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Molecular and cellular signatures of human vaccine adjuvants.

Mosca, F and Tritto, Elaine and Muzzi, A and Monaci, Elisabetta and Bagnoli, Fabio and Iavarone, C and O'Hagan, D and Rappuoli, Rino and De Gregorio, Ennio (2008) Molecular and cellular signatures of human vaccine adjuvants. Proceedings of the National Academy of Sciences of the United States of America, 105 (30). pp. 10501-10506. ISSN 1091-6490

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.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: innate immunity; microarray; MF59; alum; CpG; oligonucleotide
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Date Deposited: 14 Dec 2009 13:55
Last Modified: 14 Dec 2009 13:55
URI: https://oak.novartis.com/id/eprint/687

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