Molecular and cellular signatures of human vaccine adjuvants.

Abstract:

:Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 induced a time-dependent change in the expression of 891 genes, whereas CpG and alum regulated 387 and 312 genes, respectively. All adjuvants modulated a common set of 168 genes and promoted antigen-presenting cell recruitment. MF59 was the stronger inducer of cytokines, cytokine receptors, adhesion molecules involved in leukocyte migration, and antigen-presentation genes. In addition, MF59 triggered a more rapid influx of CD11b+ blood cells compared with other adjuvants. The early biomarkers selected by microarray, JunB and Ptx3, were used to identify skeletal muscle as a direct target of MF59. We propose that oil-in-water emulsions are the most efficient human vaccine adjuvants, because they induce an early and strong immunocompetent environment at the injection site by targeting muscle cells.

authors

Mosca F,Tritto E,Muzzi A,Monaci E,Bagnoli F,Iavarone C,O'Hagan D,Rappuoli R,De Gregorio E

doi

10.1073/pnas.0804699105

subject

Has Abstract

pub_date

2008-07-29 00:00:00

pages

10501-6

issue

30

eissn

0027-8424

issn

1091-6490

pii

0804699105

journal_volume

105

pub_type

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