Immunization by particle bombardment of antigen-loaded poly-(DL-lactide-co-glycolide) microspheres in mice.
In the present study, we investigated whether poly-(DL-lactide-co-glycolide) (50:50) microspheres (PLG MS) containing a model antigen, ovalbumin (OVA), were delivered into mouse skin and the immune responses induced using a microparticulate bombardment system, Helios gene gun system, which can painlessly deliver the powdered drug through the stratum corneum to the epidermal-dermal interface using a high velocity supersonic flow of helium gas to accelerate the particles. The introduction of OVA-loaded PLG MS shows helium pressure-dependence, so that improved introduction can be achieved by a higher helium pressure used, thereby inducing sufficient anti-OVA IgG level. Moreover, in order to determine the type of immune system induced using particle bombardment, we investigated helper T-cell response characterized by the cytokine production in the isolated splenocytes 6 weeks after immunization and consequent production of the anti-OVA IgG subclasses in the serum in mice. As a result, IL-4 production in splenocytes and anti-OVA IgG1 level were preferentially elicited by particle bombardment with OVA-loaded PLG MS compared with IFN-gamma and anti-OVA IgG2a level. It seemed likely that particle bombardment using this system led to a Th-2 type immune response, i.e. a humoral immune response. In conclusion, this microparticulate bombardment system is a promising immunization method, expected to become an alternative to needle injection used to administer a broad range of vaccines for the treatment of various diseases.
Uchida
Masaki
M
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan.
Natsume
Hideshi
H
Kishino
Tohru
T
Seki
Toshinobu
T
Ogihara
Masahiko
M
Juni
Kazuhiko
K
Kimura
Masayuki
M
Morimoto
Yasunori
Y
D000399:Air Pressure; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D006371:Helium; D007114:Immunization / Q000379:methods*; D019344:Lactic Acid / Q000008:administration & dosage* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage* / Q000633:toxicity; D012867:Skin / Q000378:metabolism
D000941:Antigens; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D006371:Helium; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin