Induction of protective antiviral cytotoxic T cells by a tubular structure capable of carrying large foreign sequences.
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.
Ghosh
Mrinal K
MK
Division of Geographic Medicine, Department of Medicine, School of Medicine, University of Alabama, Birmingham 35294, USA.
Dériaud
Edith
E
Saron
Marie Françoise
MF
Lo-Man
Richard
R
Henry
Thomas
T
Jiao
Xinan
X
Roy
Polly
P
Leclerc
Claude
C
D000818:Animals; D016503:Drug Delivery Systems; D018984:Epitopes, T-Lymphocyte; D005260:Female; D049452:Green Fluorescent Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007114:Immunization; D008164:Luminescent Proteins / Q000096:biosynthesis; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000096:biosynthesis; D018411:Spodoptera; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage* / Q000096:biosynthesis; D014765:Viral Vaccines / Q000008:administration & dosage*
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D008164:Luminescent Proteins; C078966:NS1 protein, bluetongue virus; D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; D049452:Green Fluorescent Proteins