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Journal of Virology, August 2003, p. 8702-8711, Vol. 77, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.16.8702-8711.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Oral Immunogenicity of Human Papillomavirus-Like Particles Expressed in Potato

Heribert Warzecha,1,{dagger} Hugh S. Mason,1,{ddagger} Christopher Lane,2 Anders Tryggvesson,1 Edward Rybicki,3 Anna-Lise Williamson,3 John D. Clements,4 and Robert C. Rose2*

Boyce Thompson Institute for Plant Research, Ithaca, New York 14850,1 Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642,2 Department of Medical Microbiology, University of Cape Town, Cape Town, South Africa,3 Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, Louisiana 701184

Received 10 January 2003/ Accepted 13 May 2003

Human papillomavirus-like particles (HPV VLPs) have shown considerable promise as a parenteral vaccine for the prevention of cervical cancer and its precursor lesions. Parenteral vaccines are expensive to produce and deliver, however, and therefore are not optimal for use in resource-poor settings, where most cervical HPV disease occurs. Transgenic plants expressing recombinant vaccine immunogens offer an attractive and potentially inexpensive alternative to vaccination by injection. For example, edible plants can be grown locally and can be distributed easily without special training or equipment. To assess the feasibility of an HPV VLP-based edible vaccine, in this study we synthesized a plant codon-optimized version of the HPV type 11 (HPV11) L1 major capsid protein coding sequence and introduced it into tobacco and potato. We show that full-length L1 protein is expressed and localized in plant cell nuclei and that expression of L1 in plants is enhanced by removal of the carboxy-terminal nuclear localization signal sequence. We also show that plant-expressed L1 self-assembles into VLPs with immunological properties comparable to those of native HPV virions. Importantly, ingestion of transgenic L1 potato was associated with activation of an anti-VLP immune response in mice that was qualitatively similar to that induced by VLP parenteral administration, and this response was enhanced significantly by subsequent oral boosting with purified insect cell-derived VLPs. Thus, papillomavirus L1 protein can be expressed in transgenic plants to form immunologically functional VLPs, and ingestion of such material can activate potentially protective humoral immune responses.

* Corresponding author. Mailing address: Department of Medicine, University of Rochester Medical Center, Box 689, 601 Elmwood Ave., Rochester, NY 14642. Phone: (585) 275-0263. Fax: (585) 442-9328. E-mail: Robert_Rose{at}urmc.rochester.edu.

{dagger} Present address: Lehrstuhl fuer Pharmazeutische Biologie, Wuerzburg, Germany.

{ddagger} Present address: Plant Biology Department, Arizona State University, Tempe, AZ 85287-1601.

Journal of Virology, August 2003, p. 8702-8711, Vol. 77, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.16.8702-8711.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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