Molecular and Cellular Response Profiles Induced by the TLR4 Agonist-Based Adjuvant Glucopyranosyl Lipid A

• DOI: 10.1371/journal.pone.0051618
• Publication Date: 2012-12-28T22:26:20Z
• Authors: Stacie L. Lambert; Chin-Fen Yang; Zheng Liu; Rosemary Sweetwood; Jackie Zhao; Lily Cheng; Hong Jin; Jennifer Woo
• Keywords: TRIF

Background Toll-like receptor (TLR)4 agonists are known potent immunostimulatory compounds. These compounds can be formulated as part of novel adjuvants to enhance vaccine medicated immune responses. However, the contribution formulation innate in vivo activity TLR4 agonist is not well understood. Methodology and Principal Findings We evaluated synthetic Glucopyranosyl Lipid A (GLA) for its effects on molecular cellular responses murine model. Microarray techniques were used compare GLA an aqueous or oil-in-water Stable Emulsion (GLA-SE) versus either SE alone mineral salt aluminum hydroxide (alum) at muscle injection site over multiple timepoints. In contrast minimal gene upregulation induced by alum, both GLA-SE triggered MyD88- TRIF-dependent expression. Genes chemokines, cytokine receptors, signaling molecules, complement, antigen presentation also strongly upregulated GLA-SE. included chemokines TH1-type T cells (CXCL9 CXCL10) mononuclear leukocytes (CCL2, CCL3) among others. stronger more sustained than muscle; genes detected local draining lymph nodes lower levels peripheral blood. Both resulted increased trafficking MHC molecules ICAM1 dendritic cells. transiently circulating MCP-1, TNFα, IFNγ IP-10 Conclusions/Significance While activate a large number shared proteins, induces quantitatively qualitatively response GLA, alum. The proteins could facilitate selection appropriate adjuvant doses formulations.