Plant-produced cottontail rabbit papillomavirus L1 protein protects against tumor challenge: a proof-of-concept study.
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.
Kohl
T
T
Department of Molecular and Cell Biology, University of Cape Town, Rondebosch, Cape Town 7701, South Africa.
Hitzeroth
I I
II
Stewart
D
D
Varsani
A
A
Govan
V A
VA
Christensen
N D
ND
Williamson
A-L
AL
Rybicki
E P
EP
D016960:Agrobacterium tumefaciens / Q000235:genetics*; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D001483:Base Sequence; D003001:Cloning, Molecular; D018014:Gene Transfer Techniques; D007114:Immunization; D008969:Molecular Sequence Data; D030821:Plants, Genetically Modified; D012313:RNA / Q000096:biosynthesis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014026:Nicotiana / Q000235:genetics / Q000378:metabolism / Q000821:virology; D014027:Tobacco Mosaic Virus / Q000235:genetics; D014612:Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
D000956:Antigens, Viral; C073505:L1 protein, cottontail rabbit papillomavirus; D014612:Vaccines; D015678:Viral Structural Proteins; D012313:RNA