Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting

PLoS Pathogens

Volumn 13, Issue 1, 2017, Pages

  Doria Rose, Nicole A ^a   Altae Tran, Han R ^a   Roark, Ryan S ^a   Schmidt, Stephen D ^a   Sutton, Matthew S ^a   Louder, Mark K ^a   Chuang, Gwo Yu ^a   Bailer, Robert T ^a   Cortez, Valerie ^b,c   Kong, Rui ^a   McKee, Krisha ^a   O’Dell, Sijy ^a   Wang, Felicia ^d   Abdool Karim, Salim S ^e,f   Binley, James M ^g   Connors, Mark ^a   Haynes, Barton F ^h   Martin, Malcolm A ⁱ   Montefiori, David C ^h   Morris, Lynn ^e,j,k   Overbaugh, Julie ^b   Kwong, Peter D ^a   Mascola, John R ^a   Georgiev, Ivelin S ^a,d,l   more..

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b Fred Hutchinson Cancer Research Center   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

^d VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^e UNIVERSITY OF KWAZULU NATAL   (South Africa)

^f Columbia University ^*  (United States)

^g San Diego Biomedical Research Institute   (United States)

^h DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁱ NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^j UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^k NATIONAL INSTITUTE FOR COMMUNICABLE DISEASES   (South Africa)

^l VANDERBILT UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; MONOCLONAL ANTIBODY; NEUTRALIZING ANTIBODY; POLYCLONAL ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS VACCINE;

ACCURACY; ALGORITHM; ANTIBODY RESPONSE; ANTIBODY SPECIFICITY; ARTICLE; CONTROLLED STUDY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MAJOR CLINICAL STUDY; NEXT GENERATION NEUTRALIZATION FINGERPRINTING ALGORITHM; NONHUMAN; PREVALENCE; SIMULATION; VIRUS NEUTRALIZATION; ANTIBODY PRODUCTION; COHORT ANALYSIS; COMPUTER SIMULATION; EPITOPE MAPPING; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; PROCEDURES; SERODIAGNOSIS; VIROLOGY;

AIDS VACCINES; ALGORITHMS; ANTIBODY FORMATION; ANTIBODY SPECIFICITY; COHORT STUDIES; COMPUTER SIMULATION; EPITOPE MAPPING; EPITOPES; HIV ANTIBODIES; HIV INFECTIONS; HIV-1; HUMANS; NEUTRALIZATION TESTS;

EID: 85011002666     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1006148     Document Type: Article

References (77)

1. Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, Gorman J, et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014;514(7523):455–61. doi: 10.1038/nature1380825296255
2. Korber B, Gaschen B, Yusim K, Thakallapally R, Kesmir C, Detours V, Evolutionary and immunological implications of contemporary HIV-1 variation. Br Med Bull. 2001;58:19–42. Epub 2001/11/21. 11714622
3. Karlsson Hedestam GB, Fouchier RAM, Phogat S, Burton DR, Sodroski J, Wyatt RT, The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus. Nat Rev Micro. 2008;6(2):143–55.
4. Georgiev IS, Doria-Rose NA, Zhou T, Kwon YD, Staupe RP, Moquin S, et al. Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization. Science. 2013;340(6133):751–6. Epub 2013/05/11. doi: 10.1126/science.123398923661761
5. Corti D, Langedijk JP, Hinz A, Seaman MS, Vanzetta F, Fernandez-Rodriguez BM, 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(1):e8805. doi: 10.1371/journal.pone.000880520098712
6. Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, Julien JP, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011;477(7365):466–70. Epub 2011/08/19. doi: 10.1038/nature1037321849977
7. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science. 2009;326(5950):285–9. Epub 2009/09/05. doi: 10.1126/science.117874619729618
8. Wu X, Zhou T, Zhu J, Zhang B, Georgiev I, Wang C, et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science. 2011;333(6049):1593–602. Epub 2011/08/13. doi: 10.1126/science.120753221835983
9. Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010;329(5993):856–61. Epub 2010/07/10. PubMed Central PMCID: PMC2965066. doi: 10.1126/science.118765920616233
10. Scheid JF, Mouquet H, Ueberheide B, Diskin R, Klein F, Oliveira TY, et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science. 2011;333(6049):1633–7. Epub 2011/07/19. doi: 10.1126/science.120722721764753
11. Falkowska E, Le KM, Ramos A, Doores KJ, Lee JH, Blattner C, et al. Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers. Immunity. 2014;40(5):657–68. Epub 2014/04/29. doi: 10.1016/j.immuni.2014.04.00924768347
12. Huang J, Kang B, Pancera M, Lee JH, Tong T, Feng Y, et al. Broad and potent neutralization of HIV-1 by a human antibody that recognizes an intersubunit site on the envelope glycoprotein. Nature. 2014;515(7525):138–42. doi: 10.1038/nature1360125186731
13. Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature. 2012;491(7424):406–12. Epub 2012/11/16. doi: 10.1038/nature1154423151583
14. Doria-Rose NA, Schramm CA, Gorman J, Moore PL, Bhiman JN, DeKosky BJ, et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature. 2014;509(7498):55–62. Epub 2014/03/05.
15. Mouquet H, Scharf L, Euler Z, Liu Y, Eden C, Scheid JF, et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(47):E3268–77. Epub 2012/11/02. PubMed Central PMCID: PMC3511153. doi: 10.1073/pnas.121720710923115339
16. Sok D, van Gils MJ, Pauthner M, Julien J-P, Saye-Francisco KL, Hsueh J, et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proceedings of the National Academy of Sciences. 2014. Epub 2014 Nov 24.
17. Bonsignori M, Hwang KK, Chen X, Tsao CY, Morris L, Gray E, 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. Journal of virology. 2011;85(19):9998–10009. Epub 2011/07/29. PubMed Central PMCID: PMC3196428. doi: 10.1128/JVI.05045-1121795340
18. Bonsignori M, Montefiori DC, Wu X, Chen X, Hwang KK, Tsao CY, et al. Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-infected Donor: Implications for Vaccine Design. Journal of virology. 2012. Epub 2012/02/04.
19. Kong R, Xu K, Zhou T, Acharya P, Lemmin T, Liu K, et al. Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science. 2016;352(6287):828–33. doi: 10.1126/science.aae047427174988
20. MacLeod Daniel T, Choi Nancy M, Briney B, Garces F, Ver Lorena S, Landais E, 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(5):1215–26. doi: 10.1016/j.immuni.2016.04.01627192579
21. Saunders KO, Pegu A, Georgiev IS, Zeng M, Joyce MG, Yang Z-Y, et al. Sustained Delivery of a Broadly Neutralizing Antibody in Nonhuman Primates Confers Long-Term Protection against Simian/Human Immunodeficiency Virus Infection. Journal of virology. 2015;89(11):5895–903. doi: 10.1128/JVI.00210-1525787288
22. Rudicell RS, Kwon YD, Ko S-Y, Pegu A, Louder MK, Georgiev IS, et al. Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo. Journal of virology. 2014;88(21):12669–82. doi: 10.1128/JVI.02213-1425142607
23. Pegu A, Yang Z-y, Boyington JC, Wu L, Ko S-Y, Schmidt SD, et al. Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Science translational medicine. 2014;6(243):243ra88–ra88. doi: 10.1126/scitranslmed.300899224990883
24. Barouch D, Whitney J, Moldt B, Klein F, Oliveira T, Liu J, et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature. 2013;503:224–8. doi: 10.1038/nature1274424172905
25. Moldt B, Rakasz E, Schultz N, Chan-Hui P, Swiderek K, Weisgrau K, et al. Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2012;109:18921–5. doi: 10.1073/pnas.121478510923100539
26. Balazs AB, Chen J, Hong CM, Rao DS, Yang L, Baltimore D, Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature. 2012;481(7379):81–4. Epub 2011/12/06. PubMed Central PMCID: PMC3253190.
27. Klein F, Halper-Stromberg A, Horwitz JA, Gruell H, Scheid JF, Bournazos S, et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature. 2012;492(7427):118–22. doi: 10.1038/nature1160423103874
28. Shingai M, Nishimura Y, Klein F, Mouquet H, Donau O, Plishka R, et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature. 2013;503:277–80. doi: 10.1038/nature1274624172896
29. Horwitz JA, Halper-Stromberg A, Mouquet H, Gitlin AD, Tretiakova A, Eisenreich TR, et al. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proceedings of the National Academy of Sciences. 2013;110(41):16538–43.
30. Hessell AJ, Haigwood NL, Animal models in HIV-1 protection and therapy. Current Opinion in HIV and AIDS. 2015;10(3):170–6. doi: 10.1097/COH.000000000000015225730345
31. 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(4):633–48. Epub 2014/02/18. doi: 10.1016/j.cell.2014.01.05224529371
32. Mouquet H, Tailored immunogens for rationally designed antibody-based HIV-1 vaccines. Trends in Immunology. 2015;36(8):437–9. doi: 10.1016/j.it.2015.07.00126169255
33. Kwong PD, Mascola JR, Nabel GJ, Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat Rev Immunol. 2013;13(9):693–701. doi: 10.1038/nri351623969737
34. Jardine J, Julien J-P, Menis S, Ota T, Kalyuzhniy O, McGuire A, et al. Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors. Science. 2013;340(6133):711–6. doi: 10.1126/science.123415023539181
35. Cortez V, Wang B, Dingens A, Chen MM, Ronen K, Georgiev IS, et al. The Broad Neutralizing Antibody Responses after HIV-1 Superinfection Are Not Dominated by Antibodies Directed to Epitopes Common in Single Infection. PLoS pathogens. 2015;11(7):e1004973. Epub 2015/07/15. PubMed Central PMCID: PMCPmc4497680. doi: 10.1371/journal.ppat.100497326158467
36. Scharf L, Scheid JF, Lee JH, West AP, Jr.Chen C, Gao H, et al. Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike. Cell reports. 2014;7(3):785–95. doi: 10.1016/j.celrep.2014.04.00124767986
37. Gray ES, Madiga MC, Hermanus T, Moore PL, Wibmer CK, Tumba NL, et al. The neutralization breadth of HIV-1 develops incrementally over four years and is associated with CD4+ T cell decline and high viral load during acute infection. Journal of virology. 2011;85(10):4828–40. Epub 2011/03/11. PubMed Central PMCID: PMC3126191. doi: 10.1128/JVI.00198-1121389135
38. Gao F, Bonsignori M, Liao H-X, Kumar A, Xia S-M, Lu X, et al. Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies. Cell. 2014;158(3):481–91. doi: 10.1016/j.cell.2014.06.02225065977
39. Permar SR, Fong Y, Vandergrift N, Fouda GG, Gilbert P, Parks R, et al. Maternal HIV-1 envelope–specific antibody responses and reduced risk of perinatal transmission. The Journal of Clinical Investigation. 2015;125(7):2702–6. doi: 10.1172/JCI8159326053661
40. 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. Proceedings of the National Academy of Sciences of the United States of America. 2012. Epub 2012/06/30.
41. Chung Amy W, Kumar Manu P, Arnold Kelly B, Yu Wen H, Schoen Matthew K, Dunphy Laura J, et al. Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology. Cell. 2015;163(4):988–98. doi: 10.1016/j.cell.2015.10.02726544943
42. Euler Z, van den Kerkhof TL, van Gils MJ, Burger JA, Edo-Matas D, Phung P, et al. Longitudinal Analysis of Early HIV-1-Specific Neutralizing Activity in an Elite Neutralizer and in Five Patients Who Developed Cross-Reactive Neutralizing Activity. Journal of virology. 2012;86(4):2045–55. Epub 2011/12/14. doi: 10.1128/JVI.06091-1122156522
43. Hicar MD, Kalams SA, Spearman PW, Crowe JE, JrEmerging studies of human HIV-specific antibody repertoires. Vaccine. 2010;28, Supplement 2:B18–B23.
44. Bar KJ, Tsao CY, Iyer SS, Decker JM, Yang Y, Bonsignori M, et al. Early Low-Titer Neutralizing Antibodies Impede HIV-1 Replication and Select for Virus Escape. PLoS pathogens. 2012;8(5):e1002721. Epub 2012/06/14. PubMed Central PMCID: PMC3364956. doi: 10.1371/journal.ppat.100272122693447
45. Tomaras GD, Binley JM, Gray ES, Crooks ET, Osawa K, Moore PL, et al. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. Journal of virology. 2011;85(21):11502–19. Epub 2011/08/19. PubMed Central PMCID: PMC3194956. doi: 10.1128/JVI.05363-1121849452
46. Moore PL, Gray ES, Sheward D, Madiga M, Ranchobe N, Lai Z, et al. Potent and broad neutralization of HIV-1 subtype C by plasma antibodies targeting a quaternary epitope including residues in the V2 loop. Journal of virology. 2011;85(7):3128–41. Epub 2011/01/29. PubMed Central PMCID: PMC3067856. doi: 10.1128/JVI.02658-1021270156
47. Mikell I, Sather DN, Kalams SA, Altfeld M, Alter G, Stamatatos L, Characteristics of the earliest cross-neutralizing antibody response to HIV-1. PLoS pathogens. 2011;7(1):e1001251. Epub 2011/01/21. PubMed Central PMCID: PMC3020924. doi: 10.1371/journal.ppat.100125121249232
48. Jardine JG, Ota T, Sok D, Pauthner M, Kulp DW, Kalyuzhniy O, et al. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen. Science. 2015;349(6244):156–61. doi: 10.1126/science.aac589426089355
49. Dosenovic P, von Boehmer L, Escolano A, Jardine J, Freund NT, Gitlin AD, et al. Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice. Cell. 2015;161(7):1505–15. Epub 2015/06/20. doi: 10.1016/j.cell.2015.06.00326091035
50. Walker LM, Simek MD, Priddy F, Gach JS, Wagner D, Zwick MB, et al. A limited number of antibody specificities mediate broad and potent serum neutralization in selected HIV-1 infected individuals. PLoS pathogens. 2010;6(8)(8):e1001028. Epub 2010/08/12. PubMed Central PMCID: PMC2916884. doi: 10.1371/journal.ppat.100102820700449
51. Gray ES, Taylor N, Wycuff D, Moore PL, Tomaras GD, Wibmer CK, et al. Antibody specificities associated with neutralization breadth in plasma from human immunodeficiency virus type 1 subtype C-infected blood donors. Journal of virology. 2009;83(17):8925–37. Epub 2009/06/26. doi: 10.1128/JVI.00758-0919553335
52. Li Y, Svehla K, Louder MK, Wycuff D, Phogat S, Tang M, et al. Analysis of neutralization specificities in polyclonal sera derived from human immunodeficiency virus type 1-infected individuals. Journal of virology. 2009;83(2):1045–59. Epub 2008/11/14. doi: 10.1128/JVI.01992-0819004942
53. 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(8):866–70. Epub 2009/06/16. doi: 10.1038/nm.194919525964
54. Binley JM, Lybarger EA, Crooks ET, Seaman MS, Gray E, Davis KL, 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. Journal of virology. 2008;82(23):11651–68. Epub 2008/09/26. doi: 10.1128/JVI.01762-0818815292
55. Dhillon AK, Donners H, Pantophlet R, Johnson WE, Decker JM, Shaw GM, et al. Dissecting the neutralizing antibody specificities of broadly neutralizing sera from human immunodeficiency virus type 1-infected donors. Journal of virology. 2007;81(12):6548–62. Epub 2007/04/06. doi: 10.1128/JVI.02749-0617409160
56. Doria-Rose NA, Klein RM, Manion MM, O'Dell S, Phogat A, Chakrabarti B, et al. Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. Journal of virology. 2009;83(1):188–99. Epub 2008/10/17. PubMed Central PMCID: PMC2612342. doi: 10.1128/JVI.01583-0818922865
57. Li Y, Migueles SA, Welcher B, Svehla K, Phogat A, Louder MK, et al. Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat Med. 2007;13(9):1032–4. doi: 10.1038/nm162417721546
58. Lacerda M, Moore PL, Ngandu NK, Seaman M, Gray ES, Murrell B, et al. Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models. Virology Journal. 2013;10(1):1–18.
59. Crooks ET, Tong T, Chakrabarti B, Narayan K, Georgiev IS, Menis S, 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 pathogens. 2015;11(5):e1004932. Epub 2015/05/30. PubMed Central PMCID: PMCPmc4449185. doi: 10.1371/journal.ppat.100493226023780
60. Kong R, Louder MK, Wagh K, Bailer RT, deCamp A, Greene K, et al. Improving Neutralization Potency and Breadth by Combining Broadly Reactive HIV-1 Antibodies Targeting Major Neutralization Epitopes. Journal of virology. 2015;89(5):2659–71. doi: 10.1128/JVI.03136-1425520506
61. Eroshkin AM, LeBlanc A, Weekes D, Post K, Li Z, Rajput A, et al. bNAber: database of broadly neutralizing HIV antibodies. Nucleic Acids Research. 2014;42(D1):D1133–D9.
62. Chuang GY, Acharya P, Schmidt SD, Yang Y, Louder MK, Zhou T, et al. Residue-level prediction of HIV-1 antibody epitopes based on neutralization of diverse viral strains. Journal of virology. 2013;87(18):10047–58. Epub 2013/07/12. PubMed Central PMCID: PMC3753990. doi: 10.1128/JVI.00984-1323843642
63. Hraber P, Seaman MS, Bailer RT, Mascola JR, Montefiori DC, Korber BT, Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS. 2014;28(2):163–9. Epub 2013/12/24. doi: 10.1097/QAD.000000000000010624361678
64. Goo L, Chohan V, Nduati R, Overbaugh J, Early development of broadly neutralizing antibodies in HIV-1-infected infants. Nat Med. 2014;20(6):655–8. doi: 10.1038/nm.356524859529
65. Georgiev I, Lilien RH, Donald BR, Improved Pruning algorithms and Divide-and-Conquer strategies for Dead-End Elimination, with application to protein design. Bioinformatics. 2006;22(14):e174–83. Epub 2006/07/29. doi: 10.1093/bioinformatics/btl22016873469
66. Wu X, Zhang Z, Schramm Chaim A, Joyce MG, Do Kwon Y, Zhou T, et al. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection. Cell. 2015;161(3):470–85. doi: 10.1016/j.cell.2015.03.00425865483
67. Walker LM, Sok D, Nishimura Y, Donau O, Sadjadpour R, Gautam R, et al. Rapid development of glycan-specific, broad, and potent anti-HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(50):20125–9. Epub 2011/11/30. doi: 10.1073/pnas.111753110822123961
68. Zhou T, Lynch RM, Chen L, Acharya P, Wu X, Doria-Rose NA, et al. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell. 2015;161(6):1280–92. Epub 2015/05/26. PubMed Central PMCID: PMCPMC4683157. doi: 10.1016/j.cell.2015.05.00726004070
69. Morris L, Chen X, Alam M, Tomaras G, Zhang R, Marshall DJ, et al. Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting. PloS one. 2011;6(9):e23532. doi: 10.1371/journal.pone.002353221980336
70. Landais E, Huang X, Havenar-Daughton C, Murrell B, Price MA, Wickramasinghe L, et al. Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort. PLoS pathogens. 2016;12(1):e1005369. doi: 10.1371/journal.ppat.100536926766578
71. Wang S, Mata-Fink J, Kriegsman B, Hanson M, Irvine Darrell J, Eisen Herman N, et al. Manipulating the Selection Forces during Affinity Maturation to Generate Cross-Reactive HIV Antibodies. Cell. 2015;160(4):785–97. doi: 10.1016/j.cell.2015.01.02725662010
72. Scheid JF, Mouquet H, Feldhahn N, Seaman MS, Velinzon K, Pietzsch J, et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature. 2009;458(7238):636–40. Epub 2009/03/17. doi: 10.1038/nature0793019287373
73. Wagh K, Bhattacharya T, Williamson C, Robles A, Bayne M, Garrity J, et al. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection. PLoS pathogens. 2016;12(3):e1005520. doi: 10.1371/journal.ppat.100552027028935
74. Sarzotti-Kelsoe M, Bailer RT, Turk E, Lin C-l, Bilska M, Greene KM, et al. Optimization and validation of the TZM-bl assay for standardized assessments of neutralizing antibodies against HIV-1. Journal of Immunological Methods. 2014;409:131–46. doi: 10.1016/j.jim.2013.11.02224291345
75. Bonsignori M, Zhou T, Sheng Z, Chen L, Gao F, Joyce MG, et al. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell. 2016;165(2):449–63. doi: 10.1016/j.cell.2016.02.02226949186
76. Hraber P, Korber BT, Lapedes AS, Bailer RT, Seaman MS, Gao H, et al. Impact of clade, geography, and age of the epidemic on HIV-1 neutralization by antibodies. Journal of Virology. 2014; 88(21):12623–43. doi: 10.1128/JVI.01705-1425142591
77. Doria-Rose NA, Altae-Tran HR, Roark RS, Schmidt SD, Sutton MS, Louder MK, et al. Data from: Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. Dryad Digital Repository. 2016.