Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization

• 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; Elsevier
• Subjects: 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; 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
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(98)00411-3

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.