GSBS Student Publications

Title

Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein

UMMS Affiliation

Department of Pathology; Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology

Date

4-15-1995

Document Type

Article

Medical Subject Headings

Amino Acid Sequence; Animals; Antibodies, Viral; *Cytotoxicity, Immunologic; DNA, Viral; Gene Transfer Techniques; Immunity, Cellular; Immunologic Memory; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Nucleoproteins; Peptides; T-Lymphocytes, Cytotoxic; Viral Vaccines

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Anti-viral CTL were induced in vitro using a particle bombardment device or "gene-gun" to deliver plasmid DNA encoding the nucleoprotein of the lymphocytic choriomeningitis virus (LCMV). Using this plasmid we were able to study T cell-mediated immunity in the absence of a neutralizing Ab response. Upon a single DNA immunization, a nearly 2 log10 reduction in splenic viral titers was observed 3 days after LCMV infection. After two or three immunizations a greater than 3 log10 inhibition of viral titers in the spleen was observed, with most animals having no detectable virus. C57BL/6 mice immunized with DNA encoding the nucleoprotein gene were also challenged with LCMV intracranially. Upon intracranial challenge, vaccinated animals displayed either protection or enhanced immunopathology leading to accelerated kinetics of death. Using limiting dilution analysis it was possible to detect LCMV-specific CTL precursors in both the spleen and lymph nodes of vaccinated animals. C57BL/6 mice inoculated with DNA demonstrated an anamnestic CTL response detectable at day 4 after LCMV challenge. Thus DNA vaccines are capable of inducing an anti-viral T cell response that can inhibit viral replication and mediate either protective immunity or immunopathology. Vaccination with DNA may therefore provide a useful alternative to current viral or subunit vaccines once the efficacy of immunization with DNA is optimized.

Rights and Permissions

Citation: J Immunol. 1995 Apr 15;154(8):4010-7.

Related Resources

Link to Article in PubMed

Journal Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

7706740