Superiority of intramuscular route and full length glycoprotein D for DNA vaccination against herpes simplex 2.: Enhancement of protection by the co-delivery of the GM-CSF gene

Immunization with naked DNA has been analyzed in two critical variables: the site of injection and the cellular compartment to which the coded protein is directed. The gene for the full length of the glycoprotein D (gD) of HSV-2 under the control of the citomegalovirus (CMV) promoter was injected via the intradermal (i.d.) or the intramuscular (i.m.) routes in mice. Immunization in the quadricep muscle was superior to the intradermal immunization in the footpads. A stronger activation of IFN-gamma-secreting cells in the spleen and draining lymph nodes (DLN) was induced, resulting in a more efficient protection against an intravaginal challenge. In order to analyze the effect of the cellular localizations of the coded protein, the DNA for the truncated form of the gD (Delta gD) was injected via the i.m. route. Immunization with a vector encoding for Delta gD resulted in higher antibody levels in serum and vaginal washes than immunization with the gene for the full length gD. However, immunization with the Delta gD DNA elicited a much weaker cell-mediated immune response and was inferior to go DNA in providing protection against a lethal intravaginal challenge with HSV. Co-injection of an expression cassette for the granulocyte macrophage colony-stimulating factor (GM-CSF) increased both the humoral and cell-mediated immune response with both gD and Delta gD. A strong activation of IL-4-secreting cells was observed in the spleen and DLN together with an increase in the number of IFN-gamma-secreting cells. In addition, a reduction in the vaginal virus titers after an intravaginal challenge was observed in mice co-injected with the GM-CSF gene as compared to those immunized with pCDNAgD only. (C) 2000 Elsevier Science Ltd. All rights reserved.