Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer

English version České info

Before the eradication of smallpox (variola virus) from nature, hundreds of million of people succumbed to the infection. The discovery of vaccinia virus (VACV), the active ingredient of the smallpox vaccine, ultimately led to the eradiation of smallpox from the human population. Vaccination with VACV leads to a strong antibody response that protects against variola virus. As the protective antibodies recognize viral proteins that are highly similar in sequence between the different orthopox strains, such as A33 used in this study, several antibodies have the capacity to neutralize a larger breath of orthopx viruses. In this study we have identified an anti-A33 antibody from a larger panel that exhibits a unique binding mode to A33. This antibody, A27D7, is also resistant to single amino acid changes throughout the protein and binds to engineered A33 variants that mimic ectromelia and orthopox A33 in the antibody-binding site. As the antibody further protects against ectromelia infection of mice, this antibody appears to be a potent orthopox cross-species protective antibody with therapeutic potential.

Vyšlo v časopise: Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005148
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005148

Souhrn

Zdroje

1. Wehrle PF. A reality in our time—certification of the global eradication of smallpox. J Infect Dis. 1980;142(4):636–8. Epub 1980/10/01. 7003037

2. Crotty S, Felgner P, Davies H, Glidewell J, Villarreal L, Ahmed R. Cutting edge: long-term B cell memory in humans after smallpox vaccination. J Immunol. 2003;171(10):4969–73. Epub 2003/11/11. 14607890

3. Hammarlund E, Lewis MW, Hansen SG, Strelow LI, Nelson JA, Sexton GJ, et al. Duration of antiviral immunity after smallpox vaccination. Nat Med. 2003;9(9):1131–7. Epub 2003/08/20. 12925846

4. Lane JM, Ruben FL, Abrutyn E, Millar JD. Deaths attributable to smallpox vaccination, 1959 to 1966, and 1968. Jama. 1970;212(3):441–4. Epub 1970/04/20. 4392370

5. Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID, World Health Organization. Smallpox and its eradication. Geneva: World Health Organization; 1988. 1460 p. p.

6. Shchelkunov SN. An increasing danger of zoonotic orthopoxvirus infections. PLoS Pathog. 2013;9(12):e1003756. Epub 2013/12/18. doi: 10.1371/journal.ppat.1003756 24339772

7. Duraffour S, Mertens B, Meyer H, van den Oord JJ, Mitera T, Matthys P, et al. Emergence of cowpox: study of the virulence of clinical strains and evaluation of antivirals. PLoS One. 2013;8(2):e55808. Epub 2013/03/05. doi: 10.1371/journal.pone.0055808 23457480

8. Favier AL, Flusin O, Lepreux S, Fleury H, Labreze C, Georges A, et al. Necrotic ulcerated lesion in a young boy caused by cowpox virus infection. Case Rep Dermatol. 2011;3(3):186–94. Epub 2011/11/24. doi: 10.1159/000331426 22110431

9. Golden JW, Hooper JW. The strategic use of novel smallpox vaccines in the post-eradication world. Expert Rev Vaccines. 2011;10(7):1021–35. Epub 2011/08/03. doi: 10.1586/erv.11.46 21806397

10. Stittelaar KJ, van Amerongen G, Kondova I, Kuiken T, van Lavieren RF, Pistoor FH, et al. Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus. J Virol. 2005;79(12):7845–51. Epub 2005/05/28. 15919938

11. Greenberg RN, Kennedy JS, Clanton DJ, Plummer EA, Hague L, Cruz J, et al. Safety and immunogenicity of new cell-cultured smallpox vaccine compared with calf-lymph derived vaccine: a blind, single-centre, randomised controlled trial. Lancet. 2005;365(9457):398–409. Epub 2005/02/01. 15680454

12. Weltzin R, Liu J, Pugachev KV, Myers GA, Coughlin B, Blum PS, et al. Clonal vaccinia virus grown in cell culture as a new smallpox vaccine. Nat Med. 2003;9(9):1125–30. Epub 2003/08/20. 12925845

13. von Krempelhuber A, Vollmar J, Pokorny R, Rapp P, Wulff N, Petzold B, et al. A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE. Vaccine. 2010;28(5):1209–16. Epub 2009/12/01. doi: 10.1016/j.vaccine.2009.11.030 19944151

14. Grosenbach DW, Jordan R, King DS, Berhanu A, Warren TK, Kirkwood-Watts DL, et al. Immune responses to the smallpox vaccine given in combination with ST-246, a small-molecule inhibitor of poxvirus dissemination. Vaccine. 2008;26(7):933–46. Epub 2008/01/30. doi: 10.1016/j.vaccine.2007.11.095 18226434

15. Hooper JW, Custer DM, Thompson E. Four-gene-combination DNA vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates. Virology. 2003;306(1):181–95. Epub 2003/03/07. 12620810

16. Sakhatskyy P, Wang S, Zhang C, Chou TH, Kishko M, Lu S. Immunogenicity and protection efficacy of subunit-based smallpox vaccines using variola major antigens. Virology. 2008;371(1):98–107. Epub 2007/10/24. 17950773

17. Pulford DJ, Gates A, Bridge SH, Robinson JH, Ulaeto D. Differential efficacy of vaccinia virus envelope proteins administered by DNA immunisation in protection of BALB/c mice from a lethal intranasal poxvirus challenge. Vaccine. 2004;22(25–26):3358–66. Epub 2004/08/17. 15308360

18. Hirao LA, Draghia-Akli R, Prigge JT, Yang M, Satishchandran A, Wu L, et al. Multivalent smallpox DNA vaccine delivered by intradermal electroporation drives protective immunity in nonhuman primates against lethal monkeypox challenge. J Infect Dis. 2011;203(1):95–102. Epub 2010/12/15. doi: 10.1093/infdis/jiq017 21148501

19. Fogg C, Lustig S, Whitbeck JC, Eisenberg RJ, Cohen GH, Moss B. Protective immunity to vaccinia virus induced by vaccination with multiple recombinant outer membrane proteins of intracellular and extracellular virions. J Virol. 2004;78(19):10230–7. Epub 2004/09/16. 15367588

20. Davies DH, McCausland MM, Valdez C, Huynh D, Hernandez JE, Mu Y, et al. Vaccinia virus H3L envelope protein is a major target of neutralizing antibodies in humans and elicits protection against lethal challenge in mice. J Virol. 2005;79(18):11724–33. Epub 2005/09/06. 16140750

21. Buchman GW, Cohen ME, Xiao Y, Richardson-Harman N, Silvera P, DeTolla LJ, et al. A protein-based smallpox vaccine protects non-human primates from a lethal monkeypox virus challenge. Vaccine. 2010;28(40):6627–36. Epub 2010/07/28. doi: 10.1016/j.vaccine.2010.07.030 20659519

22. Davies DH, Molina DM, Wrammert J, Miller J, Hirst S, Mu Y, et al. Proteome-wide analysis of the serological response to vaccinia and smallpox. Proteomics. 2007;7(10):1678–86. Epub 2007/04/20. 17443847

23. Putz MM, Midgley CM, Law M, Smith GL. Quantification of antibody responses against multiple antigens of the two infectious forms of Vaccinia virus provides a benchmark for smallpox vaccination. Nat Med. 2006;12(11):1310–5. Epub 2006/11/07. 17086190

24. Rodriguez JF, Janeczko R, Esteban M. Isolation and characterization of neutralizing monoclonal antibodies to vaccinia virus. J Virol. 1985;56(2):482–8. Epub 1985/11/01. 4057358

25. Berhanu A, Wilson RL, Kirkwood-Watts DL, King DS, Warren TK, Lund SA, et al. Vaccination of BALB/c mice with Escherichia coli-expressed vaccinia virus proteins A27L, B5R, and D8L protects mice from lethal vaccinia virus challenge. J Virol. 2008;82(7):3517–29. Epub 2008/01/18. doi: 10.1128/JVI.01854-07 18199639

26. Niles EG, Seto J. Vaccinia virus gene D8 encodes a virion transmembrane protein. J Virol. 1988;62(10):3772–8. Epub 1988/10/01. 3418784

27. Brown E, Senkevich TG, Moss B. Vaccinia virus F9 virion membrane protein is required for entry but not virus assembly, in contrast to the related L1 protein. J Virol. 2006;80(19):9455–64. Epub 2006/09/16. 16973551

28. Lin CL, Chung CS, Heine HG, Chang W. Vaccinia virus envelope H3L protein binds to cell surface heparan sulfate and is important for intracellular mature virion morphogenesis and virus infection in vitro and in vivo. J Virol. 2000;74(7):3353–65. Epub 2000/03/09. 10708453

29. Wolffe EJ, Vijaya S, Moss B. A myristylated membrane protein encoded by the vaccinia virus L1R open reading frame is the target of potent neutralizing monoclonal antibodies. Virology. 1995;211(1):53–63. 7645236

30. Chen Z, Earl P, Americo J, Damon I, Smith SK, Yu F, et al. Characterization of chimpanzee/human monoclonal antibodies to vaccinia virus A33 glycoprotein and its variola virus homolog in vitro and in a vaccinia virus mouse protection model. J Virol. 2007;81(17):8989–95. Epub 2007/06/22. 17581986

31. Paran N, Lustig S, Zvi A, Erez N, Israely T, Melamed S, et al. Active vaccination with vaccinia virus A33 protects mice against lethal vaccinia and ectromelia viruses but not against cowpoxvirus; elucidation of the specific adaptive immune response. Virol J. 2013;10:229. Epub 2013/07/12. doi: 10.1186/1743-422X-10-229 23842430

32. Roper RL, Payne LG, Moss B. Extracellular vaccinia virus envelope glycoprotein encoded by the A33R gene. J Virol. 1996;70(6):3753–62. Epub 1996/06/01. 8648710

33. McCausland MM, Benhnia MR, Crickard L, Laudenslager J, Granger SW, Tahara T, et al. Combination therapy of vaccinia virus infection with human anti-H3 and anti-B5 monoclonal antibodies in a small animal model. Antivir Ther. 2010;15(4):661–75. Epub 2010/07/01. doi: 10.3851/IMP1573 20587859

34. Engelstad M, Howard ST, Smith GL. A constitutively expressed vaccinia gene encodes a 42-kDa glycoprotein related to complement control factors that forms part of the extracellular virus envelope. Virology. 1992;188(2):801–10. 1585649

35. Duncan SA, Smith GL. Identification and characterization of an extracellular envelope glycoprotein affecting vaccinia virus egress. J Virol. 1992;66(3):1610–21. 1738204

36. Isaacs SN, Wolffe EJ, Payne LG, Moss B. Characterization of a vaccinia virus-encoded 42-kilodalton class I membrane glycoprotein component of the extracellular virus envelope. J Virol. 1992;66(12):7217–24. 1433514

37. van Eijl H, Hollinshead M, Rodger G, Zhang WH, Smith GL. The vaccinia virus F12L protein is associated with intracellular enveloped virus particles and is required for their egress to the cell surface. The Journal of general virology. 2002;83(Pt 1):195–207. 11752717

38. van Eijl H, Hollinshead M, Smith GL. The vaccinia virus A36R protein is a type Ib membrane protein present on intracellular but not extracellular enveloped virus particles. Virology. 2000;271(1):26–36. 10814567

39. Payne LG. Characterization of vaccinia virus glycoproteins by monoclonal antibody precipitation. Virology. 1992;187(1):251–60. Epub 1992/03/01. 1736527

40. Su HP, Singh K, Gittis AG, Garboczi DN. The structure of the poxvirus A33 protein reveals a dimer of unique C-type lectin-like domains. J Virol. 2010. p. 2502–10. 2009/12/25 ed doi: 10.1128/JVI.02247-09 20032175

41. Roper RL, Wolffe EJ, Weisberg A, Moss B. The envelope protein encoded by the A33R gene is required for formation of actin-containing microvilli and efficient cell-to-cell spread of vaccinia virus. J Virol. 1998;72(5):4192–204. 9557708

42. Wolffe EJ, Weisberg AS, Moss B. Role for the vaccinia virus A36R outer envelope protein in the formation of virus-tipped actin-containing microvilli and cell-to-cell virus spread. Virology. 1998;244(1):20–6. 9581774

43. Wolffe EJ, Weisberg AS, Moss B. The vaccinia virus A33R protein provides a chaperone function for viral membrane localization and tyrosine phosphorylation of the A36R protein. J Virol. 2001;75(1):303–10. 11119600

44. Chan WM, Ward BM. There is an A33-dependent mechanism for the incorporation of B5-GFP into vaccinia virus extracellular enveloped virions. Virology. 2010;402(1):83–93. Epub 2010/04/10. doi: 10.1016/j.virol.2010.03.017 20378144

45. Chan WM, Kalkanoglu AE, Ward BM. The inability of vaccinia virus A33R protein to form intermolecular disulfide-bonded homodimers does not affect the production of infectious extracellular virus. Virology. 2010;408(1):109–18. Epub 2010/10/16. doi: 10.1016/j.virol.2010.09.021 20947114

46. Benhnia MR, McCausland MM, Moyron J, Laudenslager J, Granger S, Rickert S, et al. Vaccinia virus extracellular enveloped virion neutralization in vitro and protection in vivo depend on complement. J Virol. 2009;83(3):1201–15. Epub 2008/11/21. doi: 10.1128/JVI.01797-08 19019965

47. Tomimori Y, Kawakami Y, McCausland MM, Ando T, Koriazova L, Kato S, et al. Protective murine and human monoclonal antibodies against eczema vaccinatum. Antivir Ther. 2011;16(1):67–75. doi: 10.3851/IMP1717 21311110

48. Galmiche MC, Goenaga J, Wittek R, Rindisbacher L. Neutralizing and protective antibodies directed against vaccinia virus envelope antigens. Virology. 1999;254(1):71–80. Epub 1999/02/03. 9927575

49. Lustig S, Fogg C, Whitbeck JC, Eisenberg RJ, Cohen GH, Moss B. Combinations of polyclonal or monoclonal antibodies to proteins of the outer membranes of the two infectious forms of vaccinia virus protect mice against a lethal respiratory challenge. J Virol. 2005;79(21):13454–62. 16227266

50. Benhnia MR, Maybeno M, Blum D, Aguilar-Sino R, Matho M, Meng X, et al. Unusual features of vaccinia virus extracellular virion form neutralization resistance revealed in human antibody responses to the smallpox vaccine. J Virol. 2013;87(3):1569–85. Epub 2012/11/16. doi: 10.1128/JVI.02152-12 23152530

51. Benhnia MR, McCausland MM, Laudenslager J, Granger SW, Rickert S, Koriazova L, et al. Heavily isotype-dependent protective activities of human antibodies against vaccinia virus extracellular virion antigen B5. J Virol. 2009;83(23):12355–67. Epub 2009/10/02. doi: 10.1128/JVI.01593-09 19793826

52. Cohen ME, Xiao Y, Eisenberg RJ, Cohen GH, Isaacs SN. Antibody against extracellular vaccinia virus (EV) protects mice through complement and Fc receptors. PLoS One. 2011;6(6):e20597. doi: 10.1371/journal.pone.0020597 21687676

53. Kaever T, Meng X, Matho MH, Schlossman A, Li S, Sela-Culang I, et al. Potent neutralization of vaccinia virus by divergent murine antibodies targeting a common site of vulnerability in L1 protein. J Virol. 2014;88(19):11339–55. doi: 10.1128/JVI.01491-14 25031354

54. Davies DR, Padlan EA, Sheriff S. Antibody-antigen complexes. Annu Rev Biochem. 1990;59:439–73. Epub 1990/01/01. 2197980

55. Matho MH, Maybeno M, Benhnia MR, Becker D, Meng X, Xiang Y, et al. Structural and biochemical characterization of the vaccinia virus envelope protein D8 and its recognition by the antibody LA5. Journal of virology. 2012;86(15):8050–8. Epub 2012/05/25. doi: 10.1128/JVI.00836-12 22623786

56. Su HP, Golden JW, Gittis AG, Hooper JW, Garboczi DN. Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein. Virology. 2007;368(2):331–41. Epub 2007/08/11. 17688903

57. Lawrence MC, Colman PM. Shape complementarity at protein/protein interfaces. J Mol Biol. 1993;234(4):946–50. Epub 1993/12/20. 8263940

58. Jones S, Thornton JM. Principles of protein-protein interactions. Proc Natl Acad Sci U S A. 1996;93(1):13–20. Epub 1996/01/09. 8552589

59. Meng X, Zhong Y, Embry A, Yan B, Lu S, Zhong G, et al. Generation and characterization of a large panel of murine monoclonal antibodies against vaccinia virus. Virology. 2011;409(2):271–9. Epub 2010/11/09. doi: 10.1016/j.virol.2010.10.019 21056889

60. Meng X, Xiang Y. Generation and characterization of monoclonal antibodies specific for vaccinia virus. Methods Mol Biol. 2012;890:219–32. Epub 2012/06/13. doi: 10.1007/978-1-61779-876-4_13 22688770

61. Benhnia MR, McCausland MM, Su HP, Singh K, Hoffmann J, Davies DH, et al. Redundancy and plasticity of neutralizing antibody responses are cornerstone attributes of the human immune response to the smallpox vaccine. J Virol. 2008;82(7):3751–68. Epub 2008/02/01. doi: 10.1128/JVI.02244-07 18234801

62. Tiller T, Busse CE, Wardemann H. Cloning and expression of murine Ig genes from single B cells. J Immunol Methods. 2009;350(1–2):183–93. Epub 2009/09/01. doi: 10.1016/j.jim.2009.08.009 19716372

63. Brochet X, Lefranc MP, Giudicelli V. IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res. 2008;36(Web Server issue):W503–8. Epub 2008/05/27. doi: 10.1093/nar/gkn316 18503082

64. Battye TG, Kontogiannis L, Johnson O, Powell HR, Leslie AG. iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr D Biol Crystallogr. 2011;67(Pt 4):271–81. Epub 2011/04/05. doi: 10.1107/S0907444910048675 21460445

65. Evans PR. An introduction to data reduction: space-group determination, scaling and intensity statistics. Acta crystallographica Section D, Biological crystallography. 2011;67(Pt 4):282–92. Epub 2011/04/05. doi: 10.1107/S090744491003982X 21460446

66. The CCP4 suite: programs for protein crystallography. Acta crystallographica Section D, Biological crystallography. 1994;50(Pt 5):760–3. Epub 1994/09/01. 15299374

67. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. Phaser crystallographic software. J Appl Crystallogr. 2007;40(Pt 4):658–74. Epub 2007/08/01. 19461840

68. Emsley P, Lohkamp B, Scott WG, Cowtan K. Features and development of Coot. Acta crystallographica Section D, Biological crystallography. 2010;66(Pt 4):486–501. Epub 2010/04/13. doi: 10.1107/S0907444910007493 20383002

69. Padilla JE, Yeates TO. A statistic for local intensity differences: robustness to anisotropy and pseudo-centering and utility for detecting twinning. Acta crystallographica Section D, Biological crystallography. 2003;59(Pt 7):1124–30. Epub 2003/07/02. 12832754.

70. Chen VB, Arendall WB 3rd, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta crystallographica Section D, Biological crystallography. 2010;66(Pt 1):12–21. Epub 2010/01/09. doi: 10.1107/S0907444909042073 20057044