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 nucleoprote...

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Published in:Vaccine Vol. 17; no. 15; pp. 2081 - 2088
Main Authors: Iwasaki, Akiko, Dela Cruz, Charles S, Young, Alex R, Barber, Brian H
Format: Journal Article
Language:English
Published: Oxford Elsevier Ltd 09-04-1999
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Abstract 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.
AbstractList 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.
Author Barber, Brian H
Young, Alex R
Dela Cruz, Charles S
Iwasaki, Akiko
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Issue 15
Keywords DNA vaccine
Minigene
Cytotoxic T lymphocyte
Leader peptide
Antigenic determinant
Major histocompatibility system
Rodentia
Cytokine
Orthomyxoviridae
Interleukin 12
Nucleoprotein
Cellular immunity
Recombinant DNA
Genetic vaccine
Virus
Vertebrata
Mammalia
Influenzavirus A
Immunogenicity
Histocompatibility restriction
Mouse
Class I histocompatibility antigen
Granulocyte macrophage colony stimulating factor
Language English
License CC BY 4.0
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Snippet Plasmid DNA vaccines encoding full-length antigen often induce both potent antibody and cytotoxic T lymphocyte (CTL) responses. Here, we examine strategies to...
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SubjectTerms Animals
Antibodies, Viral - biosynthesis
Antigen Presentation
Biolistics
Biological and medical sciences
Cytokines - genetics
Cytokines - immunology
Cytotoxic T lymphocyte
DNA vaccine
Epitopes, T-Lymphocyte - administration & dosage
Epitopes, T-Lymphocyte - genetics
Epitopes, T-Lymphocyte - immunology
Epitopes, T-Lymphocyte - metabolism
Female
Fundamental and applied biological sciences. Psychology
Genes, Viral - genetics
Histocompatibility Antigens Class I - immunology
Histocompatibility Antigens Class I - metabolism
Injections, Intramuscular
Mice
Mice, Inbred Strains
Microbiology
Minigene
Nucleoproteins - administration & dosage
Nucleoproteins - genetics
Nucleoproteins - immunology
Nucleoproteins - metabolism
Orthomyxoviridae - genetics
Orthomyxoviridae - immunology
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - virology
Peptide Fragments - administration & dosage
Peptide Fragments - genetics
Peptide Fragments - immunology
Peptide Fragments - metabolism
Plasmids - genetics
Protein Sorting Signals - genetics
Recombinant Proteins - biosynthesis
Recombinant Proteins - immunology
Recombinant Proteins - metabolism
RNA-Binding Proteins
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - metabolism
Tumor Cells, Cultured
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Vaccines, DNA - administration & dosage
Vaccines, DNA - genetics
Vaccines, DNA - immunology
Viral Core Proteins - administration & dosage
Viral Core Proteins - genetics
Viral Core Proteins - immunology
Viral Core Proteins - metabolism
Virology
Title Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization
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