Molecular and cellular signatures of human vaccine adjuvants

被引：364

作者：

Mosca, F. ^{[1
]}

Tritto, E. ^{[1
]}

Muzzi, A. ^{[1
]}

Monaci, E. ^{[1
]}

Bagnoli, F. ^{[1
]}

Iavarone, C. ^{[1
]}

O'Hagan, D. ^{[1
]}

Rappuoli, R. ^{[1
]}

De Gregorio, E. ^{[1
]}

机构：

[1] Novartis Vaccines & Diagnost, I-53100 Siena, Italy

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 30期

关键词：

innate immunity; microarray; MF59; alum; CpG; oligonucleotide;

D O I：

10.1073/pnas.0804699105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：10501 / 10506

页数：6

共 30 条

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