Construction and characterization of recombinant VLPs and Semliki-Forest virus live vectors for comparative evaluation in the SHIV monkey model.
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.
Notka
F
F
Institute of Medical Microbiology, University of Regensburg, Germany.
Stahl-Hennig
C
C
Dittmer
U
U
Wolf
H
H
Wagner
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012672:Semliki forest virus; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D018411:Spodoptera; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load; D014771:Virion
D015683:Gene Products, gag; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011993:Recombinant Fusion Proteins