Protection from Bacterial Infection by a Single Vaccination with Replication-Deficient Mutant Herpes Simplex Virus Type 1
| Autor: | Kristen M. Kerksiek, Dirk H. Busch, Penelope Mavromara, Roberto Manservigi, Peggy Marconi, Aleksandra Bozac, Henning Lauterbach, Alberto L. Epstein, Thomas Brocker, Elena Berto |
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| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunology Mice Transgenic Herpesvirus 1 Human CD8-Positive T-Lymphocytes Biology Virus Replication Major histocompatibility complex Microbiology DNA vaccination Mice Immune system Virology Vaccines and Antiviral Agents Animals Cytotoxic T cell Listeriosis Vaccines Synthetic Intracellular parasite Viral Vaccines Bacterial Infections Vaccination Bacterial vaccine Insect Science Mutation biology.protein CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of Virology. 78:4020-4028 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Adaptive immune responses in which CD8+T cells recognize pathogen-derived peptides in the context of major histocompatibility complex class I molecules play a major role in the host defense against infection with intracellular pathogens. Cells infected with intracellular bacteria such asListeria monocytogenes,Salmonella entericaserovar Typhimurium, orMycobacterium tuberculosisare directly lysed by cytotoxic CD8+T cells. For this reason, current vaccines for intracellular pathogens, such as subunit vaccines or viable bacterial vaccines, aim to generate robust cytotoxic T-cell responses. In order to investigate the capacity of a herpes simplex virus type 1 (HSV-1) vector to induce strong cytotoxic effector cell responses and protection from infection with intracellular pathogens, we developed a replication-deficient, recombinant HSV-1 (rHSV-1) vaccine. We demonstrate in side-by-side comparison with DNA vaccination that rHSV-1 vaccination induces very strong CD8+effector T-cell responses. While both vaccines provided protection from infection withL. monocytogenesat low, but lethal doses, only rHSV-1 vaccines could protect from higher infectious doses; HSV-1 induced potent memory cytotoxic T lymphocytes that, upon challenge by pathogens, efficiently protected the animals. Despite the stimulation of relatively low humoral and CD4-T-cell responses, rHSV-1 vectors are strong candidates for future vaccine strategies that confer efficient protection from subsequent infection with intracellular bacteria. |
| Databáze: | OpenAIRE |
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