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Journal of Virology logoLink to Journal of Virology
. 1996 Feb;70(2):960–965. doi: 10.1128/jvi.70.2.960-965.1996

Immunization with viruslike particles induces long-term protection of rabbits against challenge with cottontail rabbit papillomavirus.

N D Christensen 1, C A Reed 1, N M Cladel 1, R Han 1, J W Kreider 1
PMCID: PMC189900  PMID: 8551636

Abstract

Rabbits were immunized with recombinant baculovirus-produced virus-like particles (VLPs) of cottontail rabbit papillomavirus (CRPV) to determine whether these antigens could induce long-term protection against experimental challenge with CRPV. Infectious CRPV and human papillomavirus type 11 L1 VLPs were used as positive and negative control immunogens, respectively. Three groups of immunized animals were challenged with 10-fold serial dilutions of infectious CRPV at 2 weeks, 6 months, and 12 months after immunizations. Antibody titers in serum reached 1:10,000 immediately after the final booster immunization and then decayed to 1:150 at 6 months and 1:100 at 12 months in unchallenged rabbits. Serum neutralization titers followed similar kinetics. Papillomas grew on control-immunized rabbits at sites challenged with 10(-1) (100% of sites), 10(-2) (96% of sites), 10(-3) (63% of sites), and 10(-4) (13% of sites) dilutions of virus. At 2 weeks after CRPV L1 VLP immunizations, the rabbits were completely protected against virus challenge. At both 6 and 12 months after CRPV L1 VLP immunizations, strong protection was also observed. In the last two groups, three of seven rabbits were completely protected and only 4 of 14 or 29% of sites challenged with 10(-1 dilution of virus grew papillomas. Papillomas growing at these four sites were also reduced in size (3.5 +/- 0.7 mm) at 50 days postchallenge compared with sites challenged with 10(-1) dilution on control-immunized rabbits (13.2 +/- 4.2 mm). The results demonstrate that strong and long-lasting protection against experimental challenge with papillomaviruses can be achieved with VLP immunogens.

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Selected References

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  1. Breitburd F., Kirnbauer R., Hubbert N. L., Nonnenmacher B., Trin-Dinh-Desmarquet C., Orth G., Schiller J. T., Lowy D. R. Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection. J Virol. 1995 Jun;69(6):3959–3963. doi: 10.1128/jvi.69.6.3959-3963.1995. [DOI] [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. Campo M. S. Vaccination against papillomavirus in cattle. Curr Top Microbiol Immunol. 1994;186:255–266. doi: 10.1007/978-3-642-78487-3_13. [DOI] [PubMed] [Google Scholar]
  4. Christensen N. D., Höpfl R., DiAngelo S. L., Cladel N. M., Patrick S. D., Welsh P. A., Budgeon L. R., Reed C. A., Kreider J. W. 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. 1994 Sep;75(Pt 9):2271–2276. doi: 10.1099/0022-1317-75-9-2271. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Ghim S., Christensen N. D., Kreider J. W., Jenson A. B. Comparison of neutralization of BPV-1 infection of C127 cells and bovine fetal skin xenografts. Int J Cancer. 1991 Sep 9;49(2):285–289. doi: 10.1002/ijc.2910490224. [DOI] [PubMed] [Google Scholar]
  8. Hagensee M. E., Olson N. H., Baker T. S., Galloway D. A. Three-dimensional structure of vaccinia virus-produced human papillomavirus type 1 capsids. J Virol. 1994 Jul;68(7):4503–4505. doi: 10.1128/jvi.68.7.4503-4505.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hagensee M. E., Yaegashi N., Galloway D. A. 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. 1993 Jan;67(1):315–322. doi: 10.1128/jvi.67.1.315-322.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jarrett W. F., O'Neil B. W., Gaukroger J. M., Smith K. T., Laird H. M., Campo M. S. Studies on vaccination against papillomaviruses: the immunity after infection and vaccination with bovine papillomaviruses of different types. Vet Rec. 1990 May 12;126(19):473–475. [PubMed] [Google Scholar]
  11. Kelsall S. R., Kulski J. K. Expression of the major capsid protein of human papillomavirus type 16 in Escherichia coli. J Virol Methods. 1995 May;53(1):75–90. doi: 10.1016/0166-0934(95)00004-e. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Le Cann P., Coursaget P., Iochmann S., Touze A. Self-assembly of human papillomavirus type 16 capsids by expression of the L1 protein in insect cells. FEMS Microbiol Lett. 1994 Apr 15;117(3):269–274. doi: 10.1111/j.1574-6968.1994.tb06778.x. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. O'Neill R. E., Palese P. NPI-1, the human homolog of SRP-1, interacts with influenza virus nucleoprotein. Virology. 1995 Jan 10;206(1):116–125. doi: 10.1016/s0042-6822(95)80026-3. [DOI] [PubMed] [Google Scholar]
  17. OLSON C. CUTANEOUS PAPILLOMATOSIS IN CATTLE AND OTHER ANIMALS. Ann N Y Acad Sci. 1963 Nov 4;108:1042–1056. doi: 10.1111/j.1749-6632.1963.tb13435.x. [DOI] [PubMed] [Google Scholar]
  18. Roden R. B., Weissinger E. M., Henderson D. W., Booy F., Kirnbauer R., Mushinski J. F., Lowy D. R., Schiller J. T. Neutralization of bovine papillomavirus by antibodies to L1 and L2 capsid proteins. J Virol. 1994 Nov;68(11):7570–7574. doi: 10.1128/jvi.68.11.7570-7574.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rose R. C., Bonnez W., Reichman R. C., Garcea R. L. Expression of human papillomavirus type 11 L1 protein in insect cells: in vivo and in vitro assembly of viruslike particles. J Virol. 1993 Apr;67(4):1936–1944. doi: 10.1128/jvi.67.4.1936-1944.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rose R. C., Reichman R. C., Bonnez W. Human papillomavirus (HPV) type 11 recombinant virus-like particles induce the formation of neutralizing antibodies and detect HPV-specific antibodies in human sera. J Gen Virol. 1994 Aug;75(Pt 8):2075–2079. doi: 10.1099/0022-1317-75-8-2075. [DOI] [PubMed] [Google Scholar]
  21. Volpers C., Schirmacher P., Streeck R. E., Sapp M. Assembly of the major and the minor capsid protein of human papillomavirus type 33 into virus-like particles and tubular structures in insect cells. Virology. 1994 May 1;200(2):504–512. doi: 10.1006/viro.1994.1213. [DOI] [PubMed] [Google Scholar]
  22. Zhou J., Stenzel D. J., Sun X. Y., Frazer I. H. Synthesis and assembly of infectious bovine papillomavirus particles in vitro. J Gen Virol. 1993 Apr;74(Pt 4):763–768. doi: 10.1099/0022-1317-74-4-763. [DOI] [PubMed] [Google Scholar]
  23. Zhou J., Sun X. Y., Stenzel D. J., Frazer I. H. Expression of vaccinia recombinant HPV 16 L1 and L2 ORF proteins in epithelial cells is sufficient for assembly of HPV virion-like particles. Virology. 1991 Nov;185(1):251–257. doi: 10.1016/0042-6822(91)90772-4. [DOI] [PubMed] [Google Scholar]

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