Enhancement of the effectiveness of electroporation-augmented cutaneous DNA vaccination by a particulate adjuvant.
DNA vaccines are attracting increased attention due to multiple advantages over conventional vaccines. Attempts to improve these vaccines focus on enhancing DNA delivery and employing novel immunoadjuvants. Electroporation (EP) has emerged as an effective method for delivering DNA vaccines, significantly enhancing humoral and cellular responses. To further improve EP-augmented DNA vaccination, we used micron-size gold particles as a particulate adjuvant. DNA is not bound, or adsorbed, to the particles. Gold particles were coinjected intradermally with plasmid DNA encoding the hepatitis B virus surface antigen (HBsAg) into mice, both in the absence and presence of noninvasive EP. The particles enhanced the percentage of responding animals, and shortened the time for reaching maximal antibody titers by 2 weeks. Subtyping of the produced antibodies revealed a predominantly Th1-like response which did not change significantly with the absence or presence of particles. The particles likely function as an attractant for antigen-presenting cells (APCs), and probably do not affect EP or antigen expression to a significant extent. We conclude that micron-size gold particles injected intradermally together with DNA followed by EP give rise to an accelerated, potent immune response with a strong cellular component. This method may become important for the development of fast-acting therapeutic and prophylactic vaccines.
Zhang
Lei
L
Genetronics, Inc., 11199 Sorrento Valley Road, San Diego, CA 92121-1334, USA. lzhang@genetronics.com
Widera
Georg
G
Rabussay
Dietmar
D
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D003131:Combined Modality Therapy / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods*; D018274:Electroporation / Q000379:methods*; D005260:Female; D017979:Gold Colloid / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics*
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D004338:Drug Combinations; D017979:Gold Colloid; D019444:Vaccines, DNA