A highly optimized DNA vaccine confers complete protective immunity against high-dose lethal lymphocytic choriomeningitis virus challenge

Vaccine. 2011 Sep 9;29(39):6755-62. doi: 10.1016/j.vaccine.2010.12.064. Epub 2011 Jan 14.


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 8 weeks after vaccination and demonstrates the potential of 'next-generation' DNA vaccines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibody Formation
  • Enzyme-Linked Immunospot Assay
  • Female
  • Genetic Vectors
  • HEK293 Cells
  • Humans
  • Immunity, Cellular*
  • Immunity, Humoral*
  • Lethal Dose 50
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / prevention & control*
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / pathogenicity
  • Mice
  • Mice, Inbred C57BL
  • Nucleocapsid Proteins / immunology*
  • Plasmids / genetics
  • Plasmids / metabolism
  • Transfection
  • Vaccination / methods
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*


  • Nucleocapsid Proteins
  • Vaccines, DNA
  • Viral Vaccines