101. A highly optimized DNA vaccine confers complete protective immunity against high-dose lethal lymphocytic choriomeningitis virus challenge
- Author
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Niranjan Y. Sardesai, Matthew P. Morrow, Christina Cress, David B. Weiner, Steven Tuyishme, Amir S. Khan, Karuppiah Muthumani, Omkar U. Kawalekar, Devon J. Shedlock, Bernadette Ferraro, Karthik Mallilankaraman, Kendra T. Talbott, Neil J. Cisper, Hao Shen, and Stephan J. Wu
- Subjects
Enzyme-Linked Immunospot Assay ,Genetic Vectors ,chemical and pharmacologic phenomena ,Biology ,Lymphocytic Choriomeningitis ,Lymphocytic choriomeningitis ,Transfection ,Median lethal dose ,Virus ,Article ,DNA vaccination ,Lethal Dose 50 ,Mice ,Immune system ,Immunity ,medicine ,Vaccines, DNA ,Animals ,Humans ,Lymphocytic choriomeningitis virus ,Immunity, Cellular ,General Veterinary ,General Immunology and Microbiology ,Viral Vaccine ,Vaccination ,Public Health, Environmental and Occupational Health ,Viral Vaccines ,Nucleocapsid Proteins ,medicine.disease ,Virology ,Immunity, Humoral ,Mice, Inbred C57BL ,Infectious Diseases ,HEK293 Cells ,Immunology ,Antibody Formation ,Molecular Medicine ,Female ,Plasmids - Abstract
Protection against infection is the hallmark of immunity and the basis of effective vaccination. For a variety of reasons there is a great demand to develop new, safer and more effective vaccine platforms. In this regard, while ‘first-generation’ DNA vaccines were poorly immunogenic, new genetic ‘optimization’ strategies and the application of in vivo electroporation (EP) have dramatically boosted their potency. We developed a highly optimized plasmid DNA vaccine that expresses the lymphocytic choriomeningitis virus (LCMV) nucleocapsid protein (NP) and evaluated it using the LCMV challenge model, a gold standard for studying infection and immunity. When administered intramuscularly with EP, robust NP-specific cellular and humoral immune responses were elicited, the magnitudes of which approached those following acute LCMV infection. Furthermore, these responses were capable of providing 100% protection against a high-dose, normally lethal virus challenge. This is the first non-infectious vaccine conferring complete protective immunity up to eight weeks after vaccination and demonstrates the potential utility of ‘next-generation’ DNA vaccines.
- Published
- 2011