Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab 160062, India.
Int J Pharm. 2012 Feb 28;423(2):297-302. doi: 10.1016/j.ijpharm.2011.11.039. Epub 2011 Dec 6.
The aggregation of tetanus toxoid leads to reduced bioavailability of the vaccine and failure of immunization programmes in many parts of the globe. One of the main reasons for denaturation and aggregation of tetanus toxoid formulations is agitation of the protein during transport. We have identified that agitation leads to collapse of the gel matrix of aluminium hydroxide which is used as an adjuvant in these preparations. This results in desorption of the toxoid from the matrix, which then loses its antigenicity due to agitation-induced denaturation of the protein. We show that incorporation of some compatible osmolytes like sorbitol, glucose and arginine, but not trehalose, is able to protect the adjuvant matrix from degradation, and retain the integrity of the vaccine preparation in terms of its antigenicity.
破伤风类毒素的聚集会导致疫苗生物利用度降低，并使许多地区的免疫接种计划失败。破伤风类毒素制剂发生变性和聚集的主要原因之一是在运输过程中蛋白质的搅拌。我们已经发现，搅拌会导致用作这些制剂佐剂的氢氧化铝凝胶基质崩溃。这导致类毒素从基质中解吸，然后由于搅拌引起的蛋白质变性而失去抗原性。我们表明，加入一些相容的渗透剂，如山梨糖醇、葡萄糖和精氨酸，但不是海藻糖，可以保护佐剂基质不受降解，并保持疫苗制剂的完整性，包括其抗原性。
