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Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques


Antibodies specifically recognize antigenic sites on pathogens and can mediate multiple antiviral functions through engagement of effector cells via their Fc region. Current HIV-1 vaccine candidates induce polyclonal antibody responses with multiple antiviral functions, but do not induce broadly neutralizing antibodies. An improved understanding of whether certain types of non-neutralizing HIV-1 specific antibodies can individually protect against HIV-1 infection may facilitate vaccine development. Here, we test whether non-neutralizing antibodies with multiple antiviral functions mediated through FcR engagement and recognition of virus particles or virus-infected cells can limit infection, despite lacking classical virus neutralization activity. In a passive antibody infusion-rhesus macaque challenge model, we tested the ability of non-neutralizing monoclonal antibodies to limit virus acquisition. We demonstrate that two different types of non-neutralizing antibodies, one that recognizes both virus particles and infected cells (7B2) and another that recognizes only infected cells (A32) were capable of decreasing the number of transmitted founder viruses. Further, we provide the structure of 7B2 in complex with the gp41 cyclical loop motif, a motif critical for entry. These findings provide insights into the role that antibodies with antiviral properties, including virion capture and FcR mediated effector function, may play in protecting against HIV-1 acquisition.


Vyšlo v časopise: Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005042
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005042

Souhrn

Antibodies specifically recognize antigenic sites on pathogens and can mediate multiple antiviral functions through engagement of effector cells via their Fc region. Current HIV-1 vaccine candidates induce polyclonal antibody responses with multiple antiviral functions, but do not induce broadly neutralizing antibodies. An improved understanding of whether certain types of non-neutralizing HIV-1 specific antibodies can individually protect against HIV-1 infection may facilitate vaccine development. Here, we test whether non-neutralizing antibodies with multiple antiviral functions mediated through FcR engagement and recognition of virus particles or virus-infected cells can limit infection, despite lacking classical virus neutralization activity. In a passive antibody infusion-rhesus macaque challenge model, we tested the ability of non-neutralizing monoclonal antibodies to limit virus acquisition. We demonstrate that two different types of non-neutralizing antibodies, one that recognizes both virus particles and infected cells (7B2) and another that recognizes only infected cells (A32) were capable of decreasing the number of transmitted founder viruses. Further, we provide the structure of 7B2 in complex with the gp41 cyclical loop motif, a motif critical for entry. These findings provide insights into the role that antibodies with antiviral properties, including virion capture and FcR mediated effector function, may play in protecting against HIV-1 acquisition.


Zdroje

1. Mascola JR, Haynes BF (2013) HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol Rev 254: 225–244. doi: 10.1111/imr.12075 23772623

2. 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 19843557

3. 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 22475592

4. Yates NL, Liao HX, Fong Y, deCamp A, Vandergrift NA, et al. (2014) Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Sci Transl Med 6: 228ra239.

5. Tomaras GD, Ferrari G, Shen X, Alam SM, Liao HX, et al. (2013) Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG. Proc Natl Acad Sci U S A 110: 9019–9024. doi: 10.1073/pnas.1301456110 23661056

6. Tomaras GD, Haynes BF (2014) Advancing Toward HIV-1 Vaccine Efficacy through the Intersections of Immune Correlates. Vaccines (Basel) 2: 15–35.

7. Tomaras GD, Haynes BF (2010) Strategies for eliciting HIV-1 inhibitory antibodies. Curr Opin HIV AIDS 5: 421–427. doi: 10.1097/COH.0b013e32833d2d45 20978384

8. Haynes BF, Liao HX, Tomaras GD (2010) Is developing an HIV-1 vaccine possible? Curr Opin HIV AIDS 5: 362–367. doi: 10.1097/COH.0b013e32833d2e90 20978375

9. Holl V, Peressin M, Decoville T, Schmidt S, Zolla-Pazner S, et al. (2006) Nonneutralizing antibodies are able to inhibit human immunodeficiency virus type 1 replication in macrophages and immature dendritic cells. J Virol 80: 6177–6181. 16731957

10. Nyambi PN, Mbah HA, Burda S, Williams C, Gorny MK, et al. (2000) Conserved and exposed epitopes on intact, native, primary human immunodeficiency virus type 1 virions of group M. J Virol 74: 7096–7107. 10888650

11. 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 21865397

12. Liu P, Williams LD, Shen X, Bonsignori M, Vandergrift NA, et al. (2014) Capacity for infectious HIV-1 virion capture differs by envelope antibody specificity. J Virol 88: 5165–5170. doi: 10.1128/JVI.03765-13 24554654

13. Moog C, Dereuddre-Bosquet N, Teillaud JL, Biedma ME, Holl V, et al. (2014) Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal SHIV challenge in macaques. Mucosal Immunol 7: 46–56. doi: 10.1038/mi.2013.23 23591718

14. Tyler DS, Stanley SD, Zolla-Pazner S, Gorny MK, Shadduck PP, et al. (1990) Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies. J Immunol 145: 3276–3282. 1700004

15. Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, et al. (2014) Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514: 455–461. doi: 10.1038/nature13808 25296255

16. He XM, Ruker F, Casale E, Carter DC (1992) Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 89: 7154–7158. 1496010

17. Stigler RD, Ruker F, Katinger D, Elliott G, Hohne W, et al. (1995) Interaction between a Fab fragment against gp41 of human immunodeficiency virus 1 and its peptide epitope: characterization using a peptide epitope library and molecular modeling. Protein Eng 8: 471–479. 8532669

18. Ferrari G, Pollara J, Kozink D, Harms T, Drinker M, et al. (2011) An HIV-1 gp120 envelope human monoclonal antibody that recognizes a C1 conformational epitope mediates potent antibody-dependent cellular cytotoxicity (ADCC) activity and defines a common ADCC epitope in human HIV-1 serum. J Virol 85: 7029–7036. doi: 10.1128/JVI.00171-11 21543485

19. Guan Y, Pazgier M, Sajadi MM, Kamin-Lewis R, Al-Darmarki S, et al. (2013) Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding. Proc Natl Acad Sci U S A 110: E69–78. doi: 10.1073/pnas.1217609110 23237851

20. Bonsignori M, Pollara J, Moody MA, Alpert MD, Chen X, et al. (2012) Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family. J Virol 86: 11521–11532. doi: 10.1128/JVI.01023-12 22896626

21. Veillette M, Coutu M, Richard J, Batraville LA, Dagher O, et al. (2015) The HIV-1 gp120 CD4-bound conformation is preferentially targeted by antibody-dependent cellular cytotoxicity-mediating antibodies in sera from HIV-1-infected individuals. J Virol 89: 545–551. doi: 10.1128/JVI.02868-14 25339767

22. Veillette M, Desormeaux A, Medjahed H, Gharsallah NE, Coutu M, et al. (2014) Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibody-dependent cell-mediated cytotoxicity. J Virol 88: 2633–2644. doi: 10.1128/JVI.03230-13 24352444

23. Acharya P, Tolbert WD, Gohain N, Wu X, Yu L, et al. (2014) Structural definition of an antibody-dependent cellular cytotoxicity response implicated in reduced risk for HIV-1 infection. J Virol 88: 12895–12906. doi: 10.1128/JVI.02194-14 25165110

24. McElrath MJ, Haynes BF (2010) Induction of immunity to human immunodeficiency virus type-1 by vaccination. Immunity 33: 542–554. doi: 10.1016/j.immuni.2010.09.011 21029964

25. Shattock RJ, Haynes BF, Pulendran B, Flores J, Esparza J, et al. (2008) Improving defences at the portal of HIV entry: mucosal and innate immunity. PLoS Med 5: e81. doi: 10.1371/journal.pmed.0050081 18384232

26. Tomaras GD, Yates NL, Liu P, Qin L, Fouda GG, et al. (2008) Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia. J Virol 82: 12449–12463. doi: 10.1128/JVI.01708-08 18842730

27. Montefiori DC (1997) Role of complement and Fc receptors in the pathogenesis of HIV-1 infection. Springer Semin Immunopathol 18: 371–390. 9089955

28. Willey S, Aasa-Chapman MM, O'Farrell S, Pellegrino P, Williams I, et al. (2011) Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection. Retrovirology 8: 16. doi: 10.1186/1742-4690-8-16 21401915

29. Gupta S, Pegu P, Venzon DJ, Gach JS, Ma ZM, et al. (2014) Enhanced In Vitro Transcytosis of Simian Immunodeficiency Virus Mediated by Vaccine-Induced Antibody Predicts Transmitted/Founder Strain Number After Rectal Challenge. J Infect Dis.

30. Burton DR, Hessell AJ, Keele BF, Klasse PJ, Ketas TA, et al. (2011) Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody. Proc Natl Acad Sci U S A 108: 11181–11186. doi: 10.1073/pnas.1103012108 21690411

31. Hessell AJ, Haigwood NL (2012) Neutralizing antibodies and control of HIV: moves and countermoves. Curr HIV/AIDS Rep 9: 64–72. doi: 10.1007/s11904-011-0105-5 22203469

32. Hessell AJ, Hangartner L, Hunter M, Havenith CE, Beurskens FJ, et al. (2007) Fc receptor but not complement binding is important in antibody protection against HIV. Nature 449: 101–104. 17805298

33. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, et al. (2008) Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 105: 7552–7557. doi: 10.1073/pnas.0802203105 18490657

34. Li H, Bar KJ, Wang S, Decker JM, Chen Y, et al. (2010) High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men. PLoS Pathog 6: e1000890. doi: 10.1371/journal.ppat.1000890 20485520

35. Pincus SH, Fang H, Wilkinson RA, Marcotte TK, Robinson JE, et al. (2003) In vivo efficacy of anti-glycoprotein 41, but not anti-glycoprotein 120, immunotoxins in a mouse model of HIV infection. J Immunol 170: 2236–2241. 12574398

36. Montefiori DC, Karnasuta C, Huang Y, Ahmed H, Gilbert P, et al. (2012) Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials. J Infect Dis 206: 431–441. doi: 10.1093/infdis/jis367 22634875

37. Tomaras GD, Binley JM, Gray ES, Crooks ET, Osawa K, et al. (2011) Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals. J Virol 85: 11502–11519. doi: 10.1128/JVI.05363-11 21849452

38. Du AP, Limal D, Semetey V, Dali H, Jolivet M, et al. (2002) Structural and immunological characterisation of heteroclitic peptide analogues corresponding to the 600–612 region of the HIV envelope gp41 glycoprotein. J Mol Biol 323: 503–521. 12381305

39. Oldstone MB, Tishon A, Lewicki H, Dyson HJ, Feher VA, et al. (1991) Mapping the anatomy of the immunodominant domain of the human immunodeficiency virus gp41 transmembrane protein: peptide conformation analysis using monoclonal antibodies and proton nuclear magnetic resonance spectroscopy. J Virol 65: 1727–1734. 2002540

40. Aydin H, Smrke BM, Lee JE (2013) Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2-step entry mechanism. FASEB J 27: 5059–5071. doi: 10.1096/fj.13-232371 24036886

41. Fass D, Harrison SC, Kim PS (1996) Retrovirus envelope domain at 1.7 angstrom resolution. Nat Struct Biol 3: 465–469. 8612078

42. Maerz AL, Center RJ, Kemp BE, Kobe B, Poumbourios P (2000) Functional implications of the human T-lymphotropic virus type 1 transmembrane glycoprotein helical hairpin structure. J Virol 74: 6614–6621. 10864675

43. Maerz AL, Drummer HE, Wilson KA, Poumbourios P (2001) Functional analysis of the disulfide-bonded loop/chain reversal region of human immunodeficiency virus type 1 gp41 reveals a critical role in gp120-gp41 association. J Virol 75: 6635–6644. 11413331

44. Weissenhorn W, Carfi A, Lee KH, Skehel JJ, Wiley DC (1998) Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain. Mol Cell 2: 605–616. 9844633

45. Kobe B, Center RJ, Kemp BE, Poumbourios P (1999) Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins. Proc Natl Acad Sci U S A 96: 4319–4324. 10200260

46. Delos SE, La B, Gilmartin A, White JM (2010) Studies of the "chain reversal regions" of the avian sarcoma/leukosis virus (ASLV) and ebolavirus fusion proteins: analogous residues are important, and a His residue unique to EnvA affects the pH dependence of ASLV entry. J Virol 84: 5687–5694. doi: 10.1128/JVI.02583-09 20335266

47. Caffrey M, Cai M, Kaufman J, Stahl SJ, Wingfield PT, et al. (1998) Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41. EMBO J 17: 4572–4584. 9707417

48. Caffrey M (2001) Model for the structure of the HIV gp41 ectodomain: insight into the intermolecular interactions of the gp41 loop. Biochim Biophys Acta 1536: 116–122. 11406346

49. Colman PM, Laver WG, Varghese JN, Baker AT, Tulloch PA, et al. (1987) Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature 326: 358–363. 2436051

50. Rini JM, Schulze-Gahmen U, Wilson IA (1992) Structural evidence for induced fit as a mechanism for antibody-antigen recognition. Science 255: 959–965. 1546293

51. Stanfield RL, Wilson IA (1995) Protein-peptide interactions. Curr Opin Struct Biol 5: 103–113. 7773739

52. Jimenez R, Salazar G, Baldridge KK, Romesberg FE (2003) Flexibility and molecular recognition in the immune system. Proc Natl Acad Sci U S A 100: 92–97. 12518056

53. Boehr DD, Nussinov R, Wright PE (2009) The role of dynamic conformational ensembles in biomolecular recognition. Nat Chem Biol 5: 789–796. doi: 10.1038/nchembio.232 19841628

54. 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. 16474158

55. Poignard P, Moulard M, Golez E, Vivona V, Franti M, et al. (2003) Heterogeneity of envelope molecules expressed on primary human immunodeficiency virus type 1 particles as probed by the binding of neutralizing and nonneutralizing antibodies. J Virol 77: 353–365. 12477840

56. Pancera M, Wyatt R (2005) Selective recognition of oligomeric HIV-1 primary isolate envelope glycoproteins by potently neutralizing ligands requires efficient precursor cleavage. Virology 332: 145–156. 15661147

57. Dey AK, David KB, Ray N, Ketas TJ, Klasse PJ, et al. (2008) N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus. Virology 372: 187–200. 18031785

58. Herrera C, Spenlehauer C, Fung MS, Burton DR, Beddows S, et al. (2003) Nonneutralizing antibodies to the CD4-binding site on the gp120 subunit of human immunodeficiency virus type 1 do not interfere with the activity of a neutralizing antibody against the same site. J Virol 77: 1084–1091. 12502824

59. Burrer R, Haessig-Einius S, Aubertin AM, Moog C (2005) Neutralizing as well as non-neutralizing polyclonal immunoglobulin (Ig)G from infected patients capture HIV-1 via antibodies directed against the principal immunodominant domain of gp41. Virology 333: 102–113. 15708596

60. Shields RL, Namenuk AK, Hong K, Meng YG, Rae J, et al. (2001) High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem 276: 6591–6604. 11096108

61. Richards JO, Karki S, Lazar GA, Chen H, Dang W, et al. (2008) Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther 7: 2517–2527. doi: 10.1158/1535-7163.MCT-08-0201 18723496

62. Maenaka K, van der Merwe PA, Stuart DI, Jones EY, Sondermann P (2001) The human low affinity Fcgamma receptors IIa, IIb, and III bind IgG with fast kinetics and distinct thermodynamic properties. J Biol Chem 276: 44898–44904. 11544262

63. Paetz A, Sack M, Thepen T, Tur MK, Bruell D, et al. (2005) Recombinant soluble human Fcgamma receptor I with picomolar affinity for immunoglobulin G. Biochem Biophys Res Commun 338: 1811–1817. 16289041

64. Liu P, Yates NL, Shen X, Bonsignori M, Moody MA, et al. (2013) Infectious virion capture by HIV-1 gp120-specific IgG from RV144 vaccinees. J Virol 87: 7828–7836. doi: 10.1128/JVI.02737-12 23658446

65. Liao HX, Bonsignori M, Alam SM, McLellan JS, Tomaras GD, et al. (2013) Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity 38: 176–186. doi: 10.1016/j.immuni.2012.11.011 23313589

66. Fletcher PS, Elliott J, Grivel JC, Margolis L, Anton P, et al. (2006) Ex vivo culture of human colorectal tissue for the evaluation of candidate microbicides. AIDS 20: 1237–1245. 16816551

67. Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, et al. (2010) 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 84: 1302–1313. doi: 10.1128/JVI.01272-09 19906907

68. Whittle JR, Zhang R, Khurana S, King LR, Manischewitz J, et al. (2011) Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc Natl Acad Sci U S A 108: 14216–14221. doi: 10.1073/pnas.1111497108 21825125

69. Abrahams MR, Anderson JA, Giorgi EE, Seoighe C, Mlisana K, et al. (2009) Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. J Virol 83: 3556–3567. doi: 10.1128/JVI.02132-08 19193811

70. Haaland RE, Hawkins PA, Salazar-Gonzalez J, Johnson A, Tichacek A, et al. (2009) Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog 5: e1000274. doi: 10.1371/journal.ppat.1000274 19165325

71. Bar KJ, Li H, Chamberland A, Tremblay C, Routy JP, et al. (2010) Wide variation in the multiplicity of HIV-1 infection among injection drug users. J Virol 84: 6241–6247. doi: 10.1128/JVI.00077-10 20375173

72. Masharsky AE, Dukhovlinova EN, Verevochkin SV, Toussova OV, Skochilov RV, et al. (2010) A substantial transmission bottleneck among newly and recently HIV-1-infected injection drug users in St Petersburg, Russia. J Infect Dis 201: 1697–1702. doi: 10.1086/652702 20423223

73. Keele BF, Li H, Learn GH, Hraber P, Giorgi EE, et al. (2009) Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med 206: 1117–1134. doi: 10.1084/jem.20082831 19414559

74. Finzi A, Xiang SH, Pacheco B, Wang L, Haight J, et al. (2010) Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol Cell 37: 656–667. doi: 10.1016/j.molcel.2010.02.012 20227370

75. Giorgi EE, Funkhouser B, Athreya G, Perelson AS, Korber BT, et al. (2010) Estimating time since infection in early homogeneous HIV-1 samples using a poisson model. BMC Bioinformatics 11: 532. doi: 10.1186/1471-2105-11-532 20973976

76. Butler DM, Smith DM, Cachay ER, Hightower GK, Nugent CT, et al. (2008) Herpes simplex virus 2 serostatus and viral loads of HIV-1 in blood and semen as risk factors for HIV transmission among men who have sex with men. AIDS 22: 1667–1671. doi: 10.1097/QAD.0b013e32830bfed8 18670228

77. Moldt B, Shibata-Koyama M, Rakasz EG, Schultz N, Kanda Y, et al. (2012) A nonfucosylated variant of the anti-HIV-1 monoclonal antibody b12 has enhanced FcgammaRIIIa-mediated antiviral activity in vitro but does not improve protection against mucosal SHIV challenge in macaques. J Virol 86: 6189–6196. doi: 10.1128/JVI.00491-12 22457527

78. Ko SY, Pegu A, Rudicell RS, Yang ZY, Joyce MG, et al. (2014) Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature 514: 642–645. doi: 10.1038/nature13612 25119033

79. Li Q, Zeng M, Duan L, Voss JE, Smith AJ, et al. (2014) Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry. J Immunol 193: 3113–3125. doi: 10.4049/jimmunol.1400820 25135832

80. Bomsel M, Tudor D, Drillet AS, Alfsen A, Ganor Y, et al. (2011) Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges. Immunity 34: 269–280. doi: 10.1016/j.immuni.2011.01.015 21315623

81. Shen R, Drelichman ER, Bimczok D, Ochsenbauer C, Kappes JC, et al. (2010) GP41-specific antibody blocks cell-free HIV type 1 transcytosis through human rectal mucosa and model colonic epithelium. J Immunol 184: 3648–3655. doi: 10.4049/jimmunol.0903346 20208001

82. Gottardo R, Bailer RT, Korber BT, Gnanakaran S, Phillips J, et al. (2013) 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 8: e75665. doi: 10.1371/journal.pone.0075665 24086607

83. Moldt B, Rakasz EG, Schultz N, Chan-Hui PY, Swiderek K, et al. (2012) Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proc Natl Acad Sci U S A 109: 18921–18925. doi: 10.1073/pnas.1214785109 23100539

84. Cao J, Bergeron L, Helseth E, Thali M, Repke H, et al. (1993) Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein. J Virol 67: 2747–2755. 8474172

85. Sattentau QJ, Moore JP, Vignaux F, Traincard F, Poignard P (1993) Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding. J Virol 67: 7383–7393. 7693970

86. Binley JM, Sanders RW, Clas B, Schuelke N, Master A, et al. (2000) A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J Virol 74: 627–643. 10623724

87. Kwong PD, Mascola JR (2012) Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies. Immunity 37: 412–425. doi: 10.1016/j.immuni.2012.08.012 22999947

88. Alam SM, McAdams M, Boren D, Rak M, Scearce RM, et al. (2007) The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes. J Immunol 178: 4424–4435. 17372000

89. 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. 15860590

90. North B, Lehmann A, Dunbrack RL Jr. (2011) A new clustering of antibody CDR loop conformations. J Mol Biol 406: 228–256. doi: 10.1016/j.jmb.2010.10.030 21035459

91. Goepfert PA, Elizaga ML, Seaton K, Tomaras GD, Montefiori DC, et al. (2014) Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis 210: 99–110. doi: 10.1093/infdis/jiu003 24403557

92. Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, et al. (2013) Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med 369: 2083–2092. doi: 10.1056/NEJMoa1310566 24099601

93. Liao HX, Levesque MC, Nagel A, Dixon A, Zhang R, et al. (2009) High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies. J Virol Methods 158: 171–179. doi: 10.1016/j.jviromet.2009.02.014 19428587

94. Wyatt R, Moore J, Accola M, Desjardin E, Robinson J, et al. (1995) Involvement of the V1/V2 variable loop structure in the exposure of human immunodeficiency virus type 1 gp120 epitopes induced by receptor binding. J Virol 69: 5723–5733. 7543586

95. Yates NL, Stacey AR, Nolen TL, Vandergrift NA, Moody MA, et al. (2013) HIV-1 gp41 envelope IgA is frequently elicited after transmission but has an initial short response half-life. Mucosal Immunol 6: 692–703. doi: 10.1038/mi.2012.107 23299618

96. 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. 17942537

97. Liao HX, Chen X, Munshaw S, Zhang R, Marshall DJ, et al. (2011) Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. J Exp Med 208: 2237–2249. doi: 10.1084/jem.20110363 21987658

98. Shen X, Duffy R, Howington R, Cope A, Sadagopal S, et al. (2015) Vaccine Induced Epitope Specific Antibodies to SIVmac239 Envelope Are Distinct from Those Induced to the HIV-1 Envelope in Non-Human Primates. J Virol.

99. Otwinowski A, Minor W (1997) Processing of X-ray Diffraction Data Collected in Oscillation Mode. Methods in Enzymology 276: Macromolecular Crystallography, part A: 307–326.

100. Matthews BW (1968) Solvent content of protein crystals. J Mol Biol 33: 491–497. 5700707

101. Terwilliger TC, Grosse-Kunstleve RW, Afonine PV, Moriarty NW, Zwart PH, et al. (2008) Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallogr D Biol Crystallogr 64: 61–69. 18094468

102. Larson SB, Day JS, Glaser S, Braslawsky G, McPherson A (2005) The structure of an antitumor C(H)2-domain-deleted humanized antibody. J Mol Biol 348: 1177–1190. 15854653

103. Appleton BA, Wu P, Maloney J, Yin J, Liang WC, et al. (2007) Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding. EMBO J 26: 4902–4912. 17989695

104. Emsley P, Lohkamp B, Scott WG, Cowtan K (2010) Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66: 486–501. doi: 10.1107/S0907444910007493 20383002

105. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66: 213–221. doi: 10.1107/S0907444909052925 20124702

106. Lovell SC, Davis IW, Arendall WB 3rd, de Bakker PI, Word JM, et al. (2003) Structure validation by Calpha geometry: phi,psi and Cbeta deviation. Proteins 50: 437–450. 12557186

107. Verkoczy L, Moody MA, Holl TM, Bouton-Verville H, Scearce RM, et al. (2009) Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region. PLoS One 4: e7215. doi: 10.1371/journal.pone.0007215 19806186

108. Webster RL, Johnson RP (2005) Delineation of multiple subpopulations of natural killer cells in rhesus macaques. Immunology 115: 206–214. 15885126

109. Moody MA, Liao HX, Alam SM, Scearce RM, Plonk MK, et al. (2010) Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce beta-chemokines. J Exp Med 207: 763–776. doi: 10.1084/jem.20091281 20368576

110. Li M, Gao F, Mascola JR, 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. 16051804

111. Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, et al. (1986) Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol 59: 284–291. 3016298

112. Edmonds TG, Ding H, Yuan X, Wei Q, Smith KS, et al. (2010) Replication competent molecular clones of HIV-1 expressing Renilla luciferase facilitate the analysis of antibody inhibition in PBMC. Virology 408: 1–13. doi: 10.1016/j.virol.2010.08.028 20863545

113. O'Doherty U, Swiggard WJ, Malim MH (2000) Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol 74: 10074–10080. 11024136

114. Pollara J, Bonsignori M, Moody MA, Liu P, Alam SM, et al. (2014) HIV-1 Vaccine-Induced C1 and V2 Env-Specific Antibodies Synergize for Increased Antiviral Activities. J Virol 88: 7715–7726. doi: 10.1128/JVI.00156-14 24807721

115. Shen X, Dennison SM, Liu P, Gao F, Jaeger F, et al. (2010) Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution. Proc Natl Acad Sci U S A 107: 5972–5977. doi: 10.1073/pnas.0912381107 20231447

116. Leaman DP, Kinkead H, Zwick MB (2010) In-solution virus capture assay helps deconstruct heterogeneous antibody recognition of human immunodeficiency virus type 1. J Virol 84: 3382–3395. doi: 10.1128/JVI.02363-09 20089658

117. Klein K, Veazey RS, Warrier R, Hraber P, Doyle-Meyers LA, et al. (2013) Neutralizing IgG at the portal of infection mediates protection against vaginal simian/human immunodeficiency virus challenge. J Virol 87: 11604–11616. doi: 10.1128/JVI.01361-13 23966410

118. Lee HY, Giorgi EE, Keele BF, Gaschen B, Athreya GS, et al. (2009) Modeling sequence evolution in acute HIV-1 infection. J Theor Biol 261: 341–360. doi: 10.1016/j.jtbi.2009.07.038 19660475

119. Rose PP, Korber BT (2000) Detecting hypermutations in viral sequences with an emphasis on G—> A hypermutation. Bioinformatics 16: 400–401. 10869039

120. Pal R, Taylor B, Foulke JS, Woodward R, Merges M, et al. (2003) Characterization of a simian human immunodeficiency virus encoding the envelope gene from the CCR5-tropic HIV-1 Ba-L. J Acquir Immune Defic Syndr 33: 300–307. 12843740

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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