Shokri Mahdi, Roohvand Farzin, Alimohammadian Mohammad Hossein, Ebrahimirad Mina, Ajdary Soheila
Immunology Department, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran 13169-43551, Iran; Virology Department, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran 13169-43551, Iran.
Virology Department, Pasteur Institute of Iran, 69 Pasteur Ave., Tehran 13169-43551, Iran.
Mol Immunol. 2016 Aug;76:108-15. doi: 10.1016/j.molimm.2016.06.010. Epub 2016 Jul 16.
Adjuvants have a key role in subunit vaccine formulations to generate protective immune responses. Herein, we present results of a comparative study on mice immunized with E. coli-derived rLmSTI1 antigen formulated with Montanide ISA 720 (Ag-M720) and ISA 50-V2 (Ag-M50) adjuvants against Leishmania major (L. major). Groups of BALB/c mice were immunized with either Ag-M720 or Ag-M50 by 3 subcutaneous injections with 3-week intervals. Three weeks after the last injection mice were challenged by L. major promastigotes. Immune responses were evaluated before, 3 weeks, and 8 weeks after challenge. Results indicated lower parasite and lesion size in vaccinated mice (the lowest for Ag-M720 indicating the best protection) which correlated with higher IFN-γ induction in immunized groups (Ag-M720 and Ag-M50) compared to control (PBS/adjuvant alone) group. Immune assays showed comparable IFN-γ, total IgG, IgG1 and IgG2a levels for Ag-M720 and Ag-M50 immunized mice but higher induction of IL-4, IL-10 and IL-17 in Ag-M50 and the highest IL-10/IL-17 ratio in Ag-M720 group followed by Ag-M50 and control groups. Altogether, results indicated that lower induction of IL-4, IL-10 and IL-17 cytokines (and/or higher ratio of IL-10/IL-17) despite comparable IFN-γ might be the reason for the superior protection in Ag-M720 group.
佐剂在亚单位疫苗配方中对于产生保护性免疫反应起着关键作用。在此,我们展示了一项对比研究的结果,该研究针对用大肠杆菌衍生的rLmSTI1抗原与Montanide ISA 720(Ag-M720)和ISA 50-V2(Ag-M50)佐剂配制而成的疫苗免疫的小鼠,对抗硕大利什曼原虫(L. major)。将BALB/c小鼠分组,分别用Ag-M720或Ag-M50进行3次皮下注射,间隔3周。最后一次注射后3周,用硕大利什曼原虫前鞭毛体攻击小鼠。在攻击前、攻击后3周和8周评估免疫反应。结果表明,接种疫苗的小鼠体内寄生虫和损伤大小较低(Ag-M720组最低,表明保护效果最佳),这与免疫组(Ag-M720和Ag-M50)相比对照组(单独的PBS/佐剂)中更高的IFN-γ诱导相关。免疫分析显示,Ag-M720和Ag-M50免疫的小鼠中IFN-γ、总IgG、IgG1和IgG2a水平相当,但Ag-M50组中IL-4、IL-10和IL-17的诱导更高,Ag-M720组中IL-10/IL-17比值最高,其次是Ag-M50组和对照组。总之,结果表明,尽管IFN-γ相当,但IL-4、IL-10和IL-17细胞因子诱导较低(和/或IL-10/IL-17比值较高)可能是Ag-M720组具有更好保护效果的原因。