Toward a Single-Dose Vaccination Strategy with Self-Encapsulating PLGA Microspheres

被引:34
|
作者
Bailey, Brittany A. [1 ]
Ochyl, Lukasz J. [1 ]
Schwendeman, Steven P. [1 ,2 ]
Moon, James J. [1 ,2 ]
机构
[1] Univ Michigan, Biointerfaces Inst, Dept Pharmaceut Sci, 2800 Plymouth Rd, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Biomed Engn, 2800 Plymouth Rd, Ann Arbor, MI 48109 USA
关键词
antigen-presenting cells; calcium phosphate adjuvant; poly(lactic-co-glycolic acid) microspheres; self-encapsulation; vaccine delivery; TARGETING DENDRITIC CELLS; BIODEGRADABLE MICROSPHERES; ANTIGEN-DELIVERY; MICROENCAPSULATION; MICROPARTICLES; BIOMATERIALS; PHAGOCYTOSIS; ADJUVANTS; SYSTEMS; PORES;
D O I
10.1002/adhm.201601418
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Poly(lactic-co-glycolic acid) (PLGA) microspheres have been widely examined for vaccine applications due to their attractive features of biocompatibility, biodegradability, ability to be internalized by antigen-presenting cells, and long-term antigen release. However, one of the major challenges for PLGA particle vaccines is the potential for antigen instability and loss of antigenicity and immunogenicity. To address this challenge, we have developed a new method of "self-healing" encapsulation in PLGA microspheres, where premade PLGA microspheres are loaded with protein antigens under aqueous conditions with minimal impact on their antigenicity and immunogenicity. In this report, we show that mice immunized with self-encapsulating PLGA microspheres in a prime-boost regimen generated significantly enhanced antigen-specific CD8 alpha+ T cell and antibody responses, compared with mice immunized with free, soluble protein admixed with calcium phosphate gel, a widely used adjuvant. Furthermore, a single-dose of microspheres designed for > 40 day sustained antigen release elicited robust cellular and humoral immune responses as efficiently as the prime-boost vaccinations with calcium phosphate gel. Overall, these results suggest excellent potential of our self-encapsulating PLGA microspheres as a vaccine platform for multiple-dose as well as single-dose vaccinations.
引用
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页数:6
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