An Alternative Platform for Rapid Production of Effective Subunit Vaccines - Tetrahymena thermophila offers numerous advantages as an expression system, including rapid cell growth and high cell densi

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An Alternative Platform for Rapid Production of Effective Subunit Vaccines
Tetrahymena thermophila offers numerous advantages as an expression system, including rapid cell growth and high cell densities, eukaryotic protein folding, and active synthesis of membrane and secreted proteins.


BioPharm International Supplements


Summary

With its distinct biological features, Tetrahymena thermophila has served as an important model for cellular biology and genetics for more than 50 years. At the same time, Tetrahymena has numerous advantages as an expression system for subunit vaccines. These include rapid cell growth to high cell densities, eukaryotic protein folding and PTM machinery, the absence of endogenous pyrogens, and active synthesis of membrane and secreted proteins. However, among currently available platforms, Tetrahymena is unique in its ability to secrete proteins in a tightly controlled fashion. As shown here, candidate vaccine antigens can be directed to a compartment for regulated secretion that allows rapid purification of recombinant protein in association with a crystalline matrix termed PRISM. The matrix itself appears to have immunostimulatory properties analogous to those of VLPs and can be produced in large quantities and at a very low cost.

Acknowledgements

We thank Daniel Kolbin and Lynn Almli for their excellent technical assistance. We also thank Ruben O. Donis, Molecular Virology and Vaccines Branch, Centers for Disease Control and Prevention, for his generous assistance with viral neutralization assays. This work was supported by grants from the National Institutes of Health (1 R41 GMO73352-01A1) and the US Army ARO (W911NF-07-0107) to Tetragenetics Inc.

JYOTHI JAYARAM is a postdoctoral research fellow at the department of Nephrology, School of Medicine, Stanford University, Stanford, CA, ASHOT PAPOYAN is research scientist II, XUJIE ZHANG is a postdoctoral scientist, and PAUL COLUSSI is the head of protein expression, all at Tetragenetics Inc, Ithaca, NY, YELENA BISHARYAN is research scientist I, DONNA CASSIDY-HANLEY is senior research associate, and Judith A. Appleton is a professor, all at the department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, LUCILLE GAGLIARDO is a technician IV, James A. Baker Institute for Animal Health, Cornell University, Ithaca, NY and THEODORE G. CLARK Theodore G. Clark is the director of Grad Studies in the Field of Immunology Department of Microbiology and Immunology, Cornell University, Ithaca, NY, 607.253.4042,

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