1. A Potent and Effective Suicidal Listeria Vaccine Platform
- Author
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Hanson, William G, Benanti, Erin L, Lemmens, Edward E, Liu, Weiqun, Skoble, Justin, Leong, Meredith L, Rae, Chris S, Fassò, Marcella, Brockstedt, Dirk G, Chen, Chen, Portnoy, Daniel A, Dubensky, Thomas W, and Lauer, Peter
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Biological Sciences ,Immunology ,Vaccine Related ,Biotechnology ,Biodefense ,Immunization ,Infectious Diseases ,Prevention ,Digestive Diseases ,Emerging Infectious Diseases ,Foodborne Illness ,3.4 Vaccines ,5.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Animals ,Bacterial Vaccines ,Female ,Immunotherapy ,Listeria monocytogenes ,Mice ,Mice ,Inbred BALB C ,Mice ,Inbred C57BL ,T-Lymphocytes ,Vaccines ,Attenuated ,Virulence ,biotechnology ,cell-mediated immunity ,immunotherapy ,vaccines ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Microbiology ,Medical microbiology - Abstract
Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. Lm-RIID grows normally in broth but commits suicide inside host cells by inducing Cre recombinase and deleting essential genes flanked by loxP sites, resulting in a self-limiting infection even in immunocompromised mice. Lm-RIID vaccination of mice induces potent CD8+ T cells and protects against virulent challenges, similar to live L. monocytogenes vaccines. When combined with α-PD-1, Lm-RIID is as effective as live-attenuated L. monocytogenes in a therapeutic tumor model. This impressive efficacy, together with the increased clearance rate, makes Lm-RIID ideal for prophylactic immunization against diseases that require T cells for protection.
- Published
- 2019