The use of adeno-associated vírus-based gene therapy to achieve long-term expression of recombinant neutralizing antibody against ricin

Abstract

Ricin is a highly toxic plant protein for which there are no specific antidotes. Current prophylactic and emergency treatments for ricin intoxication are limited by the need for prior vaccination and the short half-life of antibody drugs in the circulation. To address these limitations, we developed a novel immunotherapeutic strategy using adeno-associated virus (AAV) gene transfer to achieve prolonged systemic serum levels of immunoglobulins to ricin. In this study, a single administration of rAAV was used to deliver protein immunotherapeutics, and its efficacy in protecting mice against lethal doses of ricin was investigated. The results revealed that the single administration of rAAV three days prior to ricin exposure effectively protected mice from lethal doses of ricin. Remarkably, this protection was sustained for up to 90 days after AAV injection, demonstrating long-term efficacy. Overall, our findings suggest that the rAAV-mediated approach holds promise for both early and long-term prevention of ricin intoxication. The favorable safety profile of this system and its potential for the development of novel ricin antibody therapeutics make it a noteworthy candidate for further exploration and development in the field.