Giuseppe
Emeritus
Molecular and cellular signatures of human vaccine adjuvants
F. Mosca*, E. Tritto*, A. Muzzi, E. Monaci, F. Bagnoli, C. Iavarone, D. O'Hagan, R. Rappuoli?, and E. De Gregorio?
-Author Affiliations: Novartis Vaccines and Diagnostics, 53100 Siena, Italy
Contributed by R. Rappuoli, May 19, 2008 - *F.M. and E.T. contributed equally to this work. (received for review April 16, 2008)
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.
Keywords: innate immunity microarray MF59 alum CpG oligonucleotide
Footnotes
?To whom correspondence may be addressed. E-mail: ennio.de_gregorio@novartis.com or rino.rappuoli@novartis.com Author contributions: D.O., R.R., and E.D.G. designed research; F.M., E.T., E.M., F.B., and C.I. performed research; A.M. analyzed data; and F.M., E.T., R.R., and E.D.G. wrote the paper.
Conflict of interest statement: R.R., F.M., E.T., A.M., E.M., F.B., C.I., D.O., and E.D.G. are employees of Novartis Vaccines and Diagnostics.
Data deposition: The complete set of microarray data has been submitted to the ArrayExpress database European Molecular Biology Laboratory?European Bioinformatics Institute, www.ebi.ac.uk/arrayexpress (accession no. E-TABM-506).
This article contains supporting information online at www.pnas.org/cgi/content/full/0804699105/DCSupplemental.
http://www.pnas.org/content/105/30/10501.short?rss=1
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F. Mosca*, E. Tritto*, A. Muzzi, E. Monaci, F. Bagnoli, C. Iavarone, D. O'Hagan, R. Rappuoli?, and E. De Gregorio?
-Author Affiliations: Novartis Vaccines and Diagnostics, 53100 Siena, Italy
Contributed by R. Rappuoli, May 19, 2008 - *F.M. and E.T. contributed equally to this work. (received for review April 16, 2008)
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.
Keywords: innate immunity microarray MF59 alum CpG oligonucleotide
Footnotes
?To whom correspondence may be addressed. E-mail: ennio.de_gregorio@novartis.com or rino.rappuoli@novartis.com Author contributions: D.O., R.R., and E.D.G. designed research; F.M., E.T., E.M., F.B., and C.I. performed research; A.M. analyzed data; and F.M., E.T., R.R., and E.D.G. wrote the paper.
Conflict of interest statement: R.R., F.M., E.T., A.M., E.M., F.B., C.I., D.O., and E.D.G. are employees of Novartis Vaccines and Diagnostics.
Data deposition: The complete set of microarray data has been submitted to the ArrayExpress database European Molecular Biology Laboratory?European Bioinformatics Institute, www.ebi.ac.uk/arrayexpress (accession no. E-TABM-506).
This article contains supporting information online at www.pnas.org/cgi/content/full/0804699105/DCSupplemental.
http://www.pnas.org/content/105/30/10501.short?rss=1
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