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Journal of Virology, September 2003, p. 9211-9220, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9211-9220.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Production of Human Papillomavirus Type 16 Virus-Like Particles in Transgenic Plants

Sophia Biemelt,1 Uwe Sonnewald,1 Petra Galmbacher,2 Lothar Willmitzer,3 and Martin Müller2*

Institut für Pflanzengenetik und Kulturpflanzenforschung, 06466 Gatersleben,1 Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg,2 Max Planck Institut für Molekulare Pflanzenphysiologie, 14476 Golm, Germany3

Received 23 January 2003/ Accepted 19 May 2003

Cervical cancer is linked to infection with human papillomaviruses (HPV) and is the third most common cancer among women worldwide. There is a strong demand for the development of an HPV preventive vaccine. Transgenic plants expressing the HPV major capsid protein L1 could be a system to produce virus-like particles for prophylactic vaccination or could even be used as edible vaccines to induce an L1-specific prophylactic immune response. Here, we describe the generation of transgenic tobacco and potato plants carrying the HPV type 16 major structural gene L1 under the control of the cauliflower mosaic virus 35S promoter. All attempts to express either the original, unmodified L1 gene or an L1 gene with a codon usage optimized for expression in plants failed. Surprisingly, small amounts of the protein were detected using an L1 gene optimized for expression in human cells. However, Northern blot analysis revealed that most of the L1 transcripts were degraded. Introduction of the translational enhancer {Omega} derived from the tobacco mosaic virus strongly increased transcript stability and resulted in accumulation of L1 protein to approximately 0.5 to 0.2% of total soluble protein in transgenic tobacco and potato plants, respectively. The plant-derived L1 protein displayed conformation-specific epitopes and assembled into virus-like particles. Furthermore, we did not find any indications of protein modification of the L1 protein produced in plants. Plant-derived L1 was as immunogenic as L1 expressed in baculovirus-infected insect cells. Feeding of tubers from transgenic potatoes to mice induced an anti-L1 antibody response in 3 out of 24 mice, although this response was only transient in two of the mice. Our data, however, indicate that an anti-L1 response was primed in about half of the 24 animals.

* Corresponding author. Mailing address: DKFZ-ATV F035, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. Phone: 49 6221 424628. Fax: 49 6221 424932. E-mail: Martin.Mueller{at}dkfz.de.

Journal of Virology, September 2003, p. 9211-9220, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9211-9220.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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