Abstract
Recombinant proteins are increasingly being used as a novel approach for antigens in vaccines. These genetically engineered antigens are poorly immunogenic and require a delivery system and adjuvant to elicit their effect at targeted site of action. A delivery system transports the antigen to site of action and an adjuvant activates the cells via interaction with cell receptors and enhances the potency of the antigen. Micro/nanoparticles made from biodegradable and biocompatible polyesters, polylactide-co-glycolides (PLG), have been extensively used as an adjuvant and delivery system. This chapter discusses the applications of PLG micro/nanoparticles as delivery systems and adjuvant for antigens. PLG microparticles are prepared by a solvent evaporation method while nanoparticles are prepared by solvent displacement method. Synthesis of PLG nanoparticles is simpler in comparison to microparticles and unlike microparticles, it also enables particles to be sterile filtered. In a direct comparison using mouse animal model, our group found that microparticles and nanoparticles exhibited similar immunogenic responses. Materials and methods for synthesis and characterization of micro/nanoparticles with adsorbed antigens are discussed in detail.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
O’Hagan, D. T., Singh, M., Ulmer, J. B. (2006) Microparticle-based technologies for vaccines. Methods 40, 10–19.
Malyala, P., Singh, M. (2008) Formulations and delivery systems for mucosal vaccines, in (Vajdy, M. ed.) Immunity Against Mucosal Pathogens. Springer Publications, Netherland, pp 499–512.
Maloy, K. J., Donachie, A. M., O’Hagan, D. T., Mowat, A. M. (1994) Induction of mucosal and systemic immune responses by immunization with ovalbumin entrapped in poly(lactide-co-glycolide) microparticles. Immunology 81, 661–667.
O’Hagan, S., Ulmer, J. (2004) Microparticles for the delivery of DNA vaccines. Immunol Rev 199, 191–200.
Singh, M., Fang, J. H., Kazzaz, J., et al. (2006) A modified process for preparing cationic polylactide-co-glycolide microparticles with adsorbed DNA. Int J Pharm 327, 1–5.
Tabata, Y., Ikada, Y. (1988) Macrophage phagocytosis of biodegradable microspheres composed of L-lactic acid/glycolic acid homo- and copolymers. J Biomed Mater Res 22, 837–858.
Wendorf, J., Chesko, J., Kazzaz, J., Vajdy, M., O’Hagan, D. T., Singh, M. (2008) A comparison of anionic nanoparticles and microparticles as vaccine delivery systems. Hum Vaccin 1, 43–48.
Diwan, M., Elamanchili, P., Cao, M., Samuel, J. (2004) Dose sparing of CpG oligodeoxynucleotide vaccine adjuvants by nanoparticle delivery. Curr Drug Deliv 1, 405–412.
Xie, H., Gursel, I., Ivins, B. E., et al. (2005) CpG oligodeoxynucleotides adsorbed onto polylactide-co-glycolide microparticles improve the immunogenicity and protective activity of the licensed anthrax vaccine. Infect Immun 73, 828–833.
Hunter, S. K., Andracki, M. E., Krieg, A. M. (2001) Biodegradable microspheres containing group B Streptococcus vaccine: immune response in mice. Am J Obstet Gynecol 185, 1174–1179.
Kazzaz, J., Singh, M., Ugozzoli, M., Chesko, J., Soenawan, E., O’Hagan, D. T. (2005) Encapsulation of the adjuvants MPL and RC529 in PLG microparticles enhance their potency. J Control Release 110, 566–573.
Singh, M., Chesko, J., Kazzaz, J., Ugozzoli, M., Malyala, P., O‘Hagan, D. T. (2007) Surface-charged poly(lactide-co-glycolide) microparticles as novel antigen delivery systems, in (Singh M., ed.) Vaccine Adjuvants and Delivery Systems. John Wiley & Sons Inc., New York, pp 223–247.
Singh, M., Kazzaz, J., Ugozzoli, M., Malyala, P., Chesko, J., O’Hagan, D. T. (2006) Polylactide-co-glycolide microparticles with surface adsorbed antigens as vaccine delivery systems. Curr Drug Deliv 3, 115–120.
Chesko, J., Kazzaz, J., Ugozzoli, M., O’Hagan, D. T., Singh, M. (2005) An investigation of the factors controlling the adsorption of protein antigens to anionic PLG microparticles. J Pharm Sci 94, 2510–2519.
Chesko, J., Kazzaz, J., Ugozzoli, M., et al. (2004) Adsorption of a novel recombinant glycoprotein from HIV (env gp120dv2) to anionic PLG microparticles retains structural integrity, while encapsulation in PLG microparticles does not. Pharm Res 21, 2148–2152.
Singh, M., Kazzaz, J., Ugozzoli, M., Chesko, J., O’Hagan, D. T. (2004) Charged polylactide co-glycolide microparticles as antigen delivery systems. Expert Opin Biol Ther 4, 483–491.
Malyala, P., Chesko, J., Ugozzoli, M., et al. (2008) The potency of the adjuvant, CpG oligos, is enhanced by encapsulation in PLG microparticles. J Pharm Sci 97, 1155–1164.
Acknowledgments
The authors deeply acknowledge the contributions of Janet Wendorf and Aravind Chakrapani who worked extensively on formulation and characterization of PLG nanoparticles in their post doctoral tenure with us. Thanks are also due to the Vaccine Formulation and Delivery group in Novartis Corporation.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Malyala, P., Singh, M. (2010). Micro/Nanoparticle Adjuvants: Preparation and Formulation with Antigens. In: Davies, G. (eds) Vaccine Adjuvants. Methods in Molecular Biology, vol 626. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-585-9_7
Download citation
DOI: https://doi.org/10.1007/978-1-60761-585-9_7
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-584-2
Online ISBN: 978-1-60761-585-9
eBook Packages: Springer Protocols