Induction of single and dual cytotoxic T-lymphocyte responses to viral proteins in mice using recombinant hybrid Ty-virus-like particles.
The induction of cytotoxic T-lymphocyte (CTL) responses to viral proteins is thought to be an essential component of protective immunity against viral infections. Methods for generating such responses in a reproducible manner would be of great value in vaccine development. We demonstrate here that the recombinant antigen-presentation system based on the yeast transposon (Ty) particle-forming p1 protein is a potent means of inducing CTL responses to a variety of viral CTL epitopes, including influenza virus nucleoprotein (two epitopes), Sendai virus and vesicular stomatitis virus nucleoproteins, and the V3 loop of human immunodeficiency virus type-1 (HIV-1) gp120. CTL were primed by hybrid Ty-virus-like particles (VLP) carrying the minimal epitope or as much as 19,000 MW of protein. Ty-VLP carrying two different epitopes (dual-epitope Ty-VLP) were capable of priming CTL responses in two different strains of mice or against two epitopes in the same individual. Furthermore, co-administration of a mixture of two different Ty-VLP carrying single epitopes could induce responses to both epitopes in the same individual. Ty-VLP appear to represent a reproducible and flexible system for inducing CTL responses in mice, and warrant further evaluation in primates.
Layton
G T
GT
British Biotech Pharmaceuticals Ltd, Oxford, UK.
Harris
S J
SJ
Myhan
J
J
West
D
D
Gotch
F
F
Hill-Perkins
M
M
Cole
J S
JS
Meyers
N
N
Woodrow
S
S
French
T J
TJ
Adams
S E
SE
Kingsman
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004251:DNA Transposable Elements / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
D000956:Antigens, Viral; D004251:DNA Transposable Elements; D000939:Epitopes; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014758:Viral Core Proteins