3 years ago

Expression optimization of a cell membrane-penetrating human papillomavirus type 16 therapeutic vaccine candidate in <i>Nicotiana benthamiana</i>

Renate Lamprecht, Romana J. R. Yanez, Brandon Weber, Isis Torrens, Inga I. Hitzeroth, Edward P. Rybicki, Milaid Granadillo

by Romana J. R. Yanez, Renate Lamprecht, Milaid Granadillo, Brandon Weber, Isis Torrens, Edward P. Rybicki, Inga I. Hitzeroth

High-risk human papillomaviruses (hr-HPVs) cause cervical cancer, the fourth most common cancer in women worldwide. A HPV-16 candidate therapeutic vaccine, LALF32-51-E7, was developed by fusing a modified E7 protein to a bacterial cell-penetrating peptide (LALF): this elicited both tumour protection and regression in pre-clinical immunization studies. In the current study, we investigated the potential for producing LALF32-51-E7 in a plant expression system by evaluating the effect of subcellular localization and usage of different expression vectors and gene silencing suppressors. The highest expression levels of LALF32-51-E7 were obtained by using a self-replicating plant expression vector and chloroplast targeting, which increased its accumulation by 27-fold compared to cytoplasmic localization. The production and extraction of LALF32-51-E7 was scaled-up and purification optimized by affinity chromatography. If further developed, this platform could potentially allow for the production of a more affordable therapeutic vaccine for HPV-16. This would be extremely relevant in the context of developing countries, where cervical cancer and other HPV-related malignancies are most prevalent, and where the population have limited or no access to preventative vaccines due to their typical high costs.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.pone.0183177

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