Oral immunogenicity of human papillomavirus-like particles expressed in potato

Heribert Warzecha, Hugh Mason, Christopher Lane, Anders Tryggvesson, Edward Rybicki, Anna Lise Williamson, John D. Clements, Robert C. Rose

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8702-8711
Number of pages10
JournalJournal of virology
Volume77
Issue number16
DOIs
StatePublished - Aug 1 2003

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Warzecha, H., Mason, H., Lane, C., Tryggvesson, A., Rybicki, E., Williamson, A. L., Clements, J. D., & Rose, R. C. (2003). Oral immunogenicity of human papillomavirus-like particles expressed in potato. Journal of virology, 77(16), 8702-8711. https://doi.org/10.1128/JVI.77.16.8702-8711.2003