Basic mechanisms of DNA-raised antibody responses to intramuscular and gene gun immunizations.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Basic mechanisms of DNA-raised antibody responses to intramuscular and gene gun immunizations.

DNA Cell Biol. 2000 Mar;19(3):157-65. Unique Identifier : AIDSLINE MED/20210726
Boyle CM; Robinson HL; Department of Pathology, University of Massachusetts Medical; School, Worcester, USA.

Abstract: DNA-raised antibody (Ab) responses have been compared for the dependence on CD4+ and CD8+ cells, the longevity of functional antigen (Ag) expression, and the nature of the Ag-presenting cell after intramuscular (i.m.) and gene gun inoculations. A plasmid expressing the hemagglutinin (HA) glycoprotein of influenza virus was used for immunizations of BALB/c mice. Intramuscular and gene gun-raised Abs had similar dependencies on CD4+ and CD8+ cells but different temporal patterns of functional Ag expression. The two methods of DNA immunization also appeared to have different frequencies or types of Ag-presenting cells in the draining lymph nodes and spleen. For both methods of DNA delivery, Ab was independent of CD8+ cells but dependent on CD4+ cells. The CD4 dependence occurred at priming but not booster immunizations and resulted in a 1-month delay in the Ab response. Temporal T-cell transfers from TCR+/+ mice into immunized TCR-/- mice revealed the persistence of DNA-expressed Ag for up to 1 month after both i.m. and gene gun inoculations. For gene gun, but not i.m. immunizations, approximately 90% of the functional Ag expression was lost by 1 week, consistent with the sloughing of the epidermal target site. Despite similar titers of raised Ab, Ag-presenting dendritic cells could be detected in the draining lymph nodes and spleen of gene gun- but not i.m. DNA-immunized mice. In the gene gun-immunized mice, Ag-presenting dendritic cells appeared in the draining lymph nodes before the spleen.

Keywords: JOURNAL ARTICLE Animal Antibodies, Viral/*BLOOD Antibody Formation Antibody Specificity *Biolistics Comparative Study CD4-Positive T-Lymphocytes/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Enzyme-Linked Immunosorbent Assay Female Hemagglutinin Glycoproteins, Influenza Virus/*GENETICS/IMMUNOLOGY Injections, Intramuscular Interferon Type II/BIOSYNTHESIS Lymphocyte Depletion Mice Mice, Inbred BALB C Mice, Knockout Receptors, Antigen, T-Cell, alpha-beta/DEFICIENCY/GENETICS/ IMMUNOLOGY Support, U.S. Gov't, P.H.S. T-Lymphocytes/*IMMUNOLOGY Time Factors Vaccines, DNA/ADMINISTRATION & DOSAGE/*IMMUNOLOGY

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