Taleghani Nastaran, Bozorg Ali, Azimi Amin, Zamani Homa
Biotechnology Department, College of Science, University of Tehran, Tehran, Iran.
Department of Cell Therapy and Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
APMIS. 2019 Mar;127(3):150-157. doi: 10.1111/apm.12927.
Monophosphoryl lipid A (MPL), a purified and detoxified product of lipopolysaccharide (LPS) of Salmonella minnesota R595, has been used as an adjuvant in different vaccines. In this study, the efficacy of human papillomaviruses (HPV) and hepatitis B virus (HBV) vaccines formulated with aluminum hydroxide combined with two different synthetic MPLs, 3D-(6-acyl)-PHAD or 3D-PHAD, or aluminum hydroxide combined with the mixtures of such MPLs, has been assessed. The immunogenicity in female BALB/c mice was verified by two intramuscular injections of differently formulated HPV and HBV vaccines and the total immunoglobulin G (IgG) antibody response was considered to compare the employed adjuvants. As verified experimentally, a mixture of 3D-(6-acyl)-PHAD and 3D-PHAD was able to induce significantly higher antibody titer than that of either 3D-(6-acyl)-PHAD or 3D-PHAD, when used individually. Interestingly, based on the responses achieved in terms of the total antibody levels, such mixture of synthetic MPLs was found to be even more effective than the bacterially derived MPL. Accordingly, the obtained results indicated that, if designed appropriately, synthetic MPL molecules could provide improved adjuvanticity with high level of consistency.
单磷酰脂质A（MPL）是明尼苏达沙门氏菌R595脂多糖（LPS）的纯化解毒产物，已被用作不同疫苗的佐剂。在本研究中，评估了用氢氧化铝与两种不同的合成MPL（3D-(6-酰基)-PHAD或3D-PHAD）组合配制的人乳头瘤病毒（HPV）和乙型肝炎病毒（HBV）疫苗，或氢氧化铝与此类MPL混合物组合配制的疫苗的效力。通过两次肌肉注射不同配方的HPV和HBV疫苗来验证雌性BALB/c小鼠的免疫原性，并通过总免疫球蛋白G（IgG）抗体反应来比较所使用的佐剂。实验证明，当单独使用时，3D-(6-酰基)-PHAD和3D-PHAD的混合物能够诱导出比单独使用3D-(6-酰基)-PHAD或3D-PHAD显著更高的抗体滴度。有趣的是，基于总抗体水平所获得的反应，发现这种合成MPL的混合物甚至比细菌来源 的MPL更有效。因此，所获得 的结果表明，如果设计得当，合成MPL分子可以提供具有高度一致性的更好的佐剂性。
