Meza Beatriz, Ascencio Felipe, Sierra-Beltrán Arturo Pedro, Torres Javier, Angulo Carlos
Grupo de Inmunología & Vacunología, Centro de Investigaciones Biológicas del Noroeste, La Paz, B.C.S., Mexico; Laboratorio de Patogénesis Microbiana, Centro de Investigaciones Biológicas del Noroeste, La Paz, B.C.S., Mexico.
Laboratorio de Patogénesis Microbiana, Centro de Investigaciones Biológicas del Noroeste, La Paz, B.C.S., Mexico.
Infect Genet Evol. 2017 Apr;49:309-317. doi: 10.1016/j.meegid.2017.02.007. Epub 2017 Feb 7.
Helicobacter pylori have colonized the gastric mucosa of half of the population worldwide. This bacterium is classified as a definitive type I carcinogen by the World Health Organization and no effective vaccine has been found against it yet. Thus, a logical and rational vaccine design against H. pylori is necessary. Because of its tremendous complexity and elicited immune responses, the vaccine design should considered multiple antigens to enhance immune-protection, involved in the different stages of pathogenesis besides inducing a specific immune response by B- and T-cell multi-epitopes. In this study, emphasis was placed on the design of a new unique vaccine named CTB-multiHp. In silico techniques were used to design a chimeric construct consisting of cholera toxin B subunit fused to multi-epitope of urease B (residue 148-158, 188-198), cytotoxin-associated gene A (residue 584-602), neutrophil activating protein (residue 4-28), vacuolating cytotoxin gene A (residue 63-81), H. pylori adhesine A (residue77-99), heat shock protein A (residue 32-54) and gamma glutamyl transpeptidase (residue 271-293). The tertiary structure and features of the vaccine were analyzed. The chimeric protein was expressed in Escherichia coli BL21 and the serology analyses indicated that the CTB-multiHp protein produced exhibit immune-reactivity. The results showed that CTB-multiHp could be a good vaccine candidate against H. pylori. Ongoing studies will evaluate the effects of CTB-multiHp against H. pylori infection.
幽门螺杆菌已在全球一半人口的胃黏膜中定植。这种细菌被世界卫生组织列为明确的Ⅰ类致癌物,目前尚未发现针对它的有效疫苗。因此,有必要设计一种合理的抗幽门螺杆菌疫苗。由于其极其复杂并能引发免疫反应,疫苗设计应考虑多种抗原以增强免疫保护,除了通过B细胞和T细胞多表位诱导特异性免疫反应外,还应涉及发病机制的不同阶段。在本研究中,重点是设计一种名为CTB-multiHp的新型独特疫苗。利用计算机技术设计了一种嵌合构建体,该构建体由霍乱毒素B亚基与尿素酶B(第148 - 158位、188 - 198位氨基酸)、细胞毒素相关基因A(第584 - 602位氨基酸)、中性粒细胞激活蛋白(第4 - 28位氨基酸)、空泡毒素基因A(第63 - 81位氨基酸)、幽门螺杆菌黏附素A(第77 - 99位氨基酸)、热休克蛋白A(第32 - 54位氨基酸)和γ-谷氨酰转肽酶(第271 - 293位氨基酸)的多表位融合而成。分析了该疫苗的三级结构和特性。嵌合蛋白在大肠杆菌BL21中表达,血清学分析表明所产生的CTB-multiHp蛋白具有免疫反应性。结果表明,CTB-multiHp可能是一种良好的抗幽门螺杆菌疫苗候选物。正在进行的研究将评估CTB-multiHp对幽门螺杆菌感染的影响。