Fibronectin EDA and CpG synergize to enhance antigen-specific Th1 and cytotoxic responses

Ziad Julier, Alexandre De Titta, Alizée J. Grimm, Eleonora Simeoni, Melody A. Swartz, Jeffrey A. Hubbell

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)


Subunit vaccines, employing purified protein antigens rather than intact pathogens, require the addition of adjuvants for enhanced immunogenicity with a correct balance between strong activation of the immune system and low toxicity. Here we show that the endogenous (i.e., autologous) non-toxic TLR4 agonist extra domain A type III repeat of fibronectin (FNIII EDA) can synergize with the exogenous (i.e., bacterial), toxic-at-high-dose, TLR9 agonist CpG to induce efficient cellular immune responses while keeping the dose of CpG low. The efficacy of the combined TLR agonists, even at half-doses, led to stronger dendritic cell activation, enhanced cytotoxic T lymphocyte activation as well as stronger humoral response, compared to the individual agonists given at full doses. Immune cells induced after vaccination with the co-adjuvanted formulation could mediate tumor regression in an E.G7-OVA tumor model, and eradicate circulating hepatitis B virus (HBV) in a transgenic HBV model. Together, these results show that endogenous TLR agonists, such as variants of FNIII EDA, can synergize with exogenous TLR ligands, such as CpG, and strongly enhance cellular immune responses, while improving their safety profile.

Original languageEnglish
Pages (from-to)2453-2459
Number of pages7
Issue number21
Publication statusPublished - 5 May 2016
Externally publishedYes


  • Adaptive immunity
  • Adjuvant
  • Cancer vaccine
  • CpG
  • Hepatitis B virus
  • Pattern recognition receptors
  • Toll-like receptors

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