Tissue damage in vaccination protocols based on electroporation: pH fronts and tissue natural buffering

M MARINO ; N OLAIZ; E. SIGNORI ; F MAGLIETTI; C SUAREZ ; L COLOMBO; P TURJANSKI; S MICHINSKI; G MARSHALL

Roma

Conferencia; PIVAC-14; 2014

Gene electrotransfer vaccination protocols (GET) constitute a safe and powerful way for introducing foreign antigens into the host for inducing an immune response. Optimal GET requires a compromise between maximum transgene expression and minimal tissue damage. Though GET in skeletal muscle can be improved by pretreatment with hyaluronidase, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efficiency [1]. In previous works [2, 3] it was shown that pH fronts generated by GET protocols produced non negligible pH changes and that these changes were the principal cause of tissue damage. Here we analyze the role of pH in the presence of tissue bicarbonate buffering system in tissue damage in GET protocols through in silico modeling using the Poisson-Nernst-Planck equations for ion transport. The model is contrasted with experimental measurements using intravital microscopy in a dorsal skinfold chamber (DSC). Theoretical modeling confirms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, regardless of the presence of tissue natural buffer attenuation, pH fronts are the principal cause of muscle damage near the electrodes.