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. 1995 Jun;69(6):3959–3963. doi: 10.1128/jvi.69.6.3959-3963.1995

Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection.

F Breitburd 1, R Kirnbauer 1, N L Hubbert 1, B Nonnenmacher 1, C Trin-Dinh-Desmarquet 1, G Orth 1, J T Schiller 1, D R Lowy 1
PMCID: PMC189126  PMID: 7745754

Abstract

We tested the ability of vaccination with virus-like particles (VLPs) to protect domestic rabbits against papillomas induced by the cottontail rabbit papillomavirus (CRPV). A recombinant baculovirus system that expressed only the L1 major papillomavirus structural protein or L1 plus the minor L2 protein was used in insect cells as the source of VLPs. Groups of 10 rabbits were immunized with native or denatured VLPs from CRPV or type 1 bovine papillomavirus by using Freund's adjuvant. Alum was used as the adjuvant for an additional group immunized with CRPV L1-L2 VLPs. Animals were challenged with 5 x 10(10) and 2 x 10(11) particles on opposing flanks. No protection was seen in rabbits immunized with native or denatured bovine papillomavirus L1-L2 or with denatured CRPV L1-L2. In these groups, the lower and higher challenge doses resulted in 27 of 30 animals with extensive papillomas, with each of the remaining animals having a smaller number of persistent papillomas. Progression to carcinoma developed in 20 rabbits. Animals inoculated with native CRPV VLPs composed of L1 alone or L1-L2 developed many fewer lesions; the lower and higher challenge doses resulted in 17 of 29 and 5 of 29 rabbits, respectively, with no lesions, and the remainder developed only one to eight papillomas, which all regressed except for those on 1 rabbit. None developed cancer within 1 year of infection. Rabbits vaccinated with native CRPV VLPs developed high-titer antibodies in an enzyme-linked immunosorbent assay based on native VLPs, and passive transfer of serum or immunoglobulin G from rabbits immunized with CRPV VLPs protected against CRPV challenge. We conclude that native VLPs can induce antibody-mediated, type-specific protection against experimental papillomavirus infection.

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Selected References

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  1. Cason J., Khan S. A., Best J. M. Towards vaccines against human papillomavirus type-16 genital infections. Vaccine. 1993;11(6):603–611. doi: 10.1016/0264-410x(93)90302-e. [DOI] [PubMed] [Google Scholar]
  2. Chan S. Y., Bernard H. U., Ong C. K., Chan S. P., Hofmann B., Delius H. Phylogenetic analysis of 48 papillomavirus types and 28 subtypes and variants: a showcase for the molecular evolution of DNA viruses. J Virol. 1992 Oct;66(10):5714–5725. doi: 10.1128/jvi.66.10.5714-5725.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Christensen N. D., Kreider J. W. Antibody-mediated neutralization in vivo of infectious papillomaviruses. J Virol. 1990 Jul;64(7):3151–3156. doi: 10.1128/jvi.64.7.3151-3156.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Christensen N. D., Kreider J. W., Kan N. C., DiAngelo S. L. The open reading frame L2 of cottontail rabbit papillomavirus contains antibody-inducing neutralizing epitopes. Virology. 1991 Apr;181(2):572–579. doi: 10.1016/0042-6822(91)90890-n. [DOI] [PubMed] [Google Scholar]
  5. Crawford L. Prospects for cervical cancer vaccines. Cancer Surv. 1993;16:215–229. [PubMed] [Google Scholar]
  6. DiMaio D. Transforming activity of bovine and human papillomaviruses in cultured cells. Adv Cancer Res. 1991;56:133–159. doi: 10.1016/s0065-230x(08)60480-7. [DOI] [PubMed] [Google Scholar]
  7. EVANS C. A., GORMAN L. R., ITO Y., WEISER R. S. Antitumor immunity in the Shope papilloma-carcinoma complex of rabbits. I. Papilloma regression induced by homologous and autologous tissue vaccines. J Natl Cancer Inst. 1962 Aug;29:277–285. [PubMed] [Google Scholar]
  8. Evans C. A., Ito Y. Antitumor immunity in the Shope papilloma-carcinoma complex of rabbits. 3. Response to reinfection with viral nucleic acid. J Natl Cancer Inst. 1966 Jun;36(6):1161–1166. [PubMed] [Google Scholar]
  9. Favre M. Structural polypeptides of rabbit, bovine, and human papillomaviruses. J Virol. 1975 May;15(5):1239–1247. doi: 10.1128/jvi.15.5.1239-1247.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Galloway D. A. Human papillomavirus vaccines: a warty problem. Infect Agents Dis. 1994 Aug;3(4):187–193. [PubMed] [Google Scholar]
  11. Gissmann L., Jochmus I., Nindl I., Müller M. Immune response to genital papillomavirus infections in women. Prospects for the development of a vaccine against cervical cancer. Ann N Y Acad Sci. 1993 Aug 12;690:80–85. doi: 10.1111/j.1749-6632.1993.tb43998.x. [DOI] [PubMed] [Google Scholar]
  12. Han R., Breitburd F., Marche P. N., Orth G. Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes. Nature. 1992 Mar 5;356(6364):66–68. doi: 10.1038/356066a0. [DOI] [PubMed] [Google Scholar]
  13. Jarrett W. F., Smith K. T., O'Neil B. W., Gaukroger J. M., Chandrachud L. M., Grindlay G. J., McGarvie G. M., Campo M. S. Studies on vaccination against papillomaviruses: prophylactic and therapeutic vaccination with recombinant structural proteins. Virology. 1991 Sep;184(1):33–42. doi: 10.1016/0042-6822(91)90819-w. [DOI] [PubMed] [Google Scholar]
  14. Jin X. W., Cowsert L., Marshall D., Reed D., Pilacinski W., Lim L. Y., Jenson A. B. Bovine serological response to a recombinant BPV-1 major capsid protein vaccine. Intervirology. 1990;31(6):345–354. doi: 10.1159/000150171. [DOI] [PubMed] [Google Scholar]
  15. Kirnbauer R., Booy F., Cheng N., Lowy D. R., Schiller J. T. Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12180–12184. doi: 10.1073/pnas.89.24.12180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kirnbauer R., Hubbert N. L., Wheeler C. M., Becker T. M., Lowy D. R., Schiller J. T. 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. 1994 Apr 6;86(7):494–499. doi: 10.1093/jnci/86.7.494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kirnbauer R., Taub J., Greenstone H., Roden R., Dürst M., Gissmann L., Lowy D. R., Schiller J. T. Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles. J Virol. 1993 Dec;67(12):6929–6936. doi: 10.1128/jvi.67.12.6929-6936.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kreider J. W., Bartlett G. L. The Shope papilloma-carcinoma complex of rabbits: a model system of neoplastic progression and spontaneous regression. Adv Cancer Res. 1981;35:81–110. doi: 10.1016/s0065-230x(08)60909-4. [DOI] [PubMed] [Google Scholar]
  19. Lin Y. L., Borenstein L. A., Selvakumar R., Ahmed R., Wettstein F. O. Effective vaccination against papilloma development by immunization with L1 or L2 structural protein of cottontail rabbit papillomavirus. Virology. 1992 Apr;187(2):612–619. doi: 10.1016/0042-6822(92)90463-y. [DOI] [PubMed] [Google Scholar]
  20. Lin Y. L., Borenstein L. A., Selvakumar R., Ahmed R., Wettstein F. O. Progression from papilloma to carcinoma is accompanied by changes in antibody response to papillomavirus proteins. J Virol. 1993 Jan;67(1):382–389. doi: 10.1128/jvi.67.1.382-389.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Orth G., Breitburd F., Favre M. Evidence for antigenic determinants shared by the structural polypeptides of (Shope) rabbit papillomavirus and human papillomavirus type 1. Virology. 1978 Dec;91(2):243–255. doi: 10.1016/0042-6822(78)90373-2. [DOI] [PubMed] [Google Scholar]
  22. Pilacinski W. P., Glassman D. L., Glassman K. F., Reed D. E., Lum M. A., Marshall R. F., Muscoplat C. C., Faras A. J. Immunization against bovine papillomavirus infection. Ciba Found Symp. 1986;120:136–156. doi: 10.1002/9780470513309.ch10. [DOI] [PubMed] [Google Scholar]
  23. Schiffman M. H., Bauer H. M., Hoover R. N., Glass A. G., Cadell D. M., Rush B. B., Scott D. R., Sherman M. E., Kurman R. J., Wacholder S. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst. 1993 Jun 16;85(12):958–964. doi: 10.1093/jnci/85.12.958. [DOI] [PubMed] [Google Scholar]
  24. Vousden K. Interactions of human papillomavirus transforming proteins with the products of tumor suppressor genes. FASEB J. 1993 Jul;7(10):872–879. doi: 10.1096/fasebj.7.10.8393818. [DOI] [PubMed] [Google Scholar]
  25. Werness B. A., Münger K., Howley P. M. Role of the human papillomavirus oncoproteins in transformation and carcinogenic progression. Important Adv Oncol. 1991:3–18. [PubMed] [Google Scholar]
  26. zur Hausen H. Human papillomaviruses in the pathogenesis of anogenital cancer. Virology. 1991 Sep;184(1):9–13. doi: 10.1016/0042-6822(91)90816-t. [DOI] [PubMed] [Google Scholar]

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