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
2019-10-17
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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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