TLR8 agonists stimulate newly recruited monocyte-derived cells into potent APCs that enhance HBsAg immunogenicity.
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-gamma 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.
Du
Jun
J
State Key Laboratory of Molecular Oncology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China.
Wu
Zhiyuan
Z
Ren
Shurong
S
Wei
Yong
Y
Gao
Meihua
M
Randolph
Gwendalyn J
GJ
Qu
Chunfeng
C
D000534:Alum Compounds / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011804:Quinolines / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology*; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D051200:Toll-Like Receptor 8 / Q000819:agonists*
D000534:Alum Compounds; D000634:Aminoquinolines; D000914:Antibodies, Viral; C551788:CL 075; C547051:CL097 compound; D006514:Hepatitis B Surface Antigens; D007093:Imidazoles; D007074:Immunoglobulin G; D015848:Interleukin-5; D011804:Quinolines; D013844:Thiazoles; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C546771:gardiquimod; D007371:Interferon-gamma; C402365:resiquimod