Tetanus antigen modulates the gene expression profile of aluminum phosphate adjuvant in spleen lymphocytes in vivo.
Adjuvants play an important role in stimulation of the immune response to antigens. Very little is known about the molecular mechanisms of this stimulation. Here we address this issue by studying gene expression profiles from spleen lymphocytes after in vivo immunization of mice with a clinically relevant vaccine, tetanus toxoid formulated with aluminum phosphate as adjuvant (TT(ADJ)), or the adjuvant alone (ADJ). The Th1/Th2 response to TT(ADJ) was obtained from a combination of up- and downstream markers to conventional cytokines, which were in good agreement with cytokine protein levels. A clustering algorithm revealed that ADJ elicited expression of 47 genes active in cytotoxic lymphocytes, inflammation, oncogenesis, stress, toxicity and cell cycle regulation. In TT(ADJ) these adjuvant-elicited genes were expressed at lower levels and a compensatory onset of protective and inhibitory genes was observed. We conclude that the antigen, to a larger extent than previously recognized, modulates the molecular mechanism of the aluminum phosphate adjuvant and that the identified genes may serve as predictive biomarkers in the development of new adjuvants and vaccines.
Regnström
K
K
Department of Pharmacy, Uppsala University, Sweden. Karin.Regnstrom@farmaci.uu.se
Ragnarsson
E G E
EG
Rydell
N
N
Sjöholm
I
I
Artursson
P
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D007114:Immunization; D007249:Inflammation / Q000209:etiology; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010710:Phosphates / Q000494:pharmacology*; D011519:Proto-Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013745:Tetanus Toxoid / Q000276:immunology*
D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D010710:Phosphates; D013745:Tetanus Toxoid; C012714:aluminum phosphate