Molecular Biology Department Finlay Institute, Ave. 27 No. 19805, La Lisa, La Havana, Cuba, AP. 16017, CP11600.
BMC Immunol. 2013;14 Suppl 1(Suppl 1):S11. doi: 10.1186/1471-2172-14-S1-S11. Epub 2013 Feb 25.
The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.
新型结核疫苗的研发已成为科学界的主要目标之一。蛋白抗原已广泛被探索作为亚单位结核疫苗,但脂质抗原在这种疫苗中同样具有重要作用。本研究旨在证明由分枝杆菌 smegmatis (Ms) 脂质提取物组成的脂质体配方作为结核候选疫苗的潜力。我们评估了该配方的免疫原性,以及其在 BALB/c 小鼠中对结核分枝杆菌 (MTb) 抗原的交叉反应性。我们测定了结核患者和皮试阳性 (PPD+) 或阴性 (PPD-) 的健康受试者血清中的抗脂质体 IgG 反应。与所有组相比,用卡介苗 (BCG) 免疫的动物中检测到抗脂质体 IgG 显著增加 (p<0.05),与用 Ms 脂质体 (LMs) 免疫的动物相比,用 LMs 与铝佐剂 (LMs-A) 或阴性对照组 (磷酸盐缓冲盐水,PBS) 免疫的动物也显著增加。关于针对 MTb 细胞壁抗原 (CWA) 混合物的交叉反应性,与阴性对照和铝佐剂脂质体 (LMs-A) 或蒙坦尼德 (LMs-M) 相比,用 BCG 和 LMs 免疫的动物中 IgG 水平显著升高 (p<0.05)。此外,与 PPD+和 PPD-健康受试者相比,肺结核患者血清中的抗脂质体 IgG 反应明显更高 (p<0.001),这表明这些抗原在体内 MTb 感染期间表达。这些结果提供了一些证据,表明含有 Ms 总脂质提取物的脂质体可能作为结核候选疫苗。