Construction and characterization of recombinant VLPs and semliki-forest virus live vectors for comparative evaluation in the SHIV monkey model

Notka, Frank and Stahl-Hennig, Christiane and Dittmer, Ulf and Wolf, Hans and Wagner, Ralf (1999) Construction and characterization of recombinant VLPs and semliki-forest virus live vectors for comparative evaluation in the SHIV monkey model. BIOLOGICAL CHEMISTRY, 380 (3). pp. 341-352. ISSN 1431-6730,

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Abstract

For testing of recombinant virus-like particles (VLPs) in the SHIV monkey model, SIV(mac)239 Pr56(gag) 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 Pr56(gag) 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-1(IIIB) external glycoprotein gp120 was covalently linked to an Epstein-Barr virus derived transmembrane domain. Coexpression of the hybrid envelope derivative with the Pr56(gag) precursor yielded recombinant SIV derived Pr56(gag) 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.

Item Type: Article
Uncontrolled Keywords: HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-CELLS; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEINS; EXPRESSION SYSTEM; LYMPHOCYTE RESPONSES; VACCINE PROTECTION; IMMUNE-RESPONSE; HIV-1 INFECTION; RHESUS-MONKEYS; CTL activity; neutralizing antibodies; particulate antigens; SHIV challenge; Th-cell proliferation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 15 Nov 2022 08:21
Last Modified: 15 Nov 2022 08:21
URI: https://pred.uni-regensburg.de/id/eprint/48449

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