树突状细胞靶向嵌合乙型肝炎病毒免疫治疗疫苗在体内诱导

StephenW

Hum Vaccin Immunother. 2019 Nov 5. doi: 10.1080/21645515.2019.1689081. [Epub ahead of print]
A Dendritic Cell-Targeted Chimeric Hepatitis B Virus Immunotherapeutic Vaccine Induces Both Cellular and Humoral Immune Responses in vivo.
George R1, Ma A1, Motyka B2, Shi YE3, Liu Q4,5,6, Griebel P4,5.
Author information

1
    Akshaya Bio Inc., 8223 Roper Road, Edmonton, Alberta, Canada T6E 6S4.
2
    Department of Pediatrics, University of Alberta, Edmonton, AB, Canada T6G 2E1.
3
    Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
4
    Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), 120 Veterinary Road, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3.
5
    School of Public Health, University of Saskatchewan, 104 Clinic Place, Saskatoon, SK, Canada S7N 2Z4.
6
    Department of Veterinary Microbiology, University of Saskatchewan, 52 Campus DriveR, Saskatoon, SK, Canada S7N 5B4.

Abstract

Chimigen® HBV Immunotherapeutic Vaccine (C-HBV), a recombinant chimeric fusion protein comprising hepatitis B virus (HBV) S1 and S2 surface antigen fragments, Core antigen and a murine monoclonal antibody heavy chain fragment (Fc), was designed and produced in Sf9 insect cells. C-HBV targets the host immune system through specific receptors present on dendritic cells (DCs) which facilitates antigen internalization, processing and presentation on MHC class I and II to induce both cellular and humoral immune responses against HBV antigens. T cell responses, previously assessed by ex vivo antigen presentation assays using human peripheral blood mononuclear cell (PBMC)-derived DCs and T cells from uninfected and HBV chronic infected donors, demonstrated that C-HBV was highly immunogenic. A vaccine dose response study was performed in sheep to analyze the immunogenicity of C-HBV in vivo. Sheep (n = 8/group) received three consecutive subcutaneous injections of each dose of C-HBV at four-week intervals. Analysis of serum antibody levels confirmed C-HBV induced a dose-dependent antibody response to C-HBV and S1/S2-Core. Kinetics of the S1/S2-Core specific antibody response was similar to hepatitis B surface antigen (HBsAg)-specific antibody responses induced by ENGERIX-B. Analysis of cell-mediated immune responses (CMI) confirmed C-HBV induced both dose-dependent S1/S2-Core-specific lymphocyte proliferative responses and IFN-γ secretion. These responses were stronger with blood lymphocytes than with cells isolated from the lymph node draining the vaccination site. No correlation was seen between antibody titres and CMI. The results confirm C-HBV is an effective delivery vehicle for the induction of T cell responses and may be an appropriate candidate for immunotherapy for chronic HBV infections.
KEYWORDS:

Dendritic cells; Fusion Protein; Hepatitis B virus; Immune responses; Immunotherapy; Vaccine

PMID:
    31687875
DOI:
    10.1080/21645515.2019.1689081

StephenW

嗡嗡声疫苗免疫。 2019年11月5日.doi：10.1080 / 21645515.2019.1689081。 [Epub提前发布]
树突状细胞靶向嵌合乙型肝炎病毒免疫治疗疫苗在体内诱导细胞和体液免疫反应。
George R1，Ma A1，Motyka B2，Shi YE3，Liu Q4、5、6，Griebel P4、5。
作者信息

1个
    Akshaya Bio Inc.，8223 Roper Road，Edmonton，Alberta，Canada T6E 6S4。
2
    加拿大艾伯塔省艾伯塔大学，儿科，加拿大，T6G 2E1。
3
    南京医科大学附属第一医院肿瘤科，南京。
4
    疫苗和传染病组织-国际疫苗中心（VIDO-InterVac），加拿大萨斯卡通萨斯喀彻温大学兽医路120号，加拿大，S7N 5E3。
5
    萨斯喀彻温大学公共卫生学院，加拿大，萨斯卡通，诊所地址104，加拿大S7N 2Z4。
6
    萨斯喀彻温大学兽医微生物学系，加拿大萨斯卡通，52 Campus DriveR，加拿大，S7N 5B4。

抽象

设计并生产了Chimigen®HBV免疫治疗疫苗（C-HBV），该重组嵌合蛋白包含乙型肝炎病毒（HBV）S1和S2表面抗原片段，核心抗原和鼠类单克隆抗体重链片段（Fc）。昆虫细胞。 C-HBV通过树突状细胞（DC）上存在的特异性受体靶向宿主免疫系统，该受体促进抗原内化，在I类和II类MHC上的加工和呈递，从而诱导针对HBV抗原的细胞和体液免疫反应。 T细胞反应（以前使用来自未感染和HBV慢性感染供体的人外周血单核细胞（PBMC）衍生的DC和T细胞通过离体抗原呈递分析评估）证明C-HBV具有高度免疫原性。在绵羊中进行了疫苗剂量反应研究，以分析体内C-HBV的免疫原性。绵羊（n = 8 /组）以四周的间隔连续三次皮下注射每种剂量的C-HBV。血清抗体水平的分析证实，C-HBV诱导了对C-HBV和S1 / S2-Core的剂量依赖性抗体反应。 S1 / S2-Core特异性抗体反应的动力学类似于ENGERIX-B诱导的乙型肝炎表面抗原（HBsAg）特异性抗体反应。细胞介导的免疫反应（CMI）的分析证实C-HBV诱导了剂量依赖性S1 / S2-Core特异性淋巴细胞增殖反应和IFN-γ分泌。与从引流接种部位的淋巴结分离的细胞相比，血淋巴细胞的这些反应要强。抗体滴度和CMI之间没有相关性。结果证实，C-HBV是诱导T细胞反应的有效载体，并且可能是慢性HBV感染免疫治疗的合适候选者。
关键字：

树突状细胞；融合蛋白乙型肝炎病毒；免疫反应；免疫疗法疫苗

PMID：
    31687875
DOI：
    10.1080 / 21645515.2019.1689081