title: The orchestration of cellular and humoral responses is facilitated by divergent intracellular antigen trafficking in nanoparticle-based therapeutic vaccine.
abstract: Therapeutic vaccination for the treatment of chronic hepatitis B is promising but has so far shown limited clinical efficacy. Herein, we employ polylactide nanoparticles (NPs) as the vaccine adjuvant and systematically explore their effect on activation of specific immunity and the underlying theoretical mechanisms. In vitro studies show that hepatitis B surface antigen (HBsAg) accumulates in antigen-presenting cells (APCs) to a larger content (270%) with the assistant of NP in comparison with the pure-antigen group. Besides the elevated costimulators (CD80/86) and increased major histocompatibility complex (MHC) II molecules, the MHC I molecules are also found upregulated. This result is mostly owing to the divergent antigen trafficking ways of NP-antigen in APCs, especially for the escape of exogenous HBsAg from the lysosomes to the cytosol. Interestingly, the MHC I level is downregulated in alum-antigen group, indicating a possible reason for its inefficiency in priming cellular response. Further in vivo experiments establish that NP-antigen group indeed enhances the CD8(+) CTL cytotoxicity and IFN-γ cytokine secretion. Meanwhile, specific antibody titer is also upregulated, and even surpasses that of the commercialized alum-antigen. All these results strongly support that NP-based antigen promotes an orchestration of cellular and humoral immune response, exhibiting favorable intrinsic properties to be applied in therapeutic vaccines.
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, PR China.
authors: Hua
authors: H
authors: Yue
authors: Wei
authors: W
authors: Wei
authors: Bei
authors: B
authors: Fan
authors: Zhanguo
authors: Z
authors: Yue
authors: Lianyan
authors: L
authors: Wang
authors: Guanghui
authors: G
authors: Ma
authors: Zhiguo
authors: Z
authors: Su
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport / Q000276:immunology; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D011091:Polyesters / Q000008:administration & dosage; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000941:Antigens; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011091:Polyesters; D014612:Vaccines; C033616:poly(lactide); D007371:Interferon-gamma