Broad‐Spectrum Antiviral Prophylaxis: Inhibition of Viral Infection by Polymer Grafting with Methoxypoly(Ethylene Glycol)

Immunocamouflage of latex surfaces by grafted methoxypoly(ethylene glycol) (mPEG): Proteomic analysis of plasma protein adsorption

“…Previous studies have shown that hydrophilic surfaces have decreased total protein adsorption and are also more biocompatible [12]. Thus, mPEG grafting generates a steric barrier while simultaneously biophysically camouflaging surface charge thus reducing immune recognition of implantable biomaterials, allogeneic red blood cells [5,[13][14][15][16][17][18], lymphocytes [3,4,[19][20][21] and viruses ( Figure 6BD) [22]. As shown in this study, consequent to PEGylation, latex particles demonstrated significant inhibition of protein adsorption in a polymer doseand length-dependent manner, as measured quantitatively with colorimetric protein assay and flow cytometry ( Figure 2A and B) and qualitatively by SDS-PAGE, fluorescent microscopy and iTRAQ-MS analysis (Figures 3-5).…”

Use of Flow Cytometry in the In Vitro and In Vivo Analysis of Tolerance/Anergy Induction by Immunocamouflage

“…[Bradley et al, 2002, Bradley & Scott, 2004, Chen & Scott, 2001, Chen & Scott, 2003, Le & Scott, 2010, McCoy & Scott, 2005, Murad et al, 1999b, Rossi et al, 2010a, Rossi et al, 2010b, Scott et al, 1997, Sutton & Scott, 2010 The immunocamouflage of cells and tissues is created by the covalent grafting of safe, non-toxic and low-immunogenic biocompatible polymers such as methoxypoly(ethylene glycol, PEGylation) and hyperbranched polyglycerols (HPG) to the surface of cells. The efficacy of immunocamouflage is dependent upon both the density and depth (i.e., thickness) of the polymer layer.…”

“…[Rossi et al, 2010a, Rossi et al, 2010b www.intechopen.com Previous studies in our laboratory on red blood cells, lymphocytes, pancreatic islets and viral models have demonstrated that the immunocamouflage of tissues is effective, reproducible and does not impair tissue function. [Bradley et al, 2002, Bradley & Scott, 2004, Chen & Scott, 2001, Chen & Scott, 2003, Le & Scott, 2010, McCoy & Scott, 2005, Murad et al, 1999b, Rossi et al, 2010a, Rossi et al, 2010b, Scott et al, 1997, Sutton & Scott, 2010 For example, the PEGylated red blood cell function (i.e., O 2 delivery and cellular deformability) were unaffected by the grafted polymer and exhibited normal in vivo circulation and lifespan (~50 day) in a murine transfusion model even after repeated transfusions (Figure 3). With relevance to tissue transplantation, our studies have demonstrated that transfusion of immunocamouflaged allogeneic murine splenocytes prevents allorecognition by either the donor cells (e.g., Transfusion-Associated Graft vs.…”

Polymer-Mediated Broad Spectrum Antiviral Prophylaxis: Utility in High Risk Environments

“…Moreover, the global camouflage of the cell surface effectively masks both known and unknown viral receptors resulting in a nonspecific, non-immunological, broad-spectrum antiviral effect. [McCoy & Scott, 2005, Sutton & Scott, 2010 The biophysical basis of this antiviral effect is schematically shown in Figures 3-4. The PEG layer obscures the inherent electrical charge associated with surface proteins since the charged molecules become buried beneath the viscous, hydrated, neutral PEG layer.…”

“…However, the safe, low cost, low technology, and non-toxic bioengineering of the terminally differentiated nasal pharyngeal epithelial host cells may provide a radically new antiviral prophylactic approach that gives rise to a transient, broad-spectrum, prophylaxis against virally transmitted respiratory infections (Figure 1). [ McCoy & Scott, 2005, Sutton & Scott, 2010 This polymer-based technology is derivative of the polymer-based "immunocamouflage" technology of blood cells being actively developed within the Canadian Blood Services to reduce the risk of transfusion reactions and alloimmunization to donor red blood cells. [Scott et al, 1997, Scott & Murad, 1998, Murad et al, 1999a, Murad et al, 1999b, Bradley et al, 2001, Bradley et al, 2002, Bradley & Scott, 2007, Rossi et al, 2010b As schematically shown in Figure 1, the non-toxic bioengineering of the nasal cavity attenuates or prevents viral respiratory infections at the primary site of infection -the nasopharyngeal cell surface of the upper respiratory tract.…”