TY - JOUR
T1 - TLR8 agonists stimulate newly recruited monocyte-derived cells into potent APCs that enhance HBsAg immunogenicity
AU - Du, Jun
AU - Wu, Zhiyuan
AU - Ren, Shurong
AU - Wei, Yong
AU - Gao, Meihua
AU - Randolph, Gwendalyn J.
AU - Qu, Chunfeng
N1 - Funding Information:
This work was supported by a grant from National Natural Science Foundation of China , 30872301 . The authors are grateful to Dr. Zongtang Sun at Cancer Institute of CAMS for his critical review and valuable comments to the manuscripts.
PY - 2010/8
Y1 - 2010/8
N2 - We previously reported that synthetic or natural Toll-like receptor (TLR) 7/8 agonists present within dead cells enhanced cell-associated antigen presentation both in vitro and in vivo. Here, we investigated the immunopotency of different chemically synthesized TLR7/8 agonists, Resiquimod, Gardiquimod, CL075, and CL097, on HBsAg immunogenicity. These agonists stimulated inflammatory monocyte-derived cells to become potent antigen-presenting dendritic cells (DCs), which augmented HBsAg specific T cell proliferation after they were conditioned with HBsAg. The TLR8 agonist CL075 and the TLR7/8 dual agonist CL097 showed more potent effects than the TLR7 agonist. Compared with alum adjuvant, when HBsAg mixed with CL075 was injected intramuscularly into mice, more monocyte-derived DCs carried antigens into draining lymph nodes and spleens. Specific Abs, particularly IgG2a, were significantly increased, and more IL-5 and IFN-γ were produced by splenocytes and intrahepatic immunocytes in mice that received HBsAg mixed with CL075 and CL097. These results suggest that TLR8 agonists are good candidates to enhance recombinant HBsAg immunogenicity to induce specific humoral and cellular immune responses.
AB - We previously reported that synthetic or natural Toll-like receptor (TLR) 7/8 agonists present within dead cells enhanced cell-associated antigen presentation both in vitro and in vivo. Here, we investigated the immunopotency of different chemically synthesized TLR7/8 agonists, Resiquimod, Gardiquimod, CL075, and CL097, on HBsAg immunogenicity. These agonists stimulated inflammatory monocyte-derived cells to become potent antigen-presenting dendritic cells (DCs), which augmented HBsAg specific T cell proliferation after they were conditioned with HBsAg. The TLR8 agonist CL075 and the TLR7/8 dual agonist CL097 showed more potent effects than the TLR7 agonist. Compared with alum adjuvant, when HBsAg mixed with CL075 was injected intramuscularly into mice, more monocyte-derived DCs carried antigens into draining lymph nodes and spleens. Specific Abs, particularly IgG2a, were significantly increased, and more IL-5 and IFN-γ were produced by splenocytes and intrahepatic immunocytes in mice that received HBsAg mixed with CL075 and CL097. These results suggest that TLR8 agonists are good candidates to enhance recombinant HBsAg immunogenicity to induce specific humoral and cellular immune responses.
KW - Cellular immune responses
KW - Monocyte-derived dendritic cells
KW - TLR8 agonists
UR - http://www.scopus.com/inward/record.url?scp=77955656853&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2010.06.117
DO - 10.1016/j.vaccine.2010.06.117
M3 - Article
C2 - 20637759
AN - SCOPUS:77955656853
SN - 0264-410X
VL - 28
SP - 6273
EP - 6281
JO - Vaccine
JF - Vaccine
IS - 38
ER -