Journal article
Enhanced Cellular Immune Responses Elicited by an Engineered HIV-1 Subtype B Consensus-based Envelope DNA Vaccine
Molecular therapy, Vol.15(2), pp.411-421
Feb 2007
PMID: 17235321
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
An important goal for human immunodeficiency virus (HIV) vaccines is to develop immunogens that induce broader and more potent cellular immune responses. In this study of DNA vaccine potency, we constructed a novel subtype B env gene (EY2E1-B) with the goal of increasing vaccine antigen immune potency. The vaccine cassette was designed based on subtype B-specific consensus sequence with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, and a substituted immunoglobulin E leader sequence. The V1 and V2 loops were shortened and the cytoplasmic tail was truncated to prevent envelope recycling. Three different strains of mice (BALB/c, C57BL/6, and HLA-A2 transgenic mice) were immunized three times with pEY2E1-B or the primary DNA immunogen pEK2P-B alone. The analysis of specific antibody responses suggested that EY2E1-B could induce a moderate subtype B-specific antibody response. Moreover, this construct was up to four times more potent at driving cellular immune responses. Epitope mapping results indicated that there is an increase in the breadth and magnitude of cross-reactive cellular responses induced by the EY2E1-B immunogen. These properties suggest that such a synthetic immunogen deserves further examination for its potential to serve as a component antigen in an HIV vaccine cocktail.
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Details
- Title
- Enhanced Cellular Immune Responses Elicited by an Engineered HIV-1 Subtype B Consensus-based Envelope DNA Vaccine
- Creators
- Jian Yan - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAHanna Yoon - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USASanjeev Kumar - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAMathura P Ramanathan - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USANatasha Corbitt - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAMichele Kutzler - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAAnlan Dai - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAJean D Boyer - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USADavid B Weiner - Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Publication Details
- Molecular therapy, Vol.15(2), pp.411-421
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Identifiers
- 991014878457704721
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- Biotechnology & Applied Microbiology
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