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. 1995 Jan;69(1):602–605. doi: 10.1128/jvi.69.1.602-605.1995

Immunization with nonstructural proteins E1 and E2 of cottontail rabbit papillomavirus stimulates regression of virus-induced papillomas.

R Selvakumar 1, L A Borenstein 1, Y L Lin 1, R Ahmed 1, F O Wettstein 1
PMCID: PMC188618  PMID: 7983764

Abstract

Cottontail rabbit papillomavirus is the major animal model for cancer-associated papillomaviruses. Here we show that vaccination with the nonstructural proteins E1 and E2 induces the regression of virus-induced papillomas and that vaccination is equally effective when proteins are given with and without adjuvant. There was no correlation between antibody levels and regression, suggesting that tumor regression may be due to a cell-mediated response.

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Selected References

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  1. Amella C. A., Lofgren L. A., Ronn A. M., Nouri M., Shikowitz M. J., Steinberg B. M. Latent infection induced with cottontail rabbit papillomavirus. A model for human papillomavirus latency. Am J Pathol. 1994 Jun;144(6):1167–1171. [PMC free article] [PubMed] [Google Scholar]
  2. Campo M. S., Grindlay G. J., O'Neil B. W., Chandrachud L. M., McGarvie G. M., Jarrett W. F. Prophylactic and therapeutic vaccination against a mucosal papillomavirus. J Gen Virol. 1993 Jun;74(Pt 6):945–953. doi: 10.1099/0022-1317-74-6-945. [DOI] [PubMed] [Google Scholar]
  3. Chen L. P., Thomas E. K., Hu S. L., Hellström I., Hellström K. E. Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):110–114. doi: 10.1073/pnas.88.1.110. [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. Danos O., Georges E., Orth G., Yaniv M. Fine structure of the cottontail rabbit papillomavirus mRNAs expressed in the transplantable VX2 carcinoma. J Virol. 1985 Mar;53(3):735–741. doi: 10.1128/jvi.53.3.735-741.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. EVANS C. A., GORMAN L. R., ITO Y., WEISER R. S. A vaccination procedure which increases the frequency of regressions of Shope papillomas of rabbits. Nature. 1962 Jan 20;193:288–289. doi: 10.1038/193288a0. [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. Gao L., Chain B., Sinclair C., Crawford L., Zhou J., Morris J., Zhu X., Stauss H. Immune response to human papillomavirus type 16 E6 gene in a live vaccinia vector. J Gen Virol. 1994 Jan;75(Pt 1):157–164. doi: 10.1099/0022-1317-75-1-157. [DOI] [PubMed] [Google Scholar]
  10. Han R., Breitburd F., Marche P. N., Orth G. Analysis of the nucleotide sequence variation of the antigen-binding domain of DR alpha and DQ alpha molecules as related to the evolution of papillomavirus-induced warts in rabbits. J Invest Dermatol. 1994 Sep;103(3):376–380. doi: 10.1111/1523-1747.ep12395285. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. KREIDER J. W. STUDIES ON THE MECHANISM RESPONSIBLE FOR THE SPONTANEOUS REGRESSION OF THE SHOPE RABBIT PAPILLOMA. Cancer Res. 1963 Oct;23:1593–1599. [PubMed] [Google Scholar]
  13. Lin Y. L., Borenstein L. A., Ahmed R., Wettstein F. O. Cottontail rabbit papillomavirus L1 protein-based vaccines: protection is achieved only with a full-length, nondenatured product. J Virol. 1993 Jul;67(7):4154–4162. doi: 10.1128/jvi.67.7.4154-4162.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. McLean C. S., Sterling J. S., Mowat J., Nash A. A., Stanley M. A. Delayed-type hypersensitivity response to the human papillomavirus type 16 E7 protein in a mouse model. J Gen Virol. 1993 Feb;74(Pt 2):239–245. doi: 10.1099/0022-1317-74-2-239. [DOI] [PubMed] [Google Scholar]
  17. Meneguzzi G., Cerni C., Kieny M. P., Lathe R. Immunization against human papillomavirus type 16 tumor cells with recombinant vaccinia viruses expressing E6 and E7. Virology. 1991 Mar;181(1):62–69. doi: 10.1016/0042-6822(91)90470-v. [DOI] [PubMed] [Google Scholar]
  18. Nasseri M., Wettstein F. O. Differences exist between viral transcripts in cottontail rabbit papillomavirus-induced benign and malignant tumors as well as non-virus-producing and virus-producing tumors. J Virol. 1984 Sep;51(3):706–712. doi: 10.1128/jvi.51.3.706-712.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. SYVERTON J. T. The pathogenesis of the rabbit papilloma-to-carcinoma sequence. Ann N Y Acad Sci. 1952 Jul 10;54(6):1126–1140. doi: 10.1111/j.1749-6632.1952.tb39983.x. [DOI] [PubMed] [Google Scholar]
  20. Schirmbeck R., Melber K., Mertens T., Reimann J. Antibody and cytotoxic T-cell responses to soluble hepatitis B virus (HBV) S antigen in mice: implication for the pathogenesis of HBV-induced hepatitis. J Virol. 1994 Mar;68(3):1418–1425. doi: 10.1128/jvi.68.3.1418-1425.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tindle R. W., Fernando G. J., Sterling J. C., Frazer I. H. A "public" T-helper epitope of the E7 transforming protein of human papillomavirus 16 provides cognate help for several E7 B-cell epitopes from cervical cancer-associated human papillomavirus genotypes. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5887–5891. doi: 10.1073/pnas.88.13.5887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ustav M., Stenlund A. Transient replication of BPV-1 requires two viral polypeptides encoded by the E1 and E2 open reading frames. EMBO J. 1991 Feb;10(2):449–457. doi: 10.1002/j.1460-2075.1991.tb07967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zeltner R., Borenstein L. A., Wettstein F. O., Iftner T. Changes in RNA expression pattern during the malignant progression of cottontail rabbit papillomavirus-induced tumors in rabbits. J Virol. 1994 Jun;68(6):3620–3630. doi: 10.1128/jvi.68.6.3620-3630.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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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