Nanovaccine for immunotherapy and reduced hepatitis-B virus in humanized model

被引:18
作者
Dewangan, Hitesh Kumar [1 ]
Pandey, Tarun [2 ]
Singh, Sanjay [1 ]
机构
[1] Banaras Hindu Univ, Indian Inst Technol, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India
[2] Sanjay Gandhi Mem Hosp, Anaesthesia & Crit Care, New Delhi, India
关键词
Chronic hepatitis B virus; PLGA nanoparticles; xenograft mice; nanovaccine; HUMAN/MOUSE RADIATION CHIMERA; BONE-MARROW-TRANSPLANTATION; HUMAN MONOCLONAL-ANTIBODIES; THERAPEUTIC VACCINATION; MOUSE MODEL; DNA; IMMUNIZATION; REPLICATION; LYMPHOCYTES; RESPONSES;
D O I
10.1080/21691401.2017.1408118
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Chronic Hepatitis B Virus (HBV) infections are severe with weak antiviral immune responses. The lack of an appropriate small animal model for chronic hepatitis, a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B viral (HBV) infection. In this study, for enhancing the antibody production efficiency the prepared polymeric HBsAg-loaded nanoparticles (nanovaccine) will be tested in immune-deficit mice, which suffer from chronic Hepatitis B virus. Vaccination of Balb/c mice by this prepared nanoparticles that were engrafted with peripheral blood mononuclear cells (PBMCs), which was already lethally irradiated and transplanted by the bone marrow of NOD (knockout mice) mice. In the present study, after the vaccination detected the high frequencies of immunoglobulin G (IgG)-secreting B cells and mitogen-responsive interferon-Y (IFN-Y) secreting T cells in serum, determined by specific ELISA technique. During the entire observation period, unvaccinated animals showed lower concentration of specific IgG secreting B cells and IFN-Y secreting T cells found in comparison to vaccinated mice group. Chronic HBV carrier PBMCs transplanted into the chimera failed to produce antigen and increased the antibodies production due to vaccination. Furthermore, another advantage was that the viral gene expression and viral DNA replication was no longer observed in vaccinated group. This prepared nanovaccine formulations is better for the cure of Hepatitis B viral infection carrier. Therefore, specific memory responses were elicited by vaccination with Hepatitis B virus surface (HBsAg) antigen of chimeric mice transplanted with PBMCs derived from HBV donors.
引用
收藏
页码:2033 / 2042
页数:10
相关论文
共 50 条
  • [1] Human complement receptor 2 (CR2/CD21) as a receptor for DNA: Implications for its roles in the immune response and the pathogenesis of systemic lupus erythematosus (SLE)
    Asokan, Rengasamy
    Banda, Nirmal K.
    Szakonyi, Gerda
    Chen, Xiaojiang S.
    Holers, V. Michael
    [J]. MOLECULAR IMMUNOLOGY, 2013, 53 (1-2) : 99 - 110
  • [2] Böcher WO, 1999, IMMUNOLOGY, V96, P634
  • [3] Reduced hepatitis B virus surface antigen-specific Th1 helper cell frequency of chronic HBV carriers is associated with a failure to produce antigen-specific antibodies in the trimera mouse
    Böcher, WO
    Galun, E
    Marcus, H
    Daudi, N
    Terkieltaub, D
    Shouval, D
    Löhr, HF
    Reisner, Y
    [J]. HEPATOLOGY, 2000, 31 (02) : 480 - 487
  • [4] ANTI-PRE-S RESPONSES AND VIRAL CLEARANCE IN CHRONIC HEPATITIS-B VIRUS-INFECTION
    BUDKOWSKA, A
    DUBREUIL, P
    POYNARD, T
    MARCELLIN, P
    LORIOT, MA
    MAILLARD, P
    PILLOT, J
    [J]. HEPATOLOGY, 1992, 15 (01) : 26 - 31
  • [5] Engrafted human T and B lymphocytes form mixed follicles in lymphoid organs of human/mouse and human/rat radiation chimera
    Burakova, T
    Marcus, H
    Canaan, A
    Dekel, B
    Shezen, E
    David, M
    Lubin, I
    Segal, H
    Yair, R
    [J]. TRANSPLANTATION, 1997, 63 (08) : 1166 - 1171
  • [6] Toward elimination and eradication of hepatitis B
    Chen, Ding-Shinn
    [J]. JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2010, 25 (01) : 19 - 25
  • [7] Nucleos(t)ide analogues for hepatitis B virus: Strategies for long-term success
    Chien, Rong-Nan
    Liaw, Yun-Fan
    [J]. BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY, 2008, 22 (06) : 1081 - 1092
  • [8] HEPATITIS-B VIRUS IMMUNOPATHOGENESIS
    CHISARI, FV
    FERRARI, C
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1995, 13 : 29 - 60
  • [9] Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus
    Dandri, M
    Burda, MR
    Török, E
    Pollok, JM
    Iwanska, A
    Sommer, G
    Rogiers, X
    Rogler, CE
    Gupta, S
    Will, H
    Greten, H
    Petersen, J
    [J]. HEPATOLOGY, 2001, 33 (04) : 981 - 988
  • [10] Intranasal immunization with recombinant antigens associated with new cationic particles induces strong mucosal as well as systemic antibody and CTL responses
    Debin, A
    Kravtzoff, R
    Santiago, JV
    Cazales, L
    Sperandio, S
    Melber, K
    Janowicz, Z
    Betbeder, D
    Moynier, M
    [J]. VACCINE, 2002, 20 (21-22) : 2752 - 2763