1887

Journal of General Virology header logo

Volume 89, Issue 1

Reactivity pattern of 92 monoclonal antibodies with 15 human papillomavirus types Free

Abstract

Most anti-human papillomavirus (HPV) capsid antibody assays are based on virus-like particles (VLP). We evaluated glutathione -transferase (GST)–L1 fusion proteins as ELISA antigens for determining type specificity and cross-reactivity of 92 VLP-specific monoclonal antibodies (mAb) generated against nine mucosal alpha papillomavirus types of species 7, 9 and 10. The antibody panel included 25 new mAb, and 24 previously published mAb are further characterized. We determined the cross-reactivity patterns with 15 different HPV types representing 6 species (alpha1, 2, 4, 7, 9 and 10) and neutralization and cross-neutralization properties with HPV types 6, 11, 16, 18 and 45. Eighty-nine (97 %) of the antibodies including 34, 71 and 14 recognizing neutralizing, conformational and linear epitopes, respectively, reacted with the GST–L1 protein of the HPV type used as immunogen, with log titres ranging from 2.0 to 7.3. Of these 89 antibodies, 52 % were monotypic, 20 % showed intra-species and 28 % inter-species cross-reactivity. Log neutralization titres to the immunogen HPV ranged from 1.7 to 5.6. A single cross-neutralizing mAb (H6.L12) was found. ELISA titres were always higher than neutralization titres. All neutralizing epitopes were conformational and mostly type-specific. Our data show that bacterially expressed, affinity-purified GST–L1 fusion proteins display a broad variety of epitopes and thus are well suited for detection of HPV antibodies. Cross-reactivity is associated with linear as well as conformational epitopes. Distantly related mucosal and skin alpha papillomaviruses share some conformational epitopes and the phylogenetic L1-based species definition may not define a serological unit since no species-specific epitope was found.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83145-0
2008-01-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/1/117.html?itemId=/content/journal/jgv/10.1099/vir.0.83145-0&mimeType=html&fmt=ahah

References

  1. Bosch F. X., de Sanjose S. 2003; Chapter 1: human papillomavirus and cervical cancer -- burden and assessment of causality. J Natl Cancer Inst Monogr 31:3–13
     [Google Scholar]
  2. Bouwes Bavinck J. N., Stark S., Petridis A. K., Marugg M. E., Ter Schegget J., Westendorp R. G., Fuchs P. G., Vermeer B. J., Pfister H. 2000; The presence of antibodies against virus-like particles of epidermodysplasia verruciformis-associated humanpapillomavirus type 8 in patients with actinic keratoses. Br J Dermatol 142:103–109 [CrossRef]
     [Google Scholar]
  3. Buck C. B., Pastrana D. V., Lowy D. R., Schiller J. T. 2005; Generation of HPV pseudovirions using transfection and their use in neutralization assays. Methods Mol Med 119:445–462
     [Google Scholar]
  4. Carter J. J., Galloway D. A. 1997; Humoral immune response to human papillomavirus infection. Clin Dermatol 15:249–259 [CrossRef]
     [Google Scholar]
  5. Carter J. J., Hagensee M., Taflin M. C., Lee S. K., Koutsky L. A., Galloway D. A. 1993; HPV-1 capsids expressed in vitro detect human serum antibodies associated with foot warts. Virology 195:456–462 [CrossRef]
     [Google Scholar]
  6. Carter J. J., Koutsky L. A., Wipf G. C., Christensen N. D., Lee S. K., Kuypers J., Kiviat N., Galloway D. A. 1996; The natural history of human papillomavirus type 16 capsid antibodies among a cohort of university women. J Infect Dis 174:927–936 [CrossRef]
     [Google Scholar]
  7. Carter J. J., Koutsky L. A., Hughes J. P., Lee S. K., Kuypers J., Kiviat N., Galloway D. A. 2000; Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis 181:1911–1919 [CrossRef]
     [Google Scholar]
  8. Chen X. S., Garcea R. L., Goldberg I., Casini G., Harrison S. C. 2000; Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol Cell 5:557–567 [CrossRef]
     [Google Scholar]
  9. Chen X. S., Casini G., Harrison S. C., Garcea R. L. 2001; Papillomavirus capsid protein expression in Escherichia coli : purification and assembly of HPV11 and HPV16 L1. J Mol Biol 307:173–182 [CrossRef]
     [Google Scholar]
  10. Christensen N. D., Kreider J. W., Cladel N. M., Patrick S. D., Welsh P. A. 1990; Monoclonal antibody-mediated neutralization of infectious human papillomavirus type 11. J Virol 64:5678–5681
     [Google Scholar]
  11. Christensen N. D., Hopfl R., DiAngelo S. L., Cladel N. M., Patrick S. D., Welsh P. A., Budgeon L. R., Reed C. A., Kreider J. W. 1994a; Assembled baculovirus-expressed human papillomavirus type 11 L1 capsid protein virus-like particles are recognized by neutralizing monoclonal antibodies and induce high titres of neutralizing antibodies. J Gen Virol 75:2271–2276 [CrossRef]
     [Google Scholar]
  12. Christensen N. D., Kirnbauer R., Schiller J. T., Ghim S. J., Schlegel R., Jenson A. B., Kreider J. W. 1994b; Human papillomavirus types 6 and 11 have antigenically distinct strongly immunogenic conformationally dependent neutralizing epitopes. Virology 205:329–335 [CrossRef]
     [Google Scholar]
  13. Christensen N. D., Dillner J., Eklund C., Carter J. J., Wipf G. C., Reed C. A., Cladel N. M., Galloway D. A. 1996a; Surface conformational and linear epitopes on HPV-16 and HPV-18 L1 virus-like particles as defined by monoclonal antibodies. Virology 223:174–184 [CrossRef]
     [Google Scholar]
  14. Christensen N. D., Reed C. A., Cladel N. M., Hall K., Leiserowitz G. S. 1996b; Monoclonal antibodies to HPV-6 L1 virus-like particles identify conformational and linear neutralizing epitopes on HPV-11 in addition to type-specific epitopes on HPV-6. Virology 224:477–486 [CrossRef]
     [Google Scholar]
  15. Christensen N. D., Cladel N. M., Reed C. A., Budgeon L. R., Embers M. E., Skulsky D. M., McClements W. L., Ludmerer S. W., Jansen K. U. 2001; Hybrid papillomavirus L1 molecules assemble into virus-like particles that reconstitute conformational epitopes and induce neutralizing antibodies to distinct HPV types. Virology 291:324–334 [CrossRef]
     [Google Scholar]
  16. Clifford G. M., Smith J. S., Plummer M., Munoz N., Franceschi S. 2003; Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 88:63–73 [CrossRef]
     [Google Scholar]
  17. Combita A. L., Touze A., Bousarghin L., Christensen N. D., Coursaget P. 2002; Identification of two cross-neutralizing linear epitopes within the L1 major capsid protein of human papillomaviruses. J Virol 76:6480–6486 [CrossRef]
     [Google Scholar]
  18. Culp T. D., Spatz C. M., Reed C. A., Christensen N. D. 2007; Binding and neutralization efficiencies of monoclonal antibodies, Fab fragments, and scFv specific for L1 epitopes on the capsid of infectious HPV particles. Virology 361:435–446 [CrossRef]
     [Google Scholar]
  19. Davidson E. J., Sehr P., Faulkner R. L., Parish J. L., Gaston K., Moore R. A., Pawlita M., Kitchener H. C., Stern P. L. 2003; Human papillomavirus type 16 E2- and L1-specific serological and T-cell responses in women with vulval intraepithelial neoplasia. J Gen Virol 84:2089–2097 [CrossRef]
     [Google Scholar]
  20. de Villiers E. M., Fauquet C., Broker T. R., Bernard H. U., zur Hausen H. 2004; Classification of papillomaviruses. Virology 324:17–27 [CrossRef]
     [Google Scholar]
  21. Dillner J. 1999; The serological response to papillomaviruses. Semin Cancer Biol 9:423–430 [CrossRef]
     [Google Scholar]
  22. Favre M., Orth G., Majewski S., Baloul S., Pura A., Jablonska S. 1998; Psoriasis: a possible reservoir for human papillomavirus type 5, the virus associated with skin carcinomas of epidermodysplasia verruciformis. J Invest Dermatol 110:311–317 [CrossRef]
     [Google Scholar]
  23. Feltkamp M. C., Broer R., di Summa F. M., Struijk L., van der Meijden W., Verlaan B. P., Westendorp R. G., ter Schegget J., Spaan W. J., Bouwes Bavinck J. N. 2003; Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer. Cancer Res 63:2695–2700
     [Google Scholar]
  24. Giroglou T., Sapp M., Lane C., Fligge C., Christensen N. D., Streeck R. E., Rose R. C. 2001; Immunological analyses of human papillomavirus capsids. Vaccine 19:1783–1793 [CrossRef]
     [Google Scholar]
  25. Hagensee M. E., Yaegashi N., Galloway D. A. 1993; Self-assembly of human papillomavirus type 1 capsids by expression of the L1 protein alone or by coexpression of the L1 and L2 capsid proteins. J Virol 67:315–322
     [Google Scholar]
  26. Karagas M. R., Nelson H. H., Sehr P., Waterboer T., Stukel T. A., Andrew A., Green A. C., Bavinck J. N., Perry A. other authors 2006; Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin. J Natl Cancer Inst 98:389–395 [CrossRef]
     [Google Scholar]
  27. Kirnbauer R. 1996; Papillomavirus-like particles for serology and vaccine development. Intervirology 39:54–61
     [Google Scholar]
  28. Kirnbauer R., Booy F., Cheng N., Lowy D. R., Schiller J. T. 1992; Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci U S A 89:12180–12184 [CrossRef]
     [Google Scholar]
  29. Kirnbauer R., Hubbert N. L., Wheeler C. M., Becker T. M., Lowy D. R., Schiller J. T. 1994; A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. J Natl Cancer Inst 86:494–499 [CrossRef]
     [Google Scholar]
  30. Kirnbauer R., Chandrachud L. M., O'Neil B. W., Wagner E. R., Grindlay G. J., Armstrong A., McGarvie G. M., Schiller J. T., Lowy D. R., Campo M. S. 1996; Virus-like particles of bovine papillomavirus type 4 in prophylactic and therapeutic immunization. Virology 219:37–44 [CrossRef]
     [Google Scholar]
  31. Kreider J. W., Howett M. K., Leure-Dupree A. E., Zaino R. J., Weber J. A. 1987; Laboratory production in vivo of infectious human papillomavirus type 11. J Virol 61:590–593
     [Google Scholar]
  32. Le Cann P., Coursaget P., Iochmann S., Touze A. 1994; Self-assembly of human papillomavirus type 16 capsids by expression of the L1 protein in insect cells. FEMS Microbiol Lett 117:269–274 [CrossRef]
     [Google Scholar]
  33. Lehtinen M., Pawlita M., Zumbach K., Lie K., Hakama M., Jellum E., Koskela P., Luostarinen T., Paavonen J. other authors 2003; Evaluation of antibody response to human papillomavirus early proteins in women in whom cervical cancer developed 1 to 20 years later. Am J Obstet Gynecol 188:49–55 [CrossRef]
     [Google Scholar]
  34. Li M., Cripe T. P., Estes P. A., Lyon M. K., Rose R. C., Garcea R. L. 1997; Expression of the human papillomavirus type 11 L1 capsid protein in Escherichia coli : characterization of protein domains involved in DNA binding and capsid assembly. J Virol 71:2988–2995
     [Google Scholar]
  35. Ludmerer S. W., Benincasa D., Mark G. E. III 1996; Two amino acid residues confer type specificity to a neutralizing, conformationally dependent epitope on human papillomavirus type 11. J Virol 70:4791–4794
     [Google Scholar]
  36. Ludmerer S. W., Benincasa D., Mark G. E. III, Christensen N. D. 1997; A neutralizing epitope of human papillomavirus type 11 is principally described by a continuous set of residues which overlap a distinct linear, surface-exposed epitope. J Virol 71:3834–3839
     [Google Scholar]
  37. Ludmerer S. W., McClements W. L., Wang X. M., Ling J. C., Jansen K. U., Christensen N. D. 2000; HPV11 mutant virus-like particles elicit immune responses that neutralize virus and delineate a novel neutralizing domain. Virology 266:237–245 [CrossRef]
     [Google Scholar]
  38. McClements W. L., Wang X. M., Ling J. C., Skulsky D. M., Christensen N. D., Jansen K. U., Ludmerer S. W. 2001; A novel human papillomavirus type 6 neutralizing domain comprising two discrete regions of the major capsid protein L1. Virology 289:262–268 [CrossRef]
     [Google Scholar]
  39. Meschede W., Zumbach K., Braspenning J., Scheffner M., Benitez-Bribiesca L., Luande J., Gissmann L., Pawlita M. 1998; Antibodies against early proteins of human papillomaviruses as diagnostic markers for invasive cervical cancer. J Clin Microbiol 36:475–480
     [Google Scholar]
  40. Meyers C., Laimins L. A. 1994; In vitro systems for the study and propagation of human papillomaviruses. Curr Top Microbiol Immunol 186:199–215
     [Google Scholar]
  41. Muller M., Zhou J., Reed T. D., Rittmuller C., Burger A., Gabelsberger J., Braspenning J., Gissmann L. 1997; Chimeric papillomavirus-like particles. Virology 234:93–111 [CrossRef]
     [Google Scholar]
  42. Munoz N., Bosch F. X., de Sanjose S., Herrero R., Castellsague X., Shah K. V., Snijders P. J., Meijer C. J. 2003; Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527 [CrossRef]
     [Google Scholar]
  43. Pastrana D. V., Buck C. B., Pang Y. Y., Thompson C. D., Castle P. E., FitzGerald P. C., Kruger Kjaer S., Lowy D. R., Schiller J. T. 2004; Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18. Virology 321:205–216 [CrossRef]
     [Google Scholar]
  44. Roden R. B., Greenstone H. L., Kirnbauer R., Booy F. P., Jessie J., Lowy D. R., Schiller J. T. 1996; In vitro generation and type-specific neutralization of a human papillomavirus type 16 virion pseudotype. J Virol 70:5875–5883
     [Google Scholar]
  45. Roden R. B., Armstrong A., Haderer P., Christensen N. D., Hubbert N. L., Lowy D. R., Schiller J. T., Kirnbauer R. 1997; Characterization of a human papillomavirus type 16 variant-dependent neutralizing epitope. J Virol 71:6247–6252
     [Google Scholar]
  46. Rose R. C., White W. I., Li M., Suzich J. A., Lane C., Garcea R. L. 1998; Human papillomavirus type 11 recombinant L1 capsomeres induce virus-neutralizing antibodies. J Virol 72:6151–6154
     [Google Scholar]
  47. Sasagawa T., Pushko P., Steers G., Gschmeissner S. E., Hajibagheri M. A., Finch J., Crawford L., Tommasino M. 1995; Synthesis and assembly of virus-like particles of human papillomaviruses type 6 and type 16 in fission yeast Schizosaccharomyces pombe . Virology 206:126–135 [CrossRef]
     [Google Scholar]
  48. Sehr P., Zumbach K., Pawlita M. 2001; A generic capture ELISA for recombinant proteins fused to glutathione S -transferase: validation for HPV serology. J Immunol Methods 253:153–162 [CrossRef]
     [Google Scholar]
  49. Sehr P., Muller M., Hopfl R., Widschwendter A., Pawlita M. 2002; HPV antibody detection by ELISA with capsid protein L1 fused to glutathione S -transferase. J Virol Methods 106:61–70 [CrossRef]
     [Google Scholar]
  50. Silins I., Avall-Lundqvist E., Tadesse A., Jansen K. U., Stendahl U., Lenner P., Zumbach K., Pawlita M., Dillner J., Frankendal B. 2002; Evaluation of antibodies to human papillomavirus as prognostic markers in cervical cancer patients. Gynecol Oncol 85:333–338 [CrossRef]
     [Google Scholar]
  51. Suzich J. A., Ghim S. J., Palmer-Hill F. J., White W. I., Tamura J. K., Bell J. A., Newsome J. A., Jenson A. B., Schlegel R. 1995; Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas. Proc Natl Acad Sci U S A 92:11553–11557 [CrossRef]
     [Google Scholar]
  52. Touze A., Coursaget P. 1998; In vitro gene transfer using human papillomavirus-like particles. Nucleic Acids Res 26:1317–1323 [CrossRef]
     [Google Scholar]
  53. Touze A., Dupuy C., Chabaud M., Le Cann P., Coursaget P. 1996; Production of human papillomavirus type 45 virus-like particles in insect cells using a recombinant baculovirus. FEMS Microbiol Lett 141:111–116 [CrossRef]
     [Google Scholar]
  54. Touze A., Dupuy C., Mahe D., Sizaret P. Y., Coursaget P. 1998; Production of recombinant virus-like particles from human papillomavirus types 6 and 11, and study of serological reactivities between HPV 6, 11, 16 and 45 by ELISA: implications for papillomavirus prevention and detection. FEMS Microbiol Lett 160:111–118 [CrossRef]
     [Google Scholar]
  55. Unckell F., Streeck R. E., Sapp M. 1997; Generation and neutralization of pseudovirions of human papillomavirus type 33. J Virol 71:2934–2939
     [Google Scholar]
  56. van Doornum G., Prins M., Andersson-Ellstrom A., Dillner J. 1998; Immunoglobulin A, G, and M responses to L1 and L2 capsids of human papillomavirus types 6, 11, 16, 18, and 33 L1 after newly acquired infection. Sex Transm Infect 74:354–360 [CrossRef]
     [Google Scholar]
  57. van Doornum G. J., Korse C. M., Buning-Kager J. C., Bonfrer J. M., Horenblas S., Taal B. G., Dillner J. 2003; Reactivity to human papillomavirus type 16 L1 virus-like particles in sera from patients with genital cancer and patients with carcinomas at five different extragenital sites. Br J Cancer 88:1095–1100 [CrossRef]
     [Google Scholar]
  58. Wang Z., Hansson B. G., Forslund O., Dillner L., Sapp M., Schiller J. T., Bjerre B., Dillner J. 1996; Cervical mucus antibodies against human papillomavirus type 16, 18, and 33 capsids in relation to presence of viral DNA. J Clin Microbiol 34:3056–3062
     [Google Scholar]
  59. Wang Z., Christensen N., Schiller J. T., Dillner J. 1997; A monoclonal antibody against intact human papillomavirus type 16 capsids blocks the serological reactivity of most human sera. J Gen Virol 78:2209–2215
     [Google Scholar]
  60. Waterboer T., Sehr P., Michael K. M., Franceschi S., Nieland J. D., Joos T. O., Templin M. F., Pawlita M. 2005; Multiplex human papillomavirus serology based on in situ-purified glutathione S -transferase fusion proteins. Clin Chem 51:1845–1853 [CrossRef]
     [Google Scholar]
  61. White W. I., Wilson S. D., Bonnez W., Rose R. C., Koenig S., Suzich J. A. 1998; In vitro infection and type-restricted antibody-mediated neutralization of authentic human papillomavirus type 16. J Virol 72:959–964
     [Google Scholar]
  62. White W. I., Wilson S. D., Palmer-Hill F. J., Woods R. M., Ghim S. J., Hewitt L. A., Golman D. M., Burke S. J., Jenson A. B. other authors 1999; Characterization of a major neutralizing epitope on human papillomavirus type 16 L1. J Virol 73:4882–4889
     [Google Scholar]
  63. Wideroff L., Schiffman M., Haderer P., Armstrong A., Greer C. E., Manos M. M., Burk R. D., Scott D. R., Sherman M. E. other authors 1999; Seroreactivity to human papillomavirus types 16, 18, 31, and 45 virus-like particles in a case-control study of cervical squamous intraepithelial lesions. J Infect Dis 180:1424–1428 [CrossRef]
     [Google Scholar]
  64. Yuan H., Estes P. A., Chen Y., Newsome J., Olcese V. A., Garcea R. L., Schlegel R. 2001; Immunization with a pentameric L1 fusion protein protects against papillomavirus infection. J Virol 75:7848–7853 [CrossRef]
     [Google Scholar]
  65. Zumbach K., Kisseljov F., Sacharova O., Shaichaev G., Semjonova L., Pavlova L., Pawlita M. 2000; Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in cervical-carcinoma patients from Russia. Int J Cancer 85:313–318 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83145-0
Loading
Reactivity pattern of 92 monoclonal antibodies with 15 human papillomavirus types
J. Gen. Virol. 89, 117 (2008); https://doi.org/10.1099/vir.0.83145-0
/content/journal/jgv/10.1099/vir.0.83145-0
/content/journal/jgv/10.1099/vir.0.83145-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error