期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 113, 期 -, 页码 312-319出版社
ELSEVIER
DOI: 10.1016/j.colsurfb.2013.09.006
关键词
Vaccine adjuvant formulation; TLR4 agonist; In vitro bioactivity; Particle size; Physicochemical characterization; Glucopyranosyl lipid adjuvant
资金
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800045C]
- Biomedical Advanced Research and Development Authority, Department of Health and Human Services [HHSO100201000039C]
- Bill and Melinda Gates Foundation [42387]
Effective in vitro evaluation of vaccine adjuvants would allow higher throughput screening compared to in vivo studies. However, vaccine adjuvants comprise a wide range of structures and formulations ranging from soluble TLR agonists to complex lipid-based formulations. The effects of formulation parameters on in vitro bioactivity assays and the correlations with in vivo adjuvant activity is not well understood. In the present work, we employ the Limulus amebocyte lysate assay and a human macrophage cellular cytokine production assay to demonstrate the differences in in vitro bioactivity of four distinct formulations of the synthetic TLR4 agonist GLA: an aqueous nanosuspension (GLA-AF), an oil-in-water emulsion (GLA-SE), a liposome (GLA-LS), and an alum-adsorbed formulation (GLA-Alum). Furthermore, we demonstrate the importance of the localization of GLA on in vitro potency. By comparing to previous published reports on the in vivo bioactivity of these GLA-containing formulations, we conclude that the most potent activators of the in vitro systems may not be the most potent in vivo adjuvant formulations. Furthermore, we discuss the formulation considerations which should be taken into account when interpreting data from in vitro adjuvant activity assays. (C) 2013 Elsevier B.V. All rights reserved.
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