Heterologous Protection Against Influenza by Injection of DNA Encoding a Viral Protein

• Published in: Science (American Association for the Advancement of Science) 1993-03, Vol.259 (5102), p.1745-1749
• Main Authors: Ulmer, Jeffrey B., Donnelly, John J., Parker, Suezanne E., Rhodes, Gary H., Felgner, Philip L., Dwarki, V. J., Gromkowski, Stanislaw H., Deck, R. Randall, DeWitt, Corrille M., Friedman, Arthur, Hawe, Linda A., Leander, Karen R., Martinez, Douglas, Perry, Helen C., Shiver, John W., Montgomery, Donna L., Liu, Margaret A.
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antibodies; Antibody-dependent cell cytotoxicity; Base Sequence; Biological and medical sciences; DNA; DNA, Viral - genetics; DNA, Viral - therapeutic use; Experimental viral diseases and models; Gene Expression; Genetic Vectors; Histocompatibility Antigens Class I - immunology; Immunization; Infections; Infectious diseases; Influenza A virus; Influenza A virus - genetics; Influenza A virus - immunology; Influenza A virus - isolation & purification; Influenza research; Lung - microbiology; Lungs; Lymphocytes; Medical sciences; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Muscles - metabolism; Nucleoproteins - genetics; Nucleoproteins - immunology; Orthomyxoviridae Infections - microbiology; Orthomyxoviridae Infections - prevention & control; Plasmids; RNA-Binding Proteins; Spleen cells; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Transfection; Vaccines; Viral antigens; Viral Core Proteins - genetics; Viral Core Proteins - immunology; Viral diseases; Viral proteins; Viral Vaccines - genetics; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8456302

Cytotoxic T lymphocytes (CTLs) specific for conserved viral antigens can respond to different strains of virus, in contrast to antibodies, which are generally strain-specific. The generation of such CTLs in vivo usually requires endogenous expression of the antigen, as occurs in the case of virus infection. To generate a viral antigen for presentation to the immune system without the limitations of direct peptide delivery or viral vectors, plasmid DNA encoding influenza A nucleoprotein was injected into the quadriceps of BALB/c mice. This resulted in the generation of nucleoprotein-specific CTLs and protection from a subsequent challenge with a heterologous strain of influenza A virus, as measured by decreased viral lung titers, inhibition of mass loss, and increased survival.