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首页> 外文期刊>Vaccine >Poly(D,L)-lactide-co-glycolide (PLGA) microspheres as immunoadjuvant for Brugia malayi antigens
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Poly(D,L)-lactide-co-glycolide (PLGA) microspheres as immunoadjuvant for Brugia malayi antigens

机译：聚（D，L）-丙交酯-乙交酯（PLGA）微球作为马来西亚马来酸抗原的免疫佐剂

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Recently we identified in Brugia malayi adult worm extract (BmA) a pro-inflammatory 54-68 kDa SDS-PAGE resolved fraction F6 that protects the host from the parasite via Th1/Th2 type responses. We are currently investigating F6 as a potential source of vaccine candidate(s) and the present study is aimed at investigating the suitability of poly(D,L)-lactide-co-glycolide microspheres (PLGA-Ms) as immunoadjuvant for the antigen administration in a single dose. PLGA-Ms were prepared aseptically by a modified double emulsion (w/o/w) solvent evaporation technique and their size, shape, antigen adsorption efficiency, in-process stability, and antigen release were characterized. Swiss mice were immunized by a single subcutaneous administration of BmA and F6 adsorbed on PLGA-Ms (lactide:glycolide ratios 50:50 and 75:25) and the immune responses were compared with administration of 1 or 2 doses of plain BmA and F6. Specific IgG, IgG1, IgG2a, IgG2b, IgE levels in serum, cellular-proliferative response and release of IFN-gamma, TNF-alpha and nitric oxide from the cells of immunized host in response to the antigens/LPS/Con A challenge and antibody-dependant cellular cytotoxicity (ADCC) to parasite life stages were determined. The average size of PLGA-Ms 50:50 was smaller than the size of PLGA-Ms 75:25 and the % antigen adsorption efficiency of PLGA-Ms 50:50 was greater than PLGA-Ms 75:25. Single shot injection of PLGA-Ms 50:50/75:25-BmA/F6 produced better and stronger IgG, IgG1/IgG2a and cell-mediated immune responses than even two injections of plain BmA or F6. Further, PLGA-Ms 50:50-F6 produced stronger responses than PLGA-Ms 50:50-BmA. Anti-PLGA-Ms 50:50-F6 antibodies elicited higher ADCC response to infective larval and microfilarial stages of the parasite than anti-PLGA-Ms 75:25-F6 antibodies. The findings demonstrate that PLGA-Ms 50:50 is an excellent adjuvant for use with F6 in a single administration. This is the first ever report on PLGA as immunoadjuvant for filarial antigens.
机译：最近，我们在马来亚布鲁吉虫（Brugia malayi）成虫提取物中（BmA）确定了促炎的54-68 kDa SDS-PAGE解析级分F6，可通过Th1 / Th2型反应保护宿主免受寄生虫侵害。我们目前正在研究F6作为候选疫苗的潜在来源，并且本研究旨在研究聚（D，L）-丙交酯-共-乙交酯乙交酯微球（PLGA-Ms）作为抗原佐剂的免疫佐剂的适用性。一次服用。 PLGA-Ms是通过改良的双乳剂（w / o / w）溶剂蒸发技术无菌制备的，并对其大小，形状，抗原吸附效率，过程稳定性和抗原释放进行了表征。通过单次皮下注射吸附在PLGA-Ms上的BmA和F6（丙交酯：乙交酯的比例为50:50和75:25）对瑞士小鼠进行免疫，并将免疫应答与1或2剂量的普通BmA和F6进行比较。血清中的特异性IgG，IgG1，IgG2a，IgG2b，IgE水平，细胞增殖反应以及对抗原/ LPS / Con A挑战和抗体的免疫宿主细胞中IFN-γ，TNF-α和一氧化氮的释放确定了对寄生虫生命阶段的依赖细胞毒性（ADCC）。 PLGA-Ms 50:50的平均大小小于PLGA-Ms 75:25的大小，PLGA-Ms 50:50的％抗原吸附效率大于PLGA-Ms 75:25。单次注射PLGA-Ms 50：50/75：25-BmA / F6甚至比两次普通BmA或F6注射都能产生更好，更强的IgG，IgG1 / IgG2a和细胞介导的免疫反应。此外，PLGA-Ms 50：50-F6比PLGA-Ms 50：50-BmA产生更强的响应。与抗PLGA-Ms 75：25-F6抗体相比，抗PLGA-Ms 50：50-F6抗体引起对寄生虫的感染性幼虫和微丝期更高的ADCC反应。这些发现表明，PLGA-Ms 50:50是单次给药与F6一起使用的极好的佐剂。这是关于PLGA作为丝状抗原免疫佐剂的首次报道。

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