Accelerated immune response to DNA vaccines.
DNA vaccines offer considerable promise for improvement over conventional vaccines. For the crucial step of delivering DNA vaccines intracellularly, electroporation (EP) has proven to be highly effective. This method has yielded powerful humoral and cellular responses in various species, including nonhuman primates. In an attempt to further improve DNA vaccination we used micron-size gold particles (which do not bind or adsorb DNA) as a particulate adjuvant which was coinjected with DNA intramuscularly into mice, followed by EP of the target site. The presence of gold particles accelerated the antibody response significantly. Maximum titers against hepatitis B surface antigen (HBsAg) were reached after one boost in 6 weeks, whereas 8 weeks were required without particles. These immunizations were effective in protecting mice against tumor challenge with cancer cells expressing HBsAg as a surrogate cancer antigen. Computer modeling of electric fields and gene expression studies indicate that gold particles do not stimulate EP and subsequent antigen expression. The particles may act as an attractant for immune cells, especially antigen presenting cells. We conclude that particulate adjuvants combined with DNA vaccine delivery by EP reduces the immune response time and may increase vaccine efficacy. This method may become valuable for developing prophylactic as well as therapeutic vaccines. The rapid response may be of particular interest in countering bio-terrorism.
Zhang
Lei
L
Genetronics, Inc., San Diego, California 92121, USA. lzhang@genetronics.com
Widera
Georg
G
Bleecher
Susan
S
Zaharoff
David A
DA
Mossop
Brian
B
Rabussay
Dietmar
D
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000628:therapy; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D003198:Computer Simulation; D018274:Electroporation; D005260:Female; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D051379:Mice; D008812:Mice, Hairless; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019076:Transgenes; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA; D006046:Gold; D000469:Alkaline Phosphatase