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Intralymphatic Immunotherapy and Vaccination in Mice
Published on: February 2, 2014
Immunization by particle bombardment of antigen-loaded poly-(DL-lactide-co-glycolide) microspheres in mice
Masaki Uchida1, Hideshi Natsume, Tohru Kishino
1Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan.
Abstract:
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.
Insights
The Helios gene gun system effectively delivers ovalbumin-loaded microspheres into mouse skin, inducing a robust Th-2 immune response. This microparticulate delivery method shows promise as an alternative to needle-based vaccines.
Area of Science:
- Biotechnology
- Immunology
- Materials Science
Background:
- Conventional vaccine delivery methods like needle injections can be painful and may not always elicit optimal immune responses.
- Microparticulate systems offer potential for improved antigen delivery and immune modulation.
- The Helios gene gun system utilizes helium gas to propel microparticles, enabling painless transdermal delivery.
Purpose of the Study:
- To evaluate the efficacy of poly-(DL-lactide-co-glycolide) (50:50) microspheres (PLG MS) loaded with ovalbumin (OVA) for skin immunization using the Helios gene gun system.
- To investigate the immune responses, including antibody and T-cell profiles, induced by this microparticulate bombardment method.
- To determine the type of immune response (Th-1 vs. Th-2) elicited by OVA-loaded PLG MS delivered via particle bombardment.
Main Methods:
- Ovalbumin (OVA)-loaded PLG MS were prepared and delivered into mouse skin using the Helios gene gun system at varying helium pressures.
- Humoral immune responses were assessed by measuring anti-OVA IgG and its subclasses (IgG1, IgG2a) in mouse serum.
- Cellular immune responses were evaluated by analyzing cytokine production (IL-4, IFN-gamma) from isolated splenocytes.
Main Results:
- Helios gene gun delivery of OVA-loaded PLG MS demonstrated helium pressure-dependence, with higher pressures leading to increased anti-OVA IgG levels.
- Particle bombardment preferentially induced IL-4 production in splenocytes and a higher anti-OVA IgG1 subclass level.
- The observed cytokine and antibody profiles indicated a predominant Th-2 type immune response, characteristic of humoral immunity.
Conclusions:
- The microparticulate bombardment system using the Helios gene gun is an effective and painless method for delivering antigen-loaded microspheres into the skin.
- This approach elicits a Th-2 biased immune response, suggesting its potential for developing humoral vaccines.
- The Helios gene gun system presents a promising alternative to traditional needle-based immunization for various diseases.

