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

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 (IM) 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 IM and gene gun inoculations. For gene gun, but not IM 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 IM DNA-immunized mice. In the gene gun-immunized mice, Ag-presenting dendritic cells appeared in the draining lymph nodes before the spleen.