Abstract：
:We recently reported that administration of low doses of myotoxins at vaccination sites potentiated antigen-specific T-cell immunity induced by genetic cancer vaccines in mice, an effect which was superior to TLR agonists. In the current study, we found unexpectedly that the mechanism of this potent adjuvant effect was immune-mediated. Myotoxins induced sterile inflammation at vaccination sites, associated with a predominant infiltration of dendritic cells (DC). Inhibition of DC recruitment abrogated the immune stimulation effect of myotoxins, suggesting the requirement for DC. Genetic profiling of myotoxin-treated tissues revealed characteristics of an immune microenvironment with up-regulation of chemokines, proinflammatory cytokines, Toll-like receptors (TLR) and their endogenous ligands, and activation of innate immunity. Mechanistic experiments in vivo also elucidated the requirement for genes triggering DC maturation including TLR signaling and CD40. These studies suggest that myotoxins-induced sterile inflammation generates a favorable microenvironment that promotes multiple stages in the development of adaptive immunity. This novel mechanism of immune potentiation may be exploited for development of adjuvants for genetic vaccines against infectious pathogens and cancer.
journal_name
Vaccinejournal_title
Vaccineauthors
Qin H,Cha SC,Neelapu SS,Liu C,Wang YH,Wei J,Qin XF,Liu YJ,Kwak LWdoi
10.1016/j.vaccine.2010.09.084subject
Has Abstractpub_date
2010-11-23 00:00:00pages
7970-8issue
50eissn
0264-410Xissn
1873-2518pii
S0264-410X(10)01426-Xjournal_volume
28pub_type
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