, Hogerkorp C-M, Schief WR, et al. (2010) Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329: 856-861 doi:10.1126/science.1187659.
27. Balla-Jhagjhoorsingh SS, Willems B, Heyndrickx L, Heyndrickx L, Vereecken K, et al. (2011) Characterization of neutralizing profiles in HIV-1 infected patients from whom the HJ16, HGN194 and HK20 mAbs were obtained. PLoS ONE 6: e25488 doi:10.1371/journal.pone.0025488.
28. 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.
29. Moore PL, Gray ES, Choge IA, Ranchobe N, Mlisana K, et al. (2008) The c3-v4 region is a major target of autologous neutralizing antibodies in human immunodeficiency virus type 1 subtype C infection. J Virol 82: 1860-1869 doi:10.1128/JVI.02187-07.
30. Walker LM, Phogat SK, Chan-Hui P-Y, Wagner D, Phung P, et al. (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326: 285-289 doi:10.1126/science.1178746.
31. McLellan JS, Pancera M, Carrico C, Gorman J, Julien J-P, et al. (2011) Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 480: 336-343 doi:10.1038/nature10696.
32. Gabuzda DH, Lever A, Terwilliger E, Sodroski J, (1992) Effects of deletions in the cytoplasmic domain on biological functions of human immunodeficiency virus type 1 envelope glycoproteins. J Virol 66: 3306-3315.
33. Xu JY, Gorny MK, Palker T, Karwowska S, Zolla-Pazner S, (1991) Epitope mapping of two immunodominant domains of gp41, the transmembrane protein of human immunodeficiency virus type 1, using ten human monoclonal antibodies. J Virol 65: 4832-4838.
34. Poumbourios P, McPhee DA, Kemp BE, (1992) Antibody epitopes sensitive to the state of human immunodeficiency virus type 1 gp41 oligomerization map to a putative alpha-helical region. AIDS Res Hum Retroviruses 8: 2055-2062.
35. Chiodi F, von Gegerfeldt A, Albert J, Fenyö EM, Gaines H, et al. (1987) Site-directed ELISA with synthetic peptides representing the HIV transmembrane glycoprotein. J Med Virol 23: 1-9.
36. Gnann JW Jr, Nelson JA, Oldstone MB, (1987) Fine mapping of an immunodominant domain in the transmembrane glycoprotein of human immunodeficiency virus. J Virol 61: 2639-2641.
37. Muster T, Steindl F, Purtscher M, Trkola A, Klima A, et al. (1993) A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol 67: 6642-6647.
38. 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.
39. 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 doi:10.1128/JVI.75.22.10892-10905.2001.
40. Cleveland SM, Buratti E, Jones TD, North P, Baralle F, et al. (2000) Immunogenic and antigenic dominance of a nonneutralizing epitope over a highly conserved neutralizing epitope in the gp41 envelope glycoprotein of human immunodeficiency virus type 1: its deletion leads to a strong neutralizing response. Virology 266: 66-78 doi:10.1006/viro.1999.0041.
41. Gray ES, Moore PL, Choge IA, Decker JM, Bibollet-Ruche F, et al. (2007) Neutralizing antibody responses in acute human immunodeficiency virus type 1 subtype C infection. J Virol 81: 6187-6196 doi:10.1128/JVI.00239-07.
42. Gray ES, Taylor N, Wycuff D, Moore PL, Tomaras GD, et al. (2009) Antibody specificities associated with neutralization breadth in plasma from human immunodeficiency virus type 1 subtype C-infected blood donors. J Virol 83: 8925-8937 doi:10.1128/JVI.00758-09.
43. Li B, Decker JM, Johnson RW, Bibollet-Ruche F, Wei X, et al. (2006) Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1. J Virol 80: 5211-5218 doi:10.1128/JVI.00201-06.
44. Rong R, Li B, Lynch RM, Haaland RE, Murphy MK, et al. (2009) Escape from autologous neutralizing antibodies in acute/early subtype C HIV-1 infection requires multiple pathways. PLoS Pathog 5: e1000594 doi:10.1371/journal.ppat.1000594.
45. Shankarappa R, Chatterjee R, Learn GH, Neogi D, Ding M, et al. (2001) Human immunodeficiency virus type 1 env sequences from Calcutta in eastern India: identification of features that distinguish subtype C sequences in India from other subtype C sequences. J Virol 75: 10479-10487 doi:10.1128/JVI.75.21.10479-10487.2001.
46. Jere A, Tripathy S, Agnihotri K, Jadhav S, Paranjape R, (2004) Genetic analysis of Indian HIV-1 nef: subtyping, variability and implications. Microbes Infect 6: 279-289 doi:10.1016/j.micinf.2003.11.012.
47. Kulkarni SS, Lapedes A, Tang H, Gnanakaran S, Daniels MG, et al. (2009) Highly complex neutralization determinants on a monophyletic lineage of newly transmitted subtype C HIV-1 Env clones from India. Virology 385: 505-520 doi:10.1016/j.virol.2008.12.032.
48. Lakhashe S, Thakar M, Godbole S, Tripathy S, Paranjape R, (2008) HIV infection in India: epidemiology, molecular epidemiology and pathogenesis. J Biosci 33: 515-525.
49. Spenlehauer C, Saragosti S, Fleury HJ, Kirn A, Aubertin AM, et al. (1998) Study of the V3 loop as a target epitope for antibodies involved in the neutralization of primary isolates versus T-cell-line-adapted strains of human immunodeficiency virus type 1. J Virol 72: 9855-9864.
50. Mascola JR, Louder MK, Winter C, Prabhakara R, De Rosa SC, et al. (2002) Human immunodeficiency virus type 1 neutralization measured by flow cytometric quantitation of single-round infection of primary human T cells. J Virol 76: 4810-4821.
51. Li M, Gao F, Mascola John R, Stamatatos L, Polonis VR, et al. (2005) Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J Virol 79: 10108-10125 doi:10.1128/JVI.79.16.10108-10125.2005.
52. Seaman MS, Janes H, Hawkins N, Grandpre LE, Devoy C, et al. (2010) Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J Virol 84: 1439-1452 doi:10.1128/JVI.02108-09.
53. Montefiori DC, (2005) Evaluating neutralizing antibodies against HIV, SIV, and SHIV in luciferase reporter gene assays. Curr Protoc Immunol Chapter 12: Unit 12.11 doi:10.1002/0471142735.im1211s64.
54. Walker LM, Simek MD, Priddy F, Gach JS, Wagner D, et al. (2010) A limited number of antibody specificities mediate broad and potent serum neutralization in selected HIV-1 infected individuals. PLoS Pathog 6: e1001028 doi:10.1371/journal.ppat.1001028.
55. 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 doi:10.1371/journal.ppat.1001251.
56. Sather DN, Stamatatos L, (2010) Epitope specificities of broadly neutralizing plasmas from HIV-1 infected subjects. Vaccine 28 Suppl 2: B8-12 doi:10.1016/j.vaccine.2009.07.085.
57. Dhillon AK, Donners H, Pantophlet R, Johnson WE, Decker JM, et al. (2007) Dissecting the neutralizing antibody specificities of broadly neutralizing sera from human immunodeficiency virus type 1-infected donors. J Virol 81: 6548-6562 doi:10.1128/JVI.02749-06.
58. Li Y, Svehla K, Louder MK, Wycuff D, Phogat S, et al. (2009) Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals. J Virol 83: 1045-1059 doi:10.1128/JVI.01992-08.
59. Lakhashe SK, Kulkarni SS, Thakar MR, Ghate MV, Paranjape RS, (2007) Extensive cross-reactive neutralizing antibody response in Indian patients with limited genetic diversity of HIV-1. Virology 359: 295-301 doi:10.1016/j.virol.2006.09.019.
60. Bures R, Morris L, Williamson C, Ramjee G, Deers M, et al. (2002) Regional clustering of shared neutralization determinants on primary isolates of clade C human immunodeficiency virus type 1 from South Africa. J Virol 76: 2233-2244.
61. Rademeyer C, Moore PL, Taylor N, Martin DP, Choge IA, et al. (2007) Genetic characteristics of HIV-1 subtype C envelopes inducing cross-neutralizing antibodies. Virology 368: 172-181 doi:10.1016/j.virol.2007.06.013.
62. Mascola JR, Louder MK, Surman SR, Vancott TC, Yu XF, et al. (1996) Human immunodeficiency virus type 1 neutralizing antibody serotyping using serum pools and an infectivity reduction assay. AIDS Res Hum Retroviruses 12: 1319-1328.
63. Louisirirotchanakul S, Beddows S, Cheingsong-Popov R, Shaffer N, Mastro TD, et al. (1998) Characterization of sera from subjects infected with HIV-1 subtypes B and E in Thailand by antibody binding and neutralization. J Acquir Immune Defic Syndr Hum Retrovirol 19: 315-320.
64. Braibant M, Brunet S, Costagliola D, Rouzioux C, Agut H, et al. (2006) Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non-progressors: prevalence and association with neutralizing activity. AIDS 20: 1923-1930 doi:10.1097/01.aids.0000247113.43714.5e.
65. 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 doi:10.1128/JVI.78.23.13232-13252.2004.
66. Haynes BF, Fleming J, St Clair EW, Katinger H, Stiegler G, et al. (2005) Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science 308: 1906-1908 doi:10.1126/science.1111781.
67. Andrabi R, Choudhary AK, Bala M, Kalra R, Prakash SS, et al. (2011) Relative reactivity of HIV-1 polyclonal plasma antibodies directed to V3 and MPER regions suggests immunodominance of V3 over MPER and dependence of high anti-V3 antibody titers on virus persistence. Arch Virol 156: 1787-1794 doi:10.1007/s00705-011-1053-5.
68. Alam SM, Scearce RM, Parks RJ, Plonk K, Plonk SG, et al. (2008) Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection. J Virol 82: 115-125 doi:10.1128/JVI.00927-07.
69. Frey G, Chen J, Rits-Volloch S, Freeman MM, Zolla-Pazner S, et al. (2010) Distinct conformational states of HIV-1 gp41 are recognized by neutralizing and non-neutralizing antibodies. Nat Struct Mol Biol 17: 1486-1491 doi:10.1038/nsmb.1950.
70. Nicely NI, Dennison SM, Spicer L, Scearce RM, Kelsoe G, et al. (2010) Crystal structure of a non-neutralizing antibody to the HIV-1 gp41 membrane-proximal external region. Nat Struct Mol Biol 17: 1492-1494 doi:10.1038/nsmb.1944.
71. Choudhary AK, Andrabi R, Prakash SS, Kumar R, Choudhury SD, et al. (2012) Neutralization potential of the plasma of HIV-1 infected Indian patients in the context of anti-V3 antibody content and antiretroviral theraphy. J Microbiol 50: 149-154 doi:10.1007/s12275-012-1246-y.
72. Pinter A, Honnen WJ, He Y, Gorny MK, Zolla-Pazner S, et al. (2004) 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 78: 5205-5215.
73. Krachmarov C, Pinter A, Honnen WJ, Gorny MK, Nyambi PN, et al. (2005) Antibodies that are cross-reactive for human immunodeficiency virus type 1 clade a and clade B v3 domains are common in patient sera from Cameroon, but their neutralization activity is usually restricted by epitope masking. J Virol 79: 780-790 doi:10.1128/JVI.79.2.780-790.2005.
74. Moore PL, Crooks ET, Porter L, Zhu P, Cayanan CS, et al. (2006) Nature of nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1. J Virol 80: 2515-2528 doi:10.1128/JVI.80.5.2515-2528.2006.
75. Davis KL, Gray ES, Moore PL, Decker JM, Salomon A, et al. (2009) High titer HIV-1 V3-specific antibodies with broad reactivity but low neutralizing potency in acute infection and following vaccination. Virology 387: 414-426 doi:10.1016/j.virol.2009.02.022.
76. Moore JP, Ho DD, (1993) Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of human immunodeficiency virus type 1 are highly prevalent in sera of infected humans. J Virol 67: 863-875.
77. Moore JP, Cao Y, Ho DD, Koup RA, (1994) Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J Virol 68: 5142-5155.
78. Zwick MB, Jensen R, Church S, Wang M, Stiegler G, et al. (2005) Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1. J Virol 79: 1252-1261 doi:10.1128/JVI.79.2.1252-1261.2005.
79. Shen X, Parks RJ, Montefiori DC, Kirchherr JL, Keele BF, et al. (2009) In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth. J Virol 83: 3617-3625 doi:10.1128/JVI.02631-08.
80. Binley JM, Lybarger EA, Crooks ET, Seaman MS, Gray E, et al. (2008) 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 82: 11651-11668 doi:10.1128/JVI.01762-08.
81. Pancera M, McLellan JS, Wu X, Zhu J, Changela A, et al. (2010) Crystal structure of PG16 and chimeric dissection with somatically related PG9: structure-function analysis of two quaternary-specific antibodies that effectively neutralize HIV-1. J Virol 84: 8098-8110 doi:10.1128/JVI.00966-10.
82. Changela A, Wu X, Yang Y, Zhang B, Zhu J, et al. (2011) Crystal structure of human antibody 2909 reveals conserved features of quaternary structure-specific antibodies that potently neutralize HIV-1. J Virol 85: 2524-2535 doi:10.1128/JVI.02335-10.
83. Pejchal R, Doores KJ, Walker LM, Khayat R, Huang P-S, et al. (2011) A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 334: 1097-1103 doi:10.1126/science.1213256.
84. Spurrier B, Sampson JM, Totrov M, Li H, O'Neal T, et al. (2011) Structural analysis of human and macaque mAbs 2909 and 2.5B: implications for the configuration of the quaternary neutralizing epitope of HIV-1 gp120. Structure 19: 691-699 doi:10.1016/j.str.2011.02.012.
85. Wu X, Changela A, O'Dell S, Schmidt SD, Pancera M, et al. (2011) Immunotypes of a quaternary site of HIV-1 vulnerability and their recognition by antibodies. J Virol 85: 4578-4585 doi:10.1128/JVI.02585-10.