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Biodegradable microparticles as controlled release antigen delivery systems
D T O'Hagan1, D Rahman, J P McGee
1Department of Pharmaceutical Sciences, University of Nottingham, U.K.
Abstract:
A model but poor immunogen, ovalbumin (OVA), was entrapped in a novel antigen delivery system comprising poly (D,L-lactide-co-glycolide) (PLGA) microparticles. Both the primary and the secondary IgG antibody responses obtained with OVA in microparticles were compared to those obtained with OVA emulsified in Freunds' adjuvants by two routes of immunization, intraperitoneal (i.p.) and subcutaneous (s.c.) injection. Following single i.p. or s.c. injections, the IgG serum antibody responses to OVA in microparticles were significantly greater than the responses to OVA in Freunds' complete adjuvant (FCA) for up to 10 weeks. After s.c. booster doses of OVA, the secondary IgG antibody responses to OVA in microparticles remained greater than the secondary responses to OVA in Freunds', but not significantly so. Furthermore, the primary IgG responses to OVA in microparticles obtained 8-12 weeks after a single i.p. injection were greater than the secondary responses to OVA in Freunds' obtained by repeat s.c. injections at Weeks 0 and 6. These results demonstrate that microparticles can function as potent antigen delivery systems for an entrapped antigen. Due to their ability to degrade slowly in vivo and to release entrapped antigens, microparticles have considerable potential as controlled release antigen delivery systems for the induction of long-term immune responses.
Insights
Poly (D,L-lactide-co-glycolide) (PLGA) microparticles enhance immune responses to ovalbumin (OVA). These novel antigen delivery systems show potential for long-term immunity induction.
Area of Science:
- Biotechnology
- Immunology
- Materials Science
Background:
- Ovalbumin (OVA) is a model antigen but a poor immunogen.
- Effective antigen delivery systems are crucial for potent immune responses.
- Poly (D,L-lactide-co-glycolide) (PLGA) microparticles offer controlled antigen release.
Purpose of the Study:
- To evaluate PLGA microparticles as an antigen delivery system for OVA.
- To compare immune responses induced by OVA in microparticles versus OVA in Freund's adjuvants.
- To assess the impact of immunization route (intraperitoneal and subcutaneous) on antibody responses.
Main Methods:
- Entrapment of ovalbumin (OVA) within PLGA microparticles.
- Immunization of animals with OVA in microparticles or Freund's complete adjuvant (FCA).
- Comparison of primary and secondary IgG antibody responses via ELISA at various time points post-injection.
Main Results:
- Single injections of OVA in PLGA microparticles elicited significantly greater IgG serum antibody responses than OVA in FCA for up to 10 weeks.
- Subcutaneous booster doses of OVA in microparticles resulted in sustained, though not significantly higher, secondary IgG responses compared to FCA.
- Primary IgG responses after a single intraperitoneal injection of OVA in microparticles exceeded secondary responses from repeated FCA injections.
Conclusions:
- PLGA microparticles serve as effective antigen delivery vehicles, enhancing immune responses to entrapped antigens like OVA.
- The slow in vivo degradation and controlled release properties of microparticles are key to inducing robust and long-lasting immunity.
- Microparticle-based antigen delivery holds significant promise for developing advanced vaccine strategies and long-term immune modulation.