Calcineurin B subunit triggers innate immunity and acts as a novel Engerix-B HBV vaccine adjuvant.
We showed previously that calcineurin B subunit (CnB) protein activates innate immune cells including macrophages, monocytes and dendritic cells and acts as an adjuvant of a model antigen (ovalbumin) and a recombinant pneumolysin antigen, but the detailed mechanism is not clear and whether it can serve as an adjuvant of a commercial HBV vaccine is unknown. Here, we report that CnB promotes inflammatory cytokines production, splenocytes proliferation and NK lytic activity, and that CnB-induced inflammatory cytokines (IFN-γ, IL-6, TNF-α) production is dependent on integrin αM. Animal experiments demonstrate that CnB markedly increases the total anti-HBs antibodies in a dose and time dependent manner. Furthermore, CnB increases both anti-HBs IgM and anti-HBs IgG titers and changes the balance of IgG2a and IgG1. Combined use of CnB and CpG induces more cytokines production in splenocytes, as well as more anti-HBs antibodies production in vivo. These results reveal a probable mechanism of CnB-induced inflammatory cytokines production and further demonstrate that CnB is a novel and effective adjuvant of Engerix-B HBV vaccine.
Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, PR China.
Minling
M
Hu
Zhenyi
Z
Su
Yanxia
Y
Yin
Jing
J
Li
Qun
Q
Wei
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D019703:Calcineurin / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control; D017325:Hepatitis B Vaccines / Q000276:immunology*; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D021122:Protein Subunits / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D039481:CD11b Antigen; D016207:Cytokines; C075654:Engerix-B; D006508:Hepatitis Antibodies; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D021122:Protein Subunits; D014614:Vaccines, Synthetic; D019703:Calcineurin