Comparison of motif-based and whole-unique-sequence-based analyses of phage display library datasets generated by biopanning of anti-Borrelia burgdorferi immune sera


Autoři: Yurij Ionov aff001;  Artem S. Rogovskyy aff002
Působiště autorů: Department of Cancer Genetics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States of America aff001;  Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226378

Souhrn

Detection of protection-associated epitopes via reverse vaccinology is the first step for development of subunit vaccines against microbial pathogens. Mapping subunit vaccine targets requires high throughput methods, which would allow delineation of epitopes recognized by protective antibodies on a large scale. Phage displayed random peptide library coupled to Next Generation Sequencing (PDRPL/NGS) is the universal platform that enables high-yield identification of peptides that mimic epitopes (mimotopes). Despite being unsurpassed as a tool for discovery of polyclonal serum mimotopes, the PDRPL/NGS is far inferior as a quantitative method of immune response. Difficult-to-control fluctuations in amounts of antibody-bound phages after rounds of selection and amplification diminish the quantitative capacity of the PDRPL/NGS. In an attempt to improve the accuracy of the PDRPL/NGS method, we compared the discriminating capacity of two approaches for PDRPL/NGS data analysis. The whole-unique-sequence-based analysis (WUSA) involved generation of 7-mer peptide profiles and comparison of the numbers of sequencing reads for unique peptide sequences between serum samples. The motif-based analysis (MA) included identification of 4-mer consensus motifs unifying unique 7-mer sequences and comparison of motifs between serum samples. The motif comparison was based not on the numbers of sequencing reads, but on the numbers of distinct 7-mers constituting the motifs. Our PDRPL/NGS datasets generated from biopanning of protective and non-protective anti-Borrelia burgdorferi sera of New Zealand rabbits were used to contrast the two approaches. As a result, the principle component analyses (PCA) showed that the discriminating powers of the WUSA and MA were similar. In contrast, the unsupervised hierarchical clustering obtained via the MA classified the preimmune, non-protective, and protective sera better than the WUSA-based clustering. Also, a total number of discriminating motifs was higher than that of discriminating 7-mers. In sum, our results indicate that MA approach improves the accuracy and quantitative capacity of the PDRPL/NGS method.

Klíčová slova:

Antibodies – Borrelia burgdorferi – Immune response – Phage display – Principal component analysis – Rabbits – Sequence analysis – Sequence motif analysis


Zdroje

1. Pizza M, Scarlato V, Masignani V, Giuliani MM, Arico B, Comanducci M, et al. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science. 2000;287(5459):1816–20. Epub 2000/03/10. doi: 10.1126/science.287.5459.1816 10710308.

2. Moriel DG, Bertoldi I, Spagnuolo A, Marchi S, Rosini R, Nesta B, et al. Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(20):9072–7. Epub 2010/05/05. doi: 10.1073/pnas.0915077107 20439758

3. Lauer P, Rinaudo CD, Soriani M, Margarit I, Maione D, Rosini R, et al. Genome analysis reveals pili in Group B Streptococcus. Science. 2005;309(5731):105. Epub 2005/07/05. doi: 10.1126/science.1111563 15994549.

4. Nesta B, Spraggon G, Alteri C, Moriel DG, Rosini R, Veggi D, et al. FdeC, a novel broadly conserved Escherichia coli adhesin eliciting protection against urinary tract infections. mBio. 2012;3(2). Epub 2012/04/13. doi: 10.1128/mBio.00010-12 22496310

5. McCarthy AJ, Lindsay JA. Genetic variation in Staphylococcus aureus surface and immune evasion genes is lineage associated: implications for vaccine design and host-pathogen interactions. BMC Microbiol. 2010;10:173. Epub 2010/06/17. doi: 10.1186/1471-2180-10-173 20550675

6. He M, Sebaihia M, Lawley TD, Stabler RA, Dawson LF, Martin MJ, et al. Evolutionary dynamics of Clostridium difficile over short and long time scales. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(16):7527–32. Epub 2010/04/07. doi: 10.1073/pnas.0914322107 20368420

7. Liu X, Afrane M, Clemmer DE, Zhong G, Nelson DE. Identification of Chlamydia trachomatis outer membrane complex proteins by differential proteomics. Journal of bacteriology. 2010;192(11):2852–60. Epub 2010/03/30. doi: 10.1128/JB.01628-09 20348250

8. Delany I, Rappuoli R, Seib KL. Vaccines, reverse vaccinology, and bacterial pathogenesis. Cold Spring Harb Perspect Med. 2013;3(5):a012476. Epub 2013/05/03. doi: 10.1101/cshperspect.a012476 23637311

9. Rogovskyy AS, Caoili SEC, Ionov Y, Piontkivska H, Skums P, Tsyvina V, et al. Delineating surface epitopes of Lyme disease pathogen targeted by highly protective antibodies of New Zealand White rabbits. Infection and immunity. 2019;87(8). Epub 2019/05/16. doi: 10.1128/IAI.00246-19 31085705

10. Batool M, Caoili SEC, Dangott LJ, Gerasimov E, Ionov Y, Piontkivska H, et al. Identification of surface epitopes associated with protection against highly immune-evasive VlsE-expressing Lyme disease spirochetes. Infect Immun. 2018. Epub 2018/06/06. doi: 10.1128/IAI.00182-18 29866906.

11. Hecker M, Fitzner B, Wendt M, Lorenz P, Flechtner K, Steinbeck F, et al. High-density peptide microarray analysis of IgG autoantibody reactivities in serum and cerebrospinal fluid of multiple sclerosis patients. Molecular & cellular proteomics: MCP. 2016;15(4):1360–80. Epub 2016/02/03. doi: 10.1074/mcp.M115.051664 26831522

12. Chandra A, Latov N, Wormser GP, Marques AR, Alaedini A. Epitope mapping of antibodies to VlsE protein of Borrelia burgdorferi in post-Lyme disease syndrome. Clinical immunology. 2011;141(1):103–10. doi: 10.1016/j.clim.2011.06.005 21778118

13. Tapia VE, Ay B, Volkmer R. Exploring and profiling protein function with peptide arrays. Methods in molecular biology. 2009;570:3–17. doi: 10.1007/978-1-60327-394-7_1 19649587.

14. Stafford P, Halperin R, Legutki JB, Magee DM, Galgiani J, Johnston SA. Physical characterization of the "immunosignaturing effect". Mol Cell Proteomics. 2012;11(4):M111 011593. doi: 10.1074/mcp.M111.011593 22261726

15. Stafford P, Cichacz Z, Woodbury NW, Johnston SA. Immunosignature system for diagnosis of cancer. Proc Natl Acad Sci U S A. 2014;111(30):E3072–80. doi: 10.1073/pnas.1409432111 25024171

16. Hughes AK, Cichacz Z, Scheck A, Coons SW, Johnston SA, Stafford P. Immunosignaturing can detect products from molecular markers in brain cancer. PLoS One. 2012;7(7):e40201. doi: 10.1371/journal.pone.0040201 22815729

17. Sykes KF, Legutki JB, Stafford P. Immunosignaturing: a critical review. Trends Biotechnol. 2013;31(1):45–51. doi: 10.1016/j.tibtech.2012.10.012 23219199.

18. Scott JK, Smith GP. Searching for peptide ligands with an epitope library. Science. 1990;249(4967):386–90. Epub 1990/07/27. doi: 10.1126/science.1696028 1696028.

19. Folgori A, Tafi R, Meola A, Felici F, Galfre G, Cortese R, et al. A general strategy to identify mimotopes of pathological antigens using only random peptide libraries and human sera. EMBO J. 1994;13(9):2236–43. Epub 1994/05/01. 7514533

20. Cortese R, Monaci P, Luzzago A, Santini C, Bartoli F, Cortese I, et al. Selection of biologically active peptides by phage display of random peptide libraries. Curr Opin Biotechnol. 1996;7(6):616–21. Epub 1996/12/01. doi: 10.1016/s0958-1669(96)80072-3 8939640.

21. Germaschewski V, Murray K. Identification of polyclonal serum specificities with phage-display libraries. J Virol Methods. 1996;58(1–2):21–32. Epub 1996/04/26. doi: 10.1016/0166-0934(95)01980-4 8783147.

22. Scala G, Chen X, Liu W, Telles JN, Cohen OJ, Vaccarezza M, et al. Selection of HIV-specific immunogenic epitopes by screening random peptide libraries with HIV-1-positive sera. Journal of immunology. 1999;162(10):6155–61. Epub 1999/05/07. 10229859.

23. Mintz PJ, Kim J, Do KA, Wang X, Zinner RG, Cristofanilli M, et al. Fingerprinting the circulating repertoire of antibodies from cancer patients. Nat Biotechnol. 2003;21(1):57–63. Epub 2002/12/24. doi: 10.1038/nbt774 12496764.

24. Zeder-Lutz G, Hoebeke J, Van Regenmortel MH. Differential recognition of epitopes present on monomeric and oligomeric forms of gp160 glycoprotein of human immunodeficiency virus type 1 by human monoclonal antibodies. Eur J Biochem. 2001;268(10):2856–66. Epub 2001/05/19. doi: 10.1046/j.1432-1327.2001.02167.x 11358501.

25. Fukuda MN. Peptide-displaying phage technology in glycobiology. Glycobiology. 2012;22(3):318–25. Epub 2011/09/21. doi: 10.1093/glycob/cwr140 21930649

26. Goodwin S, McPherson JD, McCombie WR. Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet. 2016;17(6):333–51. doi: 10.1038/nrg.2016.49 27184599.

27. Matochko WL, Derda R. Next-generation sequencing of phage-displayed peptide libraries. Methods Mol Biol. 2015;1248:249–66. doi: 10.1007/978-1-4939-2020-4_17 25616338.

28. Ryvkin A, Ashkenazy H, Smelyanski L, Kaplan G, Penn O, Weiss-Ottolenghi Y, et al. Deep panning: steps towards probing the IgOme. PloS one. 2012;7(8):e41469. doi: 10.1371/journal.pone.0041469 22870226

29. Liu X, Hu Q, Liu S, Tallo LJ, Sadzewicz L, Schettine CA, et al. Serum antibody repertoire profiling using in silico antigen screen. PloS one. 2013;8(6):e67181. doi: 10.1371/journal.pone.0067181 23826227

30. Christiansen A, Kringelum JV, Hansen CS, Bogh KL, Sullivan E, Patel J, et al. High-throughput sequencing enhanced phage display enables the identification of patient-specific epitope motifs in serum. Sci Rep. 2015;5:12913. doi: 10.1038/srep12913 26246327

31. Rogovskyy AS, Gillis DC, Ionov Y, Gerasimov E, Zelikovsky A. Antibody response to Lyme disease spirochetes in the context of VlsE-mediated immune evasion. Infection and immunity. 2017;85(1). doi: 10.1128/IAI.00890-16 27799330.

32. Batool M, Hillhouse AE, Ionov Y, Kochan KJ, Mohebbi F, Stoica G, et al. New Zealand White rabbits effectively clear Borrelia burgdorferi B31 despite the bacteria’s functional vlsE antigenic variation system. Infection and immunity. 2019. Epub 2019/04/17. doi: 10.1128/IAI.00164-19 30988058.

33. Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, Kaiser R, Krause A, et al. Lyme borreliosis: Clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infec. 2011;17(1):69–79. doi: 10.1111/j.1469-0691.2010.03175.x 20132258

34. van den Wijngaard CC, Hofhuis A, Simoes M, Rood E, van Pelt W, Zeller H, et al. Surveillance perspective on Lyme borreliosis across the European Union and European Economic Area. Euro Surveill. 2017;22(27). doi: 10.2807/1560-7917.ES.2017.22.27.30569 28703098.

35. Lindgren E, Jaenson TGT. Lyme borreliosis in Europe: influences of climate and climate change, epidemiology and adaptation measures. In: Menne B, Ebi KL, editors. Climate change and adaptation strategies for human health. Darmstadt, Germany: Steinkopff; 2006. p. 157–88.

36. Hubalek Z. Epidemiology of Lyme borreliosis. Curr Probl Dermatol. 2009;37:31–50. doi: 10.1159/000213069 19367096.

37. Hinckley AF, Connally NP, Meek JI, Johnson BJ, Kemperman MM, Feldman KA, et al. Lyme disease testing by large commercial laboratories in the United States. Clin Infect Dis. 2014;59(5):676–81. doi: 10.1093/cid/ciu397 24879782

38. Littman MP, Gerber B, Goldstein RE, Labato MA, Lappin MR, Moore GE. ACVIM consensus update on Lyme borreliosis in dogs and cats. J Vet Intern Med. 2018;32(3):887–903. Epub 2018/03/23. doi: 10.1111/jvim.15085 29566442

39. Brownstein JS, Holford TR, Fish D. Effect of climate change on Lyme disease risk in North America. Ecohealth. 2005;2(1):38–46. Epub 2008/11/15. doi: 10.1007/s10393-004-0139-x 19008966

40. Ostfeld RS, Brunner JL. Climate change and Ixodes tick-borne diseases of humans. Philos Trans R Soc Lond B Biol Sci. 2015;370(1665). Epub 2015/02/18. doi: 10.1098/rstb.2014.0051 25688022

41. Rizzoli A, Hauffe HC, Carpi G, Vourc’h GI, Neteler M, Rosa R. Lyme borreliosis in Europe. Eurosurveillance. 2011;16(27):2–9.

42. Peavey CA, Lane RS. Transmission of Borrelia burgdorferi by Ixodes pacificus nymphs and reservoir competence of deer mice (Peromyscus maniculatus) infected by tick-bite. J Parasitol. 1995;81(2):175–8. Epub 1995/04/01. 7707191.

43. Rand PW, Lacombe EH, Smith RP Jr., Rich SM, Kilpatrick CW, Dragoni CA, et al. Competence of Peromyscus maniculatus (Rodentia: Cricetidae) as a reservoir host for Borrelia burgdorferi (Spirochaetares: Spirochaetaceae) in the wild. Journal of medical entomology. 1993;30(3):614–8. Epub 1993/05/01. doi: 10.1093/jmedent/30.3.614 8510121.

44. Radolf JD, Caimano MJ, Stevenson B, Hu LT. Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nat Rev Microbiol. 2012;10(2):87–99. Epub 2012/01/11. doi: 10.1038/nrmicro2714 22230951

45. Anderson JF, Johnson RC, Magnarelli LA, Hyde FW. Culturing Borrelia burgdorferi from spleen and kidney tissues of wild-caught white-footed mice, Peromyscus leucopus. Zentralbl Bakteriol Mikrobiol Hyg A. 1986;263(1–2):34–9. Epub 1986/12/01. doi: 10.1016/s0176-6724(86)80099-2 3577490.

46. Anderson JF, Johnson RC, Magnarelli LA. Seasonal prevalence of Borrelia burgdorferi in natural populations of white-footed mice, Peromyscus leucopus. Journal of clinical microbiology. 1987;25(8):1564–6. Epub 1987/08/01. 3624451

47. Schwan TG, Kime KK, Schrumpf ME, Coe JE, Simpson WJ. Antibody response in white-footed mice (Peromyscus leucopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi). Infection and immunity. 1989;57(11):3445–51. Epub 1989/11/01. 2807530

48. Hudson BJ, Stewart M, Lennox VA, Fukunaga M, Yabuki M, Macorison H, et al. Culture-positive Lyme borreliosis. Med J Aust. 1998;168(10):500–2. Epub 1998/06/19. 9631675.

49. Oksi J, Marjamaki M, Nikoskelainen J, Viljanen MK. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann Med. 1999;31(3):225–32. Epub 1999/08/12. doi: 10.3109/07853899909115982 10442678.

50. Kash N, Fink-Puches R, Cerroni L. Cutaneous manifestations of B-cell chronic lymphocytic leukemia associated with Borrelia burgdorferi infection showing a marginal zone B-cell lymphoma-like infiltrate. Am J Dermatopathol. 2011;33(7):712–5. Epub 2011/09/29. doi: 10.1097/DAD.0b013e3181fc576f 21946761.

51. Middelveen MJ, Sapi E, Burke J, Filush KR, Franco A, Fesler MC, et al. Persistent Borrelia infection in patients with ongoing symptoms of Lyme disease. Healthcare (Basel). 2018;6(2). Epub 2018/04/18. doi: 10.3390/healthcare6020033 29662016

52. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. The New England journal of medicine. 1990;323(21):1438–44. Epub 1990/11/22. doi: 10.1056/NEJM199011223232102 2172819.

53. Stanek G, Klein J, Bittner R, Glogar D. Isolation of Borrelia burgdorferi from the myocardium of a patient with longstanding cardiomyopathy. The New England journal of medicine. 1990;322(4):249–52. Epub 1990/01/25. doi: 10.1056/NEJM199001253220407 2294450.

54. Rogovskyy AS, Bankhead T. Variable VlsE is critical for host reinfection by the Lyme disease spirochete. PloS one. 2013;8(4):e61226. doi: 10.1371/journal.pone.0061226 23593438

55. Vaz A, Glickstein L, Field JA, McHugh G, Sikand VK, Damle N, et al. Cellular and humoral immune responses to Borrelia burgdorferi antigens in patients with culture-positive early Lyme disease. Infection and immunity. 2001;69(12):7437–44. Epub 2001/11/14. doi: 10.1128/IAI.69.12.7437-7444.2001 11705918

56. LaRocca TJ, Benach JL. The important and diverse roles of antibodies in the host response to Borrelia infections. Curr Top Microbiol Immunol. 2008;319:63–103. doi: 10.1007/978-3-540-73900-5_4 18080415.

57. Xu Y, Bruno JF, Luft BJ. Profiling the humoral immune response to Borrelia burgdorferi infection with protein microarrays. Microbial pathogenesis. 2008;45(5–6):403–7. doi: 10.1016/j.micpath.2008.09.006 18976702.

58. Lawrenz MB, Hardham JM, Owens RT, Nowakowski J, Steere AC, Wormser GP, et al. Human antibody responses to VlsE antigenic variation protein of Borrelia burgdorferi. Journal of clinical microbiology. 1999;37(12):3997–4004. Epub 1999/11/24. 10565921

59. McDowell JV, Sung SY, Hu LT, Marconi RT. Evidence that the variable regions of the central domain of VlsE are antigenic during infection with Lyme disease spirochetes. Infection and immunity. 2002;70(8):4196–203. doi: 10.1128/IAI.70.8.4196-4203.2002 12117928.

60. Fikrig E, Bockenstedt LK, Barthold SW, Chen M, Tao H, Ali-Salaam P, et al. Sera from patients with chronic Lyme disease protect mice from Lyme borreliosis. The Journal of infectious diseases. 1994;169(3):568–74. Epub 1994/03/01. doi: 10.1093/infdis/169.3.568 8158028.

61. Zhang JR, Hardham JM, Barbour AG, Norris SJ. Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell. 1997;89(2):275–85. doi: 10.1016/s0092-8674(00)80206-8 9108482

62. Coutte L, Botkin DJ, Gao L, Norris SJ. Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection. PLoS pathogens. 2009;5(2):e1000293. Epub 2009/02/14. doi: 10.1371/journal.ppat.1000293 19214205

63. Purser JE, Norris SJ. Correlation between plasmid content and infectivity in Borrelia burgdorferi. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(25):13865–70. Epub 2000/12/06. doi: 10.1073/pnas.97.25.13865 11106398

64. Labandeira-Rey M, Skare JT. Decreased infectivity in Borrelia burgdorferi strain B31 is associated with loss of linear plasmid 25 or 28–1. Infection and immunity. 2001;69(1):446–55. doi: 10.1128/IAI.69.1.446-455.2001 11119536

65. Labandeira-Rey M, Seshu J, Skare JT. The absence of linear plasmid 25 or 28–1 of Borrelia burgdorferi dramatically alters the kinetics of experimental infection via distinct mechanisms. Infection and immunity. 2003;71(8):4608–13. Epub 2003/07/23. doi: 10.1128/IAI.71.8.4608-4613.2003 12874340

66. Iyer R, Kalu O, Purser J, Norris S, Stevenson B, Schwartz I. Linear and circular plasmid content in Borrelia burgdorferi clinical isolates. Infection and immunity. 2003;71(7):3699–706. doi: 10.1128/IAI.71.7.3699-3706.2003 12819050.

67. Lawrenz MB, Wooten RM, Norris SJ. Effects of vlsE complementation on the infectivity of Borrelia burgdorferi lacking the linear plasmid lp28-1. Infection and immunity. 2004;72(11):6577–85. doi: 10.1128/IAI.72.11.6577-6585.2004 15501789.

68. Bankhead T, Chaconas G. The role of VlsE antigenic variation in the Lyme disease spirochete: persistence through a mechanism that differs from other pathogens. Molecular microbiology. 2007;65(6):1547–58. doi: 10.1111/j.1365-2958.2007.05895.x 17714442.

69. Rogovskyy AS, Casselli T, Tourand Y, Jones CR, Owen JP, Mason KL, et al. Evaluation of the importance of VlsE antigenic variation for the enzootic cycle of Borrelia burgdorferi. PloS one. 2015;10(4):e0124268. doi: 10.1371/journal.pone.0124268 25893989

70. Barthold SW, de Souza MS, Janotka JL, Smith AL, Persing DH. Chronic Lyme borreliosis in the laboratory mouse. Am J Pathol. 1993;143(3):959–71. Epub 1993/09/01. 8362988

71. Johnson RC, Marek N, Kodner C. Infection of Syrian hamsters with Lyme disease spirochetes. J Clin Microbiol. 1984;20(6):1099–101. Epub 1984/12/01. 6520220

72. Goodman JL, Jurkovich P, Kodner C, Johnson RC. Persistent cardiac and urinary tract infections with Borrelia burgdorferi in experimentally infected Syrian hamsters. Journal of clinical microbiology. 1991;29(5):894–6. Epub 1991/05/01. 2056054

73. Burgess EC. Experimental inoculation of dogs with Borrelia burgdorferi. Zentralbl Bakteriol Mikrobiol Hyg A. 1986;263(1–2):49–54. Epub 1986/12/01. doi: 10.1016/s0176-6724(86)80102-x 3554844.

74. Greene RT, Levine JF, Breitschwerdt EB, Walker RL, Berkhoff HA, Cullen J, et al. Clinical and serologic evaluations of induced Borrelia burgdorferi infection in dogs. Am J Vet Res. 1988;49(6):752–7. Epub 1988/06/01. 3041881.

75. Straubinger RK, Summers BA, Chang YF, Appel MJ. Persistence of Borrelia burgdorferi in experimentally infected dogs after antibiotic treatment. J Clin Microbiol. 1997;35(1):111–6. Epub 1997/01/01. 8968890

76. Straubinger RK. PCR-Based quantification of Borrelia burgdorferi organisms in canine tissues over a 500-Day postinfection period. J Clin Microbiol. 2000;38(6):2191–9. Epub 2000/06/02. 10834975

77. Appel MJ, Allan S, Jacobson RH, Lauderdale TL, Chang YF, Shin SJ, et al. Experimental Lyme disease in dogs produces arthritis and persistent infection. J Infect Dis. 1993;167(3):651–64. Epub 1993/03/01. doi: 10.1093/infdis/167.3.651 8440936.

78. Preac Mursic V, Patsouris E, Wilske B, Reinhardt S, Gross B, Mehraein P. Persistence of Borrelia burgdorferi and histopathological alterations in experimentally infected animals. A comparison with histopathological findings in human Lyme disease. Infection. 1990;18(6):332–41. Epub 1990/11/01. doi: 10.1007/bf01646399 2076905.

79. Sonnesyn SW, Manivel JC, Johnson RC, Goodman JL. A guinea pig model for Lyme disease. Infect Immun. 1993;61(11):4777–84. Epub 1993/11/01. 8406878

80. Philipp MT, Aydintug MK, Bohm RP Jr., Cogswell FB, Dennis VA, Lanners HN, et al. Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans. Infection and immunity. 1993;61(7):3047–59. 8514412

81. Roberts ED, Bohm RP Jr., Cogswell FB, Lanners HN, Lowrie RC Jr., Povinelli L, et al. Chronic lyme disease in the rhesus monkey. Laboratory investigation; a journal of technical methods and pathology. 1995;72(2):146–60. 7853849.

82. Barthold SW, Beck DS, Hansen GM, Terwilliger GA, Moody KD. Lyme borreliosis in selected strains and ages of laboratory mice. The Journal of infectious diseases. 1990;162(1):133–8. doi: 10.1093/infdis/162.1.133 2141344.

83. Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008;52(5):1728–36. doi: 10.1128/AAC.01050-07 18316520

84. Chang YF, Ku YW, Chang CF, Chang CD, McDonough SP, Divers T, et al. Antibiotic treatment of experimentally Borrelia burgdorferi-infected ponies. Vet Microbiol. 2005;107(3–4):285–94. Epub 2005/05/03. doi: 10.1016/j.vetmic.2005.02.006 15863289.

85. Chang YF, Novosol V, McDonough SP, Chang CF, Jacobson RH, Divers T, et al. Experimental infection of ponies with Borrelia burgdorferi by exposure to Ixodid ticks. Vet Pathol. 2000;37(1):68–76. Epub 2000/01/22. doi: 10.1354/vp.37-1-68 10643983.

86. Barthold SW, Moody KD, Terwilliger GA, Duray PH, Jacoby RO, Steere AC. Experimental Lyme arthritis in rats infected with Borrelia burgdorferi. The Journal of infectious diseases. 1988;157(4):842–6. doi: 10.1093/infdis/157.4.842 3258003.

87. Foley DM, Gayek RJ, Skare JT, Wagar EA, Champion CI, Blanco DR, et al. Rabbit model of Lyme borreliosis: erythema migrans, infection-derived immunity, and identification of Borrelia burgdorferi proteins associated with virulence and protective immunity. J Clin Invest. 1995;96(2):965–75. doi: 10.1172/JCI118144 7635989

88. Embers ME, Liang FT, Howell JK, Jacobs MB, Purcell JE, Norris SJ, et al. Antigenicity and recombination of VlsE, the antigenic variation protein of Borrelia burgdorferi, in rabbits, a host putatively resistant to long-term infection with this spirochete. FEMS immunology and medical microbiology. 2007;50(3):421–9. Epub 2007/06/29. doi: 10.1111/j.1574-695X.2007.00276.x 17596185.

89. Liang FT, Brown EL, Wang T, Iozzo RV, Fikrig E. Protective niche for Borrelia burgdorferi to evade humoral immunity. Am J Pathol. 2004;165(3):977–85. Epub 2004/08/28. doi: 10.1016/S0002-9440(10)63359-7 15331421

90. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, et al. MEME SUITE: tools for motif discovery and searching. Nucleic acids research. 2009;37(Web Server issue):W202–8. Epub 2009/05/22. doi: 10.1093/nar/gkp335 19458158

91. Metsalu T, Vilo J. ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap. Nucleic acids research. 2015;43(W1):W566–70. Epub 2015/05/15. doi: 10.1093/nar/gkv468 25969447

92. Sette A, Rappuoli R. Reverse vaccinology: developing vaccines in the era of genomics. Immunity. 2010;33(4):530–41. Epub 2010/10/30. doi: 10.1016/j.immuni.2010.09.017 21029963

93. Rogovskyy AS, Caoili SEC, Ionov Y, Piontkivska H, Skums P, Tsyvina V, et al. Delineating surface epitopes of Borrelia burdgorferi targeted by highly protective antibody of the rabbit. Infection and immunity. 2019.

94. Wu CH, Liu IJ, Lu RM, Wu HC. Advancement and applications of peptide phage display technology in biomedical science. J Biomed Sci. 2016;23:8. doi: 10.1186/s12929-016-0223-x 26786672

95. Legutki JB, Zhao ZG, Greving M, Woodbury N, Johnston SA, Stafford P. Scalable high-density peptide arrays for comprehensive health monitoring. Nat Commun. 2014;5:4785. doi: 10.1038/ncomms5785 25183057.

96. Bastas G, Sompuram SR, Pierce B, Vani K, Bogen SA. Bioinformatic requirements for protein database searching using predicted epitopes from disease-associated antibodies. Molecular & cellular proteomics: MCP. 2008;7(2):247–56. doi: 10.1074/mcp.M700107-MCP200 17897933.

97. Ionov Y. A high throughput method for identifying personalized tumor-associated antigens. Oncotarget. 2010;1(2):148–55. doi: 10.18632/oncotarget.118 20711419

98. Paull ML, Johnston T, Ibsen KN, Bozekowski JD, Daugherty PS. A general approach for predicting protein epitopes targeted by antibody repertoires using whole proteomes. PloS one. 2019;14(9):e0217668. Epub 2019/09/07. doi: 10.1371/journal.pone.0217668 31490930.

99. Elias AF, Stewart PE, Grimm D, Caimano MJ, Eggers CH, Tilly K, et al. Clonal polymorphism of Borrelia burgdorferi strain B31 MI: Implications for mutagenesis in an infectious strain background. Infection and immunity. 2002;70(4):2139–50. doi: 10.1128/IAI.70.4.2139-2150.2002 11895980.


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PLOS One


2020 Číslo 1