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Polymeric Nanoparticles as a Self-Adjuvanting Peptide Vaccine Delivery System: The Role of Shape
Authors:Prashamsa Koirala  Sung-Po R. Chen  Jennifer C. Boer  Zeinab G. Khalil  Cyril Deceneux  Georgia Goodchild  Lantian Lu  Mohammad Omer Faruck  Ahmed O. Shalash  Sahra Bashiri  Robert J. Capon  Waleed M. Hussein  Michael J. Monteiro  Magdalena Plebanski  Istvan Toth  Mariusz Skwarczynski
Affiliation:1. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072 Australia;2. Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, 4072 Australia;3. School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, 3083 Australia;4. Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072 Australia
Abstract:Antigens incorporated in subunit vaccines are typically poorly immunogenic, so a strong immunostimulant (adjuvant) and/or delivery system is required to boost immunogenicity. In this work, the various functional polymer nanostructures, that is, rods, worms, spheres, and tadpoles are used to develop potent peptide antigen delivery systems. The antigen PADRE-J8 (PJ8), derived from Group A Streptococcus (GAS) M-protein, is either physically mixed or chemically conjugated to polymeric nanoparticles of different shapes. The physical mixture of polymeric nanoparticles and antigen is more effective in inducing antibody production than their chemical conjugates. Moreover, rod-shaped polymeric nanoparticles in physical mixture with PJ8 elicited higher and more opsonic antibody titers than powerful complete Freund's adjuvant (CFA)-adjuvanted antigen. Herein, for the first time it is demonstrated that a) the block copolymer, in nanoparticle form, can act as an immune adjuvant, b) nanoparticle shape plays a crucial role in their immunogenicity, and c) antigen conjugation is not required, nor is antigen encapsulation or absorption.
Keywords:adjuvant  conjugation  immunization  physical mixtures  polymeric nanoparticles  subunit vaccines
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