Electrolysis products, reactive oxygen species and ATP loss contribute to cell death following irreversible electroporation with microsecond-long pulsed electric fields.

Membrane permeabilization and thermal injury are the major cause of cell death during irreversible electroporation (IRE) performed using high electric field strength (EFS) and small number of pulses. In this study, we explored cell death under conditions of reduced EFS and prolonged pulse application, identifying the contributions of electrolysis, reactive oxygen species (ROS) and ATP loss. We performed ablations with conventional high-voltage low pulse (HV-LP) and low-voltage high pulse (LV-HP) conditions in a 3D tumor mimic, finding equivalent ablation volumes when using 2000 V/cm 90 pulses or 1000 V/cm 900 pulses respectively. These results were confirmed by performing ablations in swine liver. In LV-HP treatment, ablation volume was found to increase proportionally with pulse numbers, without the substantial temperature increase seen with HV-LP parameters. Peri-electrode pH changes, ATP loss and ROS production were seen in both conditions, but LV-HP treatments were more sensitive to blocking of these forms of cell injury. Increases in current drawn during HV-LP was not observed during LV-HP condition where the total ablation volume correlated to the charge delivered into the tissue which was greater than HV-LP treatment. LV-HP treatment provides a new paradigm in using pulsed electric fields for tissue ablation with clinically relevant volumes.

Antibody Responses to SARS-CoV-2 mRNA Vaccines Are Detectable in Saliva.

The approved Pfizer and Moderna mRNA vaccines are well known to induce serum antibody responses to the SARS-CoV-2 Spike (S)-protein. However, their abilities to elicit mucosal immune responses have not been reported. Saliva antibodies represent mucosal responses that may be relevant to how mRNA vaccines prevent oral and nasal SARS-CoV-2 transmission. Here, we describe the outcome of a cross-sectional study on a healthcare worker cohort (WELCOME-NYPH), in which we assessed whether IgM, IgG, and IgA antibodies to the S-protein and its receptor-binding domain (RBD) were present in serum and saliva samples. Anti-S-protein IgG was detected in 14/31 and 66/66 of saliva samples from uninfected participants after vaccine doses-1 and -2, respectively. IgA antibodies to the S-protein were present in 40/66 saliva samples after dose 2. Anti-S-protein IgG was present in every serum sample from recipients of 2 vaccine doses. Vaccine-induced antibodies against the RBD were also frequently present in saliva and sera. These findings may help our understanding of whether and how vaccines may impede SARS-CoV-2 transmission, including to oral cavity target cells.