ena-STUDY-UNIVERSITY OF BERNE-10-02-2021-13:19:39:434-722
Creation of a novel triple deletion Listeria monocytogenes-based vaccine vector to treat tumors and infectious diseases
Listeria monocytogenes (LM) has been proposed as vaccine vector in various cancers and infectious diseases since LM induces a strong immune response against tumor antigens (TAAs). We aim at developing a safe LM-based vaccine vector platform for the delivery of tumor-associated antigens (TAAs) and infectious diseases antigens. Therefore, we engineered a tiple attenuated mutant (Lm3Dx) of the wild-type LM strain JF5203 (CC 1, phylogenetic lineage I). We proved the in vitro safety of our vaccine and capacity to selectively infect antigen presenting cells (APCs). After introducing the desired Neospora caninum (Nc) antigen in Lm3Dx, we showed its capacity to secret the Nc protein upon cellular infection. We pursued in a in vivo mice model. BALB/C mice vaccinated with the Lm3Dx-Nc strain showed no signs of side effects and only shed bacteria sporadically at extremely low levels (<100 CFU/g feces). Additionally, no bacteria were isolated of the tissue of the vaccinated mice after euthanasia 2 weeks after dose injection. Upon vaccination with our LM-based NC vaccine, mice either developed a strong cellular Th1-biased immune or a humoral response depending on dose of vaccine dosage administered. Additionally, we proved that our vaccine strain does not interfere with dam's pregnancy.
Listeria monocytogenes (LM) has been proposed as vaccine vector in various cancers and infectious diseases since LM induces a strong immune response against tumor antigens (TAAs). We aim at developing a safe LM-based vaccine vector platform for the delivery of tumor-associated antigens (TAAs) and infectious diseases antigens. Therefore, we engineered a tiple attenuated mutant (Lm3Dx) of the wild-type LM strain JF5203 (CC 1, phylogenetic lineage I). We proved the in vitro safety of our vaccine and capacity to selectively infect antigen presenting cells (APCs). After introducing the desired Neospora caninum (Nc) antigen in Lm3Dx, we showed its capacity to secret the Nc protein upon cellular infection. We pursued in a in vivo mice model. BALB/C mice vaccinated with the Lm3Dx-Nc strain showed no signs of side effects and only shed bacteria sporadically at extremely low levels (<100 CFU/g feces). Additionally, no bacteria were isolated of the tissue of the vaccinated mice after euthanasia 2 weeks after dose injection. Upon vaccination with our LM-based NC vaccine, mice either developed a strong cellular Th1-biased immune or a humoral response depending on dose of vaccine dosage administered. Additionally, we proved that our vaccine strain does not interfere with dam's pregnancy.