Ubiquitin-fused and/or multiple early genes from cottontail rabbit papillomavirus as DNA vaccines

Sancy Leachman, Mark Shylankevich, Martin D. Slade, Dana Levine, Ranjini K. Sundaram, Wei Xiao, Marianne Bryan, Daniel Zelterman, Robert E. Tiegelaar, Janet L. Brandsma

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Human papillomavirus (HPV) vaccines have the potential to prevent cervical cancer by preventing HPV infection or treating premalignant disease. We previously showed that DNA vaccination with the cottontail rabbit papillomavirus (CRPV) E6 gene induced partial protection against CRPV challenge and that the vaccine's effects were greatly enhanced by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, two additional strategies for augmenting the clinical efficacy of CRPV E6 vaccination were evaluated. The first was to fuse a ubiquitin monomer to the CRPV E6 protein to enhance antigen processing and presentation through the major histocompatibility complex class I pathway. Rabbits vaccinated with the wild-type E6 gene plus GM-CSF or with the ubiquitin-fused E6 gene formed significantly fewer papillomas than the controls. The papillomas also required a longer time to appear and grew more slowly. Finally, a significant proportion of the papillomas subsequently regressed. The ubiquitin-fused E6 vaccine was significantly more effective than the wild-type E6 vaccine plus GM-CSF priming. The second strategy was to vaccinate with multiple CRPV early genes to increase the breadth of the CRPV-specific response. DNA vaccines encoding the wild-type CRPV E1-E2, E6, or E7 protein were tested alone and in all possible combinations. All vaccines and combinations suppressed papilloma formation, slowed papilloma growth, and stimulated subsequent papilloma regression. Finally, the two strategies were merged and a combination DNA vaccine containing ubiquitin-fused versions of the CRPV E1, E2, and E7 genes was tested. This last vaccine prevented papilloma formation at all challenge sites in all rabbits, demonstrating complete protection.

Original languageEnglish (US)
Pages (from-to)7616-7624
Number of pages9
JournalJournal of Virology
Volume76
Issue number15
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Cottontail rabbit papillomavirus
DNA Vaccines
Papilloma
recombinant vaccines
papilloma
ubiquitin
Ubiquitin
vaccines
granulocyte-macrophage colony-stimulating factor
Genes
Granulocyte-Macrophage Colony-Stimulating Factor
genes
Combined Vaccines
Papillomavirus Vaccines
Vaccines
Antigen Presentation
Papillomaviridae
Vaccination
Rabbits
rabbits

ASJC Scopus subject areas

  • Immunology

Cite this

Leachman, S., Shylankevich, M., Slade, M. D., Levine, D., Sundaram, R. K., Xiao, W., ... Brandsma, J. L. (2002). Ubiquitin-fused and/or multiple early genes from cottontail rabbit papillomavirus as DNA vaccines. Journal of Virology, 76(15), 7616-7624. https://doi.org/10.1128/JVI.76.15.7616-7624.2002

Ubiquitin-fused and/or multiple early genes from cottontail rabbit papillomavirus as DNA vaccines. / Leachman, Sancy; Shylankevich, Mark; Slade, Martin D.; Levine, Dana; Sundaram, Ranjini K.; Xiao, Wei; Bryan, Marianne; Zelterman, Daniel; Tiegelaar, Robert E.; Brandsma, Janet L.

In: Journal of Virology, Vol. 76, No. 15, 2002, p. 7616-7624.

Research output: Contribution to journalArticle

Leachman, S, Shylankevich, M, Slade, MD, Levine, D, Sundaram, RK, Xiao, W, Bryan, M, Zelterman, D, Tiegelaar, RE & Brandsma, JL 2002, 'Ubiquitin-fused and/or multiple early genes from cottontail rabbit papillomavirus as DNA vaccines', Journal of Virology, vol. 76, no. 15, pp. 7616-7624. https://doi.org/10.1128/JVI.76.15.7616-7624.2002
Leachman, Sancy ; Shylankevich, Mark ; Slade, Martin D. ; Levine, Dana ; Sundaram, Ranjini K. ; Xiao, Wei ; Bryan, Marianne ; Zelterman, Daniel ; Tiegelaar, Robert E. ; Brandsma, Janet L. / Ubiquitin-fused and/or multiple early genes from cottontail rabbit papillomavirus as DNA vaccines. In: Journal of Virology. 2002 ; Vol. 76, No. 15. pp. 7616-7624.
@article{c144e41120c843f9af1233a5165e3e0d,
title = "Ubiquitin-fused and/or multiple early genes from cottontail rabbit papillomavirus as DNA vaccines",
abstract = "Human papillomavirus (HPV) vaccines have the potential to prevent cervical cancer by preventing HPV infection or treating premalignant disease. We previously showed that DNA vaccination with the cottontail rabbit papillomavirus (CRPV) E6 gene induced partial protection against CRPV challenge and that the vaccine's effects were greatly enhanced by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, two additional strategies for augmenting the clinical efficacy of CRPV E6 vaccination were evaluated. The first was to fuse a ubiquitin monomer to the CRPV E6 protein to enhance antigen processing and presentation through the major histocompatibility complex class I pathway. Rabbits vaccinated with the wild-type E6 gene plus GM-CSF or with the ubiquitin-fused E6 gene formed significantly fewer papillomas than the controls. The papillomas also required a longer time to appear and grew more slowly. Finally, a significant proportion of the papillomas subsequently regressed. The ubiquitin-fused E6 vaccine was significantly more effective than the wild-type E6 vaccine plus GM-CSF priming. The second strategy was to vaccinate with multiple CRPV early genes to increase the breadth of the CRPV-specific response. DNA vaccines encoding the wild-type CRPV E1-E2, E6, or E7 protein were tested alone and in all possible combinations. All vaccines and combinations suppressed papilloma formation, slowed papilloma growth, and stimulated subsequent papilloma regression. Finally, the two strategies were merged and a combination DNA vaccine containing ubiquitin-fused versions of the CRPV E1, E2, and E7 genes was tested. This last vaccine prevented papilloma formation at all challenge sites in all rabbits, demonstrating complete protection.",
author = "Sancy Leachman and Mark Shylankevich and Slade, {Martin D.} and Dana Levine and Sundaram, {Ranjini K.} and Wei Xiao and Marianne Bryan and Daniel Zelterman and Tiegelaar, {Robert E.} and Brandsma, {Janet L.}",
year = "2002",
doi = "10.1128/JVI.76.15.7616-7624.2002",
language = "English (US)",
volume = "76",
pages = "7616--7624",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "15",

}

TY - JOUR

T1 - Ubiquitin-fused and/or multiple early genes from cottontail rabbit papillomavirus as DNA vaccines

AU - Leachman, Sancy

AU - Shylankevich, Mark

AU - Slade, Martin D.

AU - Levine, Dana

AU - Sundaram, Ranjini K.

AU - Xiao, Wei

AU - Bryan, Marianne

AU - Zelterman, Daniel

AU - Tiegelaar, Robert E.

AU - Brandsma, Janet L.

PY - 2002

Y1 - 2002

N2 - Human papillomavirus (HPV) vaccines have the potential to prevent cervical cancer by preventing HPV infection or treating premalignant disease. We previously showed that DNA vaccination with the cottontail rabbit papillomavirus (CRPV) E6 gene induced partial protection against CRPV challenge and that the vaccine's effects were greatly enhanced by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, two additional strategies for augmenting the clinical efficacy of CRPV E6 vaccination were evaluated. The first was to fuse a ubiquitin monomer to the CRPV E6 protein to enhance antigen processing and presentation through the major histocompatibility complex class I pathway. Rabbits vaccinated with the wild-type E6 gene plus GM-CSF or with the ubiquitin-fused E6 gene formed significantly fewer papillomas than the controls. The papillomas also required a longer time to appear and grew more slowly. Finally, a significant proportion of the papillomas subsequently regressed. The ubiquitin-fused E6 vaccine was significantly more effective than the wild-type E6 vaccine plus GM-CSF priming. The second strategy was to vaccinate with multiple CRPV early genes to increase the breadth of the CRPV-specific response. DNA vaccines encoding the wild-type CRPV E1-E2, E6, or E7 protein were tested alone and in all possible combinations. All vaccines and combinations suppressed papilloma formation, slowed papilloma growth, and stimulated subsequent papilloma regression. Finally, the two strategies were merged and a combination DNA vaccine containing ubiquitin-fused versions of the CRPV E1, E2, and E7 genes was tested. This last vaccine prevented papilloma formation at all challenge sites in all rabbits, demonstrating complete protection.

AB - Human papillomavirus (HPV) vaccines have the potential to prevent cervical cancer by preventing HPV infection or treating premalignant disease. We previously showed that DNA vaccination with the cottontail rabbit papillomavirus (CRPV) E6 gene induced partial protection against CRPV challenge and that the vaccine's effects were greatly enhanced by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, two additional strategies for augmenting the clinical efficacy of CRPV E6 vaccination were evaluated. The first was to fuse a ubiquitin monomer to the CRPV E6 protein to enhance antigen processing and presentation through the major histocompatibility complex class I pathway. Rabbits vaccinated with the wild-type E6 gene plus GM-CSF or with the ubiquitin-fused E6 gene formed significantly fewer papillomas than the controls. The papillomas also required a longer time to appear and grew more slowly. Finally, a significant proportion of the papillomas subsequently regressed. The ubiquitin-fused E6 vaccine was significantly more effective than the wild-type E6 vaccine plus GM-CSF priming. The second strategy was to vaccinate with multiple CRPV early genes to increase the breadth of the CRPV-specific response. DNA vaccines encoding the wild-type CRPV E1-E2, E6, or E7 protein were tested alone and in all possible combinations. All vaccines and combinations suppressed papilloma formation, slowed papilloma growth, and stimulated subsequent papilloma regression. Finally, the two strategies were merged and a combination DNA vaccine containing ubiquitin-fused versions of the CRPV E1, E2, and E7 genes was tested. This last vaccine prevented papilloma formation at all challenge sites in all rabbits, demonstrating complete protection.

UR - http://www.scopus.com/inward/record.url?scp=0036317963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036317963&partnerID=8YFLogxK

U2 - 10.1128/JVI.76.15.7616-7624.2002

DO - 10.1128/JVI.76.15.7616-7624.2002

M3 - Article

C2 - 12097575

AN - SCOPUS:0036317963

VL - 76

SP - 7616

EP - 7624

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 15

ER -