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Increased Immunogenicity of a DNA-Launched Venezuelan Equine Encephalitis Virus-Based Replicon DNA Vaccineâ–¿
- Publication Year :
- 2007
- Publisher :
- American Society for Microbiology (ASM), 2007.
-
Abstract
- A novel genetic vaccine that is based on a Venezuelan equine encephalitis virus (VEE) replicon launched from plasmid DNA is described. The plasmid encodes a VEE replicon under the transcriptional control of the cytomegalovirus immediate-early promoter (VEE DNA). The VEE DNA consistently expressed 3- to 15-fold more green fluorescent protein in vitro than did a conventional DNA vaccine. Furthermore, transfection with the DNA-launched VEE replicon induced apoptosis and type I interferon production. Inoculation of mice with VEE DNA encoding human immunodeficiency virus type 1 gp160 significantly increased humoral responses by several orders of magnitude compared to an equal dose of a conventional DNA vaccine. These increases were also observed at 10- and 100-fold-lower doses of the VEE DNA. Cellular immune responses measured by gamma interferon and interleukin 2 enzyme-linked immunospot assay were significantly higher in mice immunized with the VEE DNA at decreased doses. The immune responses induced by the VEE DNA-encoded antigen, however, were independent of an intact type I interferon signaling pathway. Moreover, the DNA-launched VEE replicon induced an efficient prime to a VEE replicon particle (VRP) boost, increasing humoral and cellular immunity by at least 1 order of magnitude compared to VEE DNA only. Importantly, immunization with VEE DNA, as opposed to VRP, did not induce any anti-VRP neutralizing antibodies. Increased potency of DNA vaccines and reduced vector immunity may ultimately have an impact on the design of vaccination strategies in humans.
- Subjects :
- Cellular immunity
animal structures
viruses
Immunology
Genetic Vectors
Apoptosis
Alphavirus
medicine.disease_cause
Antibodies, Viral
Microbiology
complex mixtures
DNA vaccination
Cell Line
HIV Envelope Protein gp160
Encephalitis Virus, Venezuelan Equine
Mice
Plasmid
L Cells
Virology
Vaccines and Antiviral Agents
Chlorocebus aethiops
medicine
Vaccines, DNA
Animals
Humans
Replicon
Promoter Regions, Genetic
Vero Cells
Mice, Knockout
Mice, Inbred BALB C
biology
virus diseases
biology.organism_classification
Type I interferon production
nervous system diseases
Type I interferon signaling pathway
Insect Science
Immunoglobulin G
Venezuelan equine encephalitis virus
Interferon Type I
HIV-1
NIH 3T3 Cells
Interleukin-2
Immunization
Plasmids
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7cd944af18032cc39d9bf3778dd8f34f