Mahboubi Arash, Fazeli Mohammad Reza, Samadi Nasrin, Dinarvand Rasoul, Azadi Saeed
Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences.
Iran J Pharm Res. 2012 Winter;11(1):39-46.
Thimerosal, which is approximately 50% mercury by weight is a preservative widely used in vaccines since the 1930's. It meets the requirements for a preservative as set forth by Pharmacopeia challenge test and has been shown to be effective against a broad spectrum of pathogens. In July 1999, the Public Health Service agencies and vaccine manufacturers agreed that thimerosal should be reduced or eliminated in vaccines as a precautionary measure but, due to the lack of appropriate alternative, it is still extensively used in multiple dose formulations of vaccines such as hepatitis-B in developing countries. In this study the effect of the removal of thimerosal in two formulations of hepatitis B vaccines containing either aluminum hydroxide or aluminum phosphate were evaluated in Balb/c mice. These formulations were administered interperitoneally and the titer of antibody was determined by ELISA technique after 28 days. The geometric mean of antibody titer (GMT), seroconversion and seroprotection rates, ED50 and relative potency of different formulations were determined. The ED50 of thimerosal-free formulations were reduced by more than 35% in both preparations. In addition, GMT of antibody titer, seroconversion and seroprotection indicated significantly higher immunogenicity for thimerosal free formulations for both aluminum phosphate and hydroxide adjuvants.
硫柳汞，按重量计约含50%的汞，自20世纪30年代以来一直是疫苗中广泛使用的防腐剂。它符合药典挑战试验规定的防腐剂要求，并已证明对多种病原体有效。1999年7月，公共卫生服务机构和疫苗制造商一致认为，作为一项预防措施，应减少或消除疫苗中的硫柳汞，但由于缺乏合适的替代品，它仍在发展中国家的多剂量疫苗制剂（如乙型肝炎疫苗）中广泛使用。在本研究中，在Balb/c小鼠中评估了去除硫柳汞对两种分别含有氢氧化铝或磷酸铝的乙型肝炎疫苗制剂的影响。这些制剂通过腹腔注射给药，28天后通过ELISA技术测定抗体滴度。测定了不同制剂的抗体滴度几何平均值（GMT）、血清转化率和血清保护率、ED50和相对效力。两种制剂中无硫柳汞制剂的ED50均降低了35%以上。此外，对于磷酸铝和氢氧化铝佐剂，无硫柳汞制剂的抗体滴度GMT、血清转化率和血清保护率均显示出显著更高的免疫原性。
