Back to Search
Start Over
Immunogenic comparison of chimeric adenovirus 5/35 vector carrying optimized human immunodeficiency virus clade C genes and various promoters
Immunogenic comparison of chimeric adenovirus 5/35 vector carrying optimized human immunodeficiency virus clade C genes and various promoters
- Source :
- PLoS ONE, Vol 7, Iss 1, p e30302 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Adenovirus vector-based vaccine is a promising approach to protect HIV infection. However, a recent phase IIb clinical trial using the vector did not show its protective efficacy against HIV infection. To improve the vaccine, we explored the transgene protein expression and its immunogenicity using optimized codon usage, promoters and adaptors. We compared protein expression and immunogenicity of adenovirus vector vaccines carrying native or codon usage-optimized HIV-1 clade C gag and env genes expression cassettes driven by different promoters (CMV, CMVi, and CA promoters) and adapters (IRES and F2A). The adenovirus vector vaccine containing optimized gag gene produced higher Gag protein expression and induced higher immune responses than the vector containing native gag gene in mice. Furthermore, CA promoter generated higher transgene expression and elicited higher immune responses than other two popularly used promoters (CMV and CMVi). The second gene expression using F2A adaptor resulted in higher protein expression and immunity than that of using IRES and direct fusion protein. Taken together, the adenovirus vector containing the expression cassette with CA promoter, optimized HIV-1 clade C gene and an F2A adaptor produced the best protein expression and elicited the highest transgene-specific immune responses. This finding would be promising for vaccine design and gene therapy.
- Subjects :
- Viral Diseases
Genetic enhancement
Blotting, Western
Genetic Vectors
Immunology
Gene Products, gag
lcsh:Medicine
Enzyme-Linked Immunosorbent Assay
Biology
Real-Time Polymerase Chain Reaction
Biochemistry
Microbiology
Cell Line
Viral vector
Retinoblastoma-like protein 1
Mice
Virology
Gene expression
Animals
Humans
Promoter Regions, Genetic
lcsh:Science
Multidisciplinary
Adenoviruses, Human
Immunogenicity
Vaccination
lcsh:R
Immunity
HIV
Group-specific antigen
Molecular biology
Fusion protein
Gene Products, rev
Infectious Diseases
HIV-1
Medicine
Female
Clinical Immunology
lcsh:Q
Expression cassette
HeLa Cells
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....0940a769c6d3626127bac682d0ae4ddb