Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization.
Plasmid DNA vaccines encoding full-length antigen often induce both potent antibody and cytotoxic T lymphocyte (CTL) responses. Here, we examine strategies to exclusively elicit epitope-specific CTL responses using DNA constructs expressing a minimal class I MHC-restricted epitope of the nucleoprotein (NP) of influenza virus. The effects of the addition of an ER leader sequence or cytokine combination on minigene-induced CTL responses in vivo were assessed following both delivery by needle injection into skeletal muscle and by gene gun bombardment into skin epidermis. Our data indicate that the leader sequence enhanced the magnitude of the CTL responses, whereas co-injection of the cytokine genes IL-12 and GM-CSF had a minimal effect. An antibody response against NP was not observed in any of the mice receiving the minigene constructs.
Iwasaki
A
A
Department of Immunology, Medical Sciences Building, University of Toronto, Ont., Canada.
Dela Cruz
C S
CS
Young
A R
AR
Barber
B H
BH
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D017951:Antigen Presentation; D019470:Biolistics; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005814:Genes, Viral / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007273:Injections, Intramuscular; D051379:Mice; D008815:Mice, Inbred Strains; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D021382:Protein Sorting Signals / Q000235:genetics; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000914:Antibodies, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins