Fonseca D M, Bonato V L D, Silva C L, Sartori A
Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Braz J Med Biol Res. 2007 Nov;40(11):1495-504. doi: 10.1590/s0100-879x2007001100010.
We previously reported that a DNA vaccine constructed with the heat shock protein (HSP65) gene from Mycobacterium leprae (DNA-HSP65) was protective and also therapeutic in experimental tuberculosis. By the intramuscular route, this vaccine elicited a predominant Th1 response that was consistent with its protective efficacy against tuberculosis. It has been suggested that the immune response to Hsp60/65 may be the link between exposure to microorganisms and increased cardiovascular risk. Additionally, the high cholesterol levels found in atherosclerosis could modulate host immunity. In this context, we evaluated if an atherogenic diet could modulate the immune response induced by the DNA-HSP65 vaccine. C57BL/6 mice (4-6 animals per group) were initially submitted to a protocol of atherosclerosis induction and then immunized by the intramuscular or intradermal route with 4 doses of 100 microg DNA-HSP65. On day 150 (15 days after the last immunization), the animals were sacrificed and antibodies and cytokines were determined. Vaccination by the intramuscular route induced high levels of anti-Hsp65 IgG2a antibodies, but not anti-Hsp65 IgG1 antibodies and a significant production of IL-6, IFN-g and IL-10, but not IL-5, indicating a Th1 profile. Immunization by the intradermal route triggered a mixed pattern (Th1/Th2) characterized by synthesis of anti-Hsp65 IgG2a and IgG1 antibodies and production of high levels of IL-5, IL-6, IL-10, and IFN-g. These results indicate that experimentally induced atherosclerosis did not affect the ability of DNA-HSP65 to induce a predominant Th1 response that is potentially protective against tuberculosis.
我们之前报道过，用来自麻风分枝杆菌的热休克蛋白（HSP65）基因构建的DNA疫苗（DNA-HSP65）在实验性结核病中具有保护作用且有治疗效果。通过肌肉注射途径，这种疫苗引发了主要的Th1反应，这与其对结核病的保护效力一致。有人提出，对Hsp60/65的免疫反应可能是接触微生物与心血管风险增加之间的联系。此外，在动脉粥样硬化中发现的高胆固醇水平可能会调节宿主免疫。在此背景下，我们评估了致动脉粥样化饮食是否会调节DNA-HSP65疫苗诱导的免疫反应。C57BL/6小鼠（每组4-6只动物）最初接受动脉粥样硬化诱导方案，然后通过肌肉注射或皮内注射途径用4剂100微克DNA-HSP65进行免疫。在第150天（最后一次免疫后15天），处死动物并测定抗体和细胞因子。通过肌肉注射途径接种疫苗诱导产生了高水平的抗Hsp65 IgG2a抗体，但没有抗Hsp65 IgG1抗体，并且显著产生了IL-6、IFN-γ和IL-10，但没有IL-5，表明是Th1型反应。通过皮内注射途径免疫引发了一种混合模式（Th1/Th2），其特征是抗Hsp65 IgG2a和IgG1抗体的合成以及高水平的IL-5、IL-6、IL-10和IFN-γ的产生。这些结果表明，实验性诱导的动脉粥样硬化并不影响DNA-HSP65诱导主要Th1反应的能力，这种反应可能对结核病具有保护作用。
