Generation of an immune microenvironment as a novel mechanism for myotoxins to potentiate genetic vaccines

Hong Qin, Soung chul Cha, Sattva S. Neelapu, Chengwen Liu, Yi Hong Wang, Jinsong Wei, Xiao Feng Qin, Yong Jun Liu, Larry W. Kwak

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7970-7978
Number of pages9
Issue number50
StatePublished - Nov 23 2010


  • Adaptive T-cell immunity
  • Immune adjuvant
  • Immune microenvironment
  • Myotoxin

ASJC Scopus subject areas

  • Molecular Medicine
  • General Immunology and Microbiology
  • General Veterinary
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases


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