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Measuring Bacterial Load and Immune Responses in Mice Infected with Listeria monocytogenes
Published on: August 9, 2011
Recombinant Listeria monocytogenes as a live vaccine vehicle and a probe for studying cell-mediated immunity
E R Jensen1, H Shen, F O Wettstein
1Department of Microbiology and Immunology, University of California at Los Angeles School of Medicine, USA.
Insights
Listeria monocytogenes can be engineered as a vaccine vehicle to induce long-term immunity. Recombinant Listeria strains expressing foreign antigens successfully generated protective CD8+ T-cell responses in animal models.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Listeria monocytogenes' cytosolic entry facilitates antigen presentation via MHC class I.
- L. monocytogenes is a promising live vaccine vehicle for heterologous antigens.
- Induction of immunological memory and CD8+ T-cell responses are key vaccine goals.
Purpose of the Study:
- To establish a genetic system for regulated antigen expression and secretion by recombinant Listeria.
- To evaluate the capacity of these recombinant strains to induce long-term immunological memory and protective immunity.
- To assess the efficacy of L. monocytogenes-based vaccines in viral and tumor models.
Main Methods:
- Developed a site-specific genetic integration system for antigen expression cassettes in Listeria.
- Utilized lymphocytic choriomeningitis virus (LCMV) model in mice to assess CD8+ T-cell induction and protection.
- Employed a cottontail rabbit papillomavirus model in rabbits to evaluate antitumor immunity.
Main Results:
- Recombinant Listeria strains expressing LCMV antigens successfully induced LCMV-specific CD8+ T cells in mice.
- Vaccinated mice demonstrated protection against LCMV challenge.
- Recombinant Listeria stimulated protective antitumor immunity in a rabbit papillomavirus model.
Conclusions:
- Recombinant L. monocytogenes vaccines demonstrate protective efficacy against viral challenge and tumors.
- The established experimental system enables systematic analysis of cytotoxic T-cell induction by intracellular bacteria.
- L. monocytogenes serves as an effective platform for developing vaccines against various pathogens and cancers.
Abstract:
The ability of Listeria monocytogenes (L. monocytogenes) to enter the cytosol of host cells allows secreted proteins to efficiently enter the endogenous antigen-processing pathway leading to presentation by MHC class I molecules. L. monocytogenes has recently been exploited as a live vaccine vehicle for the induction of immunological memory against heterologous antigens. We have established a genetic system for site-specific integration of antigen expression cassettes into the Listeria genome which allows regulated expression and secretion of heterologous proteins. The ability of recombinant strains to stimulate long-term immunological memory and CD8+ T-cell-mediated protective immunity was investigated using the lymphocytic choriomeningitis virus (LCMV) murine infection model. Vaccination of mice with recombinant Listeria strains expressing LCMV antigens induced LCMV-specific CD8+ T cells which protected mice against LCMV challenge. We have also used a cottontail rabbit papillomavirus model to test the ability of recombinant Listeria strains to stimulate protective antitumor immunity in domestic rabbits. These studies have demonstrated the protective efficacy of recombinant L. monocytogenes vaccines and have established an experimental system for systematic analysis of cytotoxic T-cell induction by an intracellular bacterium.
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