Intramuscular co-delivery of DNA and cytokines from biodegradable microspheres alters the immune response

Intramuscular naked DNA immunization has been shown to provide effective vaccination in animal models, in some diseases, a specific immune response (e.g., Th1 or Th2) is required for protection and it has been shown that administration of cytokine DNA cassettes along with epitope-producing DNA modulates the immune response. The authors have co-encapsulated lacZ DNA and interferon-γ (IFN-γ) or interleukin-4 (IL-4) proteins into biodegradable polyphosphoester microspheres, consisting of lactide and phosphate monomers. These microspheres released intact, bioactive LacZ DNA for over 25 days into phosphate-buffered saline. In balb/c mice, intramuscular immunization with either DNA/IFN-γ microspheres or DNA/IL-4 microspheres increased the serum antibody concentration relative to naked DNA controls. These controlled release formulations appeared to eliminate the need for booster shots for stimulating an effective antibody response