000219702 001__ 219702
000219702 005__ 20181203024308.0
000219702 0247_ $$2doi$$a10.1016/j.vaccine.2016.03.057
000219702 022__ $$a0264-410X
000219702 02470 $$2ISI$$a000375808000008
000219702 037__ $$aARTICLE
000219702 245__ $$aFibronectin EDA and CpG synergize to enhance antigen-specific Th1 and cytotoxic responses
000219702 269__ $$a2016
000219702 260__ $$aOxford$$bElsevier Sci Ltd$$c2016
000219702 300__ $$a7
000219702 336__ $$aJournal Articles
000219702 520__ $$aSubunit 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. (C) 2016 The Authors. Published by Elsevier Ltd.
000219702 6531_ $$aPattern recognition receptors
000219702 6531_ $$aToll-like receptors
000219702 6531_ $$aAdjuvant
000219702 6531_ $$aAdaptive immunity
000219702 6531_ $$aCancer vaccine
000219702 6531_ $$aHepatitis B virus
000219702 6531_ $$aCpG
000219702 6531_ $$aFNIII EDA
000219702 700__ $$aJulier, Ziad$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000219702 700__ $$aDe Titta, Alexandre
000219702 700__ $$aGrimm, Alizee J.$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000219702 700__ $$aSimeoni, Eleonora$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000219702 700__ $$0242992$$aSwartz, Melody A.$$g160091$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000219702 700__ $$0240350$$aHubbell, Jeffrey A.$$g141360$$uEcole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland
000219702 773__ $$j34$$k21$$q2453-2459$$tVaccine
000219702 909C0 $$0252196$$pLMRP$$xU11032
000219702 909C0 $$0252115$$pLLCB$$xU11747
000219702 909CO $$ooai:infoscience.tind.io:219702$$particle
000219702 937__ $$aEPFL-ARTICLE-219702
000219702 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000219702 980__ $$aARTICLE