Identification and specificity of broadly neutralizing antibodies against HIV

Immunological Reviews

Volumn 275, Issue 1, 2017, Pages 11-20

  McCoy, Laura E ^a,b   Burton, Dennis R ^a,c  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

B cells; HIV; monoclonal antibody isolation; neutralization

Indexed keywords

HUMAN IMMUNODEFICIENCY VIRUS VACCINE; NEUTRALIZING ANTIBODY; VIRUS ENVELOPE PROTEIN; EPITOPE; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS ANTIGEN;

ANTIBODY BLOOD LEVEL; ANTIBODY RESPONSE; ANTIBODY SPECIFICITY; B LYMPHOCYTE; FLOW CYTOMETRY; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; NONHUMAN; PRIORITY JOURNAL; REVIEW; ANIMAL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; METABOLISM; SINGLE CELL ANALYSIS; VIROLOGY;

AIDS VACCINES; ANIMALS; ANTIBODIES, NEUTRALIZING; B-LYMPHOCYTES; EPITOPES; HIV ANTIBODIES; HIV ANTIGENS; HIV INFECTIONS; HIV-1; HUMANS; SINGLE-CELL ANALYSIS; VIRAL ENVELOPE PROTEINS;

EID: 85010908338     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12484     Document Type: Review

References (103)

1. Blish CA, Dogan OC, Derby NR, et al. Human immunodeficiency virus type 1 superinfection occurs despite relatively robust neutralizing antibody responses. J Virol. 2008;82:12094–12103.
2. Gray ES, Taylor N, Wycuff D, et al. Antibody specificities associated with neutralization breadth in plasma from human immunodeficiency virus type 1 subtype C-infected blood donors. J Virol. 2009;83:8925–8937.
3. Burton DR, Hangartner L. Broadly neutralizing antibodies to HIV and their role in vaccine design. Annu Rev Immunol. 2016;34:635–659.
4. Mascola JR, Haynes BF. HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol Rev. 2013;254:225–244.
5. Kwong PD, Mascola JR. Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies. Immunity. 2012;37:412–425.
6. West AP Jr, Scharf L, Scheid JF, Klein F, Bjorkman PJ, Nussenzweig MC. Structural insights on the role of antibodies in HIV-1 vaccine and therapy. Cell. 2014;156:633–648.
7. Landais E, Huang X, Havenar-Daughton C, et al. Broadly neutralizing antibody responses in a large longitudinal sub-Saharan HIV primary infection cohort. PLoS Pathog. 2016;12:e1005369.
8. 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;83:7337–7348.
9. Hessell AJ, Haigwood NL. Animal models in HIV-1 protection and therapy. Curr Opin HIV AIDS. 2015;10:170–176.
10. Mascola JR, Montefiori DC. The role of antibodies in HIV vaccines. Annu Rev Immunol. 2010;28:413–444.
11. van Gils MJ, Sanders RW. In vivo protection by broadly neutralizing HIV antibodies. Trends Microbiol. 2014;22:550–551.
12. Burton DR, Pyati J, Koduri R, et al. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science. 1994;266:1024–1027.
13. 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 USA. 1992;89:9339–9343.
14. Barbas CF 3rd, Kang AS, Lerner RA, Benkovic SJ. Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proc Natl Acad Sci USA. 1991;88:7978–7982.
15. 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 USA. 1994;91:3348–3352.
16. Buchacher A, Predl R, Tauer C, et al. Human monoclonal antibodies against gp41 and gp120 as potential agents for passive immunization. In: Brown F, Chanock R, Ginsberg HS, Lerner R, eds. Vaccines ‘92: Modern Approaches to New Vaccines Including Prevention of AIDS. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory; 1992:191–194.
17. 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;10:359–369.
18. Stiegler G, Kunert R, Purtscher M, et al. A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 2001;17:1757–1765.
19. 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;75:10892–10905.
20. 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;78:13232–13252.
21. 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.
22. Walker LM, Huber M, Doores KJ, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011;477:466–470.
23. 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;326:285–289.
24. Falkowska E, Le KM, Ramos A, et al. Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers. Immunity. 2014;40:657–668.
25. Falkowska E, Ramos A, Feng Y, et al. PGV04, an HIV-1 gp120 CD4 binding site antibody, is broad and potent in neutralization but does not induce conformational changes characteristic of CD4. J Virol. 2012;86:4394–4403.
26. MacLeod DT, Choi NM, Briney B, et al. Early antibody lineage diversification and independent limb maturation lead to broad HIV-1 neutralization targeting the Env high-mannose patch. Immunity. 2016;44:1215–1226.
27. Sok D, Pauthner M, Briney B, et al. A prominent site of antibody vulnerability on HIV envelope incorporates a motif associated with CCR5 binding and its camouflaging glycans. Immunity. 2016;45:31–45.
28. Sok D, van Gils MJ, Pauthner M, et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc Natl Acad Sci USA. 2014;111:17624–17629.
29. 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;84:1439–1452.
30. Montefiori DC, Mascola JR. Neutralizing antibodies against HIV-1: can we elicit them with vaccines and how much do we need? Curr Opin HIV AIDS. 2009;4:347–351.
31. 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;79:10108–10125.
32. Babcook JS, Leslie KB, Olsen OA, Salmon RA, Schrader JW. A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities. Proc Natl Acad Sci USA. 1996;93:7843–7848.
33. Tiller T, Meffre E, Yurasov S, Tsuiji M, Nussenzweig MC, Wardemann H. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J Immunol Methods. 2008;329:112–124.
34. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC. Predominant autoantibody production by early human B cell precursors. Science. 2003;301:1374–1377.
35. Moldt B, Rakasz EG, Schultz N, et al. Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proc Natl Acad Sci USA. 2012;109:18921–18925.
36. Huang J, Ofek G, Laub L, et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature. 2012;491:406–412.
37. Huang J, Kang BH, Pancera M, et al. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature. 2014;515:138–142.
38. Scheid JF, Mouquet H, Feldhahn N, et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature. 2009;458:636–640.
39. Wu X, Yang ZY, Li Y, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010;329:856–861.
40. Scheid JF, Mouquet H, Ueberheide B, et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science. 2011;333:1633–1637.
41. Mouquet H, Scharf L, Euler Z, et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci USA. 2012;109:E3268–E3277.
42. Sok D, Doores KJ, Briney B, et al. Promiscuous glycan site recognition by antibodies to the high-mannose patch of gp120 broadens neutralization of HIV. Sci Transl Med. 2014;6:236ra63.
43. Scharf L, Scheid JF, Lee JH, et al. Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Rep. 2014;7:785–795.
44. Klein F, Gaebler C, Mouquet H, et al. Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein. J Exp Med. 2012;209:1469–1479.
45. Lee JH, Leaman DP, Kim AS, et al. Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike. Nat Commun. 2015;6:8167.
46. Sanders RW, Derking R, Cupo A, et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 2013;9:e1003618.
47. van Gils MJ, van den Kerkhof TLGM, Ozorowski G, et al. An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability. Nat. Microbiol. 2016;2:16199.
48. Kong R, Xu K, Zhou T, et al. Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science. 2016;352:828–833.
49. Doria-Rose NA, Bhiman JN, Roark RS, et al. New member of the V1V2-directed CAP256-VRC26 lineage that shows increased breadth and exceptional potency. J Virol. 2016;90:76–91.
50. Sok D, Laserson U, Laserson J, et al. The effects of somatic hypermutation on neutralization and binding in the PGT121 family of broadly neutralizing HIV antibodies. PLoS Pathog. 2013;9:e1003754.
51. Doria-Rose NA, Schramm CA, Gorman J, et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature. 2014;509:55–62.
52. Liao HX, Lynch R, Zhou T, et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 2013;496:469–476.
53. Bonsignori M, Zhou T, Sheng Z, et al. Maturation pathway from germline to broad HIV-1 neutralizer of a CD4-mimic antibody. Cell. 2016;165:449–463.
54. Briney B, Le K, Zhu J, Burton DR. Clonify: unseeded antibody lineage assignment from next-generation sequencing data. Sci Rep. 2016;6:23901.
55. Zhu J, Ofek G, Yang Y, et al. Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains. Proc Natl Acad Sci USA. 2013;110:6470–6475.
56. Wu X, Zhou T, Zhu J, et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science. 2011;333:1593–1602.
57. Zhou T, Zhu J, Wu X, et al. Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity. 2013;39:245–258.
58. Zhu J, Wu X, Zhang B, et al. De novo identification of VRC01 class HIV-1-neutralizing antibodies by next-generation sequencing of B-cell transcripts. Proc Natl Acad Sci USA. 2013;110:E4088–E4097.
59. Moore PL, Williamson C, Morris L. Virological features associated with the development of broadly neutralizing antibodies to HIV-1. Trends Microbiol. 2015;23:204–211.
60. Lynch RM, Tran L, Louder MK, et al. The development of CD4 binding site antibodies during HIV-1 infection. J Virol. 2012;86:7588–7595.
61. 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;82:11651–11668.
62. Pancera M, Zhou T, Druz A, et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014;514:455–461.
63. Julien JP, Lee JH, Cupo A, et al. Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9. Proc Natl Acad Sci USA. 2013;110:4351–4356.
64. McLellan JS, Pancera M, Carrico C, et al. Structure of HIV-1 gp120V1/V2 domain with broadly neutralizing antibody PG9. Nature. 2011;480:336–343.
65. 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 USA. 2010;107:11483–11488.
66. Doores KJ, Burton DR. Variable loop glycan dependency of the broad and potent HIV-1-neutralizing antibodies PG9 and PG16. J Virol. 2010;84:10510–10521.
67. Bonsignori M, Hwang KK, Chen X, et al. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol. 2011;85:9998–10009.
68. Andrabi R, Voss JE, Liang CH, et al. Identification of common features in prototype broadly neutralizing antibodies to HIV envelope V2 apex to facilitate vaccine design. Immunity. 2015;43:959–973.
69. Gorman J, Soto C, Yang MM, et al. Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design. Nat Struct Mol Biol. 2016;23:81–90.
70. McCoy LE, Falkowska E, Doores KJ, et al. Incomplete neutralization and deviation from sigmoidal neutralization curves for HIV broadly neutralizing monoclonal antibodies. PLoS Pathog. 2015;11:e1005110.
71. Kong L, Lee JH, Doores KJ, et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat Struct Mol Biol. 2013;20:796–803.
72. Pejchal R, Doores KJ, Walker LM, et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science. 2011;334:1097–1103.
73. Doores KJ, Kong L, Krumm SA, et al. Two classes of broadly neutralizing antibodies within a single lineage directed to the high-mannose patch of HIV envelope. J Virol. 2015;89:1105–1118.
74. Zhou T, Georgiev I, Wu X, et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science. 2010;329:811–817.
75. Corti D, Langedijk JP, 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.
76. Zhou T, Lynch RM, Chen L, et al. Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors. Cell. 2015;161:1280–1292.
77. West AP Jr, Diskin R, Nussenzweig MC, Bjorkman PJ. Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120. Proc Natl Acad Sci USA. 2012;109:E2083–E2090.
78. Kong L, Ju B, Chen Y, et al. Key gp120 glycans pose roadblocks to the rapid development of VRC01-class antibodies in an HIV-1-infected Chinese Donor. Immunity. 2016;44:939–950.
79. Scharf L, Wang H, Gao H, Chen S, McDowall AW, Bjorkman PJ. Broadly neutralizing antibody 8ANC195 recognizes closed and open states of HIV-1 Env. Cell. 2015;162:1379–1390.
80. Blattner C, Lee JH, Sliepen K, et al. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity. 2014;40:669–680.
81. Muster T, Steindl F, Purtscher M, et al. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol. 1993;67:6642–6647.
82. 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.
83. Liu M, Yang G, Wiehe K, et al. Polyreactivity and autoreactivity among HIV-1 antibodies. J Virol. 2015;89:784–798.
84. Scherer EM, Zwick MB, Teyton L, Burton DR. Difficulties in eliciting broadly neutralizing anti-HIV antibodies are not explained by cardiolipin autoreactivity. AIDS. 2007;21:2131–2139.
85. 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;84:1302–1313.
86. Haynes BF, Moody MA, Alam M, et al. Progress in HIV-1 vaccine development. J Allergy Clin Immunol. 2014;134:3–10; quiz 1.
87. Irimia A, Sarkar A, Stanfield RL, Wilson IA. Crystallographic identification of lipid as an integral component of the epitope of HIV broadly neutralizing antibody 4E10. Immunity. 2016;44:21–31.
88. McCoy LE, van Gils M, Ozorowski G. Holes in the glycan shield of the native HIV envelope are a target of trimer- elicited neutralizing antibodies. Cell Rep. 2016;16:2327–2338.
89. Simonich CA, Williams KL, Verkerke HP, et al. HIV-1 neutralizing antibodies with limited hypermutation from an infant. Cell. 2016;166:77–87.
90. Bradley T, Fera D, Bhiman J, et al. Structural constraints of vaccine-induced tier-2 autologous HIV neutralizing antibodies targeting the receptor-binding site. Cell Rep. 2016;14:43–54.
91. Crooks ET, Tong T, Chakrabarti B, et al. Vaccine-elicited tier 2 HIV-1 neutralizing antibodies bind to quaternary epitopes involving glycan-deficient patches proximal to the CD4 binding site. PLoS Pathog. 2015;11:e1004932.
92. McCoy LE, Weiss RA. Neutralizing antibodies to HIV-1 induced by immunization. J Exp Med. 2013;210:209–223.
93. Sanders RW, van Gils MJ, Derking R, et al. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science. 2015;349:aac4223.
94. Phad GE, Vazquez Bernat N, Feng Y, et al. Diverse antibody genetic and recognition properties revealed following HIV-1 envelope glycoprotein immunization. J Immunol. 2015;194:5903–5914.
95. Dosenovic P, von Boehmer L, Escolano A, et al. Immunization for HIV-1 broadly neutralizing antibodies in human Ig knockin mice. Cell. 2015;161:1505–1515.
96. Jardine JG, Ota T, Sok D, et al. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen. Science. 2015;349:156–161.
97. Briney B, Sok D, Jardine J. et al. Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies. Cell. 2016;166:1459–1470.
98. Escolano A, Steichen JM, Dosenovic P. etal. Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice. Cell. 2016;166:1445–1458.
99. Steichen JM, Kulp DW, Tokatlian T. et al. HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies. Immunity. 2016;45:1–14.
100. McCoy LE, Quigley AF, Strokappe NM, et al. Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization. J Exp Med. 2012;209:1091–1103.
101. McCoy LE, Rutten L, Frampton D, et al. Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1. PLoS Pathog. 2014;10:e1004552.
102. Walker LM, Burton DR. Rational antibody-based HIV-1 vaccine design: current approaches and future directions. Curr Opin Immunol. 2010;22:358–366.
103. Kwon YD, Pancera M, Acharya P, et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol. 2015;22:522–531.