期刊
BIOMATERIALS
卷 35, 期 23, 页码 6086-6097出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.04.022
关键词
Adjuvant; Nanoparticles; Vaccine formulations; Immune response; Mechanism of action
资金
- 973 Program [2013C8531500]
- Special Fund for Agro-scientific Research in the Public Interest [201303046]
- 863 Program [2012AA02A406]
Many physicochemical characteristics significantly influence the adjuvant effect of micro/nanoparticles; one critical factor is the kinetics of antigen exposure to the immune system by particle-adjuvanted vaccines. Here, we investigated how various antigen-nanoparticle formulations impacted antigen exposure to the immune system and the resultant antigen-specific immune responses. We formulated antigen with poly(lactic-co-glycolic acid) (PLGA) nanoparticles by encapsulating antigen within nanoparticles or by simply mixing soluble antigen with the nanoparticles. Our results indicated that the combined formulation (composed of antigen encapsulated in nanoparticles and antigen mixed with nanoparticles) induced more powerful antigen-specific immune responses than each single-component formulation. Mice immunized with the combined vaccine formulation displayed enhanced induction of antigen-specific IgG antibodies with high avidity, increased cytokine secretion by splenocytes, and improved generation of memory T cell. Enhanced immune responses elicited by the combined vaccine formulation might be attributed to the antigen-depot effect at the injection site, effective provision of both adequate initial antigen exposure and long-term antigen persistence, and efficient induction of dendritic cell (DC) activation and follicular helper T cell differentiation in draining lymph nodes. Understanding the effect of antigen nanoparticle formulations on the resultant immune responses might have significant implications for rational vaccine design. (C) 2014 Elsevier Ltd. All rights reserved.
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