Programming the composition of polymer blend particles for controlled immunity towards individual protein antigens. Issue 23 (28th May 2015)

• Record Type: Journal Article
• Authors: Zhan, Xi; Shen, Hong
• Is Part Of: Vaccine. Volume 33:Issue 23(2015)
• Page Start: 2719
• Page End: 2726
• Publication Date: 2015-05-28
• Subjects: Controlled release -- pH-sensitive particles -- Viral infections -- Subunit vaccines -- Herpes simplex viruses; PLGA poly(lactic-co-glycolic acid) -- PAA 2-propylacrylic acid -- BMA butyl methacrylate -- DMAEMA 2-(dimethylamino)ethyl methacrylate -- AIBN 2, 2′-azobis(2-methylpropionitrile) -- DCM dichloromethane -- PVA polyvinyl alcohol -- DOX doxorubicin -- LSZ lysozyme -- MGB myoglobin -- α-LA α-lactalbumin -- OVA ovalbumin -- HSV-2 gD type 2 Herpes Simplex glycoprotein D -- IEP isoelectric points -- BCA bicinchoninic acid -- ELISA enzyme-linked immunosorbent assay -- TMB tetramethylbenzidine -- TLR Toll-like receptor -- MPL monosphosphoryl lipid A -- IFNγ interferon gamma cytokine -- NMR nuclear magnetic resonance spectroscopy -- GPC gel permeation chromatography -- DLS dynamic light scattering -- SEM scanning electron microscope -- Mw molecular weight -- PDI polydispersity index -- DPBS Dulbecco's phosphate buffered saline; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.03.018
• Languages: English
• ISSNs: 0264-410X

Abstract

Graphical abstract: Abstract: In order for a more precise control over the quality and quantity of immune responses stimulated by synthetic particle-based vaccines, it is critical to control the colloidal stability of particles and the release of protein antigens in both extracellular space and intracellular compartments. Different proteins exhibit different sizes, charges and solubilities. This study focused on modulating the release and colloidal stability of proteins with varied isoelectric points. A polymer particle delivery platform made from the blend of three polymers, poly(lactic- co -glycolic acid) (PLGA) and two random pH-sensitive copolymers, were developed. Our study demonstrated its programmability with respective to individual proteins. We showed the colloidal stability of particles at neutral environment and the release of each individual protein at different pH environments were dependent on the ratio of two charge polymers. Subsequently, two antigenic proteins, ovalbumin (OVA) and Type 2 Herpes Simplex Virus (HSV-2) glycoprotein D (gD) protein, were incorporated into particles with systematically varied compositions. We demonstrated that the level of in vitro CD8 + T cell and in vivo immune responses were dependent on the ratio of two charged polymers, which correlated well with the release of proteins. This study provided a promising design framework of pH-responsive synthetic vaccines for protein antigens of interest.