Construction and Characterization of Recombinant VLPs and Semliki-Forest Virus Live Vectors for Comparative Evaluation in the SHIV Monkey Model
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F. Notka
Abstract
For testing of recombinant virus-like particles (VLPs) in the SHIV monkey model, Sivmac239 Pr56gag precursor- based pseudovirions were modified by HIV-1 gp160 derived peptides. First, well-characterized epitopes from the HIV-1 envelope glycoprotein were inserted into the Pr56gag precursor by replacing defined regions that were shown to be dispensable for virus particle formation. Expression of these chimeric proteins in a baculovirus expression system resulted in efficient assembly and release of non-infectious, hybrid VLPs. In a second approach the HIV-1IIIB external glycoprotein gp120 was covalently linked to an Epstein-Barr virus derived transmembrane domain. Coexpression of the hybrid envelope derivative with the Pr56gag precursor yielded recombinant SIV derived Pr56gag particles with the HIV-1 gp120 firmly anchored on the VLP surface. Immunization of rhesus monkeys with either naked VLPs or VLPs adsorbed to alum induced substantial serum antibody titers and promoted both T helper cell and cytotoxic T lymphocyte responses. Furthermore, priming macaques with the corresponding set of recombinant Semliki-Forest viruses tended to enhance the immunological outcome. Challenge of the immunized monkeys with chimeric SHIV resulted in a clearly accelerated reduction of the plasma viremia as compared to control animals.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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Artikel in diesem Heft
- Chimeric Virus-Like Particles as Vaccines
- The Core Antigen of Hepatitis B Virus as a Carrier for Immunogenic Peptides
- Enhancing the Immunogenicity of Exogenous Hepatitis B Surface Antigen-Based Vaccines for MHC-I-Restricted T Cells
- The Role of the Proteasome System and the Proteasome Activator PA28 Complex in the Cellular Immune Response
- Ty Virus-Like Particles, DNA Vaccines and Modified Vaccinia Virus Ankara; Comparisons and Combinations
- Chaperones Involved in Hepatitis B Virus Morphogenesis
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- HBV Core Particles Allow the Insertion and Surface Exposure of the Entire Potentially Protective Region of Puumala Hantavirus Nucleocapsid Protein
- Induction of HPV16 Capsid Protein-Specific Human T Cell Responses by Virus-Like Particles
- Construction and Characterization of Recombinant VLPs and Semliki-Forest Virus Live Vectors for Comparative Evaluation in the SHIV Monkey Model
- Development of HIV/AIDS Vaccine Using Chimeric gag-env Virus-Like Particles
- A Disulfide-Bound HIV-1 V3 Loop Sequence on the Surface of Human Rhinovirus 14 Induces Neutralizing Responses against HIV-1
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