A highly optimized DNA vaccine confers complete protective immunity against high-dose lethal lymphocytic choriomeningitis virus challenge.
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.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Devon J
DJ
Shedlock
Kendra T
KT
Talbott
Christina
C
Cress
Bernadette
B
Ferraro
Steven
S
Tuyishme
Karthik
K
Mallilankaraman
Neil J
NJ
Cisper
Matthew P
MP
Morrow
Stephan J
SJ
Wu
Omkar U
OU
Kawalekar
Amir S
AS
Khan
Niranjan Y
NY
Sardesai
Karuppiah
K
Muthumani
Hao
H
Shen
David B
DB
Weiner
D000818:Animals; D000917:Antibody Formation; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007928:Lethal Dose 50; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins / Q000276:immunology*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D019590:Nucleocapsid Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines
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