Molecular and cellular signatures of human vaccine adjuvants.
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.
Mosca
F
F
Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
Tritto
E
E
Muzzi
A
A
Monaci
E
E
Bagnoli
F
F
Iavarone
C
C
O'Hagan
D
D
Rappuoli
R
R
De Gregorio
E
E
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000534:Alum Compounds / Q000737:chemistry; D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007252:Influenza Vaccines / Q000737:chemistry*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D011136:Polysorbates / Q000494:pharmacology; D052097:Quadriceps Muscle / Q000378:metabolism; D013185:Squalene / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D039481:CD11b Antigen; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; C041524:aluminum sulfate; D013185:Squalene