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

被引:45
作者
Kohl, T.
Hitzeroth, I. I.
Stewart, D.
Varsani, A.
Govan, V. A.
Christensen, N. D.
Williamson, A. -L.
Rybicki, E. P. [1 ]
机构
[1] Univ Cape Town, Dept Mol & Cell Biol, ZA-7701 Cape Town, South Africa
[2] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa
[3] Univ Cape Town, Electron Microscopy Unit, ZA-7701 Rondebosch, South Africa
[4] Penn State Univ, Coll Med, Dept Pathol, Jake Gittlen Canc Res Inst, Hershey, PA 17033 USA
[5] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA
[6] Groote Schuur Hosp, Natl Hlth Lab Serv, ZA-7925 Cape Town, South Africa
关键词
D O I
10.1128/CVI.00072-06
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:845 / 853
页数:9
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