Biopharmaceuticals Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar, M.P. 470003, India.
Int J Pharm. 2011 Apr 15;408(1-2):50-7. doi: 10.1016/j.ijpharm.2011.01.045. Epub 2011 Feb 1.
Presently available marketed alum adsorbed hepatitis B vaccine used for prophylactic immunization, can effectively elicit humoral immunity but is poor inducer of cell-mediated immunity (CMI). Besides, conventional alum-adjuvant vaccines require multiple injections to achieve long-lasting protective immune responses. Therefore, as a result of insufficient immunization, infections are still the leading killer among diseases. The present investigation was therefore, aimed at developing "single-shot" HBsAg adsorbed microspheres of poly (DL)-lactide-co-glycolide (PLGA) (L/G 50:50 and 75:25) and their capability to stimulate the cell mediated immune response against hepatitis B surface antigen. These microspheres were characterized in vitro for their size, shape polydispersity index, percentage HBsAg adsorption efficiency and in vitro release profile. The immune-stimulating activities were also studied following subcutaneous injection of HBsAg adsorbed PLGA microspheres (single-dose on day 0) and compared with alum adsorbed vaccines (two-doses on 0 and 28 days) in Balb/c mice. Specific cell-mediated immune responses such as lymphocyte transformation assay (stimulation-index) including release of interferon-gamma (IFN-γ), interleukin-2 (IL-2) and nitric-oxide were determined. Cellular responses in case of alum adsorb HBsAg vaccine was very low. These studies demonstrate the potential of cationic polymeric microspheres based vaccine in stimulating cell mediated immune response along with humoral response against hepatitis B.
目前市售的明矾吸附乙型肝炎疫苗用于预防性免疫接种，能有效地引起体液免疫，但对细胞介导的免疫（CMI）的诱导作用较差。此外，常规的明矾佐剂疫苗需要多次注射才能产生持久的保护性免疫应答。因此，由于免疫接种不足，感染仍然是疾病中的主要杀手。本研究旨在开发“单剂量”乙型肝炎表面抗原吸附聚（DL）-丙交酯-co-乙交酯（PLGA）（L/G50:50 和 75:25）微球及其刺激乙型肝炎表面抗原细胞介导免疫应答的能力。这些微球在体外进行了特征描述，包括大小、形状多分散指数、HBsAg 吸附效率百分比和体外释放曲线。还研究了皮下注射 HBsAg 吸附 PLGA 微球（第 0 天单剂量）后的免疫刺激活性，并与明矾吸附疫苗（第 0 天和第 28 天两剂）在 Balb/c 小鼠中进行了比较。测定了特定的细胞介导免疫反应，如淋巴细胞转化试验（刺激指数），包括干扰素-γ（IFN-γ）、白细胞介素-2（IL-2）和一氧化氮的释放。明矾吸附 HBsAg 疫苗的细胞反应非常低。这些研究表明，阳离子聚合物微球疫苗具有刺激乙型肝炎体液免疫和细胞介导免疫的潜力。
