The role of pH fronts in vaccination protocols based on electroporation

MARSHALL GUILLERMO; OLAIZ NAHUEL; SIGNORI EMANUELLA; MAGLIETTI FELIPE; SOBA ALEJANDRO; SUÁREZ CECILIA; TURJANSKI PABLO; MICHINSKI SEBASTIÁN

Roma

Conferencia; 14th International Conference on Progess in Vaccination against Cancer (PIVAC-14); 2014

European Association for Cancer Research

Electroporation (EP) procedures have lately emerged as a major tool in medicine and biotechnology. In particular, EP protocols used in DNA intra-dermal/intra-muscular vaccinations (GET) constitute a safe and powerful way for introducing foreign antigens into the host for inducing an immune response. Efficient GET vaccination protocols require the application of a combination of a short high voltage (HV) pulse followed by a number of long low voltage (LV) pulses. This combination is also associated with some tissue damage that must be minimized. So, optimal GET vaccination requires a compromise between maximum transgene expression and minimal tissue damage. Although hyaluronidase pretreatment followed by GET significantly contributes to these requirements, damage continues to be severe near the electrodes, with a concomitant loss of efficiency. Here we demonstrate through experiments and theory the existence of pH fronts emerging from the electrodes during the application of GET vaccination protocols and that these fronts are the principal cause of tissue damage. Ways to optimize GET vaccination protocols, that is, to maximize expression and minimize tissue damage are suggested.