In this study, we conjugated the rabies-derived lipopeptide CE536 to a TLR7 agonist, imiquimod, and evaluated its adjuvanticity. The synthetic construct (Lipo-I) targeted to TLR7, induced dendritic cell phenotypic maturation and production of both type I interferon and pro-inflammatory cytokines more efficiently than unconjugated TLR7 ligands or lipopeptide alone. The immunostimulatory effects of the conjugate were apparently the result of I kappa B alpha degradation and sustained p38 and JNK phosphorylation. The analysis of IgG isotypes and T cell differentiation showed that IgG2a dominant Th1-biased humoral and CD8(+) IFN-gamma T cell responses were induced by Lipo-I. Lipo-I could facilitate the rabies vaccine to induce the production of an earlier and more vigorous rabies virus neutralizing antibody. In the post exposure test, the Lipo-I adjuvanted vaccine provided a 73.3% survival rate, while the traditional vaccine bestowed only a 26.7% survival. Therefore, Lipo-I is a promising adjuvant for the development of more effective rabies vaccines. (C) 2016 Elsevier Inc. All rights reserved.
[1]Fudan Univ, Lab Mol Immunol, State Key Lab Genet Engn, Sch Life Sci, Shanghai 200438, Peoples R China
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