In:
The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 1_Supplement ( 2009-04-01), p. 96.12-96.12
Abstract:
The efficacy of vaccines can be greatly improved by the addition of adjuvants, which enhance and modify immune responses. At present, few adjuvants are available for human use, and the most common, alum, stimulates immunity that is suboptimal for protection against many infections. We have used computer modeling and virtual screening to identify potential small molecule adjuvants that target specific cell receptors. The chemokine receptor CCR4 was posited as an adjuvant target, based on its expression on CD4+CD25+ regulatory T cells, which normally act to down-regulate immune responses. A high proportion (16%) of small molecules that were predicted by virtual screening to be CCR4 antagonists were able to inhibit CCR4-mediated cellular migration in vitro. Importantly, CCR4 antagonists enhanced human T cell proliferation in an in vitro immune response model and increased T cell and antibody responses in vivo when used in combination with vaccines. The results suggest that in silico screening will prove an aid to the rational design of molecular vaccine adjuvants targetting specific receptors.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.182.Supp.96.12
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2009
detail.hit.zdb_id:
1475085-5
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