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Controlled release microparticles as a single dose hepatitis B vaccine: evaluation of immunogenicity in mice
Abstract:
Hepatitis B surface antigen (HBsAg) was encapsulated in microparticles prepared from polylactide-co-glycolide (PLG) and polylactide (PLA) polymers using a solvent evaporation process. The immunoreactivity of the entrapped antigen was investigated by SDS-PAGE and Western blot. The microencapsulation process was modified to obtain both small (< 10 microns) and large microparticles (10-100 < microns). 80% of the antigen was encapsulated. Various combinations of small and large microparticles with controlled release characteristics were investigated in CD1 mice. Groups of animals were immunized with 30 micrograms equivalent of HBsAg in microparticles per animals. The control group received, three injections of 10 micrograms of HBsAg on alum at 0, 1 and 6 months. Results indicated that a single injection of HBsAg in microparticles could maintain the antibody response at a level comparable to the three-injection alum schedule for at least 1 year. An in vitro inhibition assay was developed to demonstrate that antigen-antibody reactivity were comparable for the microparticle immunized mice and the alum immunized mice. A competition assay with a monoclonal antibody specific for the neutralizing epitope of HBsAg demonstrated comparable binding for the sera from the microparticle and alum immunized mice.
Insights
Hepatitis B surface antigen (HBsAg) was encapsulated in biodegradable microparticles. A single HBsAg microparticle injection elicited a sustained antibody response comparable to multiple conventional vaccine doses.
Area of Science:
- Biomaterials Science
- Immunology
- Vaccine Technology
Background:
- Hepatitis B virus (HBV) infection poses a significant global health burden.
- Current HBV vaccines often require multiple doses for optimal efficacy.
- Developing novel vaccine delivery systems is crucial for improving immunization strategies.
Purpose of the Study:
- To encapsulate Hepatitis B surface antigen (HBsAg) within biodegradable polylactide-co-glycolide (PLG) and polylactide (PLA) microparticles.
- To evaluate the immunogenicity and antigen-antibody reactivity of HBsAg-loaded microparticles in a murine model.
- To compare the efficacy of a single microparticle-based HBsAg vaccination with a conventional alum-adjuvanted vaccine regimen.
Main Methods:
- HBsAg was encapsulated in PLG/PLA microparticles via solvent evaporation.
- Microparticle size was controlled (<10 microns and 10-100 microns).
- Encapsulation efficiency was determined, and immunoreactivity was assessed using SDS-PAGE and Western blot.
- CD1 mice were immunized with HBsAg microparticles or alum-adjuvanted HBsAg.
- Antibody responses were measured, and in vitro inhibition and competition assays were performed.
Main Results:
- High encapsulation efficiency (80%) of HBsAg was achieved in microparticles.
- Microparticles demonstrated controlled release characteristics.
- A single HBsAg microparticle injection induced antibody levels comparable to three alum-adjuvanted HBsAg injections for over one year.
- In vitro assays confirmed comparable antigen-antibody reactivity and neutralizing epitope binding.
Conclusions:
- Biodegradable PLG/PLA microparticles effectively encapsulate HBsAg while preserving its immunoreactivity.
- A single HBsAg microparticle vaccination can elicit a long-lasting immune response, potentially reducing the need for multiple immunizations.
- Microparticle-based vaccine delivery offers a promising strategy for enhancing Hepatitis B vaccination efficacy and compliance.