000195422 001__ 195422
000195422 005__ 20181203023406.0
000195422 0247_ $$2doi$$a10.1073/pnas.1313152110
000195422 022__ $$a0027-8424
000195422 02470 $$2ISI$$a000327744900059
000195422 037__ $$aARTICLE
000195422 245__ $$aNanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose
000195422 269__ $$a2013
000195422 260__ $$aWashington$$bNatl Acad Sciences$$c2013
000195422 300__ $$a6
000195422 336__ $$aJournal Articles
000195422 520__ $$aIn subunit vaccines, strong CD8(+) T-cell responses are desired, yet they are elusive at reasonable adjuvant doses. We show that targeting adjuvant to the lymph node (LN) via ultrasmall polymeric nanoparticles (NPs), which rapidly drain to the LN after intradermal injection, greatly enhances adjuvant efficacy at low doses. Coupling CpG-B or CpG-C oligonucleotides to NPs led to better dual-targeting of adjuvant and antigen (codelivered on separate NPs) in cross-presenting dendritic cells compared with free adjuvant. This led to enhanced dendritic cell maturation and T helper 1 (Th1)-cytokine secretion, in turn driving stronger effector C8(+) T-cell activation with enhanced cytolytic profiles and, importantly, more powerful memory recall. With only 4 mu g CpG, NP-CpG-B could substantially protect mice from syngeneic tumor challenge, even after 4 mo of vaccination, compared with free CpG-B. Together, these results show that nanocarriers can enhance vaccine efficacy at a low adjuvant dose for inducing potent and long-lived cellular immunity.
000195422 700__ $$aDe Titta, Alexandre
000195422 700__ $$aBallester, Marie$$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland
000195422 700__ $$aJulier, Ziad$$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland
000195422 700__ $$aNembrini, Chiara$$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland
000195422 700__ $$aJeanbart, Laura$$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland
000195422 700__ $$aVlies, Van Der
000195422 700__ $$aAndre, J.$$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland
000195422 700__ $$0242992$$aSwartz, Melody A.$$g160091$$uEcole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland
000195422 700__ $$0240350$$aHubbell, Jeffrey A.$$g141360
000195422 773__ $$j110$$k49$$q19902-19907$$tProceedings Of The National Academy Of Sciences Of The United States Of America
000195422 909C0 $$0252196$$pLMRP$$xU11032
000195422 909C0 $$0252115$$pLLCB$$xU11747
000195422 909CO $$ooai:infoscience.tind.io:195422$$particle
000195422 917Z8 $$x141360
000195422 937__ $$aEPFL-ARTICLE-195422
000195422 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000195422 980__ $$aARTICLE