Anugraha Gandhirajan, Madhumathi Jayaprakasam, Jeya Prita Parasurama Jawaharlal, Kaliraj Perumal
Centre for Biotechnology, Anna University, Chennai 600025, India.
Centre for Biotechnology, Anna University, Chennai 600025, India.
Eur J Pharmacol. 2015 Jan 15;747:174-80. doi: 10.1016/j.ejphar.2014.12.004. Epub 2014 Dec 13.
Modern recombinant vaccines are less immunogenic than conventional vaccines which require adjuvants to enhance the effect of a vaccine. Alum is being used as a standard adjuvant for protein based vaccines to augment immune response in several diseases. However, the problem associated with alum is it requires multiple doses at specific time intervals to achieve the adequate level of immunity. Currently the adjuvanticity of Poly-l-lactide microparticles as single dose immunization was explored to overcome multiple immunization and reported to be effective for several diseases. In this regard we adsorbed filarial recombinant chimeric multivalent vaccine candidates such as TV and FEP on to PLA by double emulsion method and analyzed the characterization of PLA encapsulated microparticles and evaluated its immune responses in mice. The efficacy of single dose of PLA encapsulated proteins was investigated in comparison with single dose of alum or protein alone. In mice, single dose of PLA encapsulated antigens such as TV and FEP elicited significantly high antibody titer of 50,000 and 64,000 respectively than single dose of alum adsorbed TV/FEP (6000/9000) and single dose of protein TV/FEP (3000/4000) alone. Further PLA encapsulated antigens induced higher levels of cellular proliferation together with significant (P<0.0001) levels of cytokine response [PLA-TV induced high levels of IL-4(Th2) and IFN-γ (Th1) cytokines whereas PLA-FEP showed high levels of IL-5(Th2) and IFN-γ (Th1)] indicating a balanced response elicited by PLA antigens. Overall strong humoral and cellular responses were observed for PLA encapsulated antigens compared with single dose of alum adsorbed or protein alone.
现代重组疫苗的免疫原性低于传统疫苗，传统疫苗需要佐剂来增强疫苗效果。明矾被用作基于蛋白质的疫苗的标准佐剂，以增强对多种疾病的免疫反应。然而，与明矾相关的问题是，它需要在特定时间间隔内多次给药才能达到足够的免疫水平。目前，人们探索了聚-L-丙交酯微粒作为单剂量免疫的佐剂活性，以克服多次免疫的问题，并报道其对多种疾病有效。在这方面，我们通过双乳液法将丝虫重组嵌合多价候选疫苗（如TV和FEP）吸附到聚乳酸上，分析了聚乳酸包封微粒的特性，并评估了其在小鼠体内的免疫反应。与单剂量明矾或单独蛋白质相比，研究了单剂量聚乳酸包封蛋白质的效果。在小鼠中，单剂量聚乳酸包封的抗原（如TV和FEP）分别引发了显著高于单剂量明矾吸附的TV/FEP（6000/9000）和单剂量蛋白质TV/FEP（3000/4000）的50000和64000的高抗体滴度。此外，聚乳酸包封的抗原诱导了更高水平的细胞增殖以及显著（P<0.0001）水平的细胞因子反应[聚乳酸-Tv诱导高水平的IL-4（Th2）和IFN-γ（Th1）细胞因子，而聚乳酸-FEP显示高水平的IL-5（Th2）和IFN-γ（Th1）]，表明聚乳酸抗原引发了平衡反应。总体而言，与单剂量明矾吸附或单独蛋白质相比，聚乳酸包封的抗原观察到了强烈的体液和细胞反应。
