1887

Abstract

The aim of this study was to determine whether antibodies induced by human papillomavirus (HPV) type 31 L1/L2 virus-like particles (VLPs) could cross-react with VLPs of the closely related HPV-16 and distantly related HPV-11, and to investigate the potential role of the L2 protein in L1/L2 VLPs in inducing cross-neutralizing antibodies. Antisera were prepared from rabbits immunized with intact or denatured HPV-31 L1/L2 VLPs. Cross-reaction and cross-neutralization were analysed by Western blotting and ELISA, and by haemagglutination inhibition, respectively. Western blotting results showed that H31 L1/L2 (D) antiserum (antiserum from a rabbit immunized with denatured HPV-31 L1/L2 VLPs) could cross-react with the L1 protein of HPV-11 and -16. HPV-31 L1/L2 VLP antiserum showed strong cross-reaction with and cross-neutralization of HPV-16 VLPs, but this was significantly less with HPV-11 VLPs. In addition, the cross-neutralizing activity against HPV-16 L1/L2 VLPs was slightly higher than that against HPV-16 L1 VLPs, although the difference was not statistically significant. Epitope-blocking ELISA showed that mAb H16.V5 could partially inhibit the cross-reaction of HPV-31 L1/L2 VLP antiserum with HPV-16 L1/L2 VLPs. These results suggested that (i) H31 L1/L2 (D) antiserum could cross-react with L1 protein from both closely related and distantly related HPV types, but HPV-31 L1/L2 VLP antiserum could only cross-neutralize closely related HPV types, (ii) surface-exposed epitopes of the L2 protein in L1/L2 VLPs may induce only low titres of cross-neutralizing antibodies and (iii) certain epitopes that cross-reacted with HPV-31 L1/L2 VLP antiserum are located close to the epitopes recognized by mAb H16.V5. These findings may provide suggestions for the design of multivalent VLP vaccines.

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2007-07-01
2021-10-27
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References

  1. Ault K. A., Giuliano A. R., Edwards R. P., Tamms G., Kim L. L., Smith J. F., Jansen K. U., Allende M., Taddeo F. J. other authors 2004; A phase I study to evaluate a human papillomavirus (HPV) type 18 L1 VLP vaccine. Vaccine 22:3004–3007 [CrossRef]
    [Google Scholar]
  2. Breitburd F., Kirnbauer R., Hubbert N. L., Nonnenmacher B., Trin-Dinh-Desmarquet C., Orth G., Schiller J. T., Lowy D. R. 1995; Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection. J Virol 69:3959–3963
    [Google Scholar]
  3. Brown D. R., Fife K. H., Wheeler C. M., Koutsky L. A., Lupinacci L. M., Railkar R., Suhr G., Barr E., Dicello A. other authors 2004; Early assessment of the efficacy of a human papillomavirus type 16 L1 virus-like particle vaccine. Vaccine 22:2936–2942 [CrossRef]
    [Google Scholar]
  4. Carpentier G. S., Fleury M. J., Touze A., Sadeyen J. R., Tourne S., Sizaret P. Y., Coursaget P. 2005; Mutations on the FG surface loop of human papillomavirus type 16 major capsid protein affect recognition by both type-specific neutralizing antibodies and cross-reactive antibodies. J Med Virol 77:558–565 [CrossRef]
    [Google Scholar]
  5. Chandrachud L. M., Grindlay G. J., McGarvie G. M., O'Neil B. W., Wagner E. R., Jarrett W. F., Campo M. S. 1995; Vaccination of cattle with the N-terminus of L2 is necessary and sufficient for preventing infection by bovine papillomavirus-4. Virology 211:204–208 [CrossRef]
    [Google Scholar]
  6. Christensen N. D., Kreider J. W., Kan N. C., DiAngelo S. L. 1991; The open reading frame L2 of cottontail rabbit papillomavirus contains antibody-inducing neutralizing epitopes. Virology 181:572–579 [CrossRef]
    [Google Scholar]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. Cook J. C., Joyce J. G., George H. A., Schultz L. D., Hurni W. M., Jansen K. U., Hepler R. W., Ip C., Lowe R. S. other authors 1999; Purification of virus-like particles of recombinant human papillomavirus type 11 major capsid protein L1 from Saccharomyces cerevisiae . Protein Expr Purif 17:477–484 [CrossRef]
    [Google Scholar]
  13. Embers M. E., Budgeon L. R., Pickel M., Christensen N. D. 2002; Protective immunity to rabbit oral and cutaneous papillomaviruses by immunization with short peptides of L2, the minor capsid protein. J Virol 76:9798–9805 [CrossRef]
    [Google Scholar]
  14. Fleury M. J., Touze A., Alvarez E., Carpentier G., Clavel C., Vautherot J. F., Coursaget P. 2006; Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31. Arch Virol 151:1511–1523 [CrossRef]
    [Google Scholar]
  15. 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]
  16. Harper D. M., Franco E. L., Wheeler C., Ferris D. G., Jenkins D., Schuind A., Zahaf T., Innis B., Naud P. other authors 2004; Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 364:1757–1765 [CrossRef]
    [Google Scholar]
  17. Harper D. M., Franco E. L., Wheeler C. M., Moscicki A. B., Romanowski B., Roteli-Martins C. M., Jenkins D., Schuind A., Costa Clemens S. A., Dubin G. 2006; Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 367:1247–1255 [CrossRef]
    [Google Scholar]
  18. Kawana K., Yoshikawa H., Taketani Y., Yoshiike K., Kanda T. 1999; Common neutralization epitope in minor capsid protein L2 of human papillomavirus types 16 and 6. J Virol 73:6188–6190
    [Google Scholar]
  19. Kawana K., Kawana Y., Yoshikawa H., Taketani Y., Yoshiike K., Kanda T. 2001; Nasal immunization of mice with peptide having a cross-neutralization epitope on minor capsid protein L2 of human papillomavirus type 16 elicit systemic and mucosal antibodies. Vaccine 19:1496–1502 [CrossRef]
    [Google Scholar]
  20. Kawana K., Yasugi T., Kanda T., Kawana Y., Hirai Y., Yoshikawa H., Taketani Y. 2002; Neutralizing antibodies against oncogenic human papillomavirus as a possible determinant of the fate of low-grade cervical intraepithelial neoplasia. Biochem Biophys Res Commun 296:102–105 [CrossRef]
    [Google Scholar]
  21. Kawana K., Yasugi T., Kanda T., Kino N., Oda K., Okada S., Kawana Y., Nei T., Takada T. other authors 2003; Safety and immunogenicity of a peptide containing the cross-neutralization epitope of HPV16 L2 administered nasally in healthy volunteers. Vaccine 21:4256–4260 [CrossRef]
    [Google Scholar]
  22. 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]
  23. Kirnbauer R., Taub J., Greenstone H., Roden R., Durst M., Gissmann L., Lowy D. R., Schiller J. T. 1993; Efficient self-assembly of human papillomavirus type 16 L1 and L1–L2 into virus-like particles. J Virol 67:6929–6936
    [Google Scholar]
  24. 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]
  25. Koutsky L. A., Ault K. A., Wheeler C. M., Brown D. R., Barr E., Alvarez F. B., Chiacchierini L. M., Jansen K. U. 2002; A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 347:1645–1651 [CrossRef]
    [Google Scholar]
  26. Mao C., Koutsky L. A., Ault K. A., Wheeler C. M., Brown D. R., Wiley D. J., Alvarez F. B., Bautista O. M., Jansen K. U., Barr E. 2006; Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol 107:18–27 [CrossRef]
    [Google Scholar]
  27. Pastrana D. V., Gambhira R., Buck C. B., Pang Y. Y., Thompson C. D., Culp T. D., Christensen N. D., Lowy D. R., Schiller J. T., Roden R. B. 2005; Cross-neutralization of cutaneous and mucosal papillomavirus types with anti-sera to the amino terminus of L2. Virology 337:365–372 [CrossRef]
    [Google Scholar]
  28. Roden R. B., Hubbert N. L., Kirnbauer R., Breitburd F., Lowy D. R., Schiller J. T. 1995; Papillomavirus L1 capsids agglutinate mouse erythrocytes through a proteinaceous receptor. J Virol 69:5147–5151
    [Google Scholar]
  29. Roden R. B., Hubbert N. L., Kirnbauer R., Christensen N. D., Lowy D. R., Schiller J. T. 1996; Assessment of the serological relatedness of genital human papillomaviruses by hemagglutination inhibition. J Virol 70:3298–3301
    [Google Scholar]
  30. Roden R. B., Yutzy W. H., Fallon R., Inglis S., Lowy D. R., Schiller J. T. 2000; Minor capsid protein of human genital papillomaviruses contains subdominant, cross-neutralizing epitopes. Virology 270:254–257 [CrossRef]
    [Google Scholar]
  31. Shi W., Liu J., Huang Y., Qiao L. 2001; Papillomavirus pseudovirus: a novel vaccine to induce mucosal and systemic cytotoxic T-lymphocyte responses. J Virol 75:10139–10148 [CrossRef]
    [Google Scholar]
  32. 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]
  33. Villa L. L., Costa R. L., Petta C. A., Andrade R. P., Ault K. A., Giuliano A. R., Wheeler C. M., Koutsky L. A., Malm C. other authors 2005; Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 6:271–278 [CrossRef]
    [Google Scholar]
  34. Wang M., Wang L. L., Chen L. F., Han Y. H., Zou Y. H., Si J. Y., Song G. X. 2003; Expression of human papillomavirus type 6 L1 and L2 isolated in China and self assembly of virus-like particles by the products. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 35:27–34
    [Google Scholar]
  35. Zhang M., Liu Y., Liu S., Zhang B., Si J., Xu X., Chen L., Song G. 2000; Assay and L1 gene sequence analysis of human papillomavirus type 6 and 11 in condylomata acuminata. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 22:463–466 (in Chinese)
    [Google Scholar]
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