Induction of protective antiviral cytotoxic T cells by a tubular structure capable of carrying large foreign sequences


Ghosh, MK; Deriaud, E; Saron, MF; lo-Man, R; Henry, T; Jiao, X; Roy, P; Leclerc, C; (2002) Induction of protective antiviral cytotoxic T cells by a tubular structure capable of carrying large foreign sequences. Vaccine, 20 (9-10). pp. 1369-77. ISSN 0264-410X DOI: https://doi.org/10.1016/S0264-410X(01)00467-4

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Abstract

Bluetongue virus (BTV) produces large numbers of tubules during infection which are formed by a single virus coded non-structural protein, NS1. The NS1 protein has been fused with full length green fluorescent protein (GFP) and was shown to retain the capacity to form tubules when expressed in heterologous expression systems. Moreover, recombinant purified chimeric tubules were demonstrated to be internalized by macrophages and dendritic cells. The ability of such chimeric tubules to induce protective cytotoxic T lymphocytes (CTL) responses has been assessed by generating chimeric tubules carrying a single CD8(+) T cell epitope from the lymphocytic choriomeningitis virus (LCMV) nucleoprotein. These chimeric tubules were recognized by MHC class I restricted T cell hybridoma in vitro and induced in vivo strong CD8(+) class I-restricted CTL responses in immunized mice. Further, the immunized mice were protected when challenged with a lethal dose of LCMV. This is the first study that demonstrates that the virus derived tubules synthesized by a recombinant non-structural protein carrying a single viral CTL epitope could induce protective immunity against a lethal viral challenge. Since recombinant tubules carrying large inserts can be purified at a large quantity from insect cells, they have potential to develop as safe multi-CTL vaccine delivery systems.

Item Type: Article
Keywords: Animal, Drug Delivery Systems, Epitopes, T-Lymphocyte, Female, Histocompatibility Antigens Class I, immunology, Immunization, Luminescent Proteins, biosynthesis, Lymphocytic choriomeningitis virus, immunology, Mice, Mice, Inbred BALB C, Recombinant Fusion Proteins, administration & dosage, biosynthesis, Spodoptera, Support, Non-U.S. Gov't, Support, U.S. Gov't, P.H.S., T-Lymphocytes, Cytotoxic, immunology, Viral Nonstructural Proteins, administration & dosage, biosynthesis, Viral Vaccines, administration & dosage
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 11818155
Web of Science ID: 173858300012
URI: http://researchonline.lshtm.ac.uk/id/eprint/18316

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