Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization

PLoS Pathogens

Volumn 12, Issue 7, 2016, Pages

  Rademeyer, Cecilia ^a   Korber, Bette ^b   Seaman, Michael S ^c   Giorgi, Elena E ^b   Thebus, Ruwayhida ^a   Robles, Alexander ^c   Sheward, Daniel J ^a   Wagh, Kshitij ^b   Garrity, Jetta ^c   Carey, Brittany R ^c   Gao, Hongmei ^d   Greene, Kelli M ^d   Tang, Haili ^d   Bandawe, Gama P ^a   Marais, Jinny C ^a   Diphoko, Thabo E ^e   Hraber, Peter ^b   Tumba, Nancy ^f   Moore, Penny L ^f,g   Gray, Glenda E ^h   Kublin, James ⁱ   McElrath, M Juliana ⁱ   Vermeulen, Marion ^j   Middelkoop, Keren ^k   Bekker, Linda Gail ^k   Hoelscher, Michael ^l   Maboko, Leonard ^m   Makhema, Joseph ^e   Robb, Merlin L ⁿ   Abdool Karim, Salim ^g   Abdool Karim, Quarraisha ^g   Kim, Jerome H ^n,o   Hahn, Beatrice H ^p   Gao, Feng ^d   Swanstrom, Ronald ^q   Morris, Lynn ^f,g   Montefiori, David C ^d   Williamson, Carolyn ^a,g   more..

^a NATIONAL HEALTH LABORATORY SERVICE   (South Africa)

^b LOS ALAMOS NATIONAL LABORATORY   (United States)

^c BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^d DUKE UNIVERSITY MEDICAL CENTER   (United States)

^e BOTSWANA HARVARD AIDS INSTITUTE PARTNERSHIP   (Botswana)

^f UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^g UNIVERSITY OF KWAZULU NATAL   (South Africa)

^h UNIVERSITY OF THE WITWATERSRAND   (South Africa)

ⁱ Fred Hutchinson Cancer Research Center   (United States)

^j SOUTH AFRICAN NATIONAL BLOOD SERVICE   (South Africa)

^k UNIVERSITY OF CAPE TOWN   (South Africa)

^l UNIVERSITY OF MUNICH   (Germany)

^m NIMR Mbeya Medical Research Center   (Tanzania)

ⁿ WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

^o International Vaccine Institute   (South Korea)

^p UNIVERSITY OF PENNSYLVANIA   (United States)

^q UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

GLYCAN; MONOCLONAL ANTIBODY; NEUTRALIZING ANTIBODY; GLYCOPROTEIN GP 120; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; VRC01 MONOCLONAL ANTIBODY;

ACTIVE IMMUNIZATION; ANTIBODY TITER; ARTICLE; CLINICAL ARTICLE; EPIDEMIC; GENE EXPRESSION REGULATION; GENE SEQUENCE; HEK293 CELL LINE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1 (STRAIN C); HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IC50; MAXIMUM LIKELIHOOD METHOD; PASSIVE IMMUNIZATION; PHASE 2 CLINICAL TRIAL; PHENOTYPE; SEQUENCE ANALYSIS; SOUTH AFRICA; VIRUS INFECTIVITY; VIRUS NEUTRALIZATION; VIRUS TRANSMISSION; CLINICAL TRIAL (TOPIC); GENETICS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; PHYLOGENY; PROCEDURES; VACCINATION;

AIDS VACCINES; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; CLINICAL TRIALS AS TOPIC; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HUMANS; IMMUNIZATION, PASSIVE; PHYLOGENY; VACCINATION;

EID: 84982958690     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1005742     Document Type: Article

References (72)

1. Ledgerwood JE, Coates EE, Yamshchikov G, Saunders JG, Holman L, Enama ME, et al. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Clin Exp Immunol. 2015; 1–23. doi: 10.1111/cei.12692
2. Derdeyn C a, Decker JM, Bibollet-Ruche F, Mokili JL, Muldoon M, Denham S a, et al. Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science. 2004;303: 2019–22. doi: 10.1126/science.109313715044802
3. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A. 2008;105: 7552–7. doi: 10.1073/pnas.080220310518490657
4. Abrahams M-R, Anderson JA, Giorgi EE, Seoighe C, Mlisana K, Ping L-H, et al. Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. J Virol. 2009;83: 3556–67. doi: 10.1128/JVI.02132-0819193811
5. Wilen CB, Parrish NF, Pfaff JM, Decker JM, Henning E a, Haim H, et al. Phenotypic and immunologic comparison of clade B transmitted/founder and chronic HIV-1 envelope glycoproteins. J Virol. 2011;85: 8514–27. doi: 10.1128/JVI.00736-1121715507
6. Ping L-H, Joseph SB, Anderson J a, Abrahams M-R, Salazar-Gonzalez JF, Kincer LP, et al. Comparison of viral Env proteins from acute and chronic infections with subtype C human immunodeficiency virus type 1 identifies differences in glycosylation and CCR5 utilization and suggests a new strategy for immunogen design. J Virol. 2013;87: 7218–33. doi: 10.1128/JVI.03577-1223616655
7. Carlson JM, Schaefer M, Monaco DC, Batorsky R, Claiborne DT, Prince J, et al. HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck. Science. 2014;345: 1254031. 25013080
8. 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. Sci Transl Med. 2014;6: 243ra88. doi: 10.1126/scitranslmed.300899224990883
9. 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. J Virol. 2014;88: 12669–12682. doi: 10.1128/JVI.02213-1425142607
10. Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366: 1275–86. doi: 10.1056/NEJMoa111342522475592
11. Zolla-Pazner S, Edlefsen PT, Rolland M, Kong X-P, deCamp A, Gottardo R, et al. Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses. EBioMedicine. Elsevier B.V.; 2014;1: 37–45. doi: 10.1016/j.ebiom.2014.10.022
12. Gottardo R, Bailer RT, Korber BT, Gnanakaran S, Phillips J, Shen X, et al. Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial. PLoS One. 2013;8: e75665. doi: 10.1371/journal.pone.007566524086607
13. Rolland M, Edlefsen PT, Larsen BB, Tovanabutra S, Sanders-buell E, Hertz T, et al. IncreasedHIV-1vaccine efficacyagainst viruseswith genetic signatures in Env V2. Nature. Nature Publishing Group; 2012;490: 417–420. doi: 10.1038/nature11519
14. Edlefsen PT, Rolland M, Hertz T, Tovanabutra S, Gartland AJ, deCamp AC, et al. Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the RV144 Vaccine Efficacy Trial. PLoS Comput Biol. 2015;11: e1003973. doi: 10.1371/journal.pcbi.100397325646817
15. 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. J Virol. 2014;88: 12623–12643. doi: 10.1128/JVI.01705-1425142591
16. Seaman MS, Janes H, Hawkins N, Grandpre LE, Devoy C, Giri A, et al. Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J Virol. 2010;84: 1439–52. doi: 10.1128/JVI.02108-0919939925
17. Binley JM, Wrin T, Korber B, Zwick MB, Wang M, Chappey C, 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. doi: 10.1128/JVI.78.23.13232-13252.200415542675
18. Bures R, Morris L, Williamson C, Ramjee G, Deers M, Fiscus SA, 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: 2233–2244. doi: 10.1128/JVI.76.5.2233-2244.200211836401
19. Li M, Salazar-Gonzalez JF, Derdeyn CA, Morris L, Williamson C, Robinson JE, et al. 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. 2006;80: 11776–90. doi: 10.1128/JVI.01730-0616971434
20. Bunnik EM, Euler Z, Welkers MRA, Boeser-nunnink BDM, Grijsen ML, Prins JM, et al. Adaptation of HIV-1 envelope gp120 to humoral immunity at a population level. Nat Med. Nature Publishing Group; 2010;16: 991–993. doi: 10.1038/nm.2203
21. Bouvin-Pley M, Morgand M, Moreau A, Jestin P, Simonnet C, Tran L, et al. Evidence for a continuous drift of the HIV-1 species towards higher resistance to neutralizing antibodies over the course of the epidemic. PLoS Pathog. 2013;9: e1003477. doi: 10.1371/journal.ppat.100347723853594
22. Bouvin-Pley M, Morgand M, Meyer L, Goujard C, Moreau A, Mouquet H, et al. Drift of the HIV-1 Envelope Glycoprotein gp120 toward Increased Neutralization Resistance over the Course of the Epidemic: a Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies. J Virol. 2014;88: 13910–7. doi: 10.1128/JVI.02083-1425231299
23. Salazar-Gonzalez JF, Bailes E, Pham KT, Salazar MG, Guffey MB, Keele BF, et al. Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing. J Virol. 2008;82: 3952–70. doi: 10.1128/JVI.02660-0718256145
24. Edmonson PF, Mullins JI, Efficient amplification of HIV half-genomes from tissue DNA. Nucleic Acids Res. 1992;20: 4933. 1408811
25. Palmer S, Kearney M, Maldarelli F, Elias K, Bixby CJ, Bazmi H, et al. Multiple, Linked Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Treatment-Experienced Patients Are Missed by Standard Genotype Analysis Multiple, Linked Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Treatment-Experie. J Clin Microbiol. 2005;43: 403.
26. Simmonds P, Balfe P, Ludlam C a, Bishop JO, Brown A J, Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1. J Virol. 1990;64: 5840–5850. 2243378
27. Montefiori DC, Measuring HIV neutralization in a luciferase reporter gene assay. Methods Mol Biol. United States; 2009;485: 395–405. doi: 10.1007/978-1-59745-170-3_26
28. Sarzotti-Kelsoe M, Bailer RT, Turk E, Lin CL, Bilska M, Greene KM, et al. Optimization and validation of the TZM-bl assay for standardized assessments of neutralizing antibodies against HIV-1. J Immunol Methods. Elsevier B.V.; 2014;409: 131–146. doi: 10.1016/j.jim.2013.11.022
29. Lengauer T, Sander O, Sierra S, Thielen A, Kaiser R, Bioinformatics prediction of HIV coreceptor usage. Nat Biotechnol. 2007;25: 1407–10. doi: 10.1038/nbt137118066037
30. Mulinge M, Lemaire M, Servais J-Y, Rybicki A, Struck D, da Silva ES, et al. HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRRF01_AE and CRF02_AG. PLoS One. 2013;8: e60566. doi: 10.1371/journal.pone.006056623667426
31. Jensen MA, Li F, Van Wout B, Nickle DC, Shriner D, He H, et al. Improved Coreceptor Usage Prediction and Genotypic Monitoring of R5-to-X4 Transition by Motif Analysis of Human Immunodeficiency. 2003;77: 13376–13388.
32. Jensen MA, Coetzer M, Wout B, Morris L, Mullins JI, A Reliable Phenotype Predictor for Human Immunodeficiency Virus Type 1 Subtype C Based on Envelope V3 Sequences †. J Virol. 2006;80: 4698–4704. 16641263
33. Crous S, Shrestha RK, Travers SA, Appraising the performance of genotyping tools in the prediction of coreceptor tropism in HIV-1 subtype C viruses. BMC Infect Dis. BMC Infectious Diseases; 2012;12: 203. doi: 10.1186/1471-2334-12-20322938574
34. Whitcomb JM, Huang W, Fransen S, Limoli K, Toma J, Wrin T, et al. Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism. Antimicrob Agents Chemother. 2007;51: 566–75. doi: 10.1128/AAC.00853-0617116663
35. Gray ES, Meyers T, Gray G, Montefiori DC, Morris L, Insensitivity of paediatric HIV-1 subtype C viruses to broadly neutralising monoclonal antibodies raised against subtype B. PLoS Med. 2006;3: e255. doi: 10.1371/journal.pmed.003025516834457
36. Li M, Gao F, Mascola JR, Stamatatos L, Polonis VR, Koutsoukos M, 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. doi: 10.1128/JVI.79.16.10108-10125.200516051804
37. Cilliers T, Willey S, Sullivan WM, Patience T, Pugach P, Coetzer M, et al. Use of alternate coreceptors on primary cells by two HIV-1 isolates. Virology. 2005;339: 136–44. doi: 10.1016/j.virol.2005.05.02715992849
38. Gaschen B, Kuiken C, Korber B, Foley B, Retrieval and on-the-fly alignment of sequence fragments from the HIV database. Bioinformatics. 2001;17: 415–418. 11331235
39. Eddy S, Profile hidden Markov models. Bioinformatics. 1998;14: 755–763. btb114 [pii] 9918945
40. Siepel AC, Halpern AL, Macken C, Korber BT, A computer program designed to screen rapidly for HIV type 1 intersubtype recombinant sequences. AIDS Res Hum Retroviruses. UNITED STATES; 1995;11: 1413–1416.
41. Alcantara LCJ, Cassol S, Libin P, Deforche K, Pybus OG, Van Ranst M, et al. A standardized framework for accurate, high-throughput genotyping of recombinant and non-recombinant viral sequences. Nucleic Acids Res. 2009;37: W634–42. doi: 10.1093/nar/gkp45519483099
42. Schultz A-K, Zhang M, Bulla I, Leitner T, Korber B, Morgenstern B, et al. jpHMM: improving the reliability of recombination prediction in HIV-1. Nucleic Acids Res. 2009;37: W647–51. doi: 10.1093/nar/gkp37119443440
43. Price MN, Dehal PS, Arkin AP, FastTree: computing large minimum evolution trees with profiles instead of a distance matrix. Mol Biol Evol. 2009;26: 1641–50. doi: 10.1093/molbev/msp07719377059
44. Deng W, Maust BS, Nickle DC, Learn GH, Liu Y, Heath L, et al. DIVEIN: a web server to analyze phylogenies, sequence divergence, diversity, and informative sites. Biotechniques. 2010;48: 405–8. doi: 10.2144/00011337020569214
45. Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O, New algorithms and methods to estimate maximum-likelihood phylogenies: Assessing the performance of PhyML 3.0. Syst Biol. 2010;59: 307–321. doi: 10.1093/sysbio/syq01020525638
46. Nickle DC, Heath L, Jensen M a, Gilbert PB, Mullins JI, Kosakovsky Pond SL, HIV-specific probabilistic models of protein evolution. PLoS One. 2007;2: e503. doi: 10.1371/journal.pone.000050317551583
47. Maljkovic Berry I, Athreya G, Kothari M, Daniels M, Bruno WJ, Korber B, et al. The evolutionary rate dynamically tracks changes in HIV-1 epidemics: Application of a simple method for optimizing the evolutionary rate in phylogenetic trees with longitudinal data. Epidemics. Elsevier B.V.; 2009;1: 230–239. doi: 10.1016/j.epidem.2009.10.003
48. Gnanakaran S, Daniels MG, Bhattacharya T, Lapedes AS, Sethi A, Li M, et al. Genetic signatures in the envelope glycoproteins of HIV-1 that associate with broadly neutralizing antibodies. PLoS Comput Biol. 2010;6: e1000955. doi: 10.1371/journal.pcbi.100095520949103
49. Mascola JR, D’Souza P, Gilbert P, Hahn BH, Haigwood NL, Morris L, et al. Recommendations for the design and use of standard virus panels to assess neutralizing antibody responses elicited by candidate human immunodeficiency virus type 1 vaccines. J Virol. 2005;79: 10103–7. doi: 10.1128/JVI.79.16.10103-10107.200516051803
50. Fiebig EW, Wright DJ, Rawal BD, Garrett PE, Schumacher RT, Peddada L, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors : implications for diagnosis and staging of primary HIV infection. AIDS. 2003;17: 1871–1879. 12960819
51. Gnanakaran S, Bhattacharya T, Daniels M, Keele BF, Hraber PT, Lapedes AS, et al. Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections. PLoS Pathog. 2011;7: e1002209. doi: 10.1371/journal.ppat.100220921980282
52. Moody MA, Gao F, Gurley TC, Amos JD, Kumar A, Hora B, et al. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. Cell Host Microbe. 2015;18: 354–362. doi: 10.1016/j.chom.2015.08.00626355218
53. 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. J Virol. 2015;89: 2659–71. doi: 10.1128/JVI.03136-1425520506
54. Moore PL, Ranchobe N, Lambson BE, Gray ES, Cave E, Abrahams M-R, et al. Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection. PLoS Pathog. 2009;5: e1000598. doi: 10.1371/journal.ppat.100059819763271
55. 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. doi: 10.1128/JVI.00141-0616973562
56. van Gils MJ, Bunnik EM, Boeser-Nunnink BD, Burger J a, Terlouw-Klein M, Verwer N, et al. Longer V1V2 region with increased number of potential N-linked glycosylation sites in the HIV-1 envelope glycoprotein protects against HIV-specific neutralizing antibodies. J Virol. 2011;85: 6986–95. doi: 10.1128/JVI.00268-1121593147
57. Sok D, Doores KJ, Briney B, Le KM, Saye-Francisco KL, Ramos A, 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. doi: 10.1126/scitranslmed.300810424828077
58. Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, Julien J-P, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. Nature Publishing Group; 2011;477: 466–70. doi: 10.1038/nature10373
59. Moore PL, Gray ES, Wibmer CK, Bhiman JN, Nonyane M, Sheward DJ, et al. Evolution of an HIV glycan—dependent broadly neutralizing antibody epitope through immune escape. Nat Med. Nature Publishing Group; 2012;18: 1–6. doi: 10.1038/nm.2985
60. Pejchal R, Doores KJ, Walker LM, Khayat R, Huang P-S, Wang S-K, et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science. 2011;334: 1097–103. doi: 10.1126/science.121325621998254
61. Whitney JB, Hill AL, Sanisetty S, Penaloza-MacMaster P, Liu J, Shetty M, et al. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature. Nature Publishing Group; 2014;512: 74–77. doi: 10.1038/nature13594
62. Huang J, Kang BH, Pancera M, Lee JH, Tong T, Feng Y, et al. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature. 2014;515: 138–42. doi: 10.1038/nature1360125186731
63. Beaumont T, Quakkelaar E, van Nuenen A, Pantophlet R, Schuitemaker H, Increased sensitivity to CD4 binding site-directed neutralization following in vitro propagation on primary lymphocytes of a neutralization-resistant human immunodeficiency virus IIIB strain isolated from an accidentally infected laboratory worker. J Virol. 2004;78: 5651–7. doi: 10.1128/JVI.78.11.5651-5657.200415140962
64. Curlin ME, Zioni R, Hawes SE, Liu Y, Deng W, Gottlieb GS, et al. HIV-1 envelope subregion length variation during disease progression. PLoS Pathog. 2010;6: e1001228. doi: 10.1371/journal.ppat.100122821187897
65. Pilcher CD, Tien HC, Eron JJ, Vernazza PL, Leu S-Y, Stewart PW, et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis. 2004;189: 1785–92. doi: 10.1086/38633315122514
66. Wawer MJ, Gray RH, Sewankambo NK, Serwadda D, Li X, Laeyendecker O, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis. 2005;191: 1403–9. doi: 10.1086/42941115809897
67. Jurkiewicz E, Hunsmann G, Schäffner J, Nisslein T, Lüke W, Petry H, Identification of the V1 region as a linear neutralizing epitope of the simian immunodeficiency virus SIVmac envelope glycoprotein. J Virol. 1997;71: 9475–9481. 9371609
68. Pinter A, Honnen WJ, He Y, Miroslaw K, Zolla-pazner S, Kayman SC, et al. 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. 2004;78: 5205–5215.
69. Li B, Decker JM, Johnson RW, Bibollet-Ruche F, Wei X, Mulenga J, et al. Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1. J Virol. 2006;80: 5211–5218. doi: 10.1128/JVI.00201-0616699001
70. 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 (80-). 2015;349: 156–161. doi: 10.1126/science.aac5894
71. Freund NT, Horwitz J a., Nogueira L, Sievers S a., Scharf L, Scheid JF, et al. A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo. PLOS Pathog. 2015;11: e1005238. doi: 10.1371/journal.ppat.100523826516768
72. 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 Pathog. 2016;12: e1005520. doi: 10.1371/journal.ppat.100552027028935