Plant-produced cottontail rabbit papillomavirus L1 protein protects against tumor challenge: A proof-of-concept study

T. Kohl, I. I. Hitzeroth, D. Stewart, A. Varsani, V. A. Govan, N. D. Christensen, A. L. Williamson, E. P. Rybicki

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The native cottontail rabbit papillomavirus (CRPV) L1 capsid protein gene was expressed transgenically via Agrobacterium tumefaciens transformation and transiently via a tobacco mosaic virus (TMV) vector in Nicotiana spp. L1 protein was detected in concentrated plant extracts at concentrations up to 1.0 mg/kg in transgenic plants and up to 0.4 mg/kg in TMV-infected plants. The protein did not detectably assemble into viruslike particles; however, immunoelectron microscopy showed presumptive pentamer aggregates, and extracted protein reacted with conformation-specific and neutralizing monoclonal antibodies. Rabbits were injected with concentrated protein extract with Freund's incomplete adjuvant. All sera reacted with baculovirus-produced CRPV L1; however, they did not detectably neutralize infectivity in an in vitro assay. Vaccinated rabbits were, however, protected against wart development on subsequent challenge with live virus. This is the first evidence that a plant-derived papillomavirus vaccine is protective in an animal model and is a proof of concept for human papillomavirus vaccines produced in plants.

Original languageEnglish (US)
Pages (from-to)845-853
Number of pages9
JournalClinical and Vaccine Immunology
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2006

Fingerprint

Tobacco Mosaic Virus
Papillomavirus Vaccines
Tumors
Viruses
Tobacco
Cottontail rabbit papillomavirus
Rabbits
Neoplasms
Agrobacterium tumefaciens
Proteins
Warts
Immunoelectron Microscopy
Baculoviridae
Genetically Modified Plants
Plant Extracts
Capsid Proteins
Neutralizing Antibodies
Animal Models
Monoclonal Antibodies
Conformations

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Kohl, T. ; Hitzeroth, I. I. ; Stewart, D. ; Varsani, A. ; Govan, V. A. ; Christensen, N. D. ; Williamson, A. L. ; Rybicki, E. P. / Plant-produced cottontail rabbit papillomavirus L1 protein protects against tumor challenge : A proof-of-concept study. In: Clinical and Vaccine Immunology. 2006 ; Vol. 13, No. 8. pp. 845-853.
@article{adb0239b88194718b7c8cd4139db0912,
title = "Plant-produced cottontail rabbit papillomavirus L1 protein protects against tumor challenge: A proof-of-concept study",
abstract = "The native cottontail rabbit papillomavirus (CRPV) L1 capsid protein gene was expressed transgenically via Agrobacterium tumefaciens transformation and transiently via a tobacco mosaic virus (TMV) vector in Nicotiana spp. L1 protein was detected in concentrated plant extracts at concentrations up to 1.0 mg/kg in transgenic plants and up to 0.4 mg/kg in TMV-infected plants. The protein did not detectably assemble into viruslike particles; however, immunoelectron microscopy showed presumptive pentamer aggregates, and extracted protein reacted with conformation-specific and neutralizing monoclonal antibodies. Rabbits were injected with concentrated protein extract with Freund's incomplete adjuvant. All sera reacted with baculovirus-produced CRPV L1; however, they did not detectably neutralize infectivity in an in vitro assay. Vaccinated rabbits were, however, protected against wart development on subsequent challenge with live virus. This is the first evidence that a plant-derived papillomavirus vaccine is protective in an animal model and is a proof of concept for human papillomavirus vaccines produced in plants.",
author = "T. Kohl and Hitzeroth, {I. I.} and D. Stewart and A. Varsani and Govan, {V. A.} and Christensen, {N. D.} and Williamson, {A. L.} and Rybicki, {E. P.}",
year = "2006",
month = "8",
day = "1",
doi = "10.1128/CVI.00072-06",
language = "English (US)",
volume = "13",
pages = "845--853",
journal = "Clinical and Vaccine Immunology",
issn = "1556-6811",
publisher = "American Society for Microbiology",
number = "8",

}

Plant-produced cottontail rabbit papillomavirus L1 protein protects against tumor challenge : A proof-of-concept study. / Kohl, T.; Hitzeroth, I. I.; Stewart, D.; Varsani, A.; Govan, V. A.; Christensen, N. D.; Williamson, A. L.; Rybicki, E. P.

In: Clinical and Vaccine Immunology, Vol. 13, No. 8, 01.08.2006, p. 845-853.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Plant-produced cottontail rabbit papillomavirus L1 protein protects against tumor challenge

T2 - A proof-of-concept study

AU - Kohl, T.

AU - Hitzeroth, I. I.

AU - Stewart, D.

AU - Varsani, A.

AU - Govan, V. A.

AU - Christensen, N. D.

AU - Williamson, A. L.

AU - Rybicki, E. P.

PY - 2006/8/1

Y1 - 2006/8/1

N2 - The native cottontail rabbit papillomavirus (CRPV) L1 capsid protein gene was expressed transgenically via Agrobacterium tumefaciens transformation and transiently via a tobacco mosaic virus (TMV) vector in Nicotiana spp. L1 protein was detected in concentrated plant extracts at concentrations up to 1.0 mg/kg in transgenic plants and up to 0.4 mg/kg in TMV-infected plants. The protein did not detectably assemble into viruslike particles; however, immunoelectron microscopy showed presumptive pentamer aggregates, and extracted protein reacted with conformation-specific and neutralizing monoclonal antibodies. Rabbits were injected with concentrated protein extract with Freund's incomplete adjuvant. All sera reacted with baculovirus-produced CRPV L1; however, they did not detectably neutralize infectivity in an in vitro assay. Vaccinated rabbits were, however, protected against wart development on subsequent challenge with live virus. This is the first evidence that a plant-derived papillomavirus vaccine is protective in an animal model and is a proof of concept for human papillomavirus vaccines produced in plants.

AB - The native cottontail rabbit papillomavirus (CRPV) L1 capsid protein gene was expressed transgenically via Agrobacterium tumefaciens transformation and transiently via a tobacco mosaic virus (TMV) vector in Nicotiana spp. L1 protein was detected in concentrated plant extracts at concentrations up to 1.0 mg/kg in transgenic plants and up to 0.4 mg/kg in TMV-infected plants. The protein did not detectably assemble into viruslike particles; however, immunoelectron microscopy showed presumptive pentamer aggregates, and extracted protein reacted with conformation-specific and neutralizing monoclonal antibodies. Rabbits were injected with concentrated protein extract with Freund's incomplete adjuvant. All sera reacted with baculovirus-produced CRPV L1; however, they did not detectably neutralize infectivity in an in vitro assay. Vaccinated rabbits were, however, protected against wart development on subsequent challenge with live virus. This is the first evidence that a plant-derived papillomavirus vaccine is protective in an animal model and is a proof of concept for human papillomavirus vaccines produced in plants.

UR - http://www.scopus.com/inward/record.url?scp=33748788855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748788855&partnerID=8YFLogxK

U2 - 10.1128/CVI.00072-06

DO - 10.1128/CVI.00072-06

M3 - Article

C2 - 16893983

AN - SCOPUS:33748788855

VL - 13

SP - 845

EP - 853

JO - Clinical and Vaccine Immunology

JF - Clinical and Vaccine Immunology

SN - 1556-6811

IS - 8

ER -