title: Inadequate activation of the HBsAg-specific Th cells by APCs leads to hyporesponsiveness to HBsAg vaccine in B10.S mice.
abstract: Hepatitis B can be effectively prevented by hepatitis B vaccination. However, hyporesponse to the hepatitis B vaccine has been found in both human and inbred mice with particular MHC alleles or haplotypes, but the mechanisms underlying this poor response remains elusive. In the present study, we investigated the mechanisms underlying the hyporesponse to hepatitis B vaccination using B10.S-H2s/SgMcdJ (B10.S, H-2(s), poor responder) and C57BL/10J (B10, H-2(b), good responder) mice. We observed that the B10.S mice displayed a hyporesponse to HBsAg vaccine but a normal response to 3 other foreign antigens (influenza A (H1N1) 2009 monovalent vaccine, tetanus toxoid and ovalbumin). In B10.S mice immunized with HBsAg, the levels of serum anti-HBs IgG, the number of HBsAg-specific IgG-secreting plasma cells and HBsAg-specific Th cells were considerably lower than that in B10 mice. Further, the findings of the insufficient maturation (CD86), co-stimulation (CD40) and migration (CCR7) activities of DCs together with the inadequate activation of the HBsAg-specific Th cells by APCs were identified as part of the reason for the HBsAg hyporesponse in B10.S mice, which supports the hypothesis that measures aimed at promoting the maturation, co-stimulation or migration of APCs to enhance Th cell activation may be a useful strategy for the development of new hepatitis B vaccines.
authors.affiliation: a Key Laboratory of Medical Molecular Virology of MOE and MOH; School of Basic Medical Sciences; Fudan University ; Shanghai , China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Lv
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Shuhui
authors.initials: S
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: He
authors.forename: Di
authors.initials: D
authors.lastname: Qu
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D051940:B7-2 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology; D006508:Hepatitis Antibodies / Q000032:analysis / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis; D007273:Injections, Intramuscular; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000276:immunology; D054400:Receptors, CCR7 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; D006508:Hepatitis Antibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D054400:Receptors, CCR7
keywords: B10 mice; B10.S mice; H-2; HBsAg; low response to hepatitis B vaccine