Levamisole is a potential facilitator for the activation of Th1 responses of the subunit HBV vaccination.
Chemical compounds activating innate responses may present potential adjuvants for the vaccine development. Levamisole (LMS), demonstrated as a potent adjuvant for DNA and viral killed vaccines in our previous studies, may activate such responses. To confirm this notion, LMS combined with the recombinant HBsAg (rHBsAg) was investigated. Compared to the vaccination with rHBsAg alone, LMS could up-regulate the expressions of TLR7&8, MyD88, IRF7 and their downstream pro-inflammatory cytokines including IFN-alpha and TNF-alpha, which promote DCs activation. Strikingly, we find that the combination of LMS and alum adjuvant synergistically enhances immunogenicity of rHBsAg and leads to a robust cell-mediated response demonstrated by the higher level of IgG2a/IgG1, T cell proliferation, and importantly, a high level of antigen-specific CTL and IFN-gamma production within these activated CD8(+) T cells. The achieved robust responses are at a comparative level with CpG+alum used as a positive control adjuvant in mice. The combination of LMS+alum with rHBsAg may provide a cost-effective, safe, and effective therapy to treat those individuals chronically infected by HBV, since antigen-specific cellular immunity is implicated for the clearance of HBV chronic infection.
Zhang
Wenjuan
W
State Key Laboratory for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, 2 Yuanmingyuan Xi Road, Beijing 100094, China.
Du
Xiaogang
X
Zhao
Gang
G
Jin
Huali
H
Kang
Youmin
Y
Xiao
Chong
C
Liu
Mingyu
M
Wang
Bin
B
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000534:Alum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D050839:Interferon Regulatory Factor-7 / Q000096:biosynthesis; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D007978:Levamisole / Q000008:administration & dosage / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000096:biosynthesis; D051200:Toll-Like Receptor 8 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D022223:Vaccines, Subunit / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; C494235:Irf7 protein, mouse; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha; D022223:Vaccines, Subunit; D007978:Levamisole; C041524:aluminum sulfate; D007371:Interferon-gamma