a Department of Pharmaceutics , Indian Institute of Technology (Banaras Hindu University) , Varanasi , India.
b Anaesthesia and Critical Care , Sanjay Gandhi Memorial Hospital , New Delhi , India.
Artif Cells Nanomed Biotechnol. 2018 Dec;46(8):2033-2042. doi: 10.1080/21691401.2017.1408118. Epub 2017 Nov 27.
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.
慢性乙型肝炎病毒(HBV)感染具有较弱的抗病毒免疫反应,病情严重。缺乏合适的慢性肝炎小动物模型是研究乙型肝炎病毒(HBV)感染诱导的免疫耐受和免疫发病机制的主要障碍。在这项研究中,为了提高抗体产生效率,将制备的载有乙型肝炎表面抗原的聚合物纳米颗粒(纳米疫苗)用于免疫缺陷小鼠,这些小鼠患有慢性乙型肝炎病毒。通过将已经致死性辐照并由 NOD(基因敲除小鼠)骨髓移植的外周血单核细胞(PBMC)移植到 Balb/c 小鼠中,用这种制备的纳米颗粒对其进行疫苗接种。在本研究中,通过特异性 ELISA 技术检测到疫苗接种后血清中免疫球蛋白 G(IgG)分泌 B 细胞和有丝分裂原反应性干扰素-Y(IFN-Y)分泌 T 细胞的高频。在整个观察期间,与接种疫苗的小鼠组相比,未接种疫苗的动物显示出较低浓度的特异性 IgG 分泌 B 细胞和 IFN-Y 分泌 T 细胞。转染到嵌合体中的慢性 HBV 携带者 PBMC 未能产生抗原,并且由于疫苗接种而增加了抗体产生。此外,另一个优点是接种疫苗后不再观察到病毒基因表达和病毒 DNA 复制。这种制备的纳米疫苗制剂更有利于治疗乙型肝炎病毒感染携带者。因此,用来自 HBV 供体的 PBMC 转染的嵌合小鼠的乙型肝炎表面(HBsAg)抗原接种引发了特异性记忆反应。