Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1

Virology

Volumn 396, Issue 2, 2010, Pages 339-348

  Nandi, Avishek ^a   Lavine, Christine L ^a   Wang, Pengcheng ^a   Lipchina, Inna ^a   Goepfert, Paul A ^b   Shaw, George M ^b   Tomaras, Georgia D ^c   Montefiori, David C ^c   Haynes, Barton F ^c   Easterbrook, Philippa ^d   Robinson, James E ^e   Sodroski, Joseph G ^f,g   Yang, Xinzhen ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^b UNIVERSITY OF ALABAMA SCHOOL OF MEDICINE   (United States)

^c DUKE UNIVERSITY MEDICAL CENTER   (United States)

^d KING'S COLLEGE LONDON   (United Kingdom)

^e TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f DANA FARBER CANCER INSTITUTE   (United States)

^g HARVARD MEDICAL SCHOOL   (United States)

Author keywords

CD4BS; Envelope glycoprotein; Glycan; HIV 1; In vivo; Neutralizing epitope; V3

Indexed keywords

ENVELOPE PROTEIN; EPITOPE; GLYCOPROTEIN GP 120; MUTANT PROTEIN; NEUTRALIZING ANTIBODY; RECOMBINANT PROTEIN; VIRUS GLYCOPROTEIN;

ANTIBODY RESPONSE; ANTIGEN BINDING; ARTICLE; BINDING SITE; CONTROLLED STUDY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IN VITRO STUDY; IN VIVO STUDY; MAJOR CLINICAL STUDY; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN;

ANTIBODIES, NEUTRALIZING; ANTIGENS, CD4; EPITOPES; HIV ANTIBODIES; HIV ANTIGENS; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HUMANS; NEUTRALIZATION TESTS; RECOMBINANT PROTEINS;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 71049141219     PISSN: 00426822     EISSN: 10960341     Source Type: Journal    
DOI: 10.1016/j.virol.2009.10.044     Document Type: Article

References (68)

1. Binley J.M., Lybarger E.A., Crooks E.T., Seaman M.S., Gray E., Davis K.L., Decker J.M., Wycuff D., Harris L., Hawkins N., Wood B., Nathe C., Richman D., Tomaras G.D., Bibollet-Ruche F., Robinson J.E., Morris L., Shaw G.M., Montefiori D.C., and Mascola J.R. 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 23 (2008) 11651-11668
2. Burton D.R., Pyati J., Koduri R., Sharp S.J., Thornton G.B., Parren P.W., Sawyer L.S., Hendry R.M., Dunlop N., Nara P.L., Lamacchia M., Garratty E.E., Stiehm R., Bryson Y.J., Cao Y., Moore J.P., Ho D.D., and Barbas 1 C.F. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 266 5187 (1994) 1024-1027
3. Chen B., Vogan E.M., Gong H., Skehel J.J., Wiley D.C., and Harrison S.C. Structure of an unliganded simian immunodeficiency virus gp120 core. Nature 433 7028 (2005) 834-841
4. Connor R.I., Chen B.K., Choe S., and Landau N.R. Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology 206 2 (1995) 935-944
5. Decker J.M., Bibollet-Ruche F., Wei X., Wang S., Levy D.N., Wang W., Delaporte E., Peeters M., Derdeyn C.A., Allen S., Hunter E., Saag M.S., Hoxie J.A., Hahn B.H., Kwong P.D., Robinson J.E., and Shaw G.M. Antigenic conservation and immunogenicity of the HIV coreceptor binding site. J. Exp. Med. 201 9 (2005) 1407-1419
6. Deeks S.G., Schweighardt B., Wrin T., Galovich J., Hoh R., Sinclair E., Hunt P., McCune J.M., Martin J.N., Petropoulos C.J., and Hecht F.M. 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. 80 12 (2006) 6155-6164
7. Dhillon A.K., Donners H., Pantophlet R., Johnson W.E., Decker J.M., Shaw G.M., Lee F.H., Richman D.D., Doms R.W., Vanham G., and Burton D.R. Dissecting the neutralizing antibody specificities of broadly neutralizing sera from human immunodeficiency virus type 1-infected donors. J. Virol. 81 12 (2007) 6548-6562
8. Gaschen B., Kuiken C., Korber B., and Foley B. Retrieval and on-the-fly alignment of sequence fragments from the HIV database. Bioinformatics 17 5 (2001) 415-418
9. Gorny M.K., VanCott T.C., Hioe C., Israel Z.R., Michael N.L., Conley A.J., Williams C., Kessler II J.A., Chigurupati P., Burda S., and Zolla-Pazner S. Human monoclonal antibodies to the V3 loop of HIV-1 with intra- and interclade cross-reactivity. J. Immunol. 159 10 (1997) 5114-5122
10. Gorny M.K., Williams C., Volsky B., Revesz K., Cohen S., Polonis V.R., Honnen W.J., Kayman S.C., Krachmarov C., Pinter A., and Zolla-Pazner S. Human monoclonal antibodies specific for conformation-sensitive epitopes of V3 neutralize human immunodeficiency virus type 1 primary isolates from various clades. J. Virol. 76 18 (2002) 9035-9045
11. Gorny M.K., Xu J.Y., Karwowska S., Buchbinder A., and Zolla-Pazner S. Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120. J. Immunol. 150 2 (1993) 635-643
12. Gray E.S., Madiga M.C., Moore P.L., Mlisana K., Karim S.S., Binley J.M., Shaw G.M., Mascola J.R., and Morris L. Broad HIV-1 neutralization mediated by plasma antibodies against the gp41 membrane proximal external region. J. Virol. 83 (2009) 11265-11274
13. Gray E.S., Taylor N., Wycuff D., Moore P.L., Tomaras G.D., Wibmer C.K., Puren A., Decamp A., Gilbert P.B., Wood B., Montefiori D.C., Binley J.M., Shaw G.M., Haynes B.F., Mascola J.R., and Morris L. Antibody specificities associated with neutralization breadth in plasma from HIV-1 subtype C infected blood donors. J. Virol. 83 17 (2009) 8925-8937
14. Haigwood N.L., Nara P.L., Brooks E., Van Nest G.A., Ott G., Higgins K.W., Dunlop N., Scandella C.J., Eichberg J.W., and Steimer K.S. Native but not denatured recombinant human immunodeficiency virus type 1 gp120 generates broad-spectrum neutralizing antibodies in baboons. J. Virol. 66 1 (1992) 172-182
15. Kang C.Y., Nara P., Chamat S., Caralli V., Ryskamp T., Haigwood N., Newman R., and Kohler H. Evidence for non-V3-specific neutralizing antibodies that interfere with gp120/CD4 binding in human immunodeficiency virus 1-infected humans. Proc. Natl. Acad. Sci. U. S. A. 88 14 (1991) 6171-6175
16. Korber B.F., F., Kuiken C., Pillai S., and Sodroksi J. Numbering positions in HIV relative to HXBc2. In: Korber B.K., Foley C., Hahn F., McCutchan B., Mellor F., and Sodroski J. (Eds). "Human Retroviruses and AIDS" (1998), Los Alamos National Laboratories, Los Alamos
17. Kuiken C., Korber B., and Shafer R.W. HIV sequence databases. AIDS. Rev. 5 1 (2003) 52-61
18. Kwong P.D., Wyatt R., Robinson J., Sweet R.W., Sodroski J., and Hendrickson W.A. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393 6686 (1998) 648-659
19. Kwong P.D., Wyatt R., Majeed S., Robinson J., Sweet R.W., Sodroski J., and Hendrickson W.A. Structures of HIV-1 gp120 envelope glycoproteins from laboratory-adapted and primary isolates. Structure. Fold. Des. 8 12 (2000) 1329-1339
20. Li M., Gao F., Mascola J.R., Stamatatos L., Polonis V.R., Koutsoukos M., Voss G., Goepfert P., Gilbert P., Greene K.M., Bilska M., Kothe D.L., Salazar-Gonzalez J.F., Wei X., Decker J.M., Hahn B.H., and Montefiori D.C. 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 16 (2005) 10108-10125
21. Li M., Salazar-Gonzalez J.F., Derdeyn C.A., Morris L., Williamson C., Robinson J.E., Decker J.M., Li Y., Salazar M.G., Polonis V.R., Mlisana K., Karim S.A., Hong K., Greene K.M., Bilska M., Zhou J., Allen S., Chomba E., Mulenga J., Vwalika C., Gao F., Zhang M., Korber B.T., Hunter E., Hahn B.H., and Montefiori D.C. Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in Southern Africa. J. Virol. 80 23 (2006) 11776-11790
22. Li Y., Migueles S.A., Welcher B., Svehla K., Phogat A., Louder M.K., Wu X., Shaw G.M., Connors M., Wyatt R.T., and Mascola J.R. Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat. Med. 13 9 (2007) 1032-1034
23. Li Y., Svehla K., Louder M.K., Wycuff D., Phogat S., Tang M., Migueles S.A., Wu X., Phogat A., Shaw G.M., Connors M., Hoxie J., Mascola J.R., and Wyatt R. Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals. J. Virol. 83 2 (2009) 1045-1059
24. Liu J., Bartesaghi A., Borgnia M.J., Sapiro G., and Subramaniam S. Molecular architecture of native HIV-1 gp120 trimers. Nature 455 7209 (2008) 109-113
25. Luallen R.J., Lin J., Fu H., Cai K.K., Agrawal C., Mboudjeka I., Lee F.H., Montefiori D., Smith D.F., Doms R.W., and Geng Y. An engineered Saccharomyces cerevisiae strain binds the broadly neutralizing human immunodeficiency virus type 1 antibody 2G12 and elicits mannose-specific gp120-binding antibodies. J. Virol. 82 13 (2008) 6447-6457
26. Mascola J.R., Lewis M.G., Stiegler G., Harris D., VanCott T.C., Hayes D., Louder M.K., Brown C.R., Sapan C.V., Frankel S.S., Lu Y., Robb M.L., Katinger H., and Birx D.L. Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J. Virol. 73 5 (1999) 4009-4018
27. Modrow S., Hahn B.H., Shaw G.M., Gallo R.C., Wong-Staal F., and 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. 61 2 (1987) 570-578
28. Moore J.P., and Ho D.D. 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 2 (1993) 863-875
29. Moore J.P., and Sodroski J. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J. Virol. 70 3 (1996) 1863-1872
30. Moore J.P., McCutchan F.E., Poon S.W., Mascola J., Liu J., Cao Y., and Ho D.D. Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies. J. Virol. 68 12 (1994) 8350-8364
31. Muster T., Steindl F., Purtscher M., Trkola A., Klima A., Himmler G., Ruker F., and Katinger H. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J. Virol. 67 11 (1993) 6642-6647
32. Myers G., berzofsky b., Korber B.T., smith r., and pavlakis g. Human Retroviruses and AIDS. A Compilation and Analysis of Nucleic and Amino Acid Sequences (1992), Los Alamos, NM.
33. Pantophlet R., Ollmann Saphire E., Poignard P., Parren P.W., Wilson I.A., and Burton D.R. Fine mapping of the interaction of neutralizing and nonneutralizing monoclonal antibodies with the CD4 binding site of human immunodeficiency virus type 1 gp120. J. Virol. 77 1 (2003) 642-658
34. Parren P.W., Marx P.A., Hessell A.J., Luckay A., Harouse J., Cheng-Mayer C., Moore J.P., and Burton D.R. 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 17 (2001) 8340-8347
35. Posner M.R., Cavacini L.A., Emes C.L., Power J., and Byrn R. Neutralization of HIV-1 by F105, a human monoclonal antibody to the CD4 binding site of gp120. J. Acquir. Immune. Defic. Syndr. 6 1 (1993) 7-14
36. Robinson J.E., Holton D., Pacheco-Morell S., Liu J., and McMurdo H. Identification of conserved and variant epitopes of human immunodeficiency virus type 1 (HIV-1) gp120 by human monoclonal antibodies produced by EBV-transformed cell lines. AIDS. Res. Hum. Retroviruses. 6 5 (1990) 567-579
37. Sanders R.W., Venturi M., Schiffner L., Kalyanaraman R., Katinger H., Lloyd K.O., Kwong P.D., and Moore J.P. The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J. Virol. 76 14 (2002) 7293-7305
38. Saphire E.O., Parren P.W., Pantophlet R., Zwick M.B., Morris G.M., Rudd P.M., Dwek R.A., Stanfield R.L., Burton D.R., and Wilson I.A. Crystal structure of a neutralizing human IGG against HIV-1: a template for vaccine design. Science 293 5532 (2001) 1155-1159
39. Sather D.N., Armann J., Ching L.K., Mavrantoni A., Sellhorn G., Caldwell Z., Yu X., Wood B., Self S., Kalams S., and Stamatatos L. Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J. Virol. 83 2 (2009) 757-769
40. Scanlan C.N., Pantophlet R., Wormald M.R., Ollmann Saphire E., Stanfield R., Wilson I.A., Katinger H., Dwek R.A., Rudd P.M., and Burton D.R. The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1->2 mannose residues on the outer face of gp120. J. Virol. 76 14 (2002) 7306-7321
41. Shen X., Parks R.J., Montefiori D.C., Kirchherr J.L., Keele B.F., Decker J.M., Blattner W.A., Gao F., Weinhold K.J., Hicks C.B., Greenberg M.L., Hahn B.H., Shaw G.M., Haynes B.F., and Tomaras G.D. In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth. J. Virol. 83 8 (2009) 3617-3625
42. Shibata R., Igarashi T., Haigwood N., Buckler-White A., Ogert R., Ross W., Willey R., Cho M.W., and Martin M.A. Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys. Nat. Med. 5 2 (1999) 204-210
43. Simek M.D., Rida W., Priddy F.H., Pung P., Carrow E., Laufer D.S., Lehrman J.K., Boaz M., Tarragona-Fiol T., Miiro G., Birungi J., Pozniak A., McPhee D.A., Manigart O., Karita E., Inwoley A., Jaoko W., Dehovitz J., Bekker L.G., Pitisuttithum P., Paris R., Walker L.M., Poignard P., Wrin T., Fast P.E., Burton D.R., and Koff W.C. 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. 83 14 (2009) 7337-7348
44. Stanfield R.L., Gorny M.K., Williams C., Zolla-Pazner S., and Wilson I.A. Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D. Structure. (Camb). 12 2 (2004) 193-204
45. Starcich B.R., Hahn B.H., Shaw G.M., McNeely P.D., Modrow S., Wolf H., Parks E.S., Parks W.P., Josephs S.F., Gallo R.C., et al. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell 45 5 (1986) 637-648
46. Stiegler G., Kunert R., Purtscher M., Wolbank S., Voglauer R., Steindl F., and Katinger H. A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS. Res. Hum. Retroviruses. 17 18 (2001) 1757-1765
47. Sullivan N., Sun Y., Binley J., Lee J., Barbas III C.F., Parren P.W., Burton D.R., and Sodroski J. Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies. J. Virol. 72 8 (1998) 6332-6338
48. Thali M., Furman C., Ho D.D., Robinson J., Tilley S., Pinter A., and Sodroski J. Discontinuous, conserved neutralization epitopes overlapping the CD4-binding region of human immunodeficiency virus type 1 gp120 envelope glycoprotein. J. Virol. 66 9 (1992) 5635-5641
49. Thali M., Moore J.P., Furman C., Charles M., Ho D.D., Robinson J., and Sodroski J. Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding. J. Virol. 67 7 (1993) 3978-3988
50. Trkola A., Purtscher M., Muster T., Ballaun C., Buchacher A., Sullivan N., Srinivasan K., Sodroski J., Moore J.P., and Katinger H. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J. Virol. 70 2 (1996) 1100-1108
51. Veazey R.S., Shattock R.J., Pope M., Kirijan J.C., Jones J., Hu Q., Ketas T., Marx P.A., Klasse P.J., Burton D.R., and Moore J.P. Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120. Nat. Med. 9 3 (2003) 343-346
52. Walker L.M., Phogat S.K., Chan-Hui P.Y., Wagner D., Phung P., Goss J.L., Wrin T., Simek M.D., Fling S., Mitcham J.L., Lehrman J.K., Priddy F.H., Olsen O.A., Frey S.M., Hammond P.W., Miiro G., Serwanga J., Pozniak A., McPhee D., Manigart O., Mwananyanda L., Karita E., Inwoley A., Jaoko W., Dehovitz J., Bekker L.G., Pitisuttithum P., Paris R., Allen S., Kaminsky S., Zamb T., Moyle M., Koff W.C., Poignard P., and Burton D.R. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326 5950 (2009) 285-289
53. Willey R.L., Rutledge R.A., Dias S., Folks T., Theodore T., Buckler C.E., and Martin M.A. Identification of conserved and divergent domains within the envelope gene of the acquired immunodeficiency syndrome retrovirus. Proc. Natl. Acad. Sci. U. S. A. 83 14 (1986) 5038-5042
54. Wu L., Zhou T., Yang Z.Y., Svehla K., O'Dell S., Louder M.K., Xu L., Mascola J.R., Burton D.R., Hoxie J.A., Doms R.W., Kwong P.D., and Nabel G.J. Enhanced exposure of the CD4-binding site to neutralizing antibodies by structural design of a membrane-anchored human immunodeficiency virus type 1 gp120 domain. J. Virol. 83 10 (2009) 5077-5086
55. Wyatt R., and Sodroski J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280 5371 (1998) 1884-1888
56. Wyatt R., Kwong P.D., Desjardins E., Sweet R.W., Robinson J., Hendrickson W.A., and Sodroski J.G. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 393 6686 (1998) 705-711
57. Xiang S.H., Kwong P.D., Gupta R., Rizzuto C.D., Casper D.J., Wyatt R., Wang L., Hendrickson W.A., Doyle M.L., and Sodroski J. Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct conformations of the human immunodeficiency virus type 1 gp120 envelope glycoprotein. J. Virol. 76 19 (2002) 9888-9899
58. Xiang S.H., Wang L., Abreu M., Huang C.C., Kwong P.D., Rosenberg E., Robinson J.E., and Sodroski J. Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains. Virology 315 1 (2003) 124-134
59. Yang X., Farzan M., Wyatt R., and Sodroski J. Characterization of stable, soluble trimers containing complete ectodomains of human immunodeficiency virus type 1 envelope glycoproteins. J. Virol. 74 12 (2000) 5716-5725
60. Yang X., Florin L., Farzan M., Kolchinsky P., Kwong P.D., Sodroski J., and Wyatt R. Modifications that stabilize human immunodeficiency virus envelope glycoprotein trimers in solution. J. Virol. 74 10 (2000) 4746-4754
61. Yang X., Wyatt R., and Sodroski J. Improved elicitation of neutralizing antibodies against primary human immunodeficiency viruses by soluble stabilized envelope glycoprotein trimers. J. Virol. 75 3 (2001) 1165-1171
62. Yang X., Lee J., Mahony E.M., Kwong P.D., Wyatt R., and Sodroski J. Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin. J. Virol. 76 9 (2002) 4634-4642
63. Yang X., Tomov V., Kurteva S., Wang L., Ren X., Gorny M.K., Zolla-Pazner S., and Sodroski J. Characterization of the outer domain of the gp120 glycoprotein from human immunodeficiency virus type 1. J. Virol. 78 23 (2004) 12975-12986
64. Yang X., Kurteva S., Lee S., and Sodroski J. Stoichiometry of antibody neutralization of human immunodeficiency virus type 1. J. Virol. 79 6 (2005) 3500-3508
65. Zhou T., Xu L., Dey B., Hessell A.J., Van Ryk D., Xiang S.H., Yang X., Zhang M.Y., Zwick M.B., Arthos J., Burton D.R., Dimitrov D.S., Sodroski J., Wyatt R., Nabel G.J., and Kwong P.D. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 445 7129 (2007) 732-737
66. Zhu P., Chertova E., Bess Jr. J., Lifson J.D., Arthur L.O., Liu J., Taylor K.A., and Roux K.H. Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Proc. Natl. Acad. Sci. U. S. A. 100 26 (2003) 15812-15817
67. Zolla-Pazner S. Improving on nature: focusing the immune response on the V3 loop. Hum. Antibodies. 14 3-4 (2005) 69-72
68. Zwick M.B., Labrijn A.F., Wang M., Spenlehauer C., Saphire E.O., Binley J.M., Moore J.P., Stiegler G., Katinger H., Burton D.R., and Parren P.W. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol. 75 22 (2001) 10892-10905